Objective: This study examined whether repeated daily treatment with naloxo
ne prevents expression of a genetic predisposition toward high alcohol drin
king in rats selectively bred for alcohol preference (P line). Methods: In
phase 1, alcohol-naive male rats were given food and water ad libitum and w
ere 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 an
d water ad libitum and scheduled access to alcohol. In phase 3, alcohol acc
ess was suspended for 14 days while rats continued to receive food and wate
r ad libitum. In phase 4, daily pretreatment with naloxone or saline, follo
wed by scheduled access to alcohol, was reinstated for an additional 30 day
s. Results. Naloxone dose-dependently retarded acquisition of alcohol drink
ing. Following discontinuation of naloxone treatment, alcohol intake increa
sed to levels comparable to those seen in the saline-treated group. Naloxon
e dose-dependently suppressed reinstatement of alcohol drinking (relapse) a
fter a period of imposed abstinence. Conclusions: The results suggest that
naloxone retards the acquisition of alcohol drinking and suppresses reinsta
tement of alcohol drinking in rats genetically predisposed toward high alco
hol intake.