Immediate and delayed anxiety- and depression-like profiles in the adolescent Wistar-Kyoto rat model of endogenous depression following postweaning social isolation.

In order to understand links that exist between inherited risk or predisposition, brain and behavioural development, endocrine regulation and social/environmental stimuli, animal models are crucial. The Wistar-Kyoto (WKY) rat has been shown to have validity as a model of adult and adolescent depression. While sex- and age-specific differences in some of the face, predictive and construct validities of the model such as depression-like behaviours have been established, anhedonia and anxiety using other induced anxiety paradigms such as elevated plus maze remain equivocal. First, post-weaning social isolation effects on inherent and induced anxiety behaviours were tested during two critical time periods, early- and mid-adolescence. Isolation induced immediate effects on novel environment-induced hyperactivity and anxiety-related behaviours. Adolescent WKYs demonstrated reduced 50-kHz ultrasonic vocalizations suggesting agoraphobia-like behaviours. Second, isolated rats, despite being subsequently social-/group-housed demonstrated longer lasting effects on social interaction measures and anhedonia. This establishes that the depression-like profile observed during early- and mid-adolescence persists into late adolescence and early adulthood in WKY. Further, that interventions at a later stage during adolescence may not be able to reverse early adolescent effects in the context of pre-disposition, thus highlighting the irreversibility of being double-hit during critical time periods of brain and behavioural development and maturation.