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 assessd in rats treated with the antioxidants sodium ascorbate or L-cysteine. There was a 30-35% re duction in the striatal concentration of 5-HT 7 days following a singl e injection of MDMA (20 mg/kg, sc). MDMA had no significant effect on striatal concentrations of 5-HT in rats that had been treated with asc orbate (250 mg/kg, ip) or cysteine (500 mg/kg, ip) 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 determi ned by in vivo microdialysis. Moreover, neither ascorbate nor cysteine altered the stimulation of dopamine release elicited by MDMA. These d ata are supportive of the view that MDMA-induced toxicity of 5-HT neur ons may be related to the production of free radicals and subsequent o xidative damage.