Received for publication July 22, 2003.
Revised August 25, 2003.
Accepted for publication September 26, 2003.

Ovarian Steroid Hormone Modulation of the Acute Effects of Cocaine on Luteinizing Hormone and Prolactin Levels in Ovariectomized Rhesus Monkeys

Abstract

Cocaine stimulates significant increases in luteinizing hormone (LH) and decreases prolactin levels in gonadally intact rhesus monkeys, but cocaine did not alter plasma levels of these anterior pituitary hormones in ovariectomized females. These findings suggested that ovarian steroid hormones may contribute to the endocrine effects of acute cocaine administration. To test this hypothesis, the acute effects of cocaine and placebo- cocaine on plasma LH and prolactin levels were examined in five ovariectomized rhesus females during three chronic hormone replacement conditions: (1) estradiol (E₂) treatment (0.0015-0.006 mg/kg/day, i.m.); (2) progesterone treatment (0.32 mg/kg/day, i.m.) and (3) combinations of progesterone (0.32 mg/kg/day, i.m.) and E₂ (0.002 and 0.004 mg/kg/day, i.m.). Cocaine (0.8 mg/kg, i.v.) did not alter prolactin or LH in ovariectomized monkeys without ovarian steroid replacement. Cocaine stimulates significant increases in luteinizing hormone (LH) and decreases prolactin levels in gonadally intact rhesus monkeys, but cocaine did not alter plasma levels of these anterior pituitary hormones in ovariectomized females. These findings suggested that ovarian steroid hormones may contribute to the endocrine effects of acute cocaine administration. To test this hypothesis, the acute effects of cocaine and placebo-cocaine on plasma LH and prolactin levels were examined in five ovariectomized rhesus females during three chronic hormone replacement conditions: (1) estradiol (E₂) treatment (0.0015-0.006 mg/kg/day, i.m.); (2) progesterone treatment (0.32 mg/kg/day, i.m.) and (3) combinations of progesterone (0.32 mg/kg/day, i.m.) and (E₂) (0.002 and 0.004 mg/kg/day, i.m.). Cocaine (0.8 mg/kg, i.v.) did not alter prolactin or LH in ovariectomized monkeys without ovarian steroid replacement. During chronic estradiol treatment, cocaine produced an estradiol dose-dependent decrease in prolactin. Cocaine also decreased prolactin during treatment with progesterone alone and progesterone + (E₂) (0.004 mg/kg/day, i.m.). Cocaine stimulated a significant increase in LH during treatment with progesterone alone, but not during treatment with progesterone + (E₂), or three of four estradiol treatment doses. Cocaine pharmacokinetics did not differ as a function of hormone replacement conditions. Taken together, these data suggest that both (E₂) and progesterone modulate cocaine's effects on prolactin, whereas (E₂ ) alone and in combination with progesterone, do not facilitate LH release in response to cocaine in ovariectomized rhesus females.

Key words: cocaine, estradiol, luteinizing hormone, ovarian steroids, progesterone, prolactin

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