Neurobiological mechanisms underlying delayed expression of posttraumatic stress disorder: A scoping review

Table 4 Overview of animal studies

Ref.	Animals (n)	Trauma/stressor	Assessment times	Anxiety and delayed effects	Neurobiological observation methods
Ardi et al[15], 2014	Rats: naïve (12), swim (12), swim + reminder (R) (12), UWT (12), UWT + R (12)	Rats were given daily 1-minute swim trials for 5 days. On day 6, ‘swim’ rats had an additional swim trial, and ‘UWT’ rats were swimming and then held underwater for 30 s using a net. On day 7, rats from the ‘reminder’ groups were exposed to 30 s of swimming	Following the ‘reminder’, rats were tested after 30 min.; ‘swim’ and ‘UWT’ rats were tested on day 7	Undergoing UWT results in reduced exploration in the open field even 24 h after the trauma compared to ‘swim’ and ‘naïve’ groups. Exposure to the reminder resulted in significantly enhanced anxiety behavior	electrophysiological recordings of hippocampal dentate gyrus GABA-ergic local circuit activity: paired-pulse inhibition (reflecting feedback inhibition), frequency-dependent inhibition (reflecting feed-forward inhibition), long-term potentiation; biochemical analysis: amygdala extracellular-signal-regulated kinase activity
Justice et al[45], 2015	Mice: wild type controls (43) and PTSD-group (65), Alzheimer’s Disease model controls (76) and PTSD-group (145)	Mice in the PTSD group were immobilized for 2h on boards with tape in a brightly lit area. For the reminder, the procedure was repeated during 15 min.	2–3 mo and 6–12 mo	Animals displayed elevated anxiety and slightly elevated startle amplitudes	resting and peak plasma corticosteroid levels, cerebrospinal fluid beta-amyloid levels
Serova et al[25], 2019	Rats: 1 wk following stress (57), 2 wk following stress (42), controls (56)	Rats were immobilized for 2 h on a board by taping the limbs and restricting motion of the head, then subjected to forced swim for 20 min.	1 or 2 wk following stress	At 1 week, 17.5%, and at 2 wk, 57.1% of animals displayed severe anxiety	Gene expression in the mediobasal hypothalamus and locus coeruleus (LC), immunohistochemistry
Wilson et al[34], 2013	Rats: PTSD-group (10), controls (10)	PTSD group rats were secured in plexiglas cylinders and placed in a cage with a cat for one hour on days 1 and 11 of a 31-day stress regimen, and their cage cohort was changed daily	day 0, day 12, day 31	The PTSD group displayed significantly higher anxiety than the control group, and significantly diminished growthrate over the 31-day stress period	Growth, plasma (corticosterone), adrenal glands (weight, oxidative stress), and hippocampus, amygdala, and pre-frontal cortex (oxidative stress and inflammatory markers: interleukin-1β, NALP3-inflammosome, glyceraldehyde 3-phosphate dehydrogenase)

UWT: Underwater trauma; GABA: Gamma aminobutyric acid; NALP3: NACHT, LRR and PYD domains-containing protein 3 (also: nucleotide-binding domain, leucine-rich repeat family pyrin domain containing 3); PTSD: Posttraumatic stress disorder.