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Effects of ethanol and 3,4-methylenedioxymethamphetamine (MDMA) alone or in combination on spontaneo

Effects of ethanol and 3,4-methylenedioxymethamphetamine (MDMA) alone or in combination on spontaneo

  1. Jatelka
    International Journal of Psychopharmacology 2008,Published online Feb 4:1-21

    Riegert C, Wedekind F, Hamida SB, Rutz S, Rothmaier AK, Jones BC, Cassel JC, Jackisch R

    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, 3 mum) and/or EtOH (2 per thousand, corresponding to 34.3 mm) 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 3 mum in striatal slices only. With nomifensine throughout, EtOH significantly potentiated the 0.3 mum 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, 3 mum 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

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