Involvement of the serotonin transporter in the formation of hydroxyl radicals induced by 3,4-methylenedioxymethamphetamine.

M Shankaran, B K Yamamoto, G A Gudelsky

College of Pharmacy, University of Cincinnati, 3223 Eden Avenue, Cincinnati, OH 45267-0004, USA.

European journal of pharmacology 1999 Dec 3

filter terms:

The mechanism of 3,4-methylenedioxymethamphetamine (MDMA)-induced depletion of brain serotonin (5-hydroxytryptamine, 5-HT) has been proposed to involve the generation of reactive oxygen species. In the present study, quantification of the extracellular concentration of 2,3-dihydroxybenzoic acid (2,3-DHBA) from salicylic acid was used as an index of hydroxyl radical generation. Although both MDMA and D-amphetamine markedly increased the extracellular concentration of dopamine in the striatum, only MDMA increased the extracellular concentration of 2,3-DHBA. Treatment with fluoxetine either 1 h prior to or 4 h following the administration of MDMA reduced the MDMA-induced formation of 2,3-DHBA and also attenuated the MDMA-induced depletion of 5-HT in the striatum. These results are supportive of the view that the MDMA-induced generation of hydroxyl radicals and, ultimately, the long-term depletion of 5-HT, is dependent, in part, on the activation of the 5-HT transporter.

Citation

M Shankaran, B K Yamamoto, G A Gudelsky. Involvement of the serotonin transporter in the formation of hydroxyl radicals induced by 3,4-methylenedioxymethamphetamine. European journal of pharmacology. 1999 Dec 3;385(2-3):103-10