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Serotonergic mechanisms of cocaine effects in humans
Authors:Sarah C. Aronson  Jed E. Black  Christopher J. McDougle  B. Ellen Scanley  George R. Heninger  Lawrence H. Price  Peter Jatlow  Thomas R. Kosten
Affiliation:(1) Clinical Neuroscience Research Unit, Abraham Ribicoff Research Facilities, Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 06519 New Haven, CT, USA;(2) Department of Psychiatry, Yale University School of Medicine, 333 Cedar Street, 06519 New Haven, CT, USA;(3) Department of Laboratory Medicine, Yale University School of Medicine, 333 Cedar Street, 06519 New Haven, CT, USA;(4) Substance Abuse Treatment Unit, Connecticut Mental Health Center, 34 Park Street, 06519 New Haven, CT, USA
Abstract:The objective of this study was to investigate the role of serotonin (5-HT) in mediating the effects of cocaine in humans. To accomplish this, 12 subjects each participated in two randomized, double-blind test sessions separated by 1 week. In one session, subjects underwent acute depletion of the 5-HT amino acid precursor tryptophan (TRP), followed by a test dose of intranasal cocaine. In the other session, the cocaine test dose was preceded by sham depletion. Subject ratings of cocaine ldquohighrdquo were significantly lower following active TRP depletion than after the sham procedure. Subjects also showed an earlier but less sustained rise in self-rated nervousness during active TRP depletion. These findings are consistent with the hypothesis that 5-HT may be involved in mediating the euphorigenic and modulating the anxiogenic effects of cocaine in humans, either directly or through actions on other (e.g., dopaminergic) systems.
Keywords:Cocaine  Serotonin  Tryptophan
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