Attenuation of 3,4-methylenedioxymethamphetamine (MDMA) induced neurotoxicity with the serotonin precursors tryptophan and 5-hydroxytryptophan.
Treatment of rats with serotonin (5-HT) precursors tryptophan (TRP, 400 mg/kg) and 5-hydroxytryptophan (5-HTP, 50 mg/kg) was shown to attenuate MDMA (20 mg/kg) induced serotonergic neurotoxicity as measured by [3H]-paroxetine binding in the striatum, hippocampus, and frontal cortex of the rat brain. Hippocampal 5-HT and 5-HIAA levels were also indicative of the protective effects of TRP and 5-HTP. These results suggest that depletion of 5-HT stores is important for MDMA-induced neurotoxicity. The possible significance of this 5-HT depletion in MDMA-induced serotonergic terminal degeneration is also discussed.
Sprague
J E
JE
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907.
Huang
X
X
Kanthasamy
A
A
Nichols
D E
DE
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009411:Nerve Endings / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000494:pharmacology*
D012701:Serotonin; D014364:Tryptophan; D006916:5-Hydroxytryptophan; D018817:N-Methyl-3,4-methylenedioxyamphetamine