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The Journal of Neuroscience, June 15, 1999, 19(12):5096-5107
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery
George Hatzidimitriou1, Una D. McCann2, and George A. Ricaurte1 1 Department of Neurology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, and 2 Unit on Anxiety Disorders, Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892
The recreational drug (±)3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is a potent and selective brain serotonin (5-HT) neurotoxin in animals and, possibly, in humans. The purpose of the present study was to determine whether brain 5-HT deficits persist in squirrel monkeys beyond the 18-month period studied previously and to identify factors that influence recovery of injured 5-HT axons. Seven years after treatment, abnormal brain 5-HT innervation patterns were still evident in MDMA-treated monkeys, although 5-HT deficits in some regions were less severe than those observed at 18 months. No loss of 5-HT nerve cell bodies in the rostral raphe nuclei was found, indicating that abnormal innervation patterns in MDMA-treated monkeys are not the result of loss of a particular 5-HT nerve cell group. Factors that influence recovery of 5-HT axons after MDMA injury are (1) the distance of the affected axon terminal field from the rostral raphe nuclei, (2) the degree of initial 5-HT axonal injury, and possibly (3) the proximity of damaged 5-HT axons to myelinated fiber tracts. Additional studies are needed to better understand these and other factors that influence the response of primate 5-HT neurons to MDMA injury and to determine whether the present findings generalize to humans who use MDMA for recreational purposes.
Key words: amphetamines; methylenedioxymethamphetamine; serotonin; neurotoxicity; regeneration; 5-HT axon
Copyright © 1999 Society for Neuroscience 0270-6474/99/19125096-12$05.00/0
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