Background: Depression often manifests during adolescence when the development and networking of social and emotional brain areas is being influenced by hormones. The Wistar Kyoto (WKY) rat has been proposed as an animal model of adolescent depression with various face, construct, and predictive validities for clinical depression having been established. Purpose: The influence of the estrous cycle on anxiety- and depression-like behaviors in female adolescents may be tested out further using this model. Methods: Female adolescent WKY rats were tested for anxiety- and depression-like behaviors in the elevated plus maze and forced swim test (FST) during different phases of the estrous cycle with inbred, age-, and phase-matched Wistar rats as controls. Results: Wistars in proestrus-estrus demonstrated reduced anxiety levels. WKY also demonstrated increased open arm time and entries and closed arm time, but less than Wistars, and as closed arm entries remained unaffected, it did not translate into a lowering of the anxiety levels. Risk taking and risk assessment behaviors were not affected by estrous phases in WKY, though exploratory behavior was reduced in proestrus-estrus. In Wistars, increased risk taking and decreased risk assessment behaviors were observed during proestrus-estrus. Increased immobility in the FST, indicative of learned helplessness was not influenced by phase in the WKY, which was at variance with Wistars that demonstrated phase-specific differences. Conclusion: Results indicate a masking effect of indicative hormones in this putative model of adolescent depression, with implications for an unravelling of the steroid milieu in predisposed adolescent depression and for taking phase-specific time windows into account for therapeutic interventions.

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