[Show abstract][Hide abstract] ABSTRACT: Fluctuations in ovarian hormones throughout the estrous cycle may underlie sex differences in behavior. In this study, estrogen plus progesterone were coadministered at different ratios to determine whether the interaction of those hormones during the estrous cycle contributes to cocaine-induced alterations in behavior. Before cocaine (15 mg/kg) or saline administration, ovariectomized female rats received either vehicle or estrogen (10 microg or 50 microg) and progesterone (100 microg or 500 microg). Cocaine-induced locomotor activity was affected by estrogen plus progesterone ratio. While administration of 50 microg estrogen plus 500 microg progesterone increased total locomotor behavior, administration of 10 microg estrogen plus 500 microg progesterone inhibited total locomotor activity. This study suggests that alterations of estrogen and progesterone serum levels may underlie the observed changes in cocaine-induced behavior during the estrous cycle.