title: Dual motor responses elicited by ethanol in the posterior VTA: Consequences of the blockade of μ-opioid receptors.
abstract: A recent hypothesis, based on electrophysiological and behavioural findings, suggests that ethanol simultaneously exerts opposed effects on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) through two parallel mechanisms, one promoting and the other reducing the GABA release onto VTA DA neurons. In this sense, the activating effects are mediated by salsolinol, a metabolite of ethanol, acting on the μ-opioid receptors (MORs) located in VTA GABA neurons. The inhibitory effects are, however, triggered by the non-metabolized fraction of ethanol which would cause the GABAA receptors-mediated inhibition of VTA DA neurons. Since both trends tend to offset each other, only the use of appropriate pharmacological tools allows analysis of this phenomenon in depth. Herein, we present new behavioural findings supporting this hypothesis. Motor activity was evaluated in rats after intra-VTA administration of ethanol 35 nmol, an apparently ineffective dose, 24 h after the irreversible blockade of MORs in the VTA with β-FNA. Our results showed that this pre-treatment turned the initially ineffective ethanol dose into a depressant one, confirming that the activating effect of ethanol can be selectively suppressed without affecting the depressant effects mediated by the non-biotransformed fraction of ethanol.
authors.affiliation: Departament de Farmàcia i Tecnologia Farmacèutica, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Martí-Prats
authors.affiliation: Departament de Farmàcia i Tecnologia Farmacèutica, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Orrico
authors.affiliation: Departament de Farmàcia i Tecnologia Farmacèutica, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Polache
authors.affiliation: Departament de Farmàcia i Tecnologia Farmacèutica, Facultat de Farmàcia, Universitat de València, Burjassot, Spain lfgran@uv.es.
authors.forename: Luis
authors.initials: L
authors.lastname: Granero
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D011963:Receptors, GABA-A; D017450:Receptors, Opioid, mu; D000431:Ethanol; D004298:Dopamine
keywords: Ethanol; mechanism of action; midbrain dopamine neurons