Altered serotonin innervation patterns in the forebrain of monkeys treated with (+/-)3,4-methylenedioxymethamphetamine seven years previously: factors influencing abnormal recovery.
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.
Hatzidimitriou
G
G
Department of Neurology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
McCann
U D
UD
Ricaurte
G A
GA
D000679:Amygdala / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D000818:Animals; D001369:Axons / Q000502:physiology; D001927:Brain Diseases / Q000139:chemically induced / Q000503:physiopathology; D002395:Catecholamines / Q000032:analysis; D003342:Corpus Striatum / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D007031:Hypothalamus / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D019579:Neocortex / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology; D016548:Prosencephalon / Q000737:chemistry* / Q000187:drug effects*; D011903:Raphe Nuclei / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D012453:Saimiri; D012701:Serotonin / Q000032:analysis*; D018490:Serotonin Agents / Q000494:pharmacology*; D013788:Thalamus / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D013997:Time Factors
D002395:Catecholamines; D009498:Neurotoxins; D018490:Serotonin Agents; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine