Corticosterone after early adolescent stress prevents social avoidance, aversive behavior, and morphine-conditioned place preference in adulthood

Abstract

Rationale: Stress during childhood or adolescence increases vulnerability to psychiatric disorders in adults. In adult rodents, the delayed effects of stress can increase anxiety-like behavior. These effects, however, can be prevented with post-stress administration of corticosterone (CORT). The effectiveness of CORT in preventing adolescent stress-induced emotional behavior alterations in adulthood has yet to be investigated.

Objectives: Here, we investigated the interactions between early adolescent stress and exogenous corticosterone on adult social, aversive, and drug-seeking behavior in mice, which are translationally related to symptoms associated with psychiatric and substance abuse disorders.

Methods and results: A single administration of CORT in drinking water (400ug/mL) for 24 h after social defeat or context fear conditioning prevents defeat-induced social avoidance, alters fear processing, prevents adolescent stress-induced anhedonia, and prevents stress-potentiated morphine place preference in adulthood. Exogenous CORT did not immediately prevent stress-induced potentiation of morphine conditioned-place preference in adolescents but did so in adult mice. However, when administered to adolescent mice, CORT also prevented the incubation of morphine-conditioned place preference into adulthood. Lastly, exogenous CORT administration blunted endogenous corticosterone but was unrelated to freezing behavior during a fear test.

Conclusions: This is the first demonstration of adolescent post-stress CORT promoting socio-emotional resilience and preventing drug-seeking behavior. Our data suggest elevated corticosterone after a stress experience promotes resilience for at least 40 days across the developmental transition from adolescence to adulthood and is effective for socio-emotional and drug-seeking behavior. These results are critical for understanding how adolescent stress impacts emotional and drug-seeking behavior into adulthood.

Keywords: Drug-seeking; Fear conditioning; Foot-shock stress; Social defeat.