Trace Amine Associated Receptor 1 Modulates Behavioral Effects of Ethanol
Sullivan, Katherine A.
Vallender, Eric J.
Rowlett, James K.
Platt, Donna M.
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CitationLynch, Laurie J., Katherine A. Sullivan, Eric J. Vallender, James K. Rowlett, Donna M. Platt, and Gregory M. Miller. 2013. “Trace Amine Associated Receptor 1 Modulates Behavioral Effects of Ethanol.” Substance Abuse: Research and Treatment 7 (1): 117-126. doi:10.4137/SART.S12110. http://dx.doi.org/10.4137/SART.S12110.
AbstractBackground: 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.
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