Effects of short- and long-term estrogen and progesterone replacement on behavioral responses and c-fos mRNA levels in female rats after acute cocaine administration.

It is well established that there are estrous cycle differences in cocaine-induced behavioral activity, implicating fluctuations in levels of estrogen and progesterone throughout the cycle in these alterations in behavior. However, the mechanisms by which steroids alter cocaine-induced behavioral responses have yet to be determined. The aim of this study was to determine whether short- or long-term estrogen and progesterone administration differentially alters behavioral responses to cocaine. Estrogen (50 microg) was administered 30 min or 48 h before cocaine (15 mg/kg, i.p.) administration; progesterone (500 microg) was administered 30 min or 24 h before cocaine. Short-term estrogen replacement decreased cocaine-induced ambulations. Short-term progesterone decreased rearing, whereas long-term progesterone decreased ambulations. Although cocaine increased levels of c-fos mRNA, none of the estrogen or progesterone replacement paradigms affected this measure. Because long-term estrogen replacement has been shown to have no effect on locomotor activity after acute cocaine administration, our observations suggest that short-term estrogen may underlie behavioral alterations. These findings suggest that after acute cocaine administration, while estrogen may activate only membrane receptors to alter behavioral responses to cocaine, progesterone activates both nuclear and membrane receptors.