Effects of Ganglioside GM1 on MDMA-Induced Serotonergic Neurotoxicity in the Rat Brain

Abstract

MDMA (Ecstasy), a methylamphetamine derivative, has been found to produce severe and somewhat selective damage to CNS serotonergic (5-HT) neurons. This damage, though extensive, does not involve cell death. The ganglioside GM 1 has demonstrated potential neurotrophic properties which may enhance the rate of recovery of the neurons from the MDMA-induced effects. To assess this GM1 effect, MDMA (20 mglkg x 4 days), GM1 (40 mgkg), MDMA and GM1 or saline was injected (i.p.) into male rats. Behavioral activity was determined for 24 hours on day 5 or day 12 following the beginning of the injections. A general increase in activity on day 5 was noted for the MDMA group (consistent with a release of 5-HT and/or catecholamines) while the activity of the MDMA/GM 1 group was lower, at the level of the control. At day 12 the MDMA group's activity was decreased relative to the control (consistent with a 5-HT depletion) while the MDWGM 1 group's activity was at or above that of the control. Biochemical analysis of brain tissue obtained from the animals sacrificed on day 7 or 14 following the beginning of the injections demonstrated a profound depletion of 5-HT, dopamine and norepinephrine with administration of MDMA. The MDMA/GMl group also showed this depletion, though to a smaller degree, suggesting some attenuation of toxic effects.