title: Tolcapone suppresses ethanol intake in alcohol-preferring rats performing a novel cued access protocol.
abstract: BACKGROUND
  Dopamine (DA) has been shown to play a central role in regulating motivated behavior and encoding reward. Chronic drug abuse elicits a state of hypodopaminergia in the mesocorticolimbic (MCL) system in both humans and preclinical rodent models of addiction, including those modeling alcohol use disorders (AUD).
  
  
  METHODS
  Working under the hypothesis that reductions in the bioavailability of DA play an integral role in the expression of the excessive drinking phenotype, the catechol-O-methyltransferase (COMT) inhibitor tolcapone was used as a means to amplify cortical DA concentration and drinking behaviors were then assessed. Sucrose and ethanol (EtOH) consumption were measured in P and Wistar rats in both a free choice drinking protocol and a novel cued access protocol.
  
  
  RESULTS
  Tolcapone attenuated the consumption of EtOH, and to a lesser extent sucrose, in P rats in the cued access protocol, while no effect was observed in the free choice drinking protocol. Tolcapone also decreased EtOH consumption in high drinking Wistar rats. A follow-up experiment using the indirect DA agonist d-amphetamine showed no change in EtOH consumption.
  
  
  CONCLUSIONS
  Collectively, these data suggest that COMT inhibitors may be capable of alleviating the extremely motivating or salient nature of stimuli associated with alcohol. The hypothesis is put forth that the relative specificity of tolcapone for cortical DA systems may mediate the suppression of the high seeking/drinking phenotype.
authors.affiliation: Department of Psychology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana.
authors.forename: Aqilah M
authors.initials: AM
authors.lastname: McCane
authors.forename: Cristine L
authors.initials: CL
authors.lastname: Czachowski
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Lapish
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics*; D000818:Animals; D001577:Benzophenones / Q000627:therapeutic use*; D065098:Catechol O-Methyltransferase Inhibitors / Q000627:therapeutic use*; D003463:Cues; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D009596:Nitrophenols / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000077867:Tolcapone
chemical_list: D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D009596:Nitrophenols; D000431:Ethanol; D000077867:Tolcapone
keywords: Alcohol Preferring Rat; Catechol-O-Methyltransferase; Dopamine; Prefrontal Cortex; Tolcapone