Short-term and long-term effects of repeated social defeat during adolescence or adulthood in female rats

Abstract

Accumulating evidence suggests that adolescence represents a sensitive period during which social stressors may serve to influence adult behavior and stress reactivity. However, relatively little is known about the impact of social stress in adolescence on behaviors or stress reactivity in females. In this study, we exposed adolescent or adult female rats to the repeated social stress of defeat for 7 consecutive days. Repeated defeat resulted in distinctly different behavioral repertoires during defeat in adolescent compared to adult female rats. Adolescent females exhibited more play and avoidant behaviors and adult females exhibited more active and aggressive behaviors toward the resident female. Examination of the short-term effects of social defeat using the Porsolt-forced swim test (FST) indicated that adolescents, regardless of their exposure to social defeat, showed increased time immobile and decreased time swimming compared to adults. Adolescent rats exposed to defeat also exhibited increased climbing compared to their age–matched naïve counterparts. These effects dissipated with age. Interestingly, no effects of defeat were observed in adult females, however, when these females were re-assessed in the FST 30 days after the end of defeat, we observed increased swimming at the expense of climbing. Using exposure to a novel restraint to assess stress reactivity, we found that stress during adolescence and adulthood led to lower basal ACTH concentrations and that both stressed and control adolescent groups exhibited a delay in recovery in adulthood compared to stressed and control adult groups. Fos protein analysis further suggested that cortical/thalamic structures serve as potential substrates that mediate these long-term impacts of stress during adolescence. Thus, repeated social stress during adolescence produces different patterns of effects as compared with repeated social stress during adulthood.

Environmental Health Factors and Sexually Dimorphic Differences in Behavioral Disruptions

“…Notably, the long-term effects of defeat stress on baseline corticosterone are quite different. Defeat stress increases male baseline corticosterone during both the active phase and the inactive phase, but has no effect on females [144••], which is similar to findings in female rats [135]. Elevated corticosterone during the inactive phase is often observed in patients diagnosed with depression, and some recent reports have suggested that this symptom is more likely to occur in men [145, 146].…”

“…Variability between different rat strains may be an important factor influencing the intensity of defeat. Sprague Dawley dams appear to have lower aggression levels, and females exposed to defeat by a dam actually had decreased levels of floating behavior in the forced swim test, compared with controls [135]. In contrast, Wistar dams appear to have higher aggression levels, and females exposed to defeat showed increased floating in the forced swim test and sucrose anhedonia [136].…”

Exposure to social defeat stress in adolescence improves the working memory and anxiety-like behavior of adult female rats with intrauterine growth restriction, independently of hippocampal neurogenesis

“…For example, while normal adult male rats generally exhibit significantly reduced hippocampal neurogenesis (Gould and Tanapat, 1999;Jacobs et al, 2000;Malberg and Duman, 2003;Shors et al, 2007;Westenbroek et al, 2004) under a variety of stress conditions, normal adult female rats have been reported to exhibit either no change (Falconer and Galea, 2003;Shors et al, 2007), a significant increase (Gould and Tanapat, 1999;Westenbroek et al, 2004), or a decrease (Kuipers et al, 2006) in neurogenesis. With regard to responses in the HPA axis, although a significant decrease in the ACTH level has been demonstrated in female rats that experienced adolescent SDS, this decrease was not accompanied by a change in the basal corticosterone level (Ver Hoeve et al, 2013). In acute stress settings, glucocorticoids are generally considered to suppress hippocampal neurogenesis (Schoenfeld and Gould, 2012).…”

Disruption of peri-adolescent endocannabinoid signaling modulates adult neuroendocrine and behavioral responses to stress in male rats

“…Preclinical studies suggest that adolescent stress exposure elicits detrimental long-term behavioral and neural alterations, depending on stressor type, duration and age of exposure. Indeed, peri-adolescent stress exposure is known to alter HPA axis stress responsivity (Ver Hoeve et al, 2013), decrease social interaction (McCormick et al, 2015), increase anxiety-like, depressive-like (McCormick et al, 2013) and aggressive behaviours (Márquez et al, 2013), facilitate amphetamine-and ethanol-stimulated locomotion, preference and selfadministration (Burke and Miczek, 2014), alter reproductive behavior (McCormick et al, 2013) and impair working memory (Novick et al, 2013) during adulthood.…”