The dopamine beta-hydroxylase inhibitor, nepicastat, reduces different alcohol-related behaviors in rats

Background: Recent experimental data indicate that treatment with the selective dopamine ?-hydroxylase inhibitor, nepicastat, suppressed different reward-related behaviors, including self-administration of chocolate and reinstatement of cocaine- and chocolate-seeking, in rats. The present study was designed to extend to different alcohol-related behaviors the investigation on the "anti-addictive" properties of nepicastat. Methods and Results: Sardinian alcohol-preferring (sP) rats, selectively bred for excessive alcohol consumption, were used. Repeated treatment with nepicastat (0, 25, 50, and 100 mg/kg, i.p., once daily for 10 consecutive days) produced a stable and dose-related reduction in daily alcohol intake in sP rats exposed to the homecage 2-bottle "alcohol (10% v/v) vs water" choice regimen with unlimited access. Acute treatment with nepicastat (0, 25, 50, and 100 mg/kg, i.p.) completely suppressed the "alcohol deprivation effect" (i.e., the temporary increase in alcohol intake occurring after a period of abstinence; model of alcohol relapse episodes) in sP rats exposed to the 2-bottle choice regimen. Acute treatment with nepicastat (0, 25, 50, and 100 mg/kg, i.p.) dose-dependently and selectively reduced oral alcohol self-administration in sP rats trained to lever-respond for alcohol (15% v/v) on a FR4 schedule of reinforcement. Finally, combination of nepicastat (0, 50, and 100 mg/kg, i.p.) and alcohol (2 g/kg, i.g.) did not alter spontaneous locomotor activity in sP rats. Conclusions: Together, these data extend to alcohol the capacity of nepicastat to suppress different behaviors motivated by natural stimuli and drugs of abuse.