The neuropharmacology of prolactin secretion elicited by 3,4-methylenedioxymethamphetamine ("ecstasy"): A concurrent microdialysis and plasma analysis study

• Type of Material: Article
• Authors: K. S. Murnane, Emory University; H. L. Kimmel, Emory University; K. C. Rice, National Institute on Alcohol Abuse and Alcoholism; Leonard Howell, Emory University
• Language: English
• Date: 2012-02-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.yhbeh.2011.10.012
• Title of Journal or Parent Work: Hormones and Behavior
• ISSN: 0018-506X
• Volume: 61
• Issue: 2
• Start Page: 181
• End Page: 190
• Grant/Funding Information: These studies were funded by the National Institutes of Health [DA000517 and DA010344 (LLH)]; and by the Yerkes Base Grant [RR00165 (KSM; HLK; LLH)].; A portion of this work was supported by the Intramural Research Programs of the National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism.
• Keywords: Serotonin Antagonists; Prolactin; Animals; Time Factors; Fluoxetine; Macaca mulatta; N-Methyl-3,4-methylenedioxyamphetamine; Serotonin Agents; Microdialysis; Stereoisomerism; Hallucinogens; Piperidines; Fluorobenzenes; Serotonin Uptake Inhibitors; Female
• Research Categories: Health Sciences, Pharmacology; Biology, Neuroscience; Health Sciences, Mental Health

Abstract

3,4-methylenedioxymethamphetamine (MDMA) is a substituted phenethylamine that is widely abused as the street drug "ecstasy". Racemic MDMA (S,R(+/-)-MDMA) and its stereoisomers elicit complex spectrums of psychobiological, neurochemical, and hormonal effects. In this regard, recent findings demonstrated that S,R(+/-)-MDMA and its stereoisomer R(-)-MDMA elicit increases in striatal extracellular serotonin levels and plasma levels of the hormone prolactin in rhesus monkeys. In the present mechanistic study, we evaluated the role of the serotonin transporter and the 5-HT 2A receptor in S,R(+/-)-MDMA- and R(-)-MDMA-elicited prolactin secretion in rhesus monkeys through concurrent microdialysis and plasma analysis determinations and drug interaction experiments. Concurrent neurochemical and hormone determinations showed a strong positive temporal correlation between serotonin release and prolactin secretion. Consistent with their distinct mechanisms of action and previous studies showing that the serotonin transporter inhibitor fluoxetine attenuates the behavioral and neurochemical effects of S,R(+/-)-MDMA, pretreatment with fluoxetine attenuated serotonin release elicited by either S,R(+/-)-MDMA or R(-)-MDMA. As hypothesized, at a dose that had no significant effects on circulating prolactin levels when administered alone, fluoxetine also attenuated prolactin secretion elicited by S,R(+/-)-MDMA. In contrast, combined pretreatment with both fluoxetine and the selective 5-HT 2A receptor antagonist M100907 was required to attenuate prolactin secretion elicited by R(-)-MDMA, suggesting that this stereoisomer of S,R(+/-)-MDMA elicits prolactin secretion through both serotonin release and direct agonism of 5-HT 2A receptors. Accordingly, these findings inform our understanding of the neuropharmacology of both S,R(+/-)-MDMA and R(-)-MDMA and the regulation of prolactin secretion.