Abstract
A single administration of 3,4-methylenedioxymethamphetamine (MDMA, 20 mg/kg, i.p.), induced significant hyperthermia in rats and reduced 5-hydroxytryptamine (5-HT) content and [3H]paroxetine-labeled 5-HT transporter density in the frontal cortex, striatum and hippocampus by 40-60% 1 week later. MDMA treatment also increased glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus. Repeated administration of the metabolic antioxidant alpha-lipoic acid (100 mg/kg, i.p., b.i.d. for 2 consecutive days) 30 min prior to MDMA did not prevent the acute hyperthermia induced by the drug; however, it fully prevented the serotonergic deficits and the changes in the glial response induced by MDMA. These results further support the hypothesis that free radical formation is responsible for MDMA-induced neurotoxicity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antioxidants / pharmacology
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Astrocytes / drug effects
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Astrocytes / metabolism
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Binding Sites / drug effects
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Carrier Proteins / metabolism
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Fever / chemically induced
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Frontal Lobe / cytology
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Frontal Lobe / drug effects*
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Frontal Lobe / metabolism
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Glial Fibrillary Acidic Protein / analysis
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Hippocampus / cytology
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Hippocampus / drug effects*
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Hippocampus / metabolism
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Hypothermia / chemically induced
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Male
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Membrane Glycoproteins / metabolism
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Membrane Transport Proteins*
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N-Methyl-3,4-methylenedioxyamphetamine / antagonists & inhibitors
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N-Methyl-3,4-methylenedioxyamphetamine / toxicity*
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Neostriatum / cytology
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Neostriatum / drug effects*
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Neostriatum / metabolism
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Nerve Tissue Proteins*
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Neuroprotective Agents / pharmacology*
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Paroxetine / metabolism
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Pyramidal Cells / drug effects
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Pyramidal Cells / metabolism
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Rats
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Rats, Wistar
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Serotonin / metabolism
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Serotonin Plasma Membrane Transport Proteins
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Thioctic Acid / pharmacology*
Substances
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Antioxidants
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Carrier Proteins
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Glial Fibrillary Acidic Protein
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Neuroprotective Agents
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Serotonin Plasma Membrane Transport Proteins
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Slc6a4 protein, rat
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Serotonin
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Paroxetine
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Thioctic Acid
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N-Methyl-3,4-methylenedioxyamphetamine