Effect of ascorbate and cysteine on the 3,4-methylenedioxymethamphetamine-induced depletion of brain serotonin.

The extent of long-term depletion of serotonin (5-HT) produced by 3,4-methylenedioxymethamphetmaine (MDMA) was assessed in rats treated with the antioxidants sodium ascorbate or L-cysteine. There was a 30-35% reduction in the striatal concentration of 5-HT 7 days following a single injection of MDMA (20 mg/kg, s.c.). MDMA had no significant effect on striatal concentrations of 5-HT in rats that had been treated with ascorbate (250 mg/kg, i.p.) or cysteine (500 mg/kg, i.p.) 30 min prior to and 5 hrs following the administration of MDMA. Treatment with ascorbate or cysteine did not alter the accumulation of MDMA in brain as determined by in vivo microdialysis. Moreover, neither ascorbate nor cysteine altered the stimulation of dopamine release elicited by MDMA. These data are supportive of the view that MDMA-induced toxicity of 5-HT neurons may be related to the production of free radicals and subsequent oxidative damage.