Attenuation of ecstasy-induced neurotoxicity by N-acetylcysteine

Exposure to 3, 4-methylenedioxymethamphetamine (MDMA) can lead to spatial memory impairments and hippocampal cell death. Numerous evidence indicates that the antioxidant N-acetylcysteine (NAC) exerts protective effects in the brain. The present study evaluates the effects of NAC on MDMA-induced neurotoxicity. Methods: We intraperitoneally injected 28 adult male Sprague-Dawley rats (200-250 g) with either 0, 10 mg/kg of MDMA, or 10 mg/kg of MDMA plus 100 mg/kg of NAC. Spatial memory was assessed with a Morris Water Maze (MWM). At the end of the study, rats' brains were removed to study the structure and ultrastructure of CA1, and measure Bcl-2 and Bax expressions in the hippocampus. In the MWM, NAC treatment significantly attenuated the MDMA-induced increase in distance traveled (p < 0.05) and escape latency (p < 0.001). The decreased time spent in the target quadrant in MDMA-treated animals was attenuated by NAC (p < 0.01). NAC significantly protected against MDMA-induced apoptosis and the up- and down-regulation of Bax and Bcl-2, respectively. These data have suggested that NAC could protect against behavioral changes and apoptosis in the hippocampus following administration of MDMA. NAC might be useful for the treatment of neurotoxicity in MDMA users.