Antidopaminergic effect of estrogens at the striatal level

Abstract

The present study investigates the possibility that a potent synthetic estrogen (moxestrol) possesses an antidopaminergic effect at the striatal level. Moxestrol and other estrogens, but not progestagens, androgens or corticosteroids, blocked the apomorphine-induced increase in striatal acetylcholine (ACh) levels. This effect required the repeated administration of moxestrol to develop and lasted for at least 24 hr after the final moxestrol injection. Moxestrol-treatment alone did not alter striatal ACh levels nor did it affect striatal choline acetyltransferase or acetylcholinesterase activities. This estrogen did not modify either the basal or the apomorphine-induced decrease in striatal dopamine turnover. In rats with a unilateral 6-OHDA lesion of the nigro-striatal dopamine pathway, moxestrol antagonized the contralateral circling elicited by apomorphine. The effect of moxestrol on the apomorphine-induced increase in striatal ACh levels was abolished by hypophysectomy and mimicked by pituitary transplants under the renal capsule. These findings, together with previous clinical and pharmacological observations, strongly support the hypothesis that moxestrol exerts an antidopaminergic effect at the striatal level by decreasing dopaminergic postsynaptic transmission via mediation of the pituitary gland.