PMID- 18248690 OWN - NLM STAT- MEDLINE DCOM- 20081218 LR - 20161020 IS - 1461-1457 (Print) IS - 1461-1457 (Linking) VI - 11 IP - 6 DP - 2008 Sep TI - Effects of ethanol and 3,4-methylenedioxymethamphetamine (MDMA) alone or in combination on spontaneous and evoked overflow of dopamine, serotonin and acetylcholine in striatal slices of the rat brain. PG - 743-63 LID - 10.1017/S1461145708008481 [doi] AB - Ethanol (EtOH) potentiates the locomotor effects of 3,4-methylenedioxymetamphetamine (MDMA) in rats. This potentiation might involve pharmacokinetic and/or pharmacodynamic mechanisms. We explored whether the latter could be local. Using a slice superfusion approach, we assessed the effects of MDMA (0.3, 3microm) and/or EtOH (2mm) on the spontaneous outflow and electrically evoked release of serotonin (5-HT), dopamine (DA) and acetylcholine (ACh) in the striatum, and for comparison, on 5-HT release in hippocampal and neocortical tissue. MDMA and less effectively EtOH, augmented the outflow of 5-HT in all regions. The electrically evoked 5-HT release was increased by MDMA at 3microm in striatal slices only. With nomifensine throughout, EtOH significantly potentiated the 0.3microm MDMA-induced outflow of 5-HT, but only in striatal slices. EtOH or MDMA also enhanced the spontaneous outflow of DA, but MDMA reduced the electrically evoked DA release. With fluvoxamine throughout superfusion, EtOH potentiated the effect of MDMA on the spontaneous outflow of DA. Finally, 3microm MDMA diminished the electrically evoked release of ACh, an effect involving several receptors (D2, 5-HT2, NMDA, nicotinic, NK1), with some interactions with EtOH. Among other results, we show for the first time a local synergistic interaction of EtOH and MDMA on the spontaneous outflow of striatal DA and 5-HT, which could be relevant to the EtOH-induced potentiation of hyperlocomotion in MDMA-treated rats. These data do not preclude the contribution of other pharmacodynamic and/or pharmacokinetic mechanisms in vivo but support the hypothesis that EtOH may affect the abuse liability of MDMA. FAU - Riegert, Celine AU - Riegert C AD - Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie der Universitat Freiburg, Neuropharmakologisches Labor, Freiburg, Germany. FAU - Wedekind, Franziska AU - Wedekind F FAU - Hamida, Sami Ben AU - Hamida SB FAU - Rutz, Susanne AU - Rutz S FAU - Rothmaier, Anna Katharina AU - Rothmaier AK FAU - Jones, Byron C AU - Jones BC FAU - Cassel, Jean-Christophe AU - Cassel JC FAU - Jackisch, Rolf AU - Jackisch R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080204 PL - England TA - Int J Neuropsychopharmacol JT - The international journal of neuropsychopharmacology JID - 9815893 RN - 0 (Central Nervous System Depressants) RN - 0 (Drug Combinations) RN - 0 (Serotonin Agents) RN - 10028-17-8 (Tritium) RN - 333DO1RDJY (Serotonin) RN - 3K9958V90M (Ethanol) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - N9YNS0M02X (Acetylcholine) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Acetylcholine/*metabolism MH - Analysis of Variance MH - Animals MH - Behavior, Animal/drug effects MH - Central Nervous System Depressants/*pharmacology MH - Corpus Striatum/*drug effects/metabolism/radiation effects MH - Dopamine/*metabolism MH - Dose-Response Relationship, Drug MH - Drug Combinations MH - Electric Stimulation/methods MH - Ethanol/*pharmacology MH - In Vitro Techniques MH - Male MH - Motor Activity/drug effects MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Rats MH - Rats, Long-Evans MH - Serotonin/*metabolism MH - Serotonin Agents/*pharmacology MH - Tritium/metabolism EDAT- 2008/02/06 09:00 MHDA- 2008/12/19 09:00 CRDT- 2008/02/06 09:00 PHST- 2008/02/06 09:00 [pubmed] PHST- 2008/12/19 09:00 [medline] PHST- 2008/02/06 09:00 [entrez] AID - S1461145708008481 [pii] AID - 10.1017/S1461145708008481 [doi] PST - ppublish SO - Int J Neuropsychopharmacol. 2008 Sep;11(6):743-63. doi: 10.1017/S1461145708008481. Epub 2008 Feb 4.