Effects of estradiol on intact and denervated striatal dopamine receptors and on dopamine levels: a biochemical and behavioral study.

Abstract

The present study describes the effect of chronic estrogen treatment on striatal dopamine levels and dopamine receptors, as well as on apomorphine-induced circling, a behavioral model reflecting dopaminergic activity in the rat striatum. Although estradiol itself does not show any affinity for the striatal dopamine receptor, its administration for 2 weeks in adult ovariectomized rats leads to a small increase in [3H]spiroperidol, [3H]haloperidol, and [3H]apomorphine binding in the striatum; this increase is associated with a greater number of binding sites. In order to dissociate possible pre- and post-synaptic effects of estrogens, these studies were next performed in animals bearing an unilateral 6-hydroxydopamine lesion of the substantia nigra. The apomorphine-induced circling behavior of rats bearing such a lesion was not affected by estrogen treatment. Estradiol treatment induced an increase of [3H]spiroperidol binding in both the intact and lesioned striatum, thus suggesting an estrogenic effect on a population of postsynaptic receptors. Chronic estradiol treatment reduced the concentration of dopamine in the striatum while the turnover of this amine measured using alpha-methyl-p-tyrosine remained unchanged. The present results show that estradiol exerts effects at the striatal level on both dopamine metabolism and receptor levels.