Modulation of apomorphine-induced stereotypy by estrogen: time course and dose response

Previous data have indicated that estrogen may either suppress or enhance the potency of dopamine and/or dopamine agonists. The effects of estrogen (estradiol benzoate; EB) in ovariectomized rats were indicative of a dose related suppression of apomorphine-induced stereotypy at 24 hours after the last dose of EB. HOwever, at 48 hours after the last dose of EB, the apomorphine-induced stereotypy was enhanced in those animals that received EB at 100 microgram/kg x 3 days. Ninety-six hours after the last injection of EB, all animals that received either the 100 or 50 microgram/kg dose of EB displayed an enhanced behavioral response to apomorphine. Animals pretreated with a low dose of EB (10 microgram/kg x 3 days) displayed a suppressed apomorphine stereotypy score at 24 hours, after the last dose, but were indistinguishable from Oil injected ovariectomized controls in all subsequent behavioral tests. These data indicate that estrogen can suppress dopamine and/or dopamine agonist potency 24 hours after the last dose of estrogen. However, an enhanced behavioral response to dopamine agonists can been seen at 48 hours (or more) after the last dose of estrogen. The time delay and the dose dependence of the enhanced response to dopamine agonists are indicative of a "withdrawal" phenomenon, suggesting the possibility that the role of endogenous estrogen is to suppress dopaminergic function.