Differential effects of ovarian steroid hormones on beta-adrenoceptor downregulation caused by the antidepressants imipramine and rolipram.

Downregulation of beta-adrenoceptors in response to repeated administration of imipramine or rolipram was investigated in the brain of pregnant rats and ovariectomized animals treated with estrone, progesterone or a combination of both hormones. Ovariectomy alone was without influence on drug responses. Pregnancy and complete hormone replacement of animals prior to drug treatment halved the response to imipramine and obliterated that to rolipram. Administration of only estrone to ovariectomized rats did not affect the extent of adrenergic downregulation caused by imipramine, but fully suppressed the rolipram action. Castrated males with or without treatment with estrone and progesterone were used as further controls. Castration alone diminished the effects of both antidepressants. Treatment of gonadectomized rats with both ovarian steroid hormones voided the actions of rolipram. The data indicate that imipramine and rolipram share a common pathway for their mechanism of action which can be attenuated by ovarian steroid hormones. In addition, imipramine has a second major site of action which is not subject to modulation by female steroids.