title: The role of varenicline on alcohol-primed self-administration and seeking behavior in rats.
abstract: BACKGROUND
  Varenicline, a smoking-cessation agent, may be useful in treating alcohol use disorders. An important consideration when studying factors that influence drinking/relapse is influence of the pharmacological effects of alcohol on these behaviors. Pre-exposure to alcohol (priming) can increase craving, drinking, and seeking behaviors.
  
  
  OBJECTIVE
  The primary goal of this work was to determine the effects of varenicline on alcohol-primed self-administration and seeking behavior in male Long-Evans rats.
  
  
  METHODS
  First, we assessed whether varenicline (0, 0.3, 1, 3 mg/kg, IP) has alcohol-like discriminative stimulus effects and whether varenicline alters sensitivity to alcohol in rats trained to discriminate a moderate alcohol dose (1 g/kg, IG) vs. water. Second, animals trained to self-administer alcohol underwent assessments to test the effects of: (i) varenicline (0, 0.3, 1, 3 mg/kg, IP) on self-administration, (ii) alcohol priming (0, 0.3, 1 g/kg, IG) on self-administration and seeking behavior, and (iii) varenicline (1 mg/kg) in combination with alcohol priming (1 g/kg) on these behaviors.
  
  
  RESULTS
  Varenicline did not substitute for alcohol but disrupted the expression of sensitivity to alcohol. Varenicline decreased self-administration but only at a motor-impairing dose (3 mg/kg). Alcohol priming decreased self-administration and seeking behavior. Varenicline (1 mg/kg) blocked this effect under self-administration conditions, but not seeking conditions, which effectively resulted in increased alcohol intake.
  
  
  CONCLUSIONS
  These findings suggest the importance of further behavioral and mechanistic studies to evaluate the use of varenicline in treating alcohol use disorders and its potential impact on drinking patterns in smokers using varenicline as a smoking-cessation aid.
authors: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB#7178, Chapel Hill, NC, 27599, USA.
authors: Patrick A
authors: PA
authors: Randall
authors: Anel A
authors: AA
authors: Jaramillo
authors: Suzanne
authors: S
authors: Frisbee
authors: Joyce
authors: J
authors: Besheer
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D066249:Craving / Q000187:drug effects; D004193:Discrimination Learning; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration; D000068580:Varenicline / Q000494:pharmacology*
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D000068580:Varenicline
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