Is adolescence a sensitive period for depression? Behavioral and neuroanatomical findings from a social stress model

Objectives: Sex differences in depressive symptoms emerge during adolescence, with females more at risk than males. However, adverse life events during development have greater impact on males. An animal model that incorporates behavioral and anatomical changes following adolescent stress is needed. Experimental Design: Sprague-Dawley rats were exposed to social stress (SS; isolation housing during P30-35) or remained group-housed (GRP) and tested in the forced swim test (FST), the triadic learned helplessness model (LH), and the elevated plus maze. Western immunoblots of myelin basic protein (MBP) and synaptophysin (SVP) and spinophillin indexed synaptic and dendritic plasticity, respectively. Principal Observations: At P36, SS increased climbing behavior in both sexes, and decreased the latency to immobility in females following a 15 min inescapable swim in the FST. Depressive-like behaviors were differentially elevated in both sexes 24 h later. GRP females exhibited higher levels of depression-related behaviors than GRP males in both FST and LH paradigms. SS significantly increased depressive behaviors in the FST in males, and impaired their ability to escape shock previously conditioned to be controllable. SS decreased open arm time in females only. The greatest reductions in synaptic plasticity proteins were observed in the prefrontal cortex: spinophillin (19.1%), SVP (7.9%), and MBP (48.7%, males only). Smaller reductions in spinophillin were observed in the hippocampus and amygdala. Conclusions: Adolescent separation produces both behavioral and neural changes associated with stress-related depression and anxiety. Additional work is needed to improve our understanding of stress as it relates to depression during this vulnerable period of development.