title: A Combination of Naltrexone + Varenicline Retards the Expression of a Genetic Predisposition Toward High Alcohol Drinking.
abstract: This study examined whether naltrexone (NTX) or varenicline (VAR), alone or in combination, can retard the phenotypic expression of a genetic predisposition toward high alcohol drinking in rats selectively bred for high alcohol intake when drug treatment is initiated prior to, or concomitantly with, the onset of alcohol drinking.
  
  
  
  Alcohol-naïve P rats were treated daily with NTX (15.0 mg/kg BW), VAR (1.0 mg/kg BW), a combination of NTX (15.0 mg/kg BW) + VAR (1.0 mg/kg BW), or vehicle (VEH) for 2 weeks prior to, or concomitantly with, their first opportunity to drink alcohol and throughout 21 days of daily 2-hour alcohol access. Drug treatment was then discontinued for 3 weeks followed by reinstatement of drug treatment for an additional 3 weeks.
  
  
  
  When P rats were pretreated with drug for 2 weeks prior to onset of alcohol access, only NTX + VAR in combination blocked the acquisition of alcohol drinking in alcohol-naïve P rats. When drug treatment was initiated concomitantly with the first opportunity to drink alcohol, NTX alone, VAR alone, and NTX + VAR blocked the acquisition of alcohol drinking. Following termination of drug treatment, NTX + VAR and VAR alone continued to reduce alcohol drinking but by the end of 3 weeks without drug treatment, alcohol intake in all groups was comparable to that seen in the vehicle-treated group as the expression of a genetic predisposition toward high alcohol drinking emerged in the drug-free P rats. After 3 weeks without drug treatment, reinstatement of NTX + VAR treatment again reduced alcohol intake.
  
  
  
  A combination of NTX + VAR, when administered prior to, or concomitantly with, the first opportunity to drink alcohol, blocks the acquisition of alcohol drinking during both initial access to alcohol and during a later period of alcohol access in P rats with a genetic predisposition toward high alcohol intake. The results suggest that NTX + VAR may be effective in curtailing alcohol drinking in individuals at high genetic risk of developing alcoholism.
authors.affiliation: Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Janice C
authors.initials: JC
authors.lastname: Froehlich
authors.affiliation: Mayo Clinic , Rochester, Minnesota.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Fischer
authors.affiliation: Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Nicholson
authors.affiliation: Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Julian E
authors.initials: JE
authors.lastname: Dilley
authors.affiliation: Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Filosa
authors.affiliation: Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Teal N
authors.initials: TN
authors.lastname: Smith
authors.affiliation: Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Logan C
authors.initials: LC
authors.lastname: Rademacher
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics*; D000818:Animals; D004359:Drug Therapy, Combination; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage; D018722:Nicotinic Agonists / Q000008:administration & dosage; D051381:Rats; D000068580:Varenicline / Q000008:administration & dosage*
chemical_list: D009292:Narcotic Antagonists; D018722:Nicotinic Agonists; D009271:Naltrexone; D000068580:Varenicline
keywords: Alcohol Drinking; Naltrexone; P rats; Varenicline