Inhibition of N-acylethanolamine acid amidase reverses effects of chronic binge ethanol drinking on ventral tegmental area dopamine neuron firing

Peroxisome proliferator-activated receptor α (PPARα) agonists reduce ethanol consumption in rodent drinking models, and decrease ventral tegmental area (VTA) dopamine (DA) neuron firing rate – suggesting a possible mechanism by which PPARα activation could regulate drinking. Signaling by endogenous PPARα agonists (oleoylethanolamide, p almitoylethanolamide) can be enhanced by blocking their hydrolysis with an inhibitor of N-acylethanolamine acid amidase (NAAA), such as the compound ARN726. The aims of this project were to determine if inhibiting NAAA in vitro reduces the spontaneous firing rate of VTA DA neurons or blocks acute po tentiation of firing by ethanol, and if chronic binge ethanol experience (six weeks drinking-in-the-dark, DID) alters either of these phenomena.

Source: Alcohol - May 1, 2017 Category: Addiction Authors: Regina Mangieri, Heather Aziz, Daniele Piomelli, Richard Morrisett Source Type: research