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Abstract
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). Alcohol-experienced P rats were given 24-hour access to food and water and scheduled access to alcohol (15% and 30% v/v) for 2h/d. After 4weeks, rats were deprived of alcohol for 2weeks, followed by reaccess to alcohol for 2weeks, 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 2.0mg/kg BW, at 1hour prior to onset of the daily alcohol reaccess period for the first 5days of each of the 3 alcohol reaccess cycles. Low-dose VAR (0.5mg/kg BW) reduced alcohol intake during the 5days of drug treatment in alcohol reaccess cycles 1 and 2. Higher doses of VAR (1.0mg/kg BW and 2.0mg/kg BW) reduced alcohol intake during the 5days of treatment in all 3 alcohol reaccess cycles. The decrease in alcohol intake disappeared with termination of VAR treatment in all alcohol reaccess cycles. 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.
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