Varenicline decreases nicotine self-administration and cue-induced reinstatement of nicotine-seeking behaviour in rats when a long pretreatment time is used

Int J Neuropsychopharmacol. 2012 Oct;15(9):1265-74. doi: 10.1017/S1461145711001398. Epub 2011 Sep 23.


Effects of varenicline (Champix), a nicotinic partial agonist, were evaluated on subjective effects of nicotine (drug discrimination), motivation for nicotine taking (progressive-ratio schedule of intravenous nicotine self-administration) and reinstatement (cue-induced reinstatement of previously extinguished nicotine-seeking behaviour). Effects on motor performance were assessed in rats trained to discriminate nicotine (0.4 mg/kg) from saline under a fixed-ratio (FR 10) schedule of food delivery and in rats trained to respond for food under a progressive-ratio schedule. At short pretreatment times (5-40 min), varenicline produced full or high levels of partial generalization to nicotine's discriminative-stimulus effects and disrupted responding for food, while there were low levels of partial generalization and no disruption of responding for food at 2- or 4-h pretreatment times. Varenicline (1 and 3 mg/kg, 2-h pretreatment time) enhanced discrimination of low doses of nicotine and to a small extent decreased discrimination of the training dose of nicotine. It also dose-dependently decreased nicotine-taking behaviour, but had no effect on food-taking behaviour under progressive-ratio schedules. Finally, varenicline significantly reduced the ability of a nicotine-associated cue to reinstate extinguished nicotine-seeking behaviour. The ability of varenicline to reduce both nicotine-taking and nicotine-seeking behaviour can contribute to its relatively high efficacy in treating human smokers.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Benzazepines / pharmacology*
  • Conditioning, Operant / drug effects
  • Cues*
  • Data Interpretation, Statistical
  • Discrimination, Psychological / drug effects
  • Dose-Response Relationship, Drug
  • Drug-Seeking Behavior / drug effects*
  • Feeding Behavior / drug effects
  • Male
  • Motivation / drug effects
  • Nicotine / pharmacology
  • Quinoxalines / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Reinforcement Schedule
  • Self Administration
  • Tobacco Use Disorder / drug therapy*
  • Tobacco Use Disorder / psychology
  • Varenicline


  • Benzazepines
  • Quinoxalines
  • Nicotine
  • Varenicline