The effect of MDMA (3,4-methylenedioxymethamphetamine) on the 5-HT synthesis rate in the rat brain: an autoradiographic study.
The effect of MDMA (3,4-methylenedioxymethamphetamine), a psychotropic amphetamine derivative, treatment on the rate of serotonin (5-hydroxytryptamine; 5-HT) synthesis in the rat brain was studied by autoradiography using alpha-[14C]-methyl-l-tryptophan method. Three different treatment protocols were compared to the control (saline) treated rats: (1) rats treated twice with 10 mg/kg every 12 h (20 mg/kg total) and injected tracer for the synthesis measurements 15 h later; (2) rats treated with four injections of 5 mg/kg every 12 h (20 mg/kg total) and injected tracer for the synthesis measurement 17 h after the last dose; and (3) rats given eight injections of 5 mg/kg every 12 h for four days (40 mg/kg) and used in the synthesis study 14 days after the last dose. Results showed a significant decrease in the rate of synthesis in the majority of cerebral structures examined in the 10 mg/kg group. In contrast the group receiving the same total amount (20 mg/kg) of MDMA but over two days (4x5 mg/kg) showed a significant increase in 5-HT synthesis in comparison to controls. The 5-HT synthesis rates measured 14 days after the last dose (four days, 8x5 mg/kg) were significantly reduced. The findings suggest that MDMA can produce either an increase or a decrease in the 5-HT synthesis a short time after a total dose of 20 mg/kg depending on the dose fractionation. However, 14 days after total dose of 40 mg/kg given over four days the synthesis rate was significantly reduced in many brain structures. The latter suggests a possible effect of the MDMA neurotoxicity on the serotonergic neurons, in addition to a possible influence on 5-HT synthesis via a feedback mechanism.
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Cone Laboratory for Neurosurgical Research, Department of Neurology and Neurosurgery, and Montreal Neurological Institute, McGill University, 3801 University St., Montreal, Quebec, Canada.
Takahashi
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Diksic
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D000465:Algorithms; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012701:Serotonin / Q000096:biosynthesis*; D018490:Serotonin Agents / Q000494:pharmacology*; D014364:Tryptophan / Q000097:blood / Q000378:metabolism
D018490:Serotonin Agents; D012701:Serotonin; D014364:Tryptophan; D018817:N-Methyl-3,4-methylenedioxyamphetamine