Activation of trace amine-associated receptor 1 (TAAR1) transiently reduces alcohol drinking in socially housed mice

Abstract

Rationale: Trace amine-associated receptor 1 (TAAR1) is an important modulator of dopaminergic neurotransmission and has been recognized as a potential therapeutic target for alcoholism treatment. The interaction of alcohol with the dopamine reward system in the brain may promote the development of alcohol abuse. Objectives: The aim of the study was to evaluate the role of TAAR1 receptor stimulation on alcohol drinking behaviors in mice. Methods: We investigated the blood-brain barrier (BBB) penetration of the RO5256390 in mice by mass spectrometry. Then, wild-type (WT) mice were housed in an automatic behavioral system, IntelliCage, and habituated to drinking alcohol. The animals were further administrated either with RO526390 (10 mg/kg, intraperitoneally) or vehicle and studied on alcohol consumption, alcohol consumption after abstinence, and motivation to drink alcohol. Results: We found that RO5256390 highly penetrated the BBB. R05256390 administration also transiently reduced alcohol consumption and alcohol consumption after abstinence in mice with a high preference for alcohol in comparison to high-drinking mice from the vehicle group. Furthermore, RO5256390 attenuated the motivation for drinking alcohol. Conclusions: Our data suggest that activation of Taar1 reduces alcohol drinking behavior in mice.