title: The dopamine β-hydroxylase inhibitor, nepicastat, reduces different alcohol-related behaviors in rats.
abstract: BACKGROUND
  Recent experimental data indicate that treatment with the selective dopamine β-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.
authors.affiliation: Section of Cagliari, Neuroscience Institute, National Research Council of Italy, Monserrato (CA), Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Colombo
authors.forename: Paola
authors.initials: P
authors.lastname: Maccioni
authors.forename: Daniela
authors.initials: D
authors.lastname: Vargiolu
authors.forename: Barbara
authors.initials: B
authors.lastname: Loi
authors.forename: Carla
authors.initials: C
authors.lastname: Lobina
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zaru
authors.forename: Mauro A M
authors.initials: MA
authors.lastname: Carai
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gessa
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012646:Self Administration; D013871:Thiones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D007093:Imidazoles; D013871:Thiones; D004299:Dopamine beta-Hydroxylase; C109487:nepicastat
keywords: Alcohol Drinking and Self-Administration; Dopamine; Dopamine β-Hydroxylase Inhibitor; Nepicastat; Noradrenaline; Sardinian Alcohol-Preferring (sP) Rats