MONOAMINERGIC REGULATION OF NEUROENDOCRINE FUNCTION AND ITS MODIFICATION BY COCAINE

Neuroendocrine pharmacology represents a potentially valuable approach to the assessment of alterations in neuronal function in the brain of human cocaine abusers. Neuroendocrine effects of the monoamine uptake inhibitor cocaine have predominantly been examined in laboratory anim als. These preclinical studies may help to identify the optimal challe nge tests to be performed in clinical studies. In laboratory animals, acute administration of cocaine activates the hypothalamic-pituitary-a drenal axis, via actions on serotonergic and dopaminergic neurons in t he brain. Cocaine also reduces prolactin secretion, probably by dopami nergic mechanisms, although the necessary studies to confirm this hypo thesis have not been performed. Cocaine also reduces renin secretion, and increases vasopressin and luteinizing hormone secretion, by mechan isms which have not been clearly established. The adrenocorticotropin, corticosterone, prolactin, and renin responses to cocaine are general ly unaltered by prior cocaine exposure, suggesting that tolerance or s ensitization to the endocrine effects of cocaine does not occur. Howev er, several studies have determined that prior cocaine exposure alters the serotonergic regulation of hormone secretion. Chronic cocaine exp osure reduces some of the hormone responses to the serotonin (5-HT) re leasers p-chloroamphetamine and d-fenfluramine, suggesting deficits in the functional status of serotonergic nerve terminals. Additionally, repeated cocaine exposure produces subsensitive 5-HT1A-mediated hormon e responses, and supersensitive 5-HT2-mediated responses. Alterations in dopaminergic- or noradrenergic-mediated hormone responses have not been examined in animals chronically exposed to cocaine. Endocrine stu dies in human cocaine abusers have largely examined basal hormone leve ls or the hormone responses to cocaine. Strong conclusions from these studies are limited because (1) many neuronal and nonneuronal systems regulate secretion of each hormone, so that alterations in basal hormo ne levels cannot be attributed to only one neurotransmitter; and (2) h ormone responses to cocaine cannot he examined in cocaine-naive subjec ts due to ethical considerations, making it impossible to determine wh ether the response in cocaine abusers is abnormal. It may be more bene ficial for studies in cocaine abusers to examine the hormone responses to drugs that specifically affect monoaminergic neurons and compare t he data with cocaine-naive individuals. (C) 1994 Academic Press, Inc.