Key role of salsolinol in ethanol actions on dopamine neuronal activity of the posterior ventral tegmental area. (17th September 2013)

• Record Type: Journal Article
• Authors: Melis, Miriam; Carboni, Ezio; Caboni, Pierluigi; Acquas, Elio
• Is Part Of: Addiction biology. Volume 20:Number 1(2015:Jan.)
• Page Start: 182
• Page End: 193
• Publication Date: 2013-09-17
• Subjects: Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.12097
• Languages: English
• ISSNs: 1355-6215

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Ethanol excites dopamine (DA) neurons in the posterior ventral tegmental area (pVTA). This effect is responsible for ethanol's motivational properties and may contribute to alcoholism. Evidence indicates that catalase‐mediated conversion of ethanol into acetaldehyde in pVTA plays a critical role in this effect. Acetaldehyde, in the presence of DA, condensates with it to generate salsolinol. Salsolinol, when administered in pVTA, excites pVTA DA cells, elicits DA transmission in nucleus accumbens and sustains its self‐administration in pVTA. Here we show, by using <italic>ex vivo</italic> electrophysiology, that ethanol and acetaldehyde, but not salsolinol, failed to stimulate pVTA DA cell activity in mice administered α‐methyl‐p‐tyrosine, a DA biosynthesis inhibitor that reduces somatodendritic DA release. This effect was specific for ethanol and acetaldehyde since morphine, similarly to salsolinol, was able to excite pVTA DA cells in α‐methyl‐p‐tyrosine‐treated mice. However, when DA was bath applied in slices from α‐methyl‐p‐tyrosine‐treated mice, ethanol‐induced excitation of pVTA DA neurons was restored. This effect requires ethanol oxidation into acetaldehyde given that, when H<sub>2</sub>O<sub>2</sub>‐catalase system was impaired by either 3‐amino‐1, 2, 4‐triazole or <italic>in vivo</italic> administration of α‐lipoic acid, ethanol did not enhance DA cell activity. Finally, high performance liquid chromatography‐tandem mass spectrometry analysis of bath medium detected salsolinol only after co‐application of ethanol and DA in α‐methyl‐p‐tyrosine‐treated mice. These results demonstrate the relationship between ethanol and salsolinol effects on pVTA DA neurons, help to untangle the mechanism(s) of action of ethanol in this area and contribute to an exciting research avenue prosperous of theoretical and practical consequences.</p> </abstract>