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The Dopamine β ‐Hydroxylase Inhibitor, Nepicastat, Reduces Different Alcohol‐Related Behaviors in Rats
Author(s) -
Colombo Giancarlo,
Maccioni Paola,
Vargiolu Daniela,
Loi Barbara,
Lobina Carla,
Zaru Alessandro,
Carai Mauro A. M.,
Gessa Gian Luigi
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12520
Subject(s) - alcohol , self administration , ethanol , abstinence , regimen , medicine , dopamine , addiction , pharmacology , psychology , anesthesia , endocrinology , chemistry , psychiatry , biochemistry
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.