The effects of pharmacologic estradiol on anxiety-related behavior in adolescent and adult female mice.

Early pubertal onset during adolescence is consistently linked with increased risk of anxiety and depression in girls. Although estradiol tends to have anxiolytic effects on behavior in adulthood, whether estradiol's anxiolytic actions change pre- to post-adolescent development is not clear. Using a rodent model, the current study tested whether anxiety-like responses to estradiol differ before and after adolescence in female mice. Prepubertal and adult C57BL/6 mice were ovariectomized, implanted with vehicle- or estradiol-filled silastic capsules, and behavioral tested 6 days later in the open field and elevated zero maze. A pharmacologic dose of estradiol was administered in silastic capsules (0.72 μg/0.02 mL) to maximize behavioral responses at both ages. In the open field, estradiol implants decreased anxiety-like behavior in adolescent females (relative to vehicle) and had negligible effects on anxiety-related behavior in adult females. These data suggest that adolescence is associated with changes in behavioral responsiveness to estradiol. In the elevated zero maze, adolescent females displayed higher levels of anxiety-like behavior than adults, irrespective of estradiol treatment. These findings demonstrate that substantial changes in anxiety-related behavior occur during adolescence, including an assay-dependent shift in behavioral responsiveness to estradiol.