PMID- 10607865 OWN - NLM STAT- MEDLINE DCOM- 20000217 LR - 20221207 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 385 IP - 2-3 DP - 1999 Dec 3 TI - Involvement of the serotonin transporter in the formation of hydroxyl radicals induced by 3,4-methylenedioxymethamphetamine. PG - 103-10 AB - 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. FAU - Shankaran, M AU - Shankaran M AD - College of Pharmacy, University of Cincinnati, 3223 Eden Avenue, Cincinnati, OH 45267-0004, USA. FAU - Yamamoto, B K AU - Yamamoto BK FAU - Gudelsky, G A AU - Gudelsky GA LA - eng GR - DA07427/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Carrier Proteins) RN - 0 (Dopamine Agents) RN - 0 (Hydroxybenzoates) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Serotonin Agents) RN - 0 (Serotonin Plasma Membrane Transport Proteins) RN - 0 (Serotonin Uptake Inhibitors) RN - 0 (Slc6a4 protein, rat) RN - 01K63SUP8D (Fluoxetine) RN - 333DO1RDJY (Serotonin) RN - 3352-57-6 (Hydroxyl Radical) RN - 70D5FBB392 (2,3-dihydroxybenzoic acid) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - O414PZ4LPZ (Salicylic Acid) RN - TZ47U051FI (Dextroamphetamine) SB - IM MH - Animals MH - Carrier Proteins/*physiology MH - Corpus Striatum/drug effects/metabolism MH - Dextroamphetamine/pharmacology MH - Dopamine Agents/pharmacology MH - Fluoxetine/pharmacology MH - Hydroxybenzoates/metabolism MH - Hydroxyl Radical/*metabolism MH - Male MH - Membrane Glycoproteins/*physiology MH - *Membrane Transport Proteins MH - Microdialysis MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - *Nerve Tissue Proteins MH - Rats MH - Rats, Sprague-Dawley MH - Salicylic Acid/metabolism MH - Serotonin/metabolism MH - Serotonin Agents/*pharmacology MH - Serotonin Plasma Membrane Transport Proteins MH - Selective Serotonin Reuptake Inhibitors/pharmacology MH - Time Factors EDAT- 1999/12/23 09:00 MHDA- 2000/02/19 09:00 CRDT- 1999/12/23 09:00 PHST- 1999/12/23 09:00 [pubmed] PHST- 2000/02/19 09:00 [medline] PHST- 1999/12/23 09:00 [entrez] AID - S0014-2999(99)00728-1 [pii] AID - 10.1016/s0014-2999(99)00728-1 [doi] PST - ppublish SO - Eur J Pharmacol. 1999 Dec 3;385(2-3):103-10. doi: 10.1016/s0014-2999(99)00728-1.