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 (15.0mg/kg BW), VAR (1.0mg/kg BW), a combination of NTX (15.0mg/kg BW)+VAR (1.0mg/kg BW), or vehicle (VEH) for 2weeks prior to, or concomitantly with, their first opportunity to drink alcohol and throughout 21days of daily 2-hour alcohol access. Drug treatment was then discontinued for 3weeks followed by reinstatement of drug treatment for an additional 3weeks. When P rats were pretreated with drug for 2weeks 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 3weeks 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 3weeks 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.