title: Differentiating the primary reinforcing and reinforcement-enhancing effects of varenicline.
abstract: BACKGROUND
  Varenicline (VAR), a smoking cessation aid that is a partial agonist at nicotinic receptors, mimics the reinforcement-enhancing effects of nicotine. Varenicline, when accompanied by non-drug cues, is self-administered by rats, though it is unclear whether this results from varenicline acting as a primary reinforcer or a reinforcement enhancer of the cues.
  
  
  OBJECTIVE
  This study sought to disentangle these two potential actions.
  
  
  METHODS
  Rats were allowed to self-administer intravenous nicotine, saline, or varenicline during 1-h sessions in operant chambers equipped with two levers. Five groups had concurrent access to drug infusions and a moderately reinforcing visual stimulus (VS) for responding on separate levers. Meeting the reinforcement schedule on one lever was reinforced with VAR (0.01, 0.06, 0.1 mg/kg/infusion), nicotine (0.06 mg/kg/infusion), or saline, while meeting the same schedule on the other lever delivered the VS. Additional groups were reinforced for pressing a single "active" lever and received VAR paired with the VS, the VS with response-independent infusions of VAR, or VAR alone (0.1 mg/kg/infusion).
  
  
  RESULTS
  Rats readily responded for VAR paired with VS on a single lever. However, when VAR was the only reinforcer contingent on a response, rats did not respond more than for saline.
  
  
  CONCLUSIONS
  These findings show that VAR does not serve as a primary reinforcer in rats at doses that increase responding for non-drug reinforcers. These data are consistent with research showing that the primary reinforcing effects of VAR are weak, at best, and that the primary reinforcing and reinforcement-enhancing actions of nicotinic drugs are pharmacologically distinct.
authors.affiliation: Department of Neuroscience, University of Pittsburgh, A210 Langley Hall, 5th and Ruskin Avenue, Pittsburgh, PA, 15260, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Schassburger
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Levin
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Weaver
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Palmatier
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Caggiula
authors.forename: Eric C
authors.initials: EC
authors.lastname: Donny
authors.forename: Alan F
authors.initials: AF
authors.lastname: Sved
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D011810:Quinoxalines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D016540:Smoking Cessation; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D009538:Nicotine; D000068580:Varenicline