title: The nicotine + alcohol interoceptive drug state: contribution of the components and effects of varenicline in rats.
abstract: Nicotine and alcohol co-use is highly prevalent, and as such, individuals experience the interoceptive effects of both substances together. Therefore, examining sensitivity to a compound nicotine and alcohol (N + A) interoceptive cue is critical to broaden our understanding of mechanisms that may contribute to nicotine and alcohol co-use.
  
  
  
  This work assessed the ability of a N + A interoceptive cue to gain control over goal-tracking behavior and determined the effects of the α4β2 nicotinic partial agonist and smoking cessation compound varenicline on sensitivity to N + A.
  
  
  
  Two groups of male Long Evans rats were trained to discriminate N + A (0.4 mg/kg nicotine + 1 g/kg alcohol, intragastric gavage (IG)) from water under two different training conditions using a Pavlovian drug discrimination task. The effects of varenicline (0, 1, 3 mg/kg, intraperitoneally (IP)) administered alone and on sensitivity to N + A and the components were determined.
  
  
  
  Under both training conditions, N + A rapidly gained control over behavior, with a greater contribution of nicotine to the N + A compound cue. Varenicline fully substituted for the N + A training dose, and varenicline (1 mg/kg) enhanced sensitivity to the lowest N + A dose (0.1 N + 0.1 A). Given the high selectivity of varenicline for the α4β2 receptor, this finding suggests a functional role for α4β2 nicotinic acetylcholine receptors (nAChRs) in modulating sensitivity to N + A.
  
  
  
  The N + A compound cue is a unique cue that is modulated, in part, by activity at the α4β2 nAChR. These findings advance understanding of the interoceptive effects of nicotine and alcohol in combination and may have implications in relation to their co-use.
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB#7178, Chapel Hill, NC, 27599-7178, USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Randall
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB#7178, Chapel Hill, NC, 27599-7178, USA.|Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7178, USA.
authors.forename: Reginald
authors.initials: R
authors.lastname: Cannady
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB#7178, Chapel Hill, NC, 27599-7178, USA. jbesheer@med.unc.edu.|Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7178, USA. jbesheer@med.unc.edu.|Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7178, USA. jbesheer@med.unc.edu.
authors.forename: Joyce
authors.initials: J
authors.lastname: Besheer
mesh_terms: D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D011978:Receptors, Nicotinic; D016540:Smoking Cessation; D000068580:Varenicline / Q000494:pharmacology*
chemical_list: D002492:Central Nervous System Depressants; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D000431:Ethanol; D009538:Nicotine; D000068580:Varenicline
keywords: Alcohol; Feature negative (FN); Feature positive (FP); Nicotine; Pavlovian drug discrimination