Rapid effects of estrogen or progesterone on the amphetamine-induced increase in striatal dopamine are enhanced by estrogen priming: A microdialysis study

There are estrous cycle-dependent differences in amphetamine stimulated beh aviors and striatal dopamine (DA) release; intact female rats exhibit a gre ater behavioral response to amphetamine on estrus than on other days of the cycle. Following ovariectomy amphetamine-induced behavior is attenuated, a s is the striatal DA response to amphetamine in vitro. Repeated estrogen tr eatment in ovariectomized rats reinstates both of these responses to a leve l comparable to estrous females. In addition, 30 min after a single treatme nt with a physiological dose of estrogen there is enhanced amphetamine-indu ced behavior and increased amphetamine-induced striatal DA detected during microdialysis. This experiment was conducted to determine whether the acute effect of estradiol and the effect of repeated exposure to estrogen are fu nctionally related. We report here that prior treatment with estrogen (thre e daily treatments of 5 mu g estradiol benzoate) results in a significant e nhancement of the effect of acute estrogen (5 mu g estradiol benzoate) or p rogesterone (500 mu g) on amphetamine-induced striatal DA release and stere otyped behaviors. Both the peak response and the duration of the response a re greater in estrogen-primed animals treated with estrogen or progesterone 30 min prior to amphetamine, than in all other groups. Either prior treatm ent with estrogen (last dose 24 h before) or a single acute injection of es trogen result in an enhanced peak response to amphetamine, with no effect o n the duration of amphetamine-induced striatal DA release. Treatment with p rogesterone in animals not primed with estrogen was not different from trea tment with oil vehicle. These results demonstrate that there are both acute and long-term. effects of estrogen on the striatum that underlie the dynam ic changes in stimulated DA release and amphetamine-induced behaviors durin g the reproductive cycle. (C) 1999 Elsevier Science Inc.