Related Experiment Video
Updated: May 9, 2026
Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder
Published on: June 23, 2023
Trace amine associated receptor 1 modulates behavioral effects of ethanol
Laurie J Lynch1, Katherine A Sullivan, Eric J Vallender
1Division of Neuroscience, New England Primate Research Center, Harvard Medical School, Southborough, MA, USA.
Background:
Few treatment options for alcohol use disorders (AUDs) exist and more are critically needed. Here, we assessed whether trace amine associated receptor 1 (TAAR1), a modulator of brain monoamine systems, is involved in the behavioral and reinforcement-related effects of ethanol and whether it could potentially serve as a therapeutic target.
Methods:
Wild-type (WT) and TAAR1 knockout (KO) mice (75% C57J/BL6 and 25% 129S1/Sv background) were compared in tests of ethanol consumption (two-bottle choice [TBC]), motor impairment (loss of righting reflex, [LORR], locomotor activity) and ethanol clearance (blood ethanol level [BEL]).
Results:
As compared with WT mice, KO mice displayed (1) significantly greater preference for and consumption of ethanol in a TBC paradigm (3%-11% vol/vol escalating over 10 weeks), with no significant difference observed in TBC with sucrose (1%-3%); (2) significantly greater sedative-like effects of acute ethanol (2.0 or 2.5 g/kg, intraperitoneal [i.p.]) manifested as LORR observed at a lower dose and for longer time, with similar BELs and rates of ethanol clearance; and (3) lower cumulative locomotor activity over 60 minutes in response to an acute ethanol challenge (1.0-2.5 g/kg, i.p.).
Conclusions:
The present findings are the first to implicate TAAR1 in the behavioral and reinforcement-related effects of ethanol and raise the question of whether specific drugs that target TAAR1 could potentially reduce alcohol consumption in humans with AUDs.
