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Teixeira MR, Silva T, Felício RDFM, Bozza PT, Zembrzuski VM, de Mello Neto CB, da Fonseca ACP, Kohlrausch FB, Salum KCR. Exploring the genetic contribution in obesity: An overview of dopaminergic system genes. Behav Brain Res 2025; 480:115401. [PMID: 39689745 DOI: 10.1016/j.bbr.2024.115401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 12/13/2024] [Accepted: 12/13/2024] [Indexed: 12/19/2024]
Abstract
Obesity is a widespread global health concern that affects a significant portion of the population and is associated with reduced quality of life, morbidity, and mortality. It is considered a pandemic, with its prevalence constantly rising in Western countries. As a result, numerous studies have focused on understanding the elements that contribute to obesity. Researchers have focused on neurotransmitters in the brain to develop weight management drugs that regulate food intake. This review explores the literature on genetic influences on dopaminergic processes to determine whether genetic variation has an association with obesity in reward-responsive regions, including mesolimbic efferent and mesocortical areas. Various neurotransmitters play an essential role in regulating food intake, such as dopamine which controls through mesolimbic circuits in the brain that modulate food reward. Appetite stimulation, including primary reinforcers such as food, leads to an increase in dopamine release in the reward centers of the brain. This release is related to motivation and reinforcement, which determines the motivational weighting of the reinforcer. Changes in dopamine expression can lead to hedonic eating behaviors and contribute to the development of obesity. Genetic polymorphisms have been investigated due to their potential role in modulating the risk of obesity and eating behaviors. Therefore, it is crucial to assess the impact of genetic alterations that disrupt this pathway on the obesity phenotype.
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Affiliation(s)
- Myrela Ribeiro Teixeira
- Human Genetics Laboratory, Department of General Biology, Institute of Biology, Federal Fluminense University, Professor Marcos Waldemar de Freitas Reis Street, Niterói, RJ 24210-201, Brazil; Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), 4365 Brazil Avenue, Leônidas Deane Pavilion, Rio de Janeiro, RJ 21040-360, Brazil; Postgraduate Program in Science and Biotechnology, Department of General Biology, Institute of Biology, Federal Fluminense University, Professor Marcos Waldemar de Freitas Reis Street, Niterói, RJ 24210-201, Brazil
| | - Tamara Silva
- Genetics Laboratory, Grande Rio University/AFYA, Professor José de Souza Herdy Street, 1160 - Jardim Vinte e Cinco de Agosto, Duque de Caxias, RJ 25071-202, Brazil
| | - Rafaela de Freitas Martins Felício
- Congenital Malformation Epidemiology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), 4365 Brazil Avenue, Leônidas Deane Pavilion, Rio de Janeiro, RJ 21040-360, Brazil
| | - Patrícia Torres Bozza
- Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), 4365 Brazil Avenue, Rio de Janeiro, RJ 21040‑360, Brazil
| | - Verônica Marques Zembrzuski
- Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), 4365 Brazil Avenue, Leônidas Deane Pavilion, Rio de Janeiro, RJ 21040-360, Brazil
| | - Cicero Brasileiro de Mello Neto
- Human Genetics Laboratory, Department of General Biology, Institute of Biology, Federal Fluminense University, Professor Marcos Waldemar de Freitas Reis Street, Niterói, RJ 24210-201, Brazil; Postgraduate Program in Science and Biotechnology, Department of General Biology, Institute of Biology, Federal Fluminense University, Professor Marcos Waldemar de Freitas Reis Street, Niterói, RJ 24210-201, Brazil
| | - Ana Carolina Proença da Fonseca
- Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), 4365 Brazil Avenue, Leônidas Deane Pavilion, Rio de Janeiro, RJ 21040-360, Brazil; Genetics Laboratory, Grande Rio University/AFYA, Professor José de Souza Herdy Street, 1160 - Jardim Vinte e Cinco de Agosto, Duque de Caxias, RJ 25071-202, Brazil; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), 4365 Brazil Avenue, Rio de Janeiro, RJ 21040‑360, Brazil; Postgraduate Program in Translational Biomedicine, Grande Rio University/AFYA, Professor José de Souza Herdy Street, 1160 - Jardim Vinte e Cinco de Agosto, Duque de Caxias, RJ 25071-202, Brazil
| | - Fabiana Barzotto Kohlrausch
- Human Genetics Laboratory, Department of General Biology, Institute of Biology, Federal Fluminense University, Professor Marcos Waldemar de Freitas Reis Street, Niterói, RJ 24210-201, Brazil
| | - Kaio Cezar Rodrigues Salum
- Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), 4365 Brazil Avenue, Leônidas Deane Pavilion, Rio de Janeiro, RJ 21040-360, Brazil; Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Professor Rodolpho Paulo Rocco Street, 255, University City, Rio de Janeiro, RJ 21941-617, Brazil.
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Cam Y, Kocum CG, Houska TK, Konrad ER, Schweizer TA, Will MJ. Palatable feeding effects on expression and reinstatement of morphine conditioned place preference in male and female rats. Behav Brain Res 2025; 477:115320. [PMID: 39489431 DOI: 10.1016/j.bbr.2024.115320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 10/02/2024] [Accepted: 10/31/2024] [Indexed: 11/05/2024]
Abstract
While many environmental factors are known to play a factor in the recovery and risk of relapse for individuals with opioid use disorder (OUD), the role of diet has been relatively unexplored. Individuals with OUD demonstrate unhealthy diet choices with an exaggerated craving for palatable "junk food," yet this relationship has not been well characterized. The present study begins to examine this relationship by first determining the influence of palatable food access on the expression of conditioned rewarding properties of acute morphine exposure in male and female rats. Following the establishment of morphine conditioned place preference (CPP) in all rats, morphine CPP expression was assessed following intra-accumbens (Acb) administration of the µ-opioid receptor agonist D-Ala2,NMe-Phe4,Glyol5-enkephalin (DAMGO) + 20 min access to no diet (ND) or high-fat (HF), in counter-balanced order. Next, all rats received 12 sessions of extinction training before CPP expression was first assessed following no treatment, then again following counter-balanced ND and HF treatments. The results showed that both male and female rats expressed similar levels of morphine CPP. Subsequent examination of morphine CPP expression revealed that HF treatment significantly reduced morphine CPP expression in males, but not females, compared to ND treatment. Neither HF or ND treatment produced morphine CPP reinstatement in either males or females following extinction. In summary, the impact of palatable feeding on the expression of conditioned drug seeking may be sex-specific and more sensitive prior to extinction.
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MESH Headings
- Animals
- Male
- Female
- Morphine/pharmacology
- Morphine/administration & dosage
- Extinction, Psychological/drug effects
- Extinction, Psychological/physiology
- Rats
- Analgesics, Opioid/pharmacology
- Rats, Sprague-Dawley
- Reward
- Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology
- Feeding Behavior/drug effects
- Feeding Behavior/physiology
- Narcotics/pharmacology
- Narcotics/administration & dosage
- Conditioning, Operant/drug effects
- Conditioning, Operant/physiology
- Sex Characteristics
- Diet, High-Fat
- Receptors, Opioid, mu/metabolism
- Receptors, Opioid, mu/agonists
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Affiliation(s)
- Yonca Cam
- Department of Psychological Sciences, University of Missouri, Columbia, MO 65211, USA.
| | - Courtney G Kocum
- Department of Psychological Sciences, University of Missouri, Columbia, MO 65211, USA
| | - Tabitha K Houska
- Department of Psychological Sciences, University of Missouri, Columbia, MO 65211, USA
| | - Ella R Konrad
- Department of Psychological Sciences, University of Missouri, Columbia, MO 65211, USA
| | - Tim A Schweizer
- Department of Psychological Sciences, University of Missouri, Columbia, MO 65211, USA
| | - Matthew J Will
- Department of Psychological Sciences, University of Missouri, Columbia, MO 65211, USA
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Demangeat T, Loison L, Huré M, do Rego J, Déchelotte P, Achamrah N, Coëffier M, Ribet D. Gut Microbiota Regulates Food Intake in a Rodent Model of Intermittent Limited Access to Palatable Food. Int J Eat Disord 2025; 58:459-465. [PMID: 39623908 PMCID: PMC11861880 DOI: 10.1002/eat.24339] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 11/10/2024] [Accepted: 11/11/2024] [Indexed: 02/27/2025]
Abstract
OBJECTIVE Binge-eating disorder is characterized by recurrent episodes of consumption of large amounts of food within a short period of time, without compensatory purging behaviors. This disease is a major public health issue and is associated with numerous comorbidities, encompassing anxiety and depression. The gut microbiota has been proposed to be an important player in the onset or maintenance of eating disorders. Here, we aim to better delineate the potential role of the gut microbiota in binge-eating disorder. METHOD We used a model of intermittent limited access to palatable food where eight-week-old C57Bl/6 female mice had access during 2 h, every 2 days over a 10-day period, to a high-fat/high-sucrose diet. Half of the animals received antibiotics to deplete their gut microbiota. Eating behavior and other behavioral parameters were compared between groups. RESULTS We observed an increase in food intake as well as tachyphagia during the intermittent access to high-fat/high-sucrose diet. We demonstrate that gut microbiota depletion further increases food intake during these episodes and promotes binge-eating behavior. No impact on anxiety or depressive-like behavior was observed in animals. DISCUSSION These results show that the gut microbiota is involved in the control of food intake during episodes of binge-eating. This strengthens the potential role of the gut bacteria in binge-eating disorder and the interest in therapeutic strategies aiming at modulating the patients' gut microbiota to treat this eating disorder.
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Affiliation(s)
- Thomas Demangeat
- Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR1073 Nutrition, Inflammation and Microbiota‐Gut‐Brain Axis, CHU Rouen, CIC‐CRB 1404Department of NutritionRouenFrance
| | - Léa Loison
- Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR1073 Nutrition, Inflammation and Microbiota‐Gut‐Brain Axis, CHU Rouen, CIC‐CRB 1404Department of NutritionRouenFrance
| | - Marion Huré
- Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR1073 Nutrition, Inflammation and Microbiota‐Gut‐Brain Axis, CHU Rouen, CIC‐CRB 1404Department of NutritionRouenFrance
| | - Jean‐Luc do Rego
- Univ Rouen Normandie, INSERM US51, CNRS UAR2026, Behavioural Analysis Platform SCACHeRacLeSRouenFrance
| | - Pierre Déchelotte
- Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR1073 Nutrition, Inflammation and Microbiota‐Gut‐Brain Axis, CHU Rouen, CIC‐CRB 1404Department of NutritionRouenFrance
| | - Najate Achamrah
- Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR1073 Nutrition, Inflammation and Microbiota‐Gut‐Brain Axis, CHU Rouen, CIC‐CRB 1404Department of NutritionRouenFrance
| | - Moïse Coëffier
- Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR1073 Nutrition, Inflammation and Microbiota‐Gut‐Brain Axis, CHU Rouen, CIC‐CRB 1404Department of NutritionRouenFrance
| | - David Ribet
- Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR1073 Nutrition, Inflammation and Microbiota‐Gut‐Brain Axis, CHU Rouen, CIC‐CRB 1404Department of NutritionRouenFrance
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Schoukroun F, Herbeaux K, Andry V, Goumon Y, Bourdy R, Befort K. Binge Eating and Obesity Differentially Alter the Mesolimbic Endocannabinoid System in Rats. Int J Mol Sci 2025; 26:1240. [PMID: 39941025 PMCID: PMC11818181 DOI: 10.3390/ijms26031240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/28/2025] [Accepted: 01/29/2025] [Indexed: 02/16/2025] Open
Abstract
Binge eating disorder (BED) is characterized by the rapid overconsumption of palatable food in a short amount of time, often leading to obesity. The endocannabinoid system (ECS), a system involved in palatable food intake, is highly expressed in reward-related brain regions and is involved in both obesity and BED. This study investigated differences in ECS expression between these conditions using male Wistar rats exposed to specific regimen over six weeks: a non-access group (NA) with a standard diet, a continuous access group (CA) with free-choice high-fat high-sugar (fcHFHS) diet modeling obesity, and an intermittent access group (IA) with intermittent fcHFHS access modeling BED. Food intake was measured, and brain tissues from the nucleus accumbens (NAc), dorsal striatum (DS), ventral tegmental area (VTA), and rostromedial tegmental nucleus (RMTg) were analyzed for ECS expression using qPCR and mass spectrometry. We identified differential ECS expression across palatable food access groups, with variations depending on the brain region (striatal or mesencephalic). Correlation analyses revealed ECS dysregulations dependent on the type (fat or sucrose) and quantity of palatable food consumed. Comparative network analysis revealed co-regulation patterns of ECS-related genes with specific signatures associated with each eating pattern, highlighting RMTg as a key region for future research in eating behavior.
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Affiliation(s)
- Florian Schoukroun
- Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Université de Strasbourg, UMR 7364, CNRS, 12 Rue Goethe, 67000 Strasbourg, France; (F.S.); (K.H.)
| | - Karin Herbeaux
- Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Université de Strasbourg, UMR 7364, CNRS, 12 Rue Goethe, 67000 Strasbourg, France; (F.S.); (K.H.)
| | - Virginie Andry
- Institut des Neurosciences Cellulaires et Intégratives (INCI), UPR 3212, CNRS, 8 Allée du Général Rouvillois, 67000 Strasbourg, France; (V.A.); (Y.G.)
| | - Yannick Goumon
- Institut des Neurosciences Cellulaires et Intégratives (INCI), UPR 3212, CNRS, 8 Allée du Général Rouvillois, 67000 Strasbourg, France; (V.A.); (Y.G.)
| | - Romain Bourdy
- Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Université de Strasbourg, UMR 7364, CNRS, 12 Rue Goethe, 67000 Strasbourg, France; (F.S.); (K.H.)
| | - Katia Befort
- Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Université de Strasbourg, UMR 7364, CNRS, 12 Rue Goethe, 67000 Strasbourg, France; (F.S.); (K.H.)
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Awad G, Aubry AS, Olmstead MC, Befort K. Altered reward processing following sucrose bingeing in male and female mice. Nutr Neurosci 2024; 27:1269-1282. [PMID: 38488783 DOI: 10.1080/1028415x.2024.2324232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Abstract
Objectives: Binge eating disorder (BED) is the most prevalent eating disorder associated with multiple adverse health effects, especially mental health issues, including substance use disorders and mood and anxiety disorders. Given these high comorbidities, the objective of our study was to examine whether bingeing behavior would lead to altered perception of reinforcing properties of EtOH and changes in well-being. Methods: We used a sucrose bingeing model based on an intermittent access paradigm with a two-bottle choice, without fasting, in male and female mice. We examined the effect of 2-week sucrose paradigm on ethanol-reinforcing properties using a conditioned place preference test (CPP). Well-being, anxiety- and depressive-like behavioral tests were performed to assess emotional state following 2 and 8-week sucrose bingeing paradigm. Results: Mice with intermittent access to sucrose developed a binge-like behavior assessed by higher sucrose intake and escalation rate during the 1st hour of access, in comparison with mice with a continuous sucrose access. We show for the first time that sucrose bingeing in mice modifies positive reinforcing effect of EtOH in a CPP paradigm without marked alteration of emotional state. Interestingly, prolonging sucrose access for 8 weeks revealed an exacerbated bingeing behavior in female mice, and some signs of emotional state alterations in female with continuous access. Discussion: In sum, our findings broaden the understanding of behavioral alterations associated with bingeing, highlighting the need to investigate addictive-like properties of palatable food both in male and female mice.
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Affiliation(s)
- Gaëlle Awad
- Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Centre de la Recherche Nationale Scientifique, 10.13039/501100003768Université de Strasbourg, Strasbourg, France
| | - Anne-Sophie Aubry
- Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Centre de la Recherche Nationale Scientifique, 10.13039/501100003768Université de Strasbourg, Strasbourg, France
| | - Mary C Olmstead
- Department of Psychology, Center for Neuroscience Studies, Queen's University, Kingston, Canada
| | - Katia Befort
- Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Centre de la Recherche Nationale Scientifique, 10.13039/501100003768Université de Strasbourg, Strasbourg, France
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Gancarz AM, Parmar R, Shwani T, Cobb MM, Crawford MN, Watson JR, Evans L, Kausch MA, Werner CT, Dietz DM. Adolescent exposure to sucrose increases cocaine-mediated behaviours in adulthood via Smad3. Addict Biol 2023; 28:e13346. [PMID: 38017636 DOI: 10.1111/adb.13346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 09/21/2023] [Accepted: 09/22/2023] [Indexed: 11/30/2023]
Abstract
Adolescence, a critical period of developmental period, is marked by neurobiological changes influenced by environmental factors. Here, we show how exposure to sucrose, which is ubiquitously available in modern diets, results in changes in behavioural response to cocaine as an adult. Rats were given daily access to either 10% sucrose or water during the adolescent period (PND28-42). Following this period, rats are left undisturbed until they reach adulthood. In adulthood, rats were tested for (i) acquisition of a low dose of cocaine, (ii) progressive ratio (PR) test, and (iii) resistance to punished cocaine taking. Sucrose exposure resulted in significant alterations in all behavioural measures. To determine the neurobiological mechanisms leading to such behavioural adaptations, we find that adolescent sucrose exposure results in an upregulation of the transcription factor Smad3 in the nucleus accumbens (NAc) when compared with water-exposed controls. Transiently blocking the active form of this transcription factor (HSV-dnSmad3) during adolescence mitigated the enhanced cocaine vulnerability-like behaviours observed in adulthood. These findings suggest that prior exposure to sucrose during adolescence can heighten the reinforcing effects of cocaine. Furthermore, they identify the TGF-beta pathway and Smad3 as playing a key role in mediating enduring and long-lasting adaptations that contribute to sucrose-induced susceptibility to cocaine. Taken together, these results have important implications for development and suggest that adolescent sucrose exposure may persistently enhance the susceptibility to substance abuse.
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Affiliation(s)
- Amy M Gancarz
- Department of Psychology, California State University, Bakersfield, California, USA
- Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
- Clinical and Research Institute on Addictions, University at Buffalo, Buffalo, New York, USA
| | - Raveena Parmar
- Department of Psychology, California State University, Bakersfield, California, USA
| | - Treefa Shwani
- Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Moriah M Cobb
- Department of Psychology, California State University, Bakersfield, California, USA
| | - Michelle N Crawford
- Department of Psychology, California State University, Bakersfield, California, USA
| | - Jacob R Watson
- Department of Psychology, California State University, Bakersfield, California, USA
| | - Lisa Evans
- Department of Psychology, California State University, Bakersfield, California, USA
| | - Michael A Kausch
- Department of Psychology, California State University, Bakersfield, California, USA
- Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Craig T Werner
- Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
| | - David M Dietz
- Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
- Clinical and Research Institute on Addictions, University at Buffalo, Buffalo, New York, USA
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Huang S, Ghasem Ardabili N, Davidson TL, Riley AL. Western diet consumption does not impact the rewarding and aversive effects of morphine in male Sprague-Dawley rats. Physiol Behav 2023; 270:114317. [PMID: 37541607 DOI: 10.1016/j.physbeh.2023.114317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 07/31/2023] [Accepted: 08/02/2023] [Indexed: 08/06/2023]
Abstract
The impacts of high-fat and/or high-sugar diets on opioid-induced effects are well documented; however, little is known about the effect of such diet on the affective responses to opiates. To address this issue, in the present experiment male Sprague-Dawley rats were given ad libitum access to a western-style diet (high in saturated fat and sugar) or a standard laboratory chow diet beginning in adolescence and continuing into adulthood at which point they were trained in a combined conditioned taste avoidance (CTA)/conditioned place preference (CPP) procedure to assess the aversive and rewarding effects of morphine, respectively. On four conditioning cycles, animals were given access to a novel saccharin solution, injected with morphine (1 mg/kg or 5 mg/kg), and then placed on one side of a place preference chamber. Animals were then tested for place preference and saccharin preference. All subjects injected with morphine displayed significant avoidance of the morphine-associated solution (CTA) and preferred the side associated with the drug (CPP). Furthermore, there were no differences between the two diet groups, indicating that chronic exposure to the western diet had no impact on the affective properties of morphine (despite increasing caloric intake, body weight, body fat and lean body mass). Given previously reported increases in drug self-administration in animals with a history of western-diet consumption, this study suggests that western-diet exposure may increase drug intake via mechanisms other than changes in the rewarding or aversive effects of the drug.
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Affiliation(s)
- Shihui Huang
- Psychopharmacology Laboratory, Department of Neuroscience, Center for Neuroscience and Behavior, American University, 4400 Massachusetts Ave, NW., Washington, D.C. 20016, United States.
| | - Negar Ghasem Ardabili
- Psychopharmacology Laboratory, Department of Neuroscience, Center for Neuroscience and Behavior, American University, 4400 Massachusetts Ave, NW., Washington, D.C. 20016, United States
| | - Terry L Davidson
- Laboratory for Behavioral and Neural Homeostasis, Department of Neuroscience, Center for Neuroscience and Behavior, American University, Washington, D.C. 20016, United States
| | - Anthony L Riley
- Psychopharmacology Laboratory, Department of Neuroscience, Center for Neuroscience and Behavior, American University, 4400 Massachusetts Ave, NW., Washington, D.C. 20016, United States.
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Bourdy R, Befort K. The Role of the Endocannabinoid System in Binge Eating Disorder. Int J Mol Sci 2023; 24:ijms24119574. [PMID: 37298525 DOI: 10.3390/ijms24119574] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 05/23/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023] Open
Abstract
Eating disorders are multifactorial disorders that involve maladaptive feeding behaviors. Binge eating disorder (BED), the most prevalent of these in both men and women, is characterized by recurrent episodes of eating large amounts of food in a short period of time, with a subjective loss of control over eating behavior. BED modulates the brain reward circuit in humans and animal models, which involves the dynamic regulation of the dopamine circuitry. The endocannabinoid system plays a major role in the regulation of food intake, both centrally and in the periphery. Pharmacological approaches together with research using genetically modified animals have strongly highlighted a predominant role of the endocannabinoid system in feeding behaviors, with the specific modulation of addictive-like eating behaviors. The purpose of the present review is to summarize our current knowledge on the neurobiology of BED in humans and animal models and to highlight the specific role of the endocannabinoid system in the development and maintenance of BED. A proposed model for a better understanding of the underlying mechanisms involving the endocannabinoid system is discussed. Future research will be necessary to develop more specific treatment strategies to reduce BED symptoms.
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Affiliation(s)
- Romain Bourdy
- Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Université de Strasbourg, UMR7364, CNRS, 12 Rue Goethe, 67000 Strasbourg, France
| | - Katia Befort
- Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Université de Strasbourg, UMR7364, CNRS, 12 Rue Goethe, 67000 Strasbourg, France
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Cuesta S, Burdisso P, Segev A, Kourrich S, Sperandio V. Gut colonization by Proteobacteria alters host metabolism and modulates cocaine neurobehavioral responses. Cell Host Microbe 2022; 30:1615-1629.e5. [PMID: 36323315 PMCID: PMC9669251 DOI: 10.1016/j.chom.2022.09.014] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 07/22/2022] [Accepted: 09/14/2022] [Indexed: 11/11/2022]
Abstract
Gut-microbiota membership is associated with diverse neuropsychological outcomes, including substance use disorders (SUDs). Here, we use mice colonized with Citrobacter rodentium or the human γ-Proteobacteria commensal Escherichia coli HS as a model to examine the mechanistic interactions between gut microbes and host responses to cocaine. We find that cocaine exposure increases intestinal norepinephrine levels that are sensed through the bacterial adrenergic receptor QseC to promote intestinal colonization of γ-Proteobacteria. Colonized mice show enhanced host cocaine-induced behaviors. The neuroactive metabolite glycine, a bacterial nitrogen source, is depleted in the gut and cerebrospinal fluid of colonized mice. Systemic glycine repletion reversed, and γ-Proteobacteria mutated for glycine uptake did not alter the host response to cocaine. γ-Proteobacteria modulated glycine levels are linked to cocaine-induced transcriptional plasticity in the nucleus accumbens through glutamatergic transmission. The mechanism outline here could potentially be exploited to modulate reward-related brain circuits that contribute to SUDs.
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Affiliation(s)
- Santiago Cuesta
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
| | - Paula Burdisso
- Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET-UNR) and Plataforma Argentina de Biología Estructural y Metabolómica (PLABEM), Rosario, Santa Fe, Argentina
| | - Amir Segev
- Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX 75390, USA
| | - Saïd Kourrich
- Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Canada; The Center of Excellence in Research on Orphan Diseases - Foundation Courtois, Université du Québec à Montréal, Montréal, QC, Canada; Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, Canada
| | - Vanessa Sperandio
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
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10
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Peters KZ, Naneix F. The role of dopamine and endocannabinoid systems in prefrontal cortex development: Adolescence as a critical period. Front Neural Circuits 2022; 16:939235. [PMID: 36389180 PMCID: PMC9663658 DOI: 10.3389/fncir.2022.939235] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Accepted: 10/14/2022] [Indexed: 01/07/2023] Open
Abstract
The prefrontal cortex plays a central role in the control of complex cognitive processes including action control and decision making. It also shows a specific pattern of delayed maturation related to unique behavioral changes during adolescence and allows the development of adult cognitive processes. The adolescent brain is extremely plastic and critically vulnerable to external insults. Related to this vulnerability, adolescence is also associated with the emergence of numerous neuropsychiatric disorders involving alterations of prefrontal functions. Within prefrontal microcircuits, the dopamine and the endocannabinoid systems have widespread effects on adolescent-specific ontogenetic processes. In this review, we highlight recent advances in our understanding of the maturation of the dopamine system and the endocannabinoid system in the prefrontal cortex during adolescence. We discuss how they interact with GABA and glutamate neurons to modulate prefrontal circuits and how they can be altered by different environmental events leading to long-term neurobiological and behavioral changes at adulthood. Finally, we aim to identify several future research directions to help highlight gaps in our current knowledge on the maturation of these microcircuits.
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Affiliation(s)
- Kate Zara Peters
- Sussex Neuroscience, School of Psychology, University of Sussex, Falmer, United Kingdom
| | - Fabien Naneix
- The Rowett Institute, University of Aberdeen, Aberdeen, United Kingdom,*Correspondence: Fabien Naneix
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11
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Neurobiological Mechanisms Modulating Emotionality, Cognition and Reward-Related Behaviour in High-Fat Diet-Fed Rodents. Int J Mol Sci 2022; 23:ijms23147952. [PMID: 35887310 PMCID: PMC9317076 DOI: 10.3390/ijms23147952] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 07/15/2022] [Accepted: 07/16/2022] [Indexed: 01/27/2023] Open
Abstract
Affective and substance-use disorders are associated with overweight and obesity-related complications, which are often due to the overconsumption of palatable food. Both high-fat diets (HFDs) and psychostimulant drugs modulate the neuro-circuitry regulating emotional processing and metabolic functions. However, it is not known how they interact at the behavioural level, and whether they lead to overlapping changes in neurobiological endpoints. In this literature review, we describe the impact of HFDs on emotionality, cognition, and reward-related behaviour in rodents. We also outline the effects of HFD on brain metabolism and plasticity involving mitochondria. Moreover, the possible overlap of the neurobiological mechanisms produced by HFDs and psychostimulants is discussed. Our in-depth analysis of published results revealed that HFDs have a clear impact on behaviour and underlying brain processes, which are largely dependent on the developmental period. However, apart from the studies investigating maternal exposure to HFDs, most of the published results involve only male rodents. Future research should also examine the biological impact of HFDs in female rodents. Further knowledge about the molecular mechanisms linking stress and obesity is a crucial requirement of translational research and using rodent models can significantly advance the important search for risk-related biomarkers and the development of clinical intervention strategies.
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12
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Ródenas-González F, Blanco-Gandía MC, Miñarro J, Rodríguez-Arias M. Effects of ketosis on cocaine-induced reinstatement in male mice. Neurosci Lett 2022; 778:136619. [PMID: 35395325 DOI: 10.1016/j.neulet.2022.136619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/31/2022] [Accepted: 04/03/2022] [Indexed: 10/18/2022]
Abstract
In recent years, the benefits of the ketogenic diet (KD) on different psychiatric disorders have been gaining attention, but the substance abuse field is still unexplored. Some studies have reported that palatable food can modulate the rewarding effects of cocaine, but the negative metabolic consequences rule out the recommendation of using it as a complementary treatment. Thus, the main aim of this study was to evaluate the effects of the KD on cocaine conditioned place preference (CPP) during acquisition, extinction, and reinstatement. 41 OF1 male mice were employed to assess the effects of the KD on a 10 mg/kg cocaine-induced CPP. Animals were divided into three groups: SD, KD, and KD after the Post-Conditioning test. The results revealed that, while access to the KD did not block CPP acquisition, it did significantly reduce the number of sessions required to extinguish the drug-associated memories and it blocked the priming-induced reinstatement.
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Affiliation(s)
- Francisco Ródenas-González
- Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de Valencia, Valencia, Spain
| | - M Carmen Blanco-Gandía
- Departamento de Psicología y Sociología, Facultad de Ciencias Sociales y Humanas, Universidad de Zaragoza, Teruel, Spain
| | - José Miñarro
- Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de Valencia, Valencia, Spain
| | - Marta Rodríguez-Arias
- Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de Valencia, Valencia, Spain.
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13
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Blanco-Gandia MC, Montagud-Romero S, Rodríguez-Arias M. Binge eating and psychostimulant addiction. World J Psychiatry 2021; 11:517-529. [PMID: 34631457 PMCID: PMC8475000 DOI: 10.5498/wjp.v11.i9.517] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 05/13/2021] [Accepted: 07/27/2021] [Indexed: 02/06/2023] Open
Abstract
Many of the various factors, characteristics, and variables involved in the addictive process can determine an individual’s vulnerability to develop drug addiction. Hedonic eating, based on pleasure rather than energy needs, modulates the same reward circuits, as do drugs of abuse. According to the last report of the World Health Organization, the worldwide obesity rate has more than doubled since 1980, reaching especially critical levels in children and young people, who are overexposed to high-fat, high-sugar, energy-dense foods. Over the past few decades, there has been an increase in the number of studies focused on how eating disorders can lead to the development of drug addiction and on the comorbidity that exists between the two disorders. Herein, we review the most recent research on the subject, focusing especially on animal models of binge eating disorders and drug addiction. The complex profile of patients with substance use and binge eating disorders requires an integrated response to dually diagnosed patients. Nutritional patterns should be considered an important variable in the treatment of substance use disorders, and future studies need to focus on specific treatments and interventions in individuals who show a special vulnerability to shift from one addiction to the other.
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Affiliation(s)
| | | | - Marta Rodríguez-Arias
- Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Valencia 46010, Spain
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14
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Ródenas-González F, Blanco-Gandía MDC, Pascual M, Molari I, Guerri C, López JM, Rodríguez-Arias M. A limited and intermittent access to a high-fat diet modulates the effects of cocaine-induced reinstatement in the conditioned place preference in male and female mice. Psychopharmacology (Berl) 2021; 238:2091-2103. [PMID: 33786639 DOI: 10.1007/s00213-021-05834-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 03/22/2021] [Indexed: 12/01/2022]
Abstract
RATIONALE Palatable food and drugs of abuse activate common neurobiological pathways and numerous studies suggest that fat consumption increases vulnerability to drug abuse. In addition, preclinical reports show that palatable food may relieve craving for drugs, showing that an ad libitum access to a high-fat diet (HFD) can reduce cocaine-induced reinstatement. OBJECTIVE The main aim of the present study was to evaluate the effect of a limited and intermittent exposure to HFD administered during the extinction and reinstatement processes of a cocaine-induced conditioned place preference (CPP). METHODS Male and female mice underwent the 10 mg/kg cocaine CPP. From post-conditioning onwards, animals were divided into four groups: SD (standard diet); HFD-MWF with 2-h access to the HFD on Mondays, Wednesdays, and Fridays; HFD-24h, with 1-h access every day; and HFD-Ext with 1-h access to the HFD before each extinction session. RESULTS Our results showed that all HFD administrations blocked reinstatement in males, while only the HFD-MWF was able to inhibit reinstatement in females. In addition, HFD-Ext males needed fewer sessions to extinguish the preference, which suggests that administration of fat before being exposed to the environmental cues is effective to extinguish drug-related memories. HFD did not affect Oprμ gene expression but increased CB1r gene expression in the striatum in HFD-Ext males. CONCLUSIONS These results support that palatable food could act as an alternative reward to cocaine, accelerating extinction and blocking reinstatement, these effects being sex specific.
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Affiliation(s)
- Francisco Ródenas-González
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain
| | | | - María Pascual
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain
- Department of Molecular and Cellular Pathology of Alcohol, Principe Felipe Research Center, C/Eduardo Primo Yúfera 3, 46012, Valencia, Spain
- Department of Physiology, School of Medicine, Universitat de Valencia, Valencia, Spain
- Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain
| | - Irene Molari
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain
| | - Consuelo Guerri
- Department of Molecular and Cellular Pathology of Alcohol, Principe Felipe Research Center, C/Eduardo Primo Yúfera 3, 46012, Valencia, Spain
- Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain
| | - José Miñarro López
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain
- Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain
| | - Marta Rodríguez-Arias
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain.
- Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain.
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15
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Blanco-Gandía MDC, Ródenas-González F, Pascual M, Reguilón MD, Guerri C, Miñarro J, Rodríguez-Arias M. Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice. Nutrients 2021; 13:nu13072167. [PMID: 34202492 PMCID: PMC8308435 DOI: 10.3390/nu13072167] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/19/2021] [Accepted: 06/22/2021] [Indexed: 01/26/2023] Open
Abstract
The classic ketogenic diet is a diet high in fat, low in carbohydrates, and well-adjusted proteins. The reduction in glucose levels induces changes in the body’s metabolism, since the main energy source happens to be ketone bodies. Recent studies have suggested that nutritional interventions may modulate drug addiction. The present work aimed to study the potential effects of a classic ketogenic diet in modulating alcohol consumption and its rewarding effects. Two groups of adult male mice were employed in this study, one exposed to a standard diet (SD, n = 15) and the other to a ketogenic diet (KD, n = 16). When a ketotic state was stable for 7 days, animals were exposed to the oral self-administration paradigm to evaluate the reinforcing and motivating effects of ethanol. Rt-PCR analyses were performed evaluating dopamine, adenosine, CB1, and Oprm gene expression. Our results showed that animals in a ketotic state displayed an overall decrease in ethanol consumption without changes in their motivation to drink. Gene expression analyses point to several alterations in the dopamine, adenosine, and cannabinoid systems. Our results suggest that nutritional interventions may be a useful complementary tool in treating alcohol-use disorders.
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Affiliation(s)
| | - Francisco Ródenas-González
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010 Valencia, Spain; (F.R.-G.); (M.P.); (M.D.R.); (J.M.)
| | - María Pascual
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010 Valencia, Spain; (F.R.-G.); (M.P.); (M.D.R.); (J.M.)
- Department of Molecular and Cellular Pathology of Alcohol, Principe Felipe Research Center, C/Eduardo Primo Yúfera 3, 46012 Valencia, Spain;
- Department of Physiology, School of Medicine, Universitat de Valencia, Avda. Blasco Ibáñez, 15, 46010 Valencia, Spain
| | - Marina Daiana Reguilón
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010 Valencia, Spain; (F.R.-G.); (M.P.); (M.D.R.); (J.M.)
| | - Consuelo Guerri
- Department of Molecular and Cellular Pathology of Alcohol, Principe Felipe Research Center, C/Eduardo Primo Yúfera 3, 46012 Valencia, Spain;
| | - José Miñarro
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010 Valencia, Spain; (F.R.-G.); (M.P.); (M.D.R.); (J.M.)
| | - Marta Rodríguez-Arias
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010 Valencia, Spain; (F.R.-G.); (M.P.); (M.D.R.); (J.M.)
- Correspondence: ; Tel.: +34-963864637
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16
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Pairing Binge Drinking and a High-Fat Diet in Adolescence Modulates the Inflammatory Effects of Subsequent Alcohol Consumption in Mice. Int J Mol Sci 2021; 22:ijms22105279. [PMID: 34067897 PMCID: PMC8157004 DOI: 10.3390/ijms22105279] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 05/08/2021] [Accepted: 05/15/2021] [Indexed: 12/12/2022] Open
Abstract
Alcohol binge drinking (BD) and poor nutritional habits are two frequent behaviors among many adolescents that alter gut microbiota in a pro-inflammatory direction. Dysbiotic changes in the gut microbiome are observed after alcohol and high-fat diet (HFD) consumption, even before obesity onset. In this study, we investigate the neuroinflammatory response of adolescent BD when combined with a continuous or intermittent HFD and its effects on adult ethanol consumption by using a self-administration (SA) paradigm in mice. The inflammatory biomarkers IL-6 and CX3CL1 were measured in the striatum 24 h after BD, 3 weeks later and after the ethanol (EtOH) SA. Adolescent BD increased alcohol consumption in the oral SA and caused a greater motivation to seek the substance. Likewise, mice with intermittent access to HFD exhibited higher EtOH consumption, while the opposite effect was found in mice with continuous HFD access. Biochemical analyses showed that after BD and three weeks later, striatal levels of IL-6 and CX3CL1 were increased. In addition, in saline-treated mice, CX3CL1 was increased after continuous access to HFD. After oral SA procedure, striatal IL-6 was increased only in animals exposed to BD and HFD. In addition, striatal CX3CL1 levels were increased in all BD- and HFD-exposed groups. Overall, our findings show that adolescent BD and intermittent HFD increase adult alcohol intake and point to neuroinflammation as an important mechanism modulating this interaction.
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17
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Converging vulnerability factors for compulsive food and drug use. Neuropharmacology 2021; 196:108556. [PMID: 33862029 DOI: 10.1016/j.neuropharm.2021.108556] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 03/29/2021] [Accepted: 04/03/2021] [Indexed: 12/12/2022]
Abstract
Highly palatable foods and substance of abuse have intersecting neurobiological, metabolic and behavioral effects relevant for understanding vulnerability to conditions related to food (e.g., obesity, binge eating disorder) and drug (e.g., substance use disorder) misuse. Here, we review data from animal models, clinical populations and epidemiological evidence in behavioral, genetic, pathophysiologic and therapeutic domains. Results suggest that consumption of highly palatable food and drugs of abuse both impact and conversely are regulated by metabolic hormones and metabolic status. Palatable foods high in fat and/or sugar can elicit adaptation in brain reward and withdrawal circuitry akin to substances of abuse. Intake of or withdrawal from palatable food can impact behavioral sensitivity to drugs of abuse and vice versa. A robust literature suggests common substrates and roles for negative reinforcement, negative affect, negative urgency, and impulse control deficits, with both highly palatable foods and substances of abuse. Candidate genetic risk loci shared by obesity and alcohol use disorders have been identified in molecules classically associated with both metabolic and motivational functions. Finally, certain drugs may have overlapping therapeutic potential to treat obesity, diabetes, binge-related eating disorders and substance use disorders. Taken together, data are consistent with the hypotheses that compulsive food and substance use share overlapping, interacting substrates at neurobiological and metabolic levels and that motivated behavior associated with feeding or substance use might constitute vulnerability factors for one another. This article is part of the special issue on 'Vulnerabilities to Substance Abuse'.
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18
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de Sa Nogueira D, Bourdy R, Filliol D, Awad G, Andry V, Goumon Y, Olmstead MC, Befort K. Binge sucrose-induced neuroadaptations: A focus on the endocannabinoid system. Appetite 2021; 164:105258. [PMID: 33864862 DOI: 10.1016/j.appet.2021.105258] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 03/24/2021] [Accepted: 04/06/2021] [Indexed: 12/26/2022]
Abstract
Binge eating, the defining feature of binge eating disorder (BED), is associated with a number of adverse health outcomes as well as a reduced quality of life. Animals, like humans, selectively binge on highly palatable food suggesting that the behaviour is driven by hedonic, rather than metabolic, signals. Given the links to both reward processing and food intake, this study examined the contribution of the endocannabinoid system (ECS) to binge-like eating in rats. Separate groups were given intermittent (12 h) or continuous (24 h) access to 10% sucrose and food over 28 days, with only the 12 h access group displaying excessive sucrose intake within a discrete period of time (i.e., binge eating). Importantly, this group also exhibited alterations in ECS transcripts and endocannabinoid levels in brain reward regions, including an increase in cannabinoid receptor 1 (CB1R) mRNA in the nucleus accumbens as well as changes in endocannabinoid levels in the prefrontal cortex and hippocampus. We then tested whether different doses (1 and 3 mg/kg) of a CB1R antagonist, Rimonabant, modify binge-like intake or the development of a conditioned place preference (CPP) to sucrose. CB1R blockade reduced binge-like intake of sucrose and blocked a sucrose CPP, but only in rats that had undergone 28 days of sucrose consumption. These findings indicate that sucrose bingeing alters the ECS in reward-related areas, modifications that exacerbate the effect of CB1R blockade on sucrose reward. Overall, our results broaden the understanding of neural alterations associated with bingeing eating and demonstrate an important role for CB1R mechanisms in reward processing. In addition, these findings have implications for understanding substance abuse, which is also characterized by excessive and maladaptive intake, pointing towards addictive-like properties of palatable food.
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Affiliation(s)
- David de Sa Nogueira
- Université de Strasbourg, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Centre de la Recherche Nationale Scientifique, 12 rue Goethe, F-67000, Strasbourg France; Current Address: Brain Health Institute, Rutgers University and Rutgers Biomedical and Health Sciences, Piscataway, NJ, USA
| | - Romain Bourdy
- Université de Strasbourg, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Centre de la Recherche Nationale Scientifique, 12 rue Goethe, F-67000, Strasbourg France
| | - Dominique Filliol
- Université de Strasbourg, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Centre de la Recherche Nationale Scientifique, 12 rue Goethe, F-67000, Strasbourg France
| | - Gaëlle Awad
- Université de Strasbourg, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Centre de la Recherche Nationale Scientifique, 12 rue Goethe, F-67000, Strasbourg France
| | - Virginie Andry
- Institut des Neurosciences Cellulaires et Intégratives (INCI), UPR 3212, CNRS, 8 Allée du Général Rouvillois, 67000, Strasbourg, France
| | - Yannick Goumon
- Institut des Neurosciences Cellulaires et Intégratives (INCI), UPR 3212, CNRS, 8 Allée du Général Rouvillois, 67000, Strasbourg, France
| | - Mary C Olmstead
- Department of Psychology, Center for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada
| | - Katia Befort
- Université de Strasbourg, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Centre de la Recherche Nationale Scientifique, 12 rue Goethe, F-67000, Strasbourg France.
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19
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Angoa-Pérez M, Kuhn DM. Evidence for Modulation of Substance Use Disorders by the Gut Microbiome: Hidden in Plain Sight. Pharmacol Rev 2021; 73:571-596. [PMID: 33597276 PMCID: PMC7896134 DOI: 10.1124/pharmrev.120.000144] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The gut microbiome modulates neurochemical function and behavior and has been implicated in numerous central nervous system (CNS) diseases, including developmental, neurodegenerative, and psychiatric disorders. Substance use disorders (SUDs) remain a serious threat to the public well-being, yet gut microbiome involvement in drug abuse has received very little attention. Studies of the mechanisms underlying SUDs have naturally focused on CNS reward circuits. However, a significant body of research has accumulated over the past decade that has unwittingly provided strong support for gut microbiome participation in drug reward. β-Lactam antibiotics have been employed to increase glutamate transporter expression to reverse relapse-induced release of glutamate. Sodium butyrate has been used as a histone deacetylase inhibitor to prevent drug-induced epigenetic alterations. High-fat diets have been used to alter drug reward because of the extensive overlap of the circuitry mediating them. This review article casts these approaches in a different light and makes a compelling case for gut microbiome modulation of SUDs. Few factors alter the structure and composition of the gut microbiome more than antibiotics and a high-fat diet, and butyrate is an endogenous product of bacterial fermentation. Drugs such as cocaine, alcohol, opiates, and psychostimulants also modify the gut microbiome. Therefore, their effects must be viewed on a complex background of cotreatment-induced dysbiosis. Consideration of the gut microbiome in SUDs should have the beneficial effects of expanding the understanding of SUDs and aiding in the design of new therapies based on opposing the effects of abused drugs on the host's commensal bacterial community. SIGNIFICANCE STATEMENT: Proposed mechanisms underlying substance use disorders fail to acknowledge the impact of drugs of abuse on the gut microbiome. β-Lactam antibiotics, sodium butyrate, and high-fat diets are used to modify drug seeking and reward, overlooking the notable capacity of these treatments to alter the gut microbiome. This review aims to stimulate research on substance abuse-gut microbiome interactions by illustrating how drugs of abuse share with antibiotics, sodium butyrate, and fat-laden diets the ability to modify the host microbial community.
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Affiliation(s)
- Mariana Angoa-Pérez
- Research and Development Service, John D. Dingell VA Medical Center, and Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan
| | - Donald M Kuhn
- Research and Development Service, John D. Dingell VA Medical Center, and Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan
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20
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Tsan L, Décarie-Spain L, Noble EE, Kanoski SE. Western Diet Consumption During Development: Setting the Stage for Neurocognitive Dysfunction. Front Neurosci 2021; 15:632312. [PMID: 33642988 PMCID: PMC7902933 DOI: 10.3389/fnins.2021.632312] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 01/19/2021] [Indexed: 01/18/2023] Open
Abstract
The dietary pattern in industrialized countries has changed substantially over the past century due to technological advances in agriculture, food processing, storage, marketing, and distribution practices. The availability of highly palatable, calorically dense foods that are shelf-stable has facilitated a food environment where overconsumption of foods that have a high percentage of calories derived from fat (particularly saturated fat) and sugar is extremely common in modern Westernized societies. In addition to being a predictor of obesity and metabolic dysfunction, consumption of a Western diet (WD) is related to poorer cognitive performance across the lifespan. In particular, WD consumption during critical early life stages of development has negative consequences on various cognitive abilities later in adulthood. This review highlights rodent model research identifying dietary, metabolic, and neurobiological mechanisms linking consumption of a WD during early life periods of development (gestation, lactation, juvenile and adolescence) with behavioral impairments in multiple cognitive domains, including anxiety-like behavior, learning and memory function, reward-motivated behavior, and social behavior. The literature supports a model in which early life WD consumption leads to long-lasting neurocognitive impairments that are largely dissociable from WD effects on obesity and metabolic dysfunction.
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Affiliation(s)
- Linda Tsan
- Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, United States.,Department of Biological Sciences, Human and Evolutionary Biology Section, University of Southern California, Los Angeles, CA, United States
| | - Léa Décarie-Spain
- Department of Biological Sciences, Human and Evolutionary Biology Section, University of Southern California, Los Angeles, CA, United States
| | - Emily E Noble
- Department of Foods and Nutrition, University of Georgia, Athens, GA, United States
| | - Scott E Kanoski
- Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, United States.,Department of Biological Sciences, Human and Evolutionary Biology Section, University of Southern California, Los Angeles, CA, United States
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21
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Clasen MM, Riley AL, Davidson TL. Hippocampal-Dependent Inhibitory Learning and Memory Processes in the Control of Eating and Drug Taking. Curr Pharm Des 2020; 26:2334-2352. [PMID: 32026771 DOI: 10.2174/1381612826666200206091447] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 12/11/2019] [Indexed: 12/11/2022]
Abstract
As manifestations of excessive and uncontrolled intake, obesity and drug addiction have generated much research aimed at identifying common neuroadaptations that could underlie both disorders. Much work has focused on changes in brain reward and motivational circuitry that can overexcite eating and drug-taking behaviors. We suggest that the regulation of both behaviors depends on balancing excitation produced by stimuli associated with food and drug rewards with the behavioral inhibition produced by physiological "satiety" and other stimuli that signal when those rewards are unavailable. Our main hypothesis is that dysregulated eating and drug use are consequences of diet- and drug-induced degradations in this inhibitory power. We first outline a learning and memory mechanism that could underlie the inhibition of both food and drug-intake, and we describe data that identifies the hippocampus as a brain substrate for this mechanism. We then present evidence that obesitypromoting western diets (WD) impair the operation of this process and generate pathophysiologies that disrupt hippocampal functioning. Next, we present parallel evidence that drugs of abuse also impair this same learning and memory process and generate similar hippocampal pathophysiologies. We also describe recent findings that prior WD intake elevates drug self-administration, and the implications of using drugs (i.e., glucagon-like peptide- 1 agonists) that enhance hippocampal functioning to treat both obesity and addiction are also considered. We conclude with a description of how both WD and drugs of abuse could initiate a "vicious-cycle" of hippocampal pathophysiology and impaired hippocampal-dependent behavioral inhibition.
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Affiliation(s)
- Matthew M Clasen
- Department of Psychology, Program in Neuroscience, Williams College, Williamstown, MA 01267, United States
| | - Anthony L Riley
- Department of Neuroscience, Center for Behavioral Neuroscience, American University, Washington, DC 20016, United States
| | - Terry L Davidson
- Department of Neuroscience, Center for Behavioral Neuroscience, American University, Washington, DC 20016, United States
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22
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Duart-Castells L, Cantacorps L, López-Arnau R, Montagud-Romero S, Puster B, Mera P, Serra D, Camarasa J, Pubill D, Valverde O, Escubedo E. Effects of High-Fat Diet and Maternal Binge-Like Alcohol Consumption and Their Influence on Cocaine Response in Female Mice Offspring. Int J Neuropsychopharmacol 2020; 24:77-88. [PMID: 32951039 PMCID: PMC7816686 DOI: 10.1093/ijnp/pyaa074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 09/08/2020] [Accepted: 09/17/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Prenatal alcohol exposure is a leading cause of neurobehavioral and neurocognitive deficits collectively known as fetal alcohol spectrum disorders, including eating disorders and increased risk for substance abuse as very common issues. In this context, the present study aimed to assess the interaction between prenatal and lactation alcohol exposure (PLAE) and a high-fat diet (HFD) during childhood and adolescence. METHODS Pregnant C57BL/6 mice underwent a procedure for alcohol binge drinking during gestation and lactation periods. Subsequently, PLAE female offspring were fed with an HFD for 8 weeks, and thereafter, nutrition-related parameters as well as their response to cocaine were assessed. RESULTS In our model, feeding young females with an HFD increased their triglyceride blood levels but did not induce overweight compared with those fed with a standard diet. Moreover, PLAE affected how females responded to the fatty diet as they consumed less food than water-exposed offspring, consistent with a lower gain of body weight. HFD increased the psychostimulant effects of cocaine. Surprisingly, PLAE reduced the locomotor responses to cocaine without modifying cocaine-induced reward. Moreover, PLAE prevented the striatal overexpression of cannabinoid 1 receptors induced by an HFD and induced an alteration of myelin damage biomarker in the prefrontal cortex, an effect that was mitigated by an HFD-based feeding. CONCLUSION Therefore, in female offspring, some effects triggered by one of these factors, PLAE or an HFD, were blunted by the other, suggesting a close interaction between the involved mechanisms.
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Affiliation(s)
- Leticia Duart-Castells
- Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB) Faculty of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain
| | - Lídia Cantacorps
- Neurobiology of Behavior Research Group (GReNeC-NeuroBio), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
| | - Raúl López-Arnau
- Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB) Faculty of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain
| | - Sandra Montagud-Romero
- Neurobiology of Behavior Research Group (GReNeC-NeuroBio), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
| | - Brigitte Puster
- Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB) Faculty of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain
| | - Paula Mera
- Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, Institute of Biomedicine (IBUB), Universitat de Barcelona, Barcelona, Spain,Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Dolors Serra
- Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, Institute of Biomedicine (IBUB), Universitat de Barcelona, Barcelona, Spain,Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Jorge Camarasa
- Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB) Faculty of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain
| | - David Pubill
- Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB) Faculty of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain,Correspondence: David Pubill, PhD, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII, 27–31, 08028, Barcelona, Spain ()
| | - Olga Valverde
- Neurobiology of Behavior Research Group (GReNeC-NeuroBio), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain,Neuroscience Research Programme. IMIM-Hospital del Mar Research Institute, Barcelona, Spain
| | - Elena Escubedo
- Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB) Faculty of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain
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23
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Darcey VL, Serafine KM. Omega-3 Fatty Acids and Vulnerability to Addiction: Reviewing Preclinical and Clinical Evidence. Curr Pharm Des 2020; 26:2385-2401. [DOI: 10.2174/1381612826666200429094158] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 04/06/2020] [Indexed: 01/05/2023]
Abstract
Omega-3 (N3) fatty acids are dietary nutrients that are essential for human health. Arguably, one of their most critical contributions to health is their involvement in the structure and function of the nervous system. N3 fatty acids accumulate in neuronal membranes through young adulthood, becoming particularly enriched in a brain region known to be the locus of cognitive control of behavior-the prefrontal cortex (PFC). The PFC undergoes a surge in development during adolescence, coinciding with a life stage when dietary quality and intake of N3 fatty acids tend to be suboptimal. Such low intake may impact neurodevelopment and normative development of cognitive functions suggested to be protective for the risk of subsequent substance and alcohol use disorders (UD). While multiple genetic and environmental factors contribute to risk for and resilience to substance and alcohol use disorders, mounting evidence suggests that dietary patterns early in life may also modulate cognitive and behavioral factors thought to elevate UD risk (e.g., impulsivity and reward sensitivity). This review aims to summarize the literature on dietary N3 fatty acids during childhood and adolescence and risk of executive/ cognitive or behavioral dysfunction, which may contribute to the risk of subsequent UD. We begin with a review of the effects of N3 fatty acids in the brain at the molecular to cellular levels–providing the biochemical mechanisms ostensibly supporting observed beneficial effects. We continue with a review of cognitive, behavioral and neurodevelopmental features thought to predict early substance and alcohol use in humans. This is followed by a review of the preclinical literature, largely demonstrating that dietary manipulation of N3 fatty acids contributes to behavioral changes that impact drug sensitivity. Finally, a review of the available evidence in human literature, suggesting an association between dietary N3 fatty and neurodevelopmental profiles associated with risk of adverse outcomes including UD. We conclude with a brief summary and call to action for additional research to extend the current understanding of the impact of dietary N3 fatty acids and the risk of drug and alcohol UD.
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Affiliation(s)
- Valerie L. Darcey
- Georgetown University, Interdisciplinary Program in Neuroscience, Washington DC, United States
| | - Katherine M. Serafine
- Department of Psychology, The University of Texas at El Paso, El Paso, TX 79968, United States
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24
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Blanco-Gandía MC, Miñarro J, Rodríguez-Arias M. Common Neural Mechanisms of Palatable Food Intake and Drug Abuse: Knowledge Obtained with Animal Models. Curr Pharm Des 2020; 26:2372-2384. [DOI: 10.2174/1381612826666200213123608] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 01/23/2020] [Indexed: 02/07/2023]
Abstract
Eating is necessary for survival, but it is also one of the great pleasures enjoyed by human beings.
Research to date shows that palatable food can be rewarding in a similar way to drugs of abuse, indicating
considerable comorbidity between eating disorders and substance-use disorders. Analysis of the common characteristics
of both types of disorder has led to a new wave of studies proposing a Gateway Theory of food as a vulnerability
factor that modulates the development of drug addiction. The homeostatic and hedonic mechanisms of
feeding overlap with some of the mechanisms implicated in drug abuse and their interaction plays a crucial role in
the development of drug addiction. Studies in animal models have shown how palatable food sensitizes the reward
circuit and makes individuals more sensitive to other substances of abuse, such as cocaine or alcohol. However,
when palatable food is administered continuously as a model of obesity, the consequences are different, and
studies provide controversial data. In the present review, we will cover the main homeostatic and hedonic mechanisms
that regulate palatable food intake behavior and will explain, using animal models, how different types of
diet and their intake patterns have direct consequences on the rewarding effects of psychostimulants and ethanol.
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Affiliation(s)
- Maria C. Blanco-Gandía
- Department of Psychology and Sociology, University of Zaragoza, C/ Ciudad Escolar s/n, 44003, Teruel, Spain
| | - José Miñarro
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicologia, Universitat de Valencia, Avda. Blasco Ibanez, 21, 46010 Valencia, Spain
| | - Marta Rodríguez-Arias
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicologia, Universitat de Valencia, Avda. Blasco Ibanez, 21, 46010 Valencia, Spain
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25
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Duart-Castells L, Blanco-Gandía MC, Ferrer-Pérez C, Puster B, Pubill D, Miñarro J, Escubedo E, Rodríguez-Arias M. Cross-reinstatement between 3,4-methylenedioxypyrovalerone (MDPV) and cocaine using conditioned place preference. Prog Neuropsychopharmacol Biol Psychiatry 2020; 100:109876. [PMID: 31991149 DOI: 10.1016/j.pnpbp.2020.109876] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 01/16/2020] [Accepted: 01/21/2020] [Indexed: 12/12/2022]
Abstract
3,4-Methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) considered to be a cocaine-like psychostimulant. The substitution of an established illicit drug as cocaine with an NPS is a pattern of use reported among drug users. The aim of this study was to investigate the relationship between cocaine and MDPV in the reinstatement of the conditioned place preference (CPP) paradigm, in order to establish whether there is cross-reinstatement between the two psychostimulants. Four experimental groups of male OF1 mice were subjected to the CPP paradigm: MDPV-MDPV, Cocaine-Cocaine, Cocaine-MDPV, and MDPV-Cocaine. The first drug refers to the substance with which the animals were conditioned (cocaine 10 mg/kg or MDPV 2 mg/kg) and the s to the substance with which preference was reinstated. In parallel, G9a, ΔFosB, CB1 receptor, CDK5, Arc and c-Fos were determined in ventral striatum. MDPV induced CPP at doses from 1 to 4 mg/kg. Although 2 mg/kg MDPV induced a stronger psychostimulant effect than 10 mg/kg cocaine, both doses seemed to be equivalent in their rewarding properties. However, memories associated with MDPV required more time to be extinguished. MDPV and cocaine restore drug-seeking behavior with respect to each other, although relapse into drug-taking is always more pronounced with the conditioning drug. The fact that MDPV-treated mice show increased ΔFosB protein levels correlates with its longer extinction time and points to the activation of neuroplasticity mechanisms that persist for at least 12 days. Moreover, in these animals, a priming-dose of cocaine can trigger significant neuroplasticity, implying a high vulnerability to cocaine abuse.
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Affiliation(s)
- Leticia Duart-Castells
- Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain
| | - M Carmen Blanco-Gandía
- Department of Psychology and Sociology, University of Zaragoza, C/ Ciudad Escolar s/n, 44003 Teruel, Spain
| | - Carmen Ferrer-Pérez
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010 Valencia, Spain
| | - Brigitte Puster
- Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain
| | - David Pubill
- Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain
| | - José Miñarro
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010 Valencia, Spain
| | - Elena Escubedo
- Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain.
| | - Marta Rodríguez-Arias
- Unit of Research Psychobiology of Drug Dependence, Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010 Valencia, Spain
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26
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Abstract
This paper is the fortieth consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2017 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (1), the roles of these opioid peptides and receptors in pain and analgesia in animals (2) and humans (3), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (4), opioid peptide and receptor involvement in tolerance and dependence (5), stress and social status (6), learning and memory (7), eating and drinking (8), drug abuse and alcohol (9), sexual activity and hormones, pregnancy, development and endocrinology (10), mental illness and mood (11), seizures and neurologic disorders (12), electrical-related activity and neurophysiology (13), general activity and locomotion (14), gastrointestinal, renal and hepatic functions (15), cardiovascular responses (16), respiration and thermoregulation (17), and immunological responses (18).
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Affiliation(s)
- Richard J Bodnar
- Department of Psychology and Neuropsychology Doctoral Sub-Program, Queens College, City University of New York, CUNY, 65-30 Kissena Blvd., Flushing, NY, 11367, United States.
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27
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Cornejo MP, Castrogiovanni D, Schiöth HB, Reynaldo M, Marie J, Fehrentz JA, Perello M. Growth hormone secretagogue receptor signalling affects high-fat intake independently of plasma levels of ghrelin and LEAP2, in a 4-day binge eating model. J Neuroendocrinol 2019; 31:e12785. [PMID: 31469195 DOI: 10.1111/jne.12785] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 08/16/2019] [Accepted: 08/27/2019] [Indexed: 12/25/2022]
Abstract
The growth hormone secretagogue receptor (GHSR) is a G protein-coupled receptor that is highly expressed in the central nervous system. GHSR acts as a receptor for ghrelin and for liver-expressed antimicrobial peptide 2 (LEAP2), which blocks ghrelin-evoked activity. GHSR also displays ligand-independent activity, including a high constitutive activity that signals in the absence of ghrelin and is reduced by LEAP2. GHSR activity modulates a variety of food intake-related behaviours, including binge eating. Previously, we reported that GHSR-deficient mice daily and time-limited exposed to a high-fat (HF) diet display an attenuated binge-like HF intake compared to wild-type mice. In the present study, we aimed to determine whether ligand-independent GHSR activity affects binge-like HF intake in a 4-day binge-like eating protocol. We found that plasma levels of ghrelin and LEAP2 were not modified in mice exposed to this binge-like eating protocol. Moreover, systemic administration of ghrelin or LEAP2 did not alter HF intake in our experimental conditions. Interestingly, we found that central administration of LEAP2 or K-(D-1-Nal)-FwLL-NH2 , which are both blockers of constitutive GHSR activity, reduced binge-like HF intake, whereas central administration of ghrelin or the ghrelin-evoked GHSR activity blockers [D-Lys3]-GHRP-6 and JMV2959 did not modify binge-like HF intake. Taken together, current data indicate that GHSR activity in the brain affects binge-like HF intake in mice independently of plasma levels of ghrelin and LEAP2.
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Affiliation(s)
- María Paula Cornejo
- Laboratory of Neurophysiology of the Multidisciplinary Institute of Cell Biology, IMBICE, Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA), National University of La Plata, La Plata, Argentina
| | - Daniel Castrogiovanni
- Laboratory of Neurophysiology of the Multidisciplinary Institute of Cell Biology, IMBICE, Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA), National University of La Plata, La Plata, Argentina
| | - Helgi B Schiöth
- Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden
- Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Mirta Reynaldo
- Laboratory of Neurophysiology of the Multidisciplinary Institute of Cell Biology, IMBICE, Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA), National University of La Plata, La Plata, Argentina
| | - Jacky Marie
- Faculté de Pharmacie, Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-Université Montpellier-ENSCM, Montpellier, France
| | - Jean-Alain Fehrentz
- Faculté de Pharmacie, Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-Université Montpellier-ENSCM, Montpellier, France
| | - Mario Perello
- Laboratory of Neurophysiology of the Multidisciplinary Institute of Cell Biology, IMBICE, Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA), National University of La Plata, La Plata, Argentina
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28
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Del Olmo N, Blanco-Gandía MC, Mateos-García A, Del Rio D, Miñarro J, Ruiz-Gayo M, Rodríguez-Arias M. Differential Impact of Ad Libitum or Intermittent High-Fat Diets on Bingeing Ethanol-Mediated Behaviors. Nutrients 2019; 11:nu11092253. [PMID: 31546853 PMCID: PMC6769939 DOI: 10.3390/nu11092253] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 09/13/2019] [Accepted: 09/15/2019] [Indexed: 01/27/2023] Open
Abstract
Background: Dietary factors have significant effects on the brain, modulating mood, anxiety, motivation and cognition. To date, no attention has been paid to the consequences that the combination of ethanol (EtOH) and a high-fat diet (HFD) have on learning and mood disorders during adolescence. The aim of the present work was to evaluate the biochemical and behavioral consequences of ethanol binge drinking and an HFD consumption in adolescent mice. Methods: Animals received either a standard diet or an HFD (ad libitum vs. binge pattern) in combination with ethanol binge drinking and were evaluated in anxiety and memory. The metabolic profile and gene expression of leptin receptors and clock genes were also evaluated. Results: Excessive white adipose tissue and an increase in plasma insulin and leptin levels were mainly observed in ad libitum HFD + EtOH mice. An upregulation of the Lepr gene expression in the prefrontal cortex and the hippocampus was also observed in ad libitum HFD groups. EtOH-induced impairment on spatial memory retrieval was absent in mice exposed to an HFD, although the aversive memory deficits persisted. Mice bingeing on an HFD only showed an anxiolytic profile, without other alterations. We also observed a mismatch between Clock and Bmal1 expression in ad libitum HFD animals, which were mostly independent of EtOH bingeing. Conclusions: Our results confirm the bidirectional influence that occurs between the composition and intake pattern of a HFD and ethanol consumption during adolescence, even when the metabolic, behavioral and chronobiological effects of this interaction are dissociated.
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Affiliation(s)
- Nuria Del Olmo
- Department of Health & Pharmaceutical Sciences, Facultad de Farmacia, Universidad CEU-San Pablo, Campus de Montepríncipe, 28668 Madrid, Spain.
| | - M Carmen Blanco-Gandía
- Department of Psychology and Sociology, University of Zaragoza, C/Ciudad Escolar s/n, 44003 Teruel, Spain.
| | - Ana Mateos-García
- Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010 Valencia, Spain.
| | - Danila Del Rio
- Department of Health & Pharmaceutical Sciences, Facultad de Farmacia, Universidad CEU-San Pablo, Campus de Montepríncipe, 28668 Madrid, Spain.
| | - José Miñarro
- Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010 Valencia, Spain.
| | - Mariano Ruiz-Gayo
- Department of Health & Pharmaceutical Sciences, Facultad de Farmacia, Universidad CEU-San Pablo, Campus de Montepríncipe, 28668 Madrid, Spain.
| | - Marta Rodríguez-Arias
- Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010 Valencia, Spain.
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29
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Affiliation(s)
- M Carmen Blanco-Gandía
- Departamento de Psicobiología, Unidad de Investigación Psicobiología de las Drogodependencias, Facultad de Psicología, Universitat de València, Valencia, Spain
| | - Marta Rodríguez-Arias
- Departamento de Psicobiología, Unidad de Investigación Psicobiología de las Drogodependencias, Facultad de Psicología, Universitat de València, Valencia, Spain
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30
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Behavioral profile of intermittent vs continuous access to a high fat diet during adolescence. Behav Brain Res 2019; 368:111891. [PMID: 31009646 DOI: 10.1016/j.bbr.2019.04.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 03/13/2019] [Accepted: 04/03/2019] [Indexed: 12/28/2022]
Abstract
Over the past few years, the effects of a high-fat diet (HFD) on cognitive functions have been broadly studied as a model of obesity, although no studies have evaluated whether these effects are maintained after the cessation of this diet. In addition, the behavioral effects of having a limited access to an HFD (binge-eating pattern) are mostly unknown, although they dramatically increase the vulnerability to drug use in contrast to having continuous access. Thus, the aim of the present study was to compare the effects of an intermittent versus a continuous exposure to an HFD during adolescence on cognition and anxiety-like behaviors, as well as to study the changes observed after the interruption of this diet. Adolescent male mice received for 40 days a standard diet, an HFD with continuous access or an HFD with sporadic limited access (2 h, three days a week). Two additional groups were fed with intermittent or continuous access to the HFD and withdrawn from this diet 15 days before the behavioral tests. Only the animals with a continuous access to the HFD showed higher circulating leptin levels, increased bodyweight, marked memory and spatial learning deficits, symptoms that disappeared after 15 days of HFD abstinence. Mice that binged on fat only showed hyperlocomotion, which normalized after 15 days of HFD cessation. However, discontinuation of fat, either in a binge or a continuous pattern, led to an increase in anxiety-like behavior. These results highlight that exposure to a high-fat diet during adolescence induces alterations in brain functions, although the way in which this diet is ingested determines the extent of these behavioral changes.
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31
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Codagnone MG, Spichak S, O'Mahony SM, O'Leary OF, Clarke G, Stanton C, Dinan TG, Cryan JF. Programming Bugs: Microbiota and the Developmental Origins of Brain Health and Disease. Biol Psychiatry 2019; 85:150-163. [PMID: 30064690 DOI: 10.1016/j.biopsych.2018.06.014] [Citation(s) in RCA: 136] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Revised: 05/29/2018] [Accepted: 06/18/2018] [Indexed: 02/06/2023]
Abstract
It has been nearly 30 years since Dr. David Barker first highlighted the importance of prenatal factors in contributing to the developmental origins of adult disease. This concept was later broadened to include postnatal events. It is clear that the interaction between genetic predisposition and early life environmental exposures is key in this regard. However, recent research has also identified another important factor in the microbiota-the trillions of microorganisms that inhabit key body niches, including the vagina and gastrointestinal tract. Because the composition of these maternal microbiome sites has been linked to maternal metabolism and is also vertically transmitted to offspring, changes in the maternal microbiota are poised to significantly affect the newborn. In fact, several lines of evidence show that the gut microbiota interacts with diet, drugs, and stress both prenatally and postnatally and that these exogenous factors could also affect the dynamic changes in the microbiota composition occurring during pregnancy. Animal models have shown great utility in illuminating how these disruptions result in behavioral and brain morphological phenotypes reminiscent of psychiatric disorders (anxiety, depression, schizophrenia, and autism spectrum disorders). Increasing evidence points to critical interactions among the microbiota, host genetics, and both the prenatal and postnatal environments to temporally program susceptibility to psychiatric disorders later in life. Sex-specific phenotypes may be programmed through the influence of the microbiota on the hypothalamic-pituitary-adrenal axis and neuroimmune system.
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Affiliation(s)
- Martin G Codagnone
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Simon Spichak
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Siobhain M O'Mahony
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Olivia F O'Leary
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; Irish Centre for Fetal and Neonatal Translational Research and Cork University Maternity Hospital, University College Cork, Cork, Ireland
| | - Catherine Stanton
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Irish Centre for Fetal and Neonatal Translational Research and Cork University Maternity Hospital, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - Timothy G Dinan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
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Smail-Crevier RL, Maracle AC, Wash SI, Olmstead MC. Binge-like intake of sucrose reduces the rewarding value of sucrose in adult rats. Physiol Behav 2018; 194:420-429. [DOI: 10.1016/j.physbeh.2018.06.027] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 06/18/2018] [Accepted: 06/18/2018] [Indexed: 12/16/2022]
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Montagud-Romero S, Blanco-Gandía MC, Reguilón MD, Ferrer-Pérez C, Ballestín R, Miñarro J, Rodríguez-Arias M. Social defeat stress: Mechanisms underlying the increase in rewarding effects of drugs of abuse. Eur J Neurosci 2018; 48:2948-2970. [PMID: 30144331 DOI: 10.1111/ejn.14127] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Revised: 06/11/2018] [Accepted: 08/14/2018] [Indexed: 12/27/2022]
Abstract
Social interaction is known to be the main source of stress in human beings, which explains the translational importance of this research in animals. Evidence reported over the last decade has revealed that, when exposed to social defeat experiences (brief episodes of social confrontations during adolescence and adulthood), the rodent brain undergoes remodeling and functional modifications, which in turn lead to an increase in the rewarding and reinstating effects of different drugs of abuse. The mechanisms by which social stress cause changes in the brain and behavior are unknown, and so the objective of this review is to contemplate how social defeat stress induces long-lasting consequences that modify the reward system. First of all, we will describe the most characteristic results of the short- and long-term consequences of social defeat stress on the rewarding effects of drugs of abuse such as psychostimulants and alcohol. Secondly, and throughout the review, we will carefully assess the neurobiological mechanisms underlying these effects, including changes in the dopaminergic system, corticotrophin releasing factor signaling, epigenetic modifications and the neuroinflammatory response. To conclude, we will consider the advantages and disadvantages and the translational value of the social defeat stress model, and will discuss challenges and future directions.
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Affiliation(s)
- Sandra Montagud-Romero
- Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Valencia, Spain
| | | | - Marina D Reguilón
- Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Valencia, Spain
| | - Carmen Ferrer-Pérez
- Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Valencia, Spain
| | - Raul Ballestín
- Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Valencia, Spain
| | - Jose Miñarro
- Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Valencia, Spain
| | - Marta Rodríguez-Arias
- Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Valencia, Spain
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Gomes JAS, Oliveira MC, Gobira PH, Silva GC, Marçal AP, Gomes GF, Ferrari CZ, Lemos VS, Oliveira ACPD, Vieira LB, Ferreira AVM, Aguiar DC. A high-refined carbohydrate diet facilitates compulsive-like behavior in mice through the nitric oxide pathway. Nitric Oxide 2018; 80:61-69. [PMID: 30125695 DOI: 10.1016/j.niox.2018.08.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Revised: 08/13/2018] [Accepted: 08/16/2018] [Indexed: 01/17/2023]
Abstract
Obesity is characterized by abnormal adipose tissue expansion and is associated with chronic inflammation. Obesity itself may induce several comorbidities, including psychiatric disorders. It has been previously demonstrated that proinflammatory cytokines are able to up-regulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) release, which both have a role in compulsive related behaviors. OBJECTIVE To evaluate whether acute or chronic consumption of a high-refined carbohydrate-containing (HC) diet will modify burying-behavior in the Marble Burying Test (MBT) through augmentation of NO signaling in the striatum, a brain region related to the reward system. Further, we also verified the effects of chronic consumption of a HC diet on the reinforcing effects induced by cocaine in the Conditioned Place Preference (CPP) test. METHODS Male BALB/c mice received a standard diet (control diet) or a HC diet for 3 days or 12 weeks. RESULTS An increase in burying behavior occurred in the MBT after chronic consumption of a HC diet that was associated with an increase of nitrite levels in the striatum. The pre-treatment with Aminoguanidine (50 mg/kg), a preferential inhibitor of iNOS, prevented such alterations. Additionally, a chronic HC diet also induced a higher expression of iNOS in this region and higher glutamate release from striatal synaptosomes. Neither statistical differences were observed in the expression levels of the neuronal isoform of NOS nor in microglia number and activation. Finally, the reinforcing effects induced by cocaine (15 mg/kg, i.p.) during the expression of the conditioned response in the CPP test were not different between the chronically HC diet fed mice and the control group. However, HC diet-feeding mice presented impairment of cocaine-preference extinction. CONCLUSION Altogether, our results suggest that the chronic consumption of a HC diet induces compulsive-like behavior through a mechanism possibly associated with NO activation in the striatum.
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Affiliation(s)
- Júlia Ariana Souza Gomes
- Laboratório de Neuropsicofarmacologia, Departamento de Farmacologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Departamento de Farmacologia, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil
| | - Marina C Oliveira
- Departmento de Nutrição, Escola de Enfermagem, Universidade Federal de Minas Gerais Belo Horizonte, MG, Brazil
| | - Pedro Henrique Gobira
- Laboratório de Neuropsicofarmacologia, Departamento de Farmacologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Grazielle C Silva
- Laboratório de Fisiologia Cardiovascular, Departmento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Anna Paula Marçal
- Laboratório de Neuropsicofarmacologia, Departamento de Farmacologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Giovanni Freitas Gomes
- Laboratório de Neurofarmacologia, Departmento de Farmacologia, Universidade Federal de Minas Gerais Belo Horizonte, MG, Brazil
| | - Carolina Zaniboni Ferrari
- Laboratório de Neurofarmacologia, Departmento de Farmacologia, Universidade Federal de Minas Gerais Belo Horizonte, MG, Brazil
| | - Virginia Soares Lemos
- Laboratório de Fisiologia Cardiovascular, Departmento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | | | - Luciene Bruno Vieira
- Laboratório de Neurofarmacologia, Departmento de Farmacologia, Universidade Federal de Minas Gerais Belo Horizonte, MG, Brazil
| | - Adaliene V M Ferreira
- Departmento de Nutrição, Escola de Enfermagem, Universidade Federal de Minas Gerais Belo Horizonte, MG, Brazil
| | - Daniele C Aguiar
- Laboratório de Neuropsicofarmacologia, Departamento de Farmacologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
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Increased ethanol consumption after interruption of fat bingeing. PLoS One 2018; 13:e0194431. [PMID: 29590149 PMCID: PMC5874030 DOI: 10.1371/journal.pone.0194431] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 03/03/2018] [Indexed: 12/21/2022] Open
Abstract
There is a marked comorbidity between alcohol abuse and eating disorders, especially in the young population. We have previously reported that bingeing on fat during adolescence increases the rewarding effects of ethanol (EtOH). The aim of the present work was to study if vulnerability to EtOH persists after cessation of binge eating. OF1 mice binged on fat (HFB: high-fat binge) during adolescence (PND 25-43) and were tested for 15 days after the last access to HFB (on PND 59) using the self-administration paradigm, the conditioned place preference (CPP) and locomotor sensitization to ethanol. Our results showed that after 15 days of cessation of fat ingestion, mice increased their consumption of ethanol and showed greater motivation to obtain ethanol. On the other hand, no effects were observed in the CPP, while an increased locomotor response to ethanol was detected. The present results confirm and extend our previous study demonstrating that the compulsive intake of fat induces long-lasting effects on the reward system that lead to an increased consumption of EtOH.
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Blanco-Gandía MC, Montagud-Romero S, Aguilar MA, Miñarro J, Rodríguez-Arias M. Housing conditions modulate the reinforcing properties of cocaine in adolescent mice that binge on fat. Physiol Behav 2018; 183:18-26. [DOI: 10.1016/j.physbeh.2017.10.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 10/11/2017] [Accepted: 10/12/2017] [Indexed: 12/22/2022]
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Blanco-Gandía MC, Aracil-Fernández A, Montagud-Romero S, Aguilar MA, Manzanares J, Miñarro J, Rodríguez-Arias M. Changes in gene expression and sensitivity of cocaine reward produced by a continuous fat diet. Psychopharmacology (Berl) 2017; 234:2337-2352. [PMID: 28456841 DOI: 10.1007/s00213-017-4630-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Accepted: 04/03/2017] [Indexed: 12/17/2022]
Abstract
RATIONALE Preclinical studies report that free access to a high-fat diet (HFD) alters the response to psychostimulants. OBJECTIVES The aim of the present study was to examine how HFD exposure during adolescence modifies cocaine effects. Gene expression of CB1 and mu-opioid receptors (MOr) in the nucleus accumbens (N Acc) and prefrontal cortex (PFC) and ghrelin receptor (GHSR) in the ventral tegmental area (VTA) were assessed. METHODS Mice were allowed continuous access to fat from PND 29, and the locomotor (10 mg/kg) and reinforcing effects of cocaine (1 and 6 mg/kg) on conditioned place preference (CPP) were evaluated on PND 69. Another group of mice was exposed to a standard diet until the day of post-conditioning, on which free access to the HFD began. RESULTS HFD induced an increase of MOr gene expression in the N Acc, but decreased CB1 receptor in the N Acc and PFC. After fat withdrawal, the reduction of CB1 receptor in the N Acc was maintained. Gene expression of GHSR in the VTA decreased during the HFD and increased after withdrawal. Following fat discontinuation, mice exhibited increased anxiety, augmented locomotor response to cocaine, and developed CPP for 1 mg/kg cocaine. HFD reduced the number of sessions required to extinguish the preference and decreased sensitivity to drug priming-induced reinstatement. CONCLUSION Our results suggest that consumption of a HFD during adolescence induces neurobiochemical changes that increased sensitivity to cocaine when fat is withdrawn, acting as an alternative reward.
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Affiliation(s)
- M Carmen Blanco-Gandía
- Departamento de Psicobiología, Facultad de Psicología, Unidad de Investigación Psicobiología de las Drogodependencias, , Universitat de València, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain
| | | | - Sandra Montagud-Romero
- Departamento de Psicobiología, Facultad de Psicología, Unidad de Investigación Psicobiología de las Drogodependencias, , Universitat de València, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain
| | - Maria A Aguilar
- Departamento de Psicobiología, Facultad de Psicología, Unidad de Investigación Psicobiología de las Drogodependencias, , Universitat de València, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain
| | - Jorge Manzanares
- Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain
| | - José Miñarro
- Departamento de Psicobiología, Facultad de Psicología, Unidad de Investigación Psicobiología de las Drogodependencias, , Universitat de València, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain
| | - Marta Rodríguez-Arias
- Departamento de Psicobiología, Facultad de Psicología, Unidad de Investigación Psicobiología de las Drogodependencias, , Universitat de València, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain.
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Blanco-Gandía MC, Ledesma JC, Aracil-Fernández A, Navarrete F, Montagud-Romero S, Aguilar MA, Manzanares J, Miñarro J, Rodríguez-Arias M. The rewarding effects of ethanol are modulated by binge eating of a high-fat diet during adolescence. Neuropharmacology 2017; 121:219-230. [PMID: 28457972 DOI: 10.1016/j.neuropharm.2017.04.040] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Revised: 04/25/2017] [Accepted: 04/26/2017] [Indexed: 12/13/2022]
Abstract
Binge-eating is considered a specific form of overeating characterized by intermittent and high caloric food intake in a short period of time. Epidemiologic studies support a positive relation between the ingestion of fat and ethanol (EtOH), specifically among adolescent subjects. The aim of this work was to clarify the role of the compulsive, limited and intermittent intake of a high-fat food during adolescence on the rewarding effects of EtOH. After binge-eating for 2 h, three days a week from postnatal day (PND) 29, the reinforcing effects of EtOH were tested with EtOH self-administration (SA), conditioned place preference (CPP) and ethanol locomotor sensitization procedures in young adult mice. Animals in the high fat binge (HFB) group that underwent the EtOH SA procedure presented greater EtOH consumption and a higher motivation to obtain the drug. HFB mice also developed preference for the paired compartment in the CPP with a subthreshold dose of EtOH. Independently of the diet, mice developed EtOH-induced locomotor sensitization. After the SA procedure, HFB mice exhibited reduced levels of the mu opioid receptor (MOr) and increased cannabinoid 1 receptor (CB1r) gene expression in the nucleus accumbens (N Acc), and decreased of tyrosine hydroxylase (TH) gene expression in the ventral tegmental area (VTA). Taken together the results suggest that bingeing on fat may represent a vulnerability factor to an escalation of EtOH consumption.
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Affiliation(s)
- M Carmen Blanco-Gandía
- Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain
| | - Juan Carlos Ledesma
- Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain
| | | | - Francisco Navarrete
- Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain
| | - Sandra Montagud-Romero
- Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain
| | - Maria A Aguilar
- Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain
| | - Jorge Manzanares
- Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain
| | - José Miñarro
- Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain
| | - Marta Rodríguez-Arias
- Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain.
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