Articles
Cocaine’s Effects on Neuroendocrine Systems: Clinical and Preclinical Studies

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Abstract

This review examines the effects of cocaine on the neuroendocrine system and summarizes findings from clinical studies of cocaine abusers and preclinical studies in rodents and rhesus monkeys. The effects of acute and chronic cocaine administration on anterior pituitary, gonadal, and adrenal hormones are described, and the functional consequences of chronic cocaine exposure are discussed. Many of cocaine’s acute effects on the endocrine system are consistent with its actions as a monoamine reuptake inhibitor. Acute cocaine administration stimulates release of gonadotropins, ACTH, and cortisol or corticosterone and suppresses prolactin levels. It has been difficult to detect changes in basal levels of most hormones or alterations in hormone responsiveness to a challenge dose of cocaine or other agents after chronic cocaine treatment. Interpretation of clinical data is often complicated by polydrug abuse involving opiates and alcohol as well as cocaine. However, preclinical studies of the effects of chronic cocaine exposure on integrated neuroendocrine function have revealed disruptions of the estrous cycle in rats and the menstrual cycle in rhesus monkeys. Furthermore, the menstrual cycle disorders observed in rhesus monkeys parallel those reported in women who abuse cocaine. Much remains to be learned about cocaine’s interactions with the endocrine system and the consequences of cocaine abuse for reproductive function.

Section snippets

Background

Prolactin exists in all vertebrates, and one of its primary physiological functions is the stimulation of milk production and the maintenance of lactation after pregnancy. Prolactin also has a number of other behavioral and physiologic effects in humans and other species 112, 147, 163, 250. For example, in addition to its effect on the mammary glands, prolactin also influences migration in birds, parenting behavior in birds and mammals, and the maintenance of water and electrolyte balance [147]

Background

The hypothalamic–pituitary–adrenal (HPA) axis is the major endogenous hormonal system that activates the integrative physiological response to stress. Corticotropin-releasing hormone (CRH) regulates the pulsatile release of ACTH from the anterior pituitary. CRH is secreted by neurons in the basal hypothalamus, and CRH and ACTH secretion are under negative feedback control by cortisol, which is released from the adrenal cortex. A number of neuronal systems are involved in the regulation of CRH

Background

The gonadotropin hormones, luteinizing hormone (LH) and follicle stimulating hormone (FSH), are released from cells called gonadotropes located in the anterior pituitary. Although most gonadotropes (60%) contain both LH and FSH, a number of small gonadotropes contain LH or FSH alone. The release of both LH and FSH is stimulated by a hypothalamic peptide hormone, luteinizing-hormone releasing-hormone (LHRH), also known as gonadotropin-releasing hormone (GnRH). LH and FSH release is pulsatile and

Background

We have seen that acute cocaine administration changes anterior pituitary and gonadal hormone levels but, with the exception of prolactin, it has been difficult to detect changes in basal hormone levels after chronic cocaine abuse or short-term cocaine exposure in animal models. We infer that chronic changes in neuroendocrine function do occur, on the basis of clinical and experimental evidence of cocaine-related disruptions in reproductive function 27, 122, 191, 193, 206. However, the ways in

Conclusions

Cocaine interacts with many neuromodulatory systems in brain and has both direct and indirect effects on anterior pituitary, gonadal, and adrenal hormones. The comodulatory interactions between these hormones have been emphasized throughout this review. An obvious limitation of studies of cocaine’s effects on single hormones, at a single time point, is that the effects measured cannot reflect the full spectrum of interactions within the neuroendocrine system. However, studies conducted thus far

Acknowledgements

Preparation of this review was supported in part by grants K05 DA 00101 and K05 DA 00064 and P-50 DA 04059 from the National Institute on Drug Abuse, NIH. We thank our colleague Dr. S. S. Negus of the Alcohol and Drug Abuse Research Center, McLean Hospital and Harvard Medical School, for his helpful comments on an earlier version of the manuscript. We are grateful to J. Wallis Sholar for preparing the figures. We thank Loretta Carvelli, Susan Grady, and Eleanor DeRubeis for their excellent

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