Effect of 3,4‐Methylenedioxymethamphetamine on 3,4‐Dihydroxyphenylalanine Accumulation in the Striatum and Nucleus Accumbens
J. Frank Nash, Herbert Y. Meltzer, Gary A. Gudelsky
Journal of Neurochemistry March 1, 1990 DOI: 10.1111/j.1471-4159.1990.tb02358.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats (nigrostriatal and mesolimbic brain regions) |
| Interventions | MDMA ketanserin |
| Dose | 20 mg/kg |
| Duration | 3 hours and 7 days after MDMA administration |
| Measures | DOPA accumulation, 5-HT concentration, 5-HIAA concentration |
| Topics | MDMA |
| Key findings | MDMA increased DOPA accumulation in the striatum more than in the nucleus accumbens, and reduced 5-HT and 5-HIAA in both regions at 3 hours but only in the striatum at 7 days. Ketanserin blocked MDMA-induced DOPA accumulation and the 7-day 5-HT depletion, suggesting MDMA acts via 5-HT2 receptors and that dopamine contributes to 5-HT depletion. |
Abstract
Abstract: The effect of the racemic mixture of 3,4‐methy‐lenedioxymethamphetamine (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.