Effect of depleting vesicular and cytoplasmic dopamine on methylenedioxymethamphetamine neurotoxicity.
The mechanism by which 3,4-methylenedioxymethamphetamine (MDMA) produces serotonin (5-HT) neurotoxicity is unknown but considerable evidence suggests that endogenous brain dopamine (DA) is involved. However, it has recently become apparent that some of the data implicating brain DA in MDMA neurotoxicity may be confounded by drug effects on thermoregulation. The purpose of the present studies was to examine the role of DA in MDMA neurotoxicity, while controlling for possible confounding effects of drug- induced changes in core temperature. Rats were treated with reserpine, alone and in combination with alpha-methyl-p -tyrosine (AMPT), to deplete vesicular and cytoplasmic stores of DA. When drug-induced hypothermia was averted (by raising ambient temperature), the 5-HT neuroprotective effects of reserpine and AMPT were no longer apparent. The lack of neuroprotection by AMPT and reserpine, alone and in combination, in studies that control for the effects of these drugs on core temperature, suggests that DA per se is not essential for the expression of MDMA-induced 5-HT neurotoxicity.
Yuan
Jie
J
Departments of Neurology and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
Cord
Branden J
BJ
McCann
Una D
UD
Callahan
Brian T
BT
Ricaurte
George A
GA
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism*; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D004357:Drug Synergism; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007035:Hypothermia / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism / Q000633:toxicity; D018490:Serotonin Agents / Q000633:toxicity; D013696:Temperature; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D004791:Enzyme Inhibitors; D018490:Serotonin Agents; D012701:Serotonin; D019805:alpha-Methyltyrosine; D012110:Reserpine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine