A Combination of Naltrexone + Varenicline Retards the Expression of a Genetic Predisposition Toward High Alcohol Drinking. (9th February 2017)

• Record Type: Journal Article
• Authors: Froehlich, Janice C.; Fischer, Stephen M.; Nicholson, Emily R.; Dilley, Julian E.; Filosa, Nicholas J.; Smith, Teal N.; Rademacher, Logan C.
• Is Part Of: Alcoholism. Volume 41:Number 3(2017)
• Page Start: 644
• Page End: 652
• Publication Date: 2017-02-09
• Subjects: Alcohol Drinking -- P rats -- Naltrexone -- Varenicline; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.13326
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract : 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. Abstract : This study examined whether naltrexone (NTX) or varenicline (VAR), alone or in combination, given prior to and during alcohol availability, alters alcohol intake in rats selectively bred for high alcohol drinking (alcohol‐preferring rats). NTX alone and VAR alone did not alter alcohol intake, but NTX+VAR completely blocked the acquisition of alcohol drinking and expression of alcohol preference. When drug treatment was delayed until alcohol was first available, NTX+VAR, NTX alone, and VAR alone each retarded the acquisition of alcohol drinking.