The spin trap reagent alpha-phenyl-N-tert-butyl nitrone prevents 'ecstasy'-induced neurodegeneration of 5-hydroxytryptamine neurones

Abstract

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.