The spin trap reagent alpha-phenyl-N-tert-butyl nitrone prevents 'ecstasy'-induced neurodegeneration of 5-hydroxytryptamine neurones.
Administration of a single dose (10 mg/kg i.p.) of 3,4-methylenedioxy-methamphetamine (MDMA or 'ecstasy') produced a 40% loss of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cortex and hippocampus of Dark Agouti rats 7 days later. Binding of [3H]paroxetine to the presynaptic 5-HT nerve terminals in cortex was decreased by approximately 30%. Injection of the spin trap reagent alpha-phenyl-N-tert-butyl nitrone (PBN; 150 mg/kg i.p.) 10 min prior and 120 min post MDMA administration totally prevented the loss in [3H]paroxetine binding in the cortex and attenuated the loss of 5-HT and 5-HIAA in both brain regions. PBN alone had no effect on [3H]paroxetine binding or brain 5-HT content. These data suggest that MDMA produces neurodegeneration of 5-HT neurones because of reactive free radical formation.
Colado
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MI
Astra Neuroscience Research Unit, London, UK.
Green
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AR
D000704:Analysis of Variance; D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003497:Cyclic N-Oxides; D005609:Free Radicals; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D009410:Nerve Degeneration / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009589:Nitrogen Oxides / Q000494:pharmacology*; D017374:Paroxetine / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D013113:Spin Labels
D003497:Cyclic N-Oxides; D005609:Free Radicals; D009589:Nitrogen Oxides; D012702:Serotonin Antagonists; D013113:Spin Labels; D012701:Serotonin; C029217:phenyl-N-tert-butylnitrone; D017374:Paroxetine; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine