Trace Amine Associated Receptor 1 Modulates Behavioral Effects of Ethanol.
PublishedJuly 21, 2013
Trace amine associated receptor 1 modulates behavioral effects of ethanol.
Subst Abuse. 2013; 7: 117-26 Lynch LJ, Sullivan KA, Vallender EJ, Rowlett JK, Platt DM, Miller GM
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.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]).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.).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. HubMed – addiction
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BMJ. 2013; 347: f4513 Ferri M, Davoli M, D’Amico R
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