Dual motor responses elicited by ethanol in the posterior VTA: Consequences of the blockade of μ-opioid receptors. (September 2015)

• Record Type: Journal Article
• Authors: Martí-Prats, Lucía; Orrico, Alejandro; Polache, Ana; Granero, Luis
• Is Part Of: Journal of psychopharmacology. Volume 29:Number 9(2015:Sep.)
• Page Start: 1029
• Page End: 1034
• Publication Date: 2015-09
• Subjects: Ethanol -- midbrain dopamine neurons -- mechanism of action; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1177/0269881115598337
• Languages: English
• ISSNs: 0269-8811

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.