Involvement of the serotonin transporter in the formation of hydroxyl radicals induced by 3,4-methylenedioxymethamphetamine.
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.
Shankaran
M
M
College of Pharmacy, University of Cincinnati, 3223 Eden Avenue, Cincinnati, OH 45267-0004, USA.
Yamamoto
B K
BK
Gudelsky
G A
GA
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D026901:Membrane Transport Proteins; D017551:Microdialysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors
D002352:Carrier Proteins; D003913:Dextroamphetamine; D015259:Dopamine Agents; D005473:Fluoxetine; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009419:Nerve Tissue Proteins; D020156:Salicylic Acid; D012701:Serotonin; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493232:Slc6a4 protein, rat; C009135:2,3-dihydroxybenzoic acid