title: The effects of varenicline on alcohol seeking and self-administration in baboons.
abstract: BACKGROUND
  Nicotinic acetylcholine receptors (nAChRs) may play a critical role in alcohol reinforcement and consumption. The effects of varenicline, an nAChR partial agonist, on alcohol seeking and self-administration responses were evaluated in 2 groups of baboons trained under a 3-component chained schedule of reinforcement (CSR).
  
  
  METHODS
  Alcohol (4% w/v; n = 4; alcohol group) or a preferred nonalcoholic beverage (n = 4; control group) was available for self-administration only in component 3 of the CSR. Responses in component 2, required to gain access to alcohol, provided indices of seeking behavior. Varenicline (0.032 to 0.32 mg/kg; 0.32 mg/kg twice daily [BID]) and vehicle were administered before CSR sessions subchronically (5 consecutive days). Higher doses (0.56, 1.0 mg/kg) were attempted, but discontinued due to adverse effects.
  
  
  RESULTS
  Subchronic varenicline administration significantly (p < 0.05) decreased the seeking response rate and increased the time to complete the response requirement to gain access to the daily supply of alcohol at the higher doses (0.32 mg/kg, 0.32 mg/kg BID dosing) in the alcohol group compared with the control group. Mean number of drinks was significantly decreased (p < 0.05), but effects did not differ between groups. The pattern of drinking was characterized by a high rate during an initial bout. Number of drinks during and duration of the initial bout were significantly decreased in the alcohol group, compared with the control group, at 0.32 mg/kg (p < 0.05).
  
  
  CONCLUSIONS
  Varenicline may be clinically useful for reducing alcohol-seeking behaviors prior to alcohol exposure. Given the modest effects on drinking itself, varenicline may be better suited as a treatment in combination with a pharmacotherapy that significantly reduces alcohol consumption.
authors.affiliation: Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Kaminski
authors.forename: Elise M
authors.initials: EM
authors.lastname: Weerts
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000523:psychology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000097:blood; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000097:blood; D008297:Male; D010215:Papio; D011810:Quinoxalines / Q000494:pharmacology*; D012646:Self Administration; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D002492:Central Nervous System Depressants; D011810:Quinoxalines; D000431:Ethanol; D000068580:Varenicline
keywords: Craving; Cues; Drinking; Ethanol; Self-Administration
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