Estudio de los mecanismos de neurotoxicidad de la 3,4-metilendioximentanfetamina (mdma,"extasis") tras su administracion en ratanuevas respuestas a antiguos interrogants

Resumen

TITULO: ESTUDIO DE LOS MECANISMOS DE NEUROTOXICIDAD DE LA 3,4-METILENDIOXIMETANFETAMINA (MDMA, "ÉXTASIS") TRAS SU ADMINISTRACIÓN EN RATA: NUEVAS RESPUESTAS A ANTIGUOS INTERROGANTES RESUMEN: 3, 4-Methylenedioxymethamphetamine (mdma, "ecstasy") is an amphetamine derivative which has become a very popular drug among young adults despite its potential neurotoxic effects and psychiatric complications reported in recreational mdma users. it is well known that single or repeated injections of mdma cause several changes in neurochemical and histologicaí markers of the serotonergic function in the brain of rodents, primates and, possibly, in humans. Despite the efforts made during the last two decades, the exact mechanisms underlying MDMA toxicity remain unclear. The aim of this investigation was the study of some of these mechanisms: an ionic/energetic dysregulation, the involvement of hyperthermia, MDMA metabolic disposition and the influence of tyrosine. %&/According to the results obtained, it could be suggested that an ionic/energetic dysregulation is not a key feature of MDMA-induced neurotoxicity. However it has been demonstrated that there is a close relationship between the ambient temperature at which the MDMA is administered and the metabolism of this drug: high ambient temperature (30°C) promotes the metabolism of the MDMA and exacerbates the hyperthermia and the serotonergic deficits induced by this amphetamine. On the contrary, the administration of MDMA at 15°C blocked the hyperthermic response and reduced the metabolism of the drug and the long-term serotonin depletion. in regard to the tyrosine involvement on MDMA-induced neurotoxicity, it can be stated that a subtoxic dose of MDMA combined with a high dose of tyrosine, caused long-term 5-HT depletions in rats treated at 21.5°C but not in those treated at 15°C, conditions known to decrease MDMA metabolism. Further, striatal perfusion of MDMA combined with tyrosine in hyperthermic rats did not cause 5-HT depletions. By contrast, rats treated with a subtoxic dose of MDMA under heating conditions or combined with entacapone or acivicin, which interfere with MDMA metabolism or increase brain MDMA metabolites availability respectively, showed significant reductions of brain serotonin contení. Altogether, these data indicate that although tyrosine may contribute to MDMA-induced toxicity, MDMA metabolism is the limiting step.