Effect of Ovarian Hormones and Estrous Cycle on Stimulation of the Hypothalamo-Pituitary-Adrenal Axis by Cocaine

摘要

Cocaine is known to exert sexually dimorphic HPA axis effects in rats and to disrupt estrous cyclicity and/or fertility in rats, nonhuman primates, and humans. The present studies inves- tigated the reciprocal interactions between ovarian hormones and HPA axis responses to cocaine. Thirty minutes after injec- tion, cocaine (15 mg/kg i.p.) increased serum ACTH and corti- costerone more in cycling than ovariectomized females or male rats. ACTH and corticosterone were highest in proestrus when estradiol was elevated. Cocaine did not alter serum estradiol in females or testosterone in males but did stimulate progester- one secretion in both sexes. Cocaine-stimulated progesterone secretion was sianificantlv areater in females than in males or ovariectomized females, and greater in proestrous than diestrous 1 rats. Cocaine stimulated corticosterone and pro- gesterone secretion in sham-adrenalectomized, but not adre- nalectomized rats, indicating that the adrenal gland and not the ovary is the source of cocaine-stimulated progesterone. Estro- gen influenced cocaine-stimulated progesterone secretion more than corticosterone, suggesting different release mecha- nisms for the two steroids in the adrenal. These results suggest that adrenally derived progesterone could contribute to co- caine-induced physiological changes, including inhibited go- nadotropin release.