Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists.
The effects of the 5-HT2 receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) on 3,4-methylenedioxymethamphetamine (MDMA)-induced dopamine release and 5-HT depletion in the striatum were studied. The MDMA-induced increase in the extracellular concentration of dopamine in the striatum was enhanced significantly in rats treated with either DOI (2 mg/kg, ip.) or 5-MeODMT (15 mg/kg, ip.), as assessed using in vivo microdialysis. Neither DOI nor 5-MeODMT alone altered the extracellular concentration of dopamine in the striatum. The striatal concentration of 5-HT was decreased, but not significantly, 7 days following a single administration of MDMA (10 mg/kg, sc.). However, 7 days following the concomitant treatment with DOI and MDMA the striatal concentration of 5-HT was significantly less than that in rats treated with MDMA alone or the vehicle-treated controls. It is concluded that activation of 5-HT2 receptors is an important determinant of the acute increase in extracellular dopamine and, consequently, the long-term depletion of brain 5-HT produced by MDMA.
Gudelsky
G A
GA
Department of Psychiatry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106.
Yamamoto
B K
BK
Nash
J F
JF
D000662:Amphetamines / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008297:Male; D008732:Methoxydimethyltryptamines / Q000008:administration & dosage / Q000494:pharmacology*; D017551:Microdialysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
D000662:Amphetamines; D008732:Methoxydimethyltryptamines; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D004298:Dopamine