Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol-Preferring (P) Rats.
- Authors
- Froehlich, Janice C; Nicholson, Emily R; Dilley, Julian E; Filosa, Nick J; Rademacher, Logan C; Smith, Teal N
- Year
- 2017
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 28617959
- DOI
- 10.1111/acer.13432
- PMCID
- PMC5541259
BACKGROUND: Most alcoholics experience periods of voluntary alcohol abstinence or imposed alcohol deprivation followed by a return to alcohol drinking. This study examined whether varenicline (VAR) reduces alcohol intake during a return to drinking after periods of alcohol deprivation in rats selectively bred for high alcohol drinking (the alcohol preferring or "P" rats). METHODS: Alcohol-experienced P rats were given 24-hour access to food and water and scheduled access to alcohol (15% and 30% v/v) for 2 h/d. After 4 weeks, rats were deprived of alcohol for 2 weeks, followed by reaccess to alcohol for 2 weeks, and this pattern was repeated for a total of 3 cycles. Rats were fed either vehicle (VEH) or VAR, in doses of 0.5, 1.0, or 2.0 mg/kg BW, at 1 hour prior to onset of the daily alcohol reaccess period for the first 5 days of each of the 3 alcohol reaccess cycles. RESULTS: Low-dose VAR (0.5 mg/kg BW) reduced alcohol intake during the 5 days of drug treatment in alcohol reaccess cycles 1 and 2. Higher doses of VAR (1.0 mg/kg BW and 2.0 mg/kg BW) reduced alcohol intake during the 5 days of treatment in all 3 alcohol reaccess cycles. The decrease in alcohol intake disappeared with termination of VAR treatment in all alcohol reaccess cycles. CONCLUSIONS: The results demonstrate that VAR decreases alcohol intake during multiple cycles of alcohol reaccess following alcohol deprivation in rats and suggests that it may prevent a return to heavy alcohol drinking during a lapse from alcohol abstinence in humans with alcohol use disorder.
Alcohol intake in male P rats given scheduled access to (15% or 30% v/v) for 8 hours a day, for 17 days followed by 4 hours a day for 11 days, and 2 hours a day for 28 days prior to the initiation of drug treatment. Each point represents the mean ± SEM.
(A) Effect of oral varenicline (VAR) (0.5 1.0 or 2.0mg/kg BW) or vehicle (VEH) on alcohol intake in male P rats given access to alcohol (15% or 30%) for 2 hours per day during the first alcohol reaccess cycle. (B) Effect of VAR or VEH on mean alcohol intake over the 5 days of drug treatment. **p<0.01, and ***p<0.001 versus vehicle. Each point represents mean ± SEM.
(A) Effect of oral varenicline (VAR) (0.5 1.0 or 2.0mg/kg BW) or vehicle (VEH) on alcohol intake in male P rats given access to alcohol (15% or 30%) for 2 hours per day during the second alcohol reaccess cycle. (B) Effect of VAR or VEH on mean alcohol intake over the 5 days of drug treatment. **p<0.01, and ***p<0.001 versus vehicle. Each point represents mean ± SEM.
(A) Effect of oral varenicline (VAR) (0.5 1.0 or 2.0mg/kg BW) or vehicle (VEH) on alcohol intake in male P rats given access to alcohol (15% or 30%) for 2 hours per day during the third alcohol reaccess cycle. (B) Effect of VAR or VEH on mean alcohol intake over the 5 days of drug treatment. **p<0.01, and ***p<0.001 versus vehicle. Each point represents mean ± SEM.
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