Combining Varenicline (Chantix) with Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in a Rodent Model of Alcoholism

Abstract

Background This study examined whether varenicline (VAR), or naltrexone (NTX), alone or in combination, reduces alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake. Methods Alcohol experienced P rats that had been drinking alcohol (15% v/v) for 2 hrs/day for 4 weeks were fed either vehicle (VEH), VAR alone (0.5, 1.0 or 2.0 mg/kg BW), NTX alone (10.0, 15.0 or 20.0 mg/kg BW) or VAR + NTX in one of four dose combinations (0.5 VAR + 10.0 NTX, 0.5 VAR + 15.0 NTX, 1.0 VAR + 10.0 NTX, or 1.0 VAR + 15.0 NTX) at 1 hour prior to alcohol access for 10 consecutive days and the effects on alcohol intake were assessed. Results When administered alone, VAR in doses of 0.5 or 1.0 mg/kg BW did not alter alcohol intake but a dose of 2.0 mg/kg BW decreased alcohol intake. This effect disappeared when drug treatment was terminated. NTX in doses of 10.0 and 15.0 mg/kg BW did not alter alcohol intake but a dose of 20.0 mg/kg BW decreased alcohol intake. Combining low doses of VAR and NTX into a single medication reduced alcohol intake as well as did high doses of each drug alone. Reduced alcohol intake occurred immediately after onset of treatment with the combined medication and continued throughout prolonged treatment. Conclusions Low doses of VAR and NTX, when combined in a single medication, reduce alcohol intake in a rodent model of alcoholism. This approach has the advantage of reducing potential side effects associated with each drug. Lowering the dose of NTX and VAR in a combined treatment approach that maintains efficacy while reducing the incidence of negative side-effects may increase patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake.

Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol‐Preferring (P) Rats

“…All rats were provided with access to food, water, a 15% (v/v) alcohol solution, and a 30% (v/v) alcohol solution. Alcohol access was introduced using a “stepdown” procedure as previously described (Froehlich et al., ,b, ) and illustrated in Fig. , to maximize alcohol intake during a daily 2‐hour alcohol access period.…”

“…VAR (Pfizer ), in doses of 0.5, 1.0, and 2.0 mg/kg BW, was incorporated into flavored, star‐shaped pieces of gelatin that were voluntarily consumed by the rats, as previously described (Froehlich et al., ,b, , ). The volume of each gelatin star (approximately 1.8 g) was determined by the body weight of each rat on a daily basis.…”

“…During the week prior to onset of the first alcohol deprivation, baseline alcohol and water intake were calculated for each rat over 5 consecutive days and the rats were ranked in descending order in terms of average daily alcohol consumption. Rats were assigned to drug dose groups (0.0, 0.5, 1.0, or 2.0 mg/kg BW) in a manner that ensured that the groups did not differ in baseline alcohol intake prior to VAR administration as previously described (Froehlich et al., ,b, , ).…”

“…Rodents that are selectively bred for high voluntary alcohol drinking, such as the alcohol‐preferring (P) rat line (Froehlich and Li, ; Li et al., ), are well suited for testing the efficacy of medications with the potential to reduce alcohol intake. We have previously reported that VAR blocks the expression of a genetic predisposition toward high alcohol drinking in alcohol‐naïve P rats (Froehlich et al., ) and reduces alcohol intake throughout prolonged periods of treatment (Froehlich et al., ). This study examined whether VAR can also decrease alcohol intake in rats during alcohol reaccess following repeated cycles of alcohol deprivation, a condition commonly experienced by individuals with AUD.…”

“…Since then, evidence has accumulated that VAR also reduces alcohol intake in both rodents and humans. In rodents, VAR reduces alcohol drinking (Chatterjee et al., ; Froehlich et al., , ; Lacroix et al., ), operant self‐administration of alcohol (Wouda et al., ), reinstatement of extinguished alcohol seeking (Funk et al., ), and flavor‐induced alcohol drinking (Steensland et al., ). In humans, VAR reduces alcohol consumption (for review, see Erwin and Slaton, ), in both alcohol‐dependent (Litten et al., ) and alcohol nondependent individuals (Mitchell et al., ) and in both smokers and nonsmokers (Litten et al., ), although a reduction in consumption is not always seen (Schacht et al., ).…”