Effect of depleting vesicular and cytoplasmic dopamine on methylenedioxymethamphetamine neurotoxicity

• Published in: Journal of neurochemistry 2002-03, Vol.80 (6), p.960-969
• Main Authors: Yuan, Jie, Cord, Branden J., McCann, Una D., Callahan, Brian T., Ricaurte, George A.
• Format: Article
• Language: English
• Subjects: 4‐methylenedioxymethamphetamine; Adrenergic Uptake Inhibitors - pharmacology; alpha-Methyltyrosine - pharmacology; Animals; Biological and medical sciences; Corpus Striatum - cytology; Corpus Striatum - drug effects; Cytoplasm - metabolism; Cytoplasmic Vesicles - metabolism; Cytoprotection - drug effects; dopamine; Dopamine - deficiency; Dopamine - metabolism; Drug addictions; Drug Synergism; Drug-Related Side Effects and Adverse Reactions - metabolism; Enzyme Inhibitors - pharmacology; Hippocampus - cytology; Hippocampus - drug effects; Hypothermia - chemically induced; Hypothermia - prevention & control; Male; Medical sciences; N-Methyl-3,4-methylenedioxyamphetamine - toxicity; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; neurotoxicity; Rats; reserpine; Reserpine - pharmacology; serotonin; Serotonin - metabolism; Serotonin - toxicity; Serotonin Agents - toxicity; Temperature; Toxicology; α‐methyl‐p‐tyrosine
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.0022-3042.2002.00758.x

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 α‐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.