Studies on the neuroprotective effect of pentobarbitone on MDMA-induced neurodegeneration.
Administration of a dose of 15 mg/kg of the recreationally used drug 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") to Dark Agouti rats resulted in an acute hyperthermic response which was followed 7 days later by a marked (approximately 45%) loss of 5-HT and its metabolite 5-HIAA in cortex, hippocampus and striatum and a similar loss of [3H]-paroxetine binding in cortex. These losses reflect the MDMA-induced neurotoxic degeneration of 5-HT nerve endings. Administration of pentobarbitone (40 mg/kg) concurrently with MDMA produced a significant attenuation of the neurotoxic damage, but also acute hypothermia. When the temperature of the MDMA plus pentobarbitone-treated group was kept elevated to that of the MDMA-treated group by the use of a homeothermic blanket, the neuroprotective effect of pentobarbitone 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.
Colado
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MI
Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain. colado@eucmax.sim.ucm.es
Esteban
B
B
O'Shea
E
E
Granados
R
R
Green
A R
AR
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017374:Paroxetine / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018696:Neuroprotective Agents; D017374:Paroxetine; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital; D018817:N-Methyl-3,4-methylenedioxyamphetamine