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.
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.
Riegert
Céline
C
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Universität Freiburg, Neuropharmakologisches Labor, Freiburg, Germany.
Wedekind
Franziska
F
Hamida
Sami Ben
SB
Rutz
Susanne
S
Rothmaier
Anna Katharina
AK
Jones
Byron C
BC
Cassel
Jean-Christophe
JC
Jackisch
Rolf
R
D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004558:Electric Stimulation / Q000379:methods; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology*; D014316:Tritium / Q000378:metabolism
D002492:Central Nervous System Depressants; D004338:Drug Combinations; D018490:Serotonin Agents; D014316:Tritium; D012701:Serotonin; D000431:Ethanol; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D000109:Acetylcholine; D004298:Dopamine