The Dopamine β-Hydroxylase Inhibitor, Nepicastat, Reduces Different Alcohol-Related Behaviors in Rats

Background: Recent experimental data indicate that treatment with the selective dopamine beta-hydroxylase inhibitor, nepicastat, suppressed different reward-related behaviors, including self-administration of chocolate and reinstatement of cocaine and chocolate seeking, in rats. This study was designed to extend to different alcohol-related behaviors the investigation on the anti-addictive properties of nepicastat. Methods: Sardinian alcohol-preferring (sP) rats, selectively bred for excessive alcohol consumption, were exposed to different procedures of alcohol drinking and self-administration. Results: Repeated treatment with nepicastat (0, 25, 50, and 100 mg/kg, intraperitoneally [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) versus 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 fixed ratio 4 schedule of reinforcement. Finally, combination of nepicastat (0, 50, and 100 mg/kg, i.p.) and alcohol (2 g/kg, intragastrically) 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.