249. The effects of gender and the estrous cycle on learned helplessness in the rat

Abstract

Women are more likely to suffer from major depressive disorder than men. Moreover, in depressed women, mood often fluctuates during the menstrual cycle. Learned helplessness is a valid animal model of stress-induced behavioral depression. Few studies have examined gender differences and influences of the estrous cycle in this and other animal behavioral models of clinical depression. We therefore tested the hypothesis that estrogen protects against depression. Learned helplessness was studied in rats using a inescapable tail shock stress followed by a shuttle box test to determine escape latencies. Rats studied were normal cycling female rats in the estrus and diestrus II phases, male and ovariectomized female rats. β-estradiol (10 μg/ml, sc) and progesterone (0.5 mg/kg) were administered to OVX females 12 or 72 hours prior to inescapable tail shock. Diazepam (2 mg/kg) and allopregnanolone (0.5 mg/kg) were administered to diestrus II females thirty minutes prior to inescapable tail shock. Pentylenetetrazole (20 mg/kg, PTZ) was administered to estrus females 10 minutes prior to shuttle box testing. Female rats in the diestrus II phase were significantly more helpless than female rats in the estrus phase. Estradiol decreased the escape latencies of OVX females. Progesterone produced a time-dependent effect such that after 12 hours escape latencies were increased but after 72 hours escape latencies were decreased. Diazepam and allopregnanolone prevented learned helplessness in diestrus II females. PTZ induced learned helplessness in estrus females. These results indicate an influence of the estrous cycle on the development of learned helplessness.