Direct effects of ovarian hormones on antidepressant binding sites.

Tricyclic antidepressants such as imipramine interact with a membrane binding site associated with the uptake of serotonin. Ovarian hormones estradiol and progesterone were found to affect the concentration and affinity of imipramine binding sites in the hypothalamus but not the cortex of female rats. In vivo and in vitro, estradiol increased the amount of imipramine binding at physiological concentrations; at high concentrations estradiol decreased imipramine binding. Ovariectomy (OVX) had no effect on imipramine binding, consonant with the biphasic dose-response relationship for estradiol. The effects of progesterone were dependent upon the concentration of estradiol. Effects of physiological concentrations of both estradiol and progesterone on imipramine binding in an isolated membrane preparation suggest that the hormones are affecting this aspect of serotonergic neuronal function by nongenomic mechanisms.