Determining whether sensitivity to the organizing actions of gonadal steroid hormones on memory function and anxiety-related behavior decreases across adolescent development in rats.

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Adolescence is the period between childhood and adulthood during which cognitive, emotional, and social behaviors develop substantially. As such, adolescence is a period of both opportunity and vulnerability, and mental illness onset typically occurs during adolescence. The factors mediating a successful transition through adolescence range from social to biological. One factor that has received increased investigation in recent years is the timing of puberty. Whether individuals undergo pubertal development early or late relative to their peers increases risk for mental illness. Scientific explanations of the relationship between pubertal timing and mental illness tend to focus on the social and emotional consequences of developing earlier or later than one's peers. However, these models do not consider the role gonadal steroid hormones play in shaping the developing nervous system and behavior. We've proposed that nervous system sensitivity to gonadal steroid hormones decreases across adolescent development. In this framework, the developing adolescent brain is a moving target for the effects of gonadal steroid hormones, and shifts in pubertal timing may alter the course of brain development toward increased vulnerability. The proposed study will test the hypothesis that sensitivity to the organizing actions of gonadal steroid hormones decreases across postnatal development. This hypothesis predicts that adult behavioral outcomes will differ between groups receiving steroid hormone treatments before, during or after the normal time of puberty. Our strategy will be to vary the postnatal age at which rats are exposed to an 18-day period of testosterone (males) or estradiol (females) and then assess anhedonia, working memory, anxiety, and social behavior in adulthood (following hormone replacement). The results of this study will advance our understanding of the neurobiological principles governing adolescent brain development in both males and females. Furthermore, this work will have implications for sex-biased psychopathologies associated with deviations in pubertal timing such as depression, anxiety, and eating disorders.