Pharmacology Biochemistry and Behavior, Vol. 66, No. 2, pp. 449–453, 2000 © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0091-3057/00/$–see front matter PII S0091-3057(00)00213-6 449 Cocaine Affects Progesterone Plasma Levels in Female Rats VANYA QUIÑONES-JENAB,*† LINDA I. PERROTTI,*† ANN HO,* SHIRZAD JENAB,† STEFAN D. SCHLUSSMAN,* JOHAN FRANCK* AND MARY JEANNE KREEK* *The Rockefeller University, New York City, NY 10021; and †Department of Psychology, Hunter College, CUNY, New York, NY 10021 Received 9 July 1999; Revised 15 November 1999; Accepted 28 November 1999 QUIÑONES-JENAB, V., L. I. PERROTTI, A. HO, S. JENAB, S. D. SCHLUSSMAN, J. FRANCK AND M. J. KREEK. Cocaine affects progesterone plasma levels in female rats. PHARMACOL BIOCHEM BEHAV 66(2) 449–453, 2000.—Female Fischer rats injected with cocaine in a “binge” pattern (15 mg/kg, IP, three times a day, at 1-h intervals) for 1 day had significantly higher levels of progesterone than saline-treated controls (p  0.001). When analyzed by the stage of the estrous cycle, animals in proestrus showed significantly higher cocaine-induced progesterone plasma levels than those in other stages of the cycle (p  0.01). Progesterone plasma levels were also increased after a single dose of cocaine (15 mg/kg). How- ever, 3 h postinjection progesterone plasma levels had returned to normal. Thus, cocaine modulation of progesterone plasma levels appears to be an acute effect. In ovariectomized rats pretreated with estrogen, progesterone, or estrogen + progester- one, no significant differences were observed in progesterone plasma levels after acute “binge” pattern cocaine administra- tion. Thus, acute cocaine induced increases in progesterone plasma levels in intact female rats are probably due to an increase in secretion rates of progesterone rather than an acceleration of its biotransformation. Due to the profound effects of progest- erone in the modulation of CNS plasticity, the modulation of progesterone plasma level by cocaine may have implications for reproductive processes and neuronal functions of women. Moreover, cocaine may affect the progesterone levels in women uti- lizing progesterone-based contraception or steroid replacement treatment after menopause. © 2000 Elsevier Science Inc. “Binge” pattern Cocaine Female Estrus Progesterone OVX COCAINE, a psychostimulant, is one of the most widely abused drugs in Western countries. Based on the 1998 Na- tional Household Survey on Drug Abuse, approximately 36% of an estimated 1.75 million Americans who used cocaine in a month were women. Females have a complex endocrinologi- cal profile. Female hormones alter a variety of reproductive (2,32) and nonreproductive behaviors (34) probably through their actions on the dopamine, serotonin, and opioid systems (10,11,13,26,33,42). It is well established that estrogen and progesterone hormones function in the brain to regulate neu- ronal activity and influence behavior in females. Because these gonadal hormones have profound effects on brain func- tion, the female’s hormonal state at the time of cocaine ad- ministration may influence cocaine-induced behaviors and molecular alterations in brain function. Several studies suggest that gonadal hormones influence the activities of psychoactive drugs on neuronal dopamine sys- tems. For example, significant differences have been shown in females during the different stages of their reproductive cycle in response to cocaine and amphetamine administration. Women in the follicular phase of their menstrual cycle, given a single challenge dose of cocaine by nasal route of administra- tion, have been reported to have higher peak plasma cocaine levels than during the luteal phase (26). However, Mendelson et al. (29) reported that there are no gender or menstrual cycle dif- ferences in cocaine levels (area under the plasma concentration curve) or half-life in humans after intravenous administration. In rats, the estrous cycle influences an animal’s motivation to self-administer cocaine (39), the intensity of cocaine-induced stereotypic and locomotor activity (36), and dopamine release in the striatum (3). Rats in estrus exhibit significantly higher behavioral responses to amphetamine than at other stages of the estrous cycle. Sensitivity to amphetamine has been re- ported to be augmented during estrus (3,12,20,38). Estrous cy- Requests for reprints should be addressed to Dr. V. Quiñones-Jenab, Department of Psychology, Hunter College, CUNY New York, NY 10021.