BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: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. RESULTS: 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. CONCLUSIONS: 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: Janice C Froehlich; Brett Hausauer; Stephen Fischer; Bradley Wise; Dennis D Rasmussen Journal: Alcohol Clin Exp Res Date: 2015-08 Impact factor: 3.455
Authors: H Rollema; L K Chambers; J W Coe; J Glowa; R S Hurst; L A Lebel; Y Lu; R S Mansbach; R J Mather; C C Rovetti; S B Sands; E Schaeffer; D W Schulz; F D Tingley; K E Williams Journal: Neuropharmacology Date: 2006-12-08 Impact factor: 5.250
Authors: Michael J Marks; Heidi C O'Neill; Kelly M Wynalda-Camozzi; Nick C Ortiz; Emily E Simmons; Caitlin A Short; Christopher M Butt; J Michael McIntosh; Sharon R Grady Journal: Neuropharmacology Date: 2015-07-17 Impact factor: 5.250
Authors: Lara A Ray; Kelly E Courtney; Dara G Ghahremani; Karen Miotto; Arthur Brody; Edythe D London Journal: Psychopharmacology (Berl) Date: 2014-04-15 Impact factor: 4.530
Authors: Joseph P Schacht; Raymond F Anton; Patrick K Randall; Xingbao Li; Scott Henderson; Hugh Myrick Journal: Psychopharmacology (Berl) Date: 2014-03-20 Impact factor: 4.530
Authors: L J Bierut; A M Goate; N Breslau; E O Johnson; S Bertelsen; L Fox; A Agrawal; K K Bucholz; R Grucza; V Hesselbrock; J Kramer; S Kuperman; J Nurnberger; B Porjesz; N L Saccone; M Schuckit; J Tischfield; J C Wang; T Foroud; J P Rice; H J Edenberg Journal: Mol Psychiatry Date: 2011-10-04 Impact factor: 15.992
Authors: Janice C Froehlich; Emily R Nicholson; Julian E Dilley; Nick J Filosa; Logan C Rademacher; Teal N Smith Journal: Alcohol Clin Exp Res Date: 2017-07-10 Impact factor: 3.455