Combined administration of a non-neurotoxic 3,4-methylenedioxymethamphetamine analogue with amphetamine produces serotonin neurotoxicity in rats.
In the present study, a central serotonin neurotoxicity was induced by combining a non-neurotoxic 3,4-methylenedioxymethamphetamine analogue, 5-methoxy-6-methyl-2-aminoindan (MMAI), with the non-vesicular dopamine (DA) releaser, S-(+)-amphetamine (Amp). With the multiple dosing regimen utilized neither drug alone resulted in any changes in serotonergic parameters, including 5-HT, 5-HIAA and the number of 5-HT uptake sites. However, MMAI (10 mg/kg) in combination with Amp (2 x 2.5 mg/kg) did result in a long-term 20% decrease in cortical serotonergic parameters. The same dose of Amp plus 20 mg/kg MMAI resulted in a 50 to 60% reduction. Effects in the hippocampus and caudate nucleus were similar. These data support the hypothesis that DA release plays a critical role in the serotonin neurotoxicity of substituted amphetamines.
Johnson
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MP
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907.
Nichols
D E
DE
D000661:Amphetamine / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006897:Hydroxyindoleacetic Acid / Q000302:isolation & purification; D007189:Indans / Q000633:toxicity*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000302:isolation & purification; D012702:Serotonin Antagonists / Q000633:toxicity*
D007189:Indans; D012702:Serotonin Antagonists; C068879:5-methoxy-6-methyl-2-aminoindan; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000661:Amphetamine; D004298:Dopamine