Studies on the neuroprotective effect at pentobarbitone on MDMA-induced neurodegeneration

Administration of a dose of 15 mg/kg of the recreationally used drug 3,4-me thylenedioxymethamphetamine (MDMA or "ecstasy") to Dark Agouti rats resulte d in an acute hyperthermic response which was followed 7 days later by a ma rked (approximate to 45%) loss off 5-HT and its metabolite 5-HIAA in cortex , hippocampus and striatum and a similar loss of [H-3]-paroxetine binding i n cortex. These losses reflect the MDMA-induced neurotoxic degeneration of 5-HT nerve endings. Administration of pentobarbitone (40 mg/kg) concurrentl y with MDMA produced a significant attenuation of the neurotoxic damage, bu t also acute hypothermia. When the temperature of the MDMA plus pentobarbit one-treated group was kept elevated to that of the MDMA-treated group by th e use of a homeothermic blanket, the neuroprotective effect of pentobarbito ne was lost. These data demonstrate that pentobarbitone appears to possess no intrinsic neuroprotective activity and the previously reported activity is due to a hypothermic action of the drug.