Exogenous estradiol impacts anxiety-like behavior of juvenile male and female Siberian hamsters in a dose-dependent manner

Anxiety is among the most prevalent mental health issues in children. While it is well established that gonadal steroids influence anxiety-like behavior in adulthood, a potential role in prepubertal juveniles has been overlooked because it is commonly thought that the gonads are quiescent during the juvenile period. However, the juvenile gonads secrete measurable amounts of steroids, and we have recently found that prepubertal ovariectomy decreases anxiety-like behavior of juvenile Siberian hamsters in the light/dark box test. The present study tested whether an injection of estradiol benzoate (1 μg or 10 μg, SC) to gonadectomized hamsters (Exp. 1) or chronic suppression of endogenous estradiol with the aromatase inhibitor, letrozole (2 mg/kg, PO), to intact hamsters (Exp. 2) affects anxiety-like behavior in the light/dark box test during the juvenile phase. Estradiol benzoate altered anxiety-like behavior of both male and female juveniles in a dose-dependent manner, with anxiolytic actions at the low dose, but no effect at the high dose. Similar effects were seen for activity measures, albeit only in females. Letrozole suppressed uterine weights demonstrating an active role for endogenous estradiol during the juvenile phase. Anxiety-like behavior, however, was impacted by the administration procedure itself, preventing conclusions on letrozole's actions on behavior. While the role for endogenous estradiol in juvenile anxiety-like behavior remains unresolved, the present findings indicate that the neural centers regulating affective behavior are responsive to exogenous estradiol prior to puberty. These findings highlight the potential impact of exogenous estrogen exposures on juvenile affective behavior.