Effect of acute monoamine depletion on 3,4-methylenedioxymethamphetamine-induced neurotoxicity.
The effect of acute, reversible depletion of either serotonin [5-hydroxytryptamine (5-HT)] or dopamine (DA) on the long-term (7-day) decrease of brain 5-HT content produced after 3,4-methylenedioxymethamphetamine (MDMA) administration was investigated. The tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (alpha-MPT) significantly attenuated the acute increase in DA efflux produced by MDMA in the striatum as measured by in vivo microdialysis. Treatment with alpha-MPT had no effect on MDMA-induced 5-HT release. alpha-MPT treatment blocked the long-term (7-day) depletion of striatal 5-HT content after MDMA administration. The tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA) completely blocked the acute increase in the extracellular concentration of 5-HT produced by MDMA. Although PCPA significantly attenuated the increase in DA efflux produced by MDMA, the effect was small in magnitude. More importantly, treatment with PCPA had no effect on MDMA-induced decrease of 5-HT uptake sites in the frontal cortex. These data are suggestive that acute depletion of DA but not 5-HT protects against the long-term neurotoxic effects of MDMA on 5-HT axon terminals. In addition, these data are supportive of the hypothesis that DA plays a major role in the neurotoxic effects of MDMA.
Brodkin
J
J
Department of Psychiatry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-5000.
Malyala
A
A
Nash
J F
JF
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D015306:Biogenic Monoamines / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D015198:Designer Drugs / Q000633:toxicity*; D003956:Dialysis; D004298:Dopamine / Q000502:physiology; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009411:Nerve Endings / Q000378:metabolism / Q000502:physiology; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D017374:Paroxetine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000502:physiology; D013238:Stereotaxic Techniques; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D015306:Biogenic Monoamines; D015198:Designer Drugs; D008781:Methyltyrosines; D011985:Receptors, Serotonin; D012701:Serotonin; D017374:Paroxetine; D015104:3,4-Methylenedioxyamphetamine; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D010134:Fenclonine; D004298:Dopamine