Adolescent social stress does not necessarily lead to a compromised adaptive capacity during adulthood: a study on the consequences of social stress in rats

Abstract

Childhood bullying or social stress in adolescent humans is generally considered to increase the risk of developing behavioral disorders like depression in adulthood. Juveniles are hypothesized to be particularly sensitive to stressors in their environment due to the relatively late maturation of brain areas that are targeted by stress such as the prefrontal cortex and hippocampus. In our study male adolescent rats were subjected to repeated social defeat on postnatal day (PND) 28, 31 and 34 (experiment 1) or to daily social defeats between PND 35 and 42 (experiment 2). Adolescent rats in experiment 1 were socially housed in pairs with a male of similar age during and after the social defeat. In experiment 2 adolescents were housed either alone or with an age-mate for 7 days (PND 35-42) next to either a highly aggressive or a non-aggressive adult male neighbor with whom a repeated physical interaction was allowed. In experiment 1 the adolescent defeats affected subsequent play behavior with the cage mate. Socially stressed rats more frequently initiated play behavior but also adopted more frequently submissive postures during the play fights. As adults, they seemed to cope behaviorally and physiologically better with a similar exposure to a residential aggressive male rat than unstressed controls. In experiment 2 acute effects of adolescent social stress were studied on neuroplasticity markers like hippocampal cell proliferation and neurogenesis as well as hippocampal brain-derived neurotrophic factor (BDNF) levels. The 2nd experiment also studied long-term effects of the adolescent stress in the response to an adult social defeat. A few acute but minor changes in brain plasticity markers and behavior were observed but these were transient and no behavioral or physiological effects persisted into adulthood. The results from both experiments support the theory developed in the so-called "match-mismatch hypothesis" which claims that the final consequence of childhood adversity depends on how well the early life environment matches the challenges in later life. Socially stressed adolescents are rather resilient to the lasting behavioral and physiological effects of the stress exposure if they are socially housed afterward and have the ability to recover.

Keywords: 5-bromodeoxiuridine; ANOVA; BDNF; BrdU; CORT; DCX; PBS; PND; SD; WTG; Wildtype Groningen rats; adolescence; analysis of variance; brain-derived neurotrophic factor; corticosterone; doublecortin; match–mismatch hypothesis; neurogenesis; phosphate-buffered saline; play behavior; postnatal day; sem; social defeat; social housing; standard error of the mean.