Naloxone retards the expression of a genetic predisposition toward alcohol drinking

This study examined whether repeated daily treatment with naloxone prevents expression of a genetic predisposition toward high alcohol drinking in rats selectively bred for alcohol preference (P line). In phase 1, alcohol-naive male rats were given food and water ad libitum and were pretreated with naloxone (2.5, 5.0, or 10.0 mg/kg, IP) or saline prior to scheduled access to alcohol (2 h/day) for 30 days. In phase 2, naloxone treatment was suspended for 30 days while rats continued to receive food and water ad libitum and scheduled access to alcohol. In phase 3, alcohol access was suspended for 14 days while rats continued to receive food and water ad libitum. In phase 4, daily pretreatment with naloxone or saline, followed by scheduled access to alcohol, was reinstated for an additional 30 days. Naloxone dose-dependently retarded acquisition of alcohol drinking. Following discontinuation of naloxone treatment, alcohol intake increased to levels comparable to those seen in the saline-treated group. Naloxone dose-dependently suppressed reinstatement of alcohol drinking (relapse) after a period of imposed abstinence. The results suggest that naloxone retards the acquisition of alcohol drinking and suppresses reinstatement of alcohol drinking in rats genetically predisposed toward high alcohol intake.