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

Bernard Le Foll*, Munmun Chakraborty-Chatterjee, Shaul Lev-Ran, Chanel Barnes, Abhiram Pushparaj, Islam Gamaleddin, Yijin Yan, Maram Khaled, Steven R. Goldberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1265-1274
Number of pages10
JournalInternational Journal of Neuropsychopharmacology
Volume15
Issue number9
DOIs
StatePublished - Oct 2012
Externally publishedYes

Keywords

  • Cue-induced reinstatement
  • drug discrimination
  • nicotine
  • progressive ratio schedule
  • varenicline

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