Susceptibility or resilience? Prenatal stress predisposes male rats to social subordination, but facilitates adaptation to subordinate status

Abstract

Mood disorders such as major depressive disorder (MDD) affect a significant proportion of the population. Although progress has been made in the development of therapeutics, a large number of individuals do not attain full remission of symptoms and adverse side effects affect treatment compliance for some. In order to develop new therapies, there is a push for new models that better reflect the multiple risk factors that likely contribute to the development of depressive illness. We hypothesized that early life stress would exacerbate the depressive-like phenotype that we have previously observed in socially subordinate (SUB), adult male rats in the visible burrow system (VBS), a semi-natural, ethologically relevant environment in which males in a colony form a dominance hierarchy. Dams were exposed to chronic variable stress (CVS) during the last week of gestation, resulting in a robust and non-habituating glucocorticoid response that did not alter maternal food intake, body weight or litter size and weight. As adults, one prenatal CVS (PCVS) and one non-stressed (NS) male were housed in the VBS with adult females. Although there were no overt differences between PCVS and NS male offspring prior to VBS housing, a greater percentage of PCVS males became SUB. However, the depressive-like phenotype of SUB males was not exacerbated in PCVS males; rather, they appeared to better cope with SUB status than NS SUB males. They had lower basal plasma corticosterone than NS SUB males at the end of VBS housing. In situ hybridization for CRH in the PVN and CeA did not reveal any prenatal treatment or status effects, while NPY expression was higher within the MeA of dominant and subordinate males exposed to the VBS in comparison with controls, but with no effect of prenatal treatment. These data suggest that prenatal chronic variable stress may confer resilience to offspring when exposed to social stress in adulthood.

Prenatal Relocation Stress Enhances Resilience Under Challenge in Infant Rhesus Macaques

“…Our results suggest that animals that were relocated while in utero may actually be more resilient when later dealing with challenge. This interpretation would be consistent with a prenatal stress inoculation effect, consistent with some human and animal studies (DiPietro et al, 2006;Ehrlich and Rainnie, 2015;Scott et al, 2017;Serpeloni et al, 2019).…”

“…DiPietro et al ( 2006 ) showed that mild to moderate amounts of perceived stress and anxiety by the mother during pregnancy were associated with more advanced mental and motor development in human children at 2 years of age. A more recent report showed that prenatal stress may confer a protective phenotype, buffering animals against future stressors (Scott et al, 2017 ). Pregnant female mice were exposed to a series of chronic variable stressors during their last week of pregnancy.…”

Exposure of Developing Male Rats to One or Multiple Noise Sessions and Different Housing Conditions: Hippocampal Thioredoxin Changes and Behavioral Alterations

“…Therefore, as the auditory system becomes active between PND7 and PND15 (de Villers-Sidani et al, 2008; Säljö et al, 2011), it could be postulated that more immature animals could be refractory to the damaging effects of noise on this type of memory, probably due to the impossibility of noise to affect CNS by means of a functional auditory system. As no effect was observed when PND15 animals were exposed to noise for 5 days, it could be suggested that repeated exposures might trigger adaptive mechanisms intended to counteract potential damage (Febbraro et al, 2017; Scott et al, 2017). The ability of EE to prevent noise-induced changes in PND15N1 animals might depend on the same adaptive mechanisms.…”

“…Although all animals retained associative memory in this task, the performance in the associative memory task was increased in rats exposed at PND7N5 and PND15N1, suggesting that these animals would have a more detailed representation of the traumatic event, as reported by Atucha and Roozendaal (2015). Again, the lack of change in the other groups might be related to either immature associative mechanisms (PND7N1) or to adaptive mechanisms (PND15N5) that could be triggered by repeated exposures, intended to counteract potential damage, as observed in different stress models (Febbraro et al, 2017; Scott et al, 2017). However, as memory retention has been observed in both groups, it should not be discarded that PND7N5 and PND15N1 rats experimented an increase in fear sense instead of an improvement in associative memory (i.e., there seems not to be a memory acquisition trouble).…”

Effect of Genotype and Maternal Affective Disorder on Intronic Methylation of FK506 Binding Protein 5 in Cord Blood DNA

“…Results from our study raises the intriguing question of whether the methylation differences are associated with alterations in neurodevelopment and stress response in the infants. Studies of prenatal stress in animals show mixed behavioral outcomes in terms of resilience, with one showing resilience in females only (Zuena et al, 2008) and another showing males becoming predisposed but better adapted to subordinate status (Scott et al, 2017). Unfortunately, there is no information available on any stress-related outcomes, mental or physical health, or sex of the BBC infants.…”