title: 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.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA; Graduate Program in Neuroscience, University of Cincinnati, Cincinnati 45237, USA. Electronic address: k.scott@ucc.ie.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Scott
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA; Graduate Program in Neuroscience, University of Cincinnati, Cincinnati 45237, USA.
authors.forename: Annette D
authors.initials: AD
authors.lastname: de Kloet
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Smeltzer
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Krause
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA; Graduate Program in Neuroscience, University of Cincinnati, Cincinnati 45237, USA.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Flak
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA; Graduate Program in Neuroscience, University of Cincinnati, Cincinnati 45237, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Melhorn
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Foster
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Kellie L K
authors.initials: KLK
authors.lastname: Tamashiro
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
authors.forename: Randall R
authors.initials: RR
authors.lastname: Sakai
mesh_terms: D000223:Adaptation, Psychological; D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000209:etiology; D004291:Dominance-Subordination; D005260:Female; D006799:Housing, Animal; D008297:Male; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000473:pathology / Q000523:psychology*; D011581:Psychological Tests; D012333:RNA, Messenger / Q000378:metabolism; D020318:Rats, Long-Evans; D055500:Resilience, Psychological; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D013739:Testosterone / Q000097:blood; D013950:Thymus Gland / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D013739:Testosterone; D003345:Corticosterone