Effect of 3,4-Methylenedioxymethamphetamine on 3,4-Dihydroxyphenylalanine Accumulation in the Striatum and Nucleus Accumbens

The effect of the racemic mixture of 3,4-methylenedioxymethamphetamine (MDMA) on the synthesis of dopamine in the terminals of nigrostriatal and mesolimbic neurons was estimated by measuring the accumulation of 3,4-dihydroxyphenylalanine (DOPA) in the striatum and nucleus accumbens 30 min following the administration of the L-aromatic amino acid decarboxylase inhibitor, 3-hydroxybenzylhydrazine. MDMA produced an increase in DOPA accumulation in the striatum which was greater in magnitude and longer in duration than that in the nucleus accumbens. Although the concentrations of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in both the striatum and nucleus accumbens were reduced 3 h following an injection of MDMA (20 mg/kg), 5-HT and 5-HIAA concentrations were significantly reduced only in the striatum 7 days after the administration of MDMA. Pretreatment with a 5-HT2 antagonist, ketanserin, significantly attenuated the reduction in 5-HT concentration in the striatum 3 h following MDMA administration and completely blocked 5-HT depletion at 7 days post administration. Moreover, ketanserin completely blocked MDMA-induced DOPA accumulation in the striatum. The results obtained in these studies suggest that MDMA activates nigrostriatal dopaminergic pathways via 5-HT2 receptors. In addition, these data are supportive of the hypothesis that dopamine plays a role in MDMA-induced 5-HT depletion.