title: Trace amine associated receptor 1 modulates behavioral effects of ethanol.
abstract: 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.
authors.affiliation: Division of Neuroscience, New England Primate Research Center, Harvard Medical School, Southborough, MA, USA.
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Lynch
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Sullivan
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Vallender
authors.forename: James K
authors.initials: JK
authors.lastname: Rowlett
authors.forename: Donna M
authors.initials: DM
authors.lastname: Platt
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Miller
keywords: addiction; alcoholism; dopamine; reward; treatment