Estradiol decreases anxiety behavior and enhances inhibitory avoidance and gestational stress produces opposite effects.

Although there is evidence that estradiol has effects in women and in animal models to reduce anxiety and depressive behavior and enhance performance in some cognitive tasks, this is not seen among all individuals. Given the interaction between estradiol and hypothalamic-pituitary-adrenal function, we hypothesized that an individual's prior exposure to stress may mitigate some of the subsequent effects of estradiol. To address this, rats were exposed to gestational stress, or not, to determine if stress exposure during development alters behavioral responses to estradiol in adulthood. If estradiol's effects on anxiety and cognitive behavior are modulated by prior stress experience, then gestationally-stressed rats administered estradiol should have decreased anti-anxiety (open field, elevated plus maze) behavior and cognitive performance in the inhibitory avoidance task. Offspring of dams that were exposed to restraint stress daily on gestational days 14-20, or no such manipulation, were used as adults either intact in behavioral estrus (high estradiol) or diestrus (low estradiol), or ovariectomized (OVX) with empty or estradiol-containing silastic implants. Rats were used for blood collection to determine plasma corticosterone and estradiol concentrations, or were used for behavioral testing. Compared with rats in diestrus or OVX and vehicle-replaced, rats in behavioral estrus and OVX rats with estradiol implants had higher estradiol concentrations, entered more central squares in an open field, spent more time on the open arms of the plus maze, and had a longer latency to crossover to the dark, shock-associated side of the inhibitory avoidance chamber. Gestational stress increased plasma corticosterone but not estradiol levels, decreased plus maze open arm time in cycling rats, and decreased inhibitory avoidance performance. Thus, estradiol and gestational stress can have opposite effects on anxiety and inhibitory avoidance performance.