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World J Psychiatry. Jan 19, 2022; 12(1): 24-58
Published online Jan 19, 2022. doi: 10.5498/wjp.v12.i1.24
Resilience to the effects of social stress on vulnerability to developing drug addiction
Claudia Calpe-López, Maria A Martínez-Caballero, Maria P García-Pardo, Maria A Aguilar
Claudia Calpe-López, Maria A Martínez-Caballero, Maria A Aguilar, Department of Psychobiology, University of Valencia, Valencia 46010, Spain
Maria P García-Pardo, Faculty of Social and Human Sciences, University of Zaragoza, Teruel 44003, Spain
Author contributions: Aguilar MA designed the review and figures and wrote the final version of the manuscript; Calpe-López C and García-Pardo MP wrote the first draft of the manuscript; Calpe-López C and Martínez-Caballero MA performed the bibliographic search and figures and wrote the reference list; all authors have read and approved the final manuscript.
Supported by the Ministerio de Ciencia, Innovación y Universidades of Spain, No. PSI2017-83023.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Maria A Aguilar, PhD, Full Professor, Department of Psychobiology, University of Valencia, Avda, Blasco Ibáñez 21, Valencia 46010, Spain. asuncion.aguilar@uv.es
Received: March 31, 2021
Peer-review started: March 31, 2021
First decision: July 15, 2021
Revised: August 1, 2021
Accepted: December 21, 2021
Article in press: December 21, 2021
Published online: January 19, 2022
Processing time: 292 Days and 12.6 Hours
Abstract

We review the still scarce but growing literature on resilience to the effects of social stress on the rewarding properties of drugs of abuse. We define the concept of resilience and how it is applied to the field of drug addiction research. We also describe the internal and external protective factors associated with resilience, such as individual behavioral traits and social support. We then explain the physiological response to stress and how it is modulated by resilience factors. In the subsequent section, we describe the animal models commonly used in the study of resilience to social stress, and we focus on the effects of chronic social defeat (SD), a kind of stress induced by repeated experience of defeat in an agonistic encounter, on different animal behaviors (depression- and anxiety-like behavior, cognitive impairment and addiction-like symptoms). We then summarize the current knowledge on the neurobiological substrates of resilience derived from studies of resilience to the effects of chronic SD stress on depression- and anxiety-related behaviors in rodents. Finally, we focus on the limited studies carried out to explore resilience to the effects of SD stress on the rewarding properties of drugs of abuse, describing the current state of knowledge and suggesting future research directions.

Keywords: Resilience; Stress; Depression; Drug addiction; Animal models; Social defeat

Core Tip: Preclinical research on drug addiction has focused on the factors that enhance vulnerability to develop drug addiction. Recent studies of resilience have determined the neurobehavioral traits that confer protection against developing an addictive disorder after stress exposure. Active coping strategies to face the stressor and the absence of depression-like symptoms are consistently associated with resilience to the stress-induced potentiation of the rewarding effects of cocaine and alcohol. Unravelling the neurobiological substrates of resilience is key to developing pharmacological and psychological interventions to enhance stress resilience in order to prevent the development of addiction and other stress-related disorders.