Varenicline blocks nicotine intake in rats with extended access to nicotine self-administration

Psychopharmacology (Berl). 2011 Feb;213(4):715-22. doi: 10.1007/s00213-010-2024-3. Epub 2010 Oct 6.


Rationale: Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine. Varenicline, a partial α4β2 nicotinic acetylcholine receptor (nAChR) agonist, is effective in reducing nicotine craving and relapse in smokers, suggesting that α4β2 nAChRs may play a key role in nicotine dependence. In rats, the effect of varenicline on nicotine intake has only been studied with limited access to the drug, a model of the positive reinforcing effect of nicotine. Varenicline has not been tested on the increase in motivation to take nicotine in nicotine-dependent rats.

Objectives: The present study evaluated the effects of varenicline on nicotine intake in rats with extended access to nicotine self-administration (23 h/day), a condition leading to the development of nicotine dependence. We hypothesized that varenicline's effects on nicotine self-administration would be greater in rats with extended than limited access to the drug and after forced abstinence rather than during baseline self-administration.

Results: Varenicline dose-dependently decreased nicotine self-administration in rats with limited (1 h/day) and extended (23 h/day) access. Despite an increased sensitivity to the motivational effects of abstinence on nicotine intake compared with limited-access rats, varenicline was equally effective in decreasing nicotine intake in dependent rats with extended access to nicotine.

Conclusion: These results suggest that α4β2 nAChRs are critical in mediating the positive reinforcing effects of nicotine but may not be a key element underlying the negative reinforcement process responsible for the increased nicotine intake after abstinence in dependent subjects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzazepines / administration & dosage
  • Benzazepines / pharmacology*
  • Dose-Response Relationship, Drug
  • Male
  • Motivation / drug effects
  • Nicotine / administration & dosage*
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology*
  • Quinoxalines / administration & dosage
  • Quinoxalines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / metabolism
  • Reinforcement, Psychology
  • Self Administration
  • Varenicline


  • Benzazepines
  • Nicotinic Agonists
  • Quinoxalines
  • Receptors, Nicotinic
  • nicotinic receptor alpha4beta2
  • Nicotine
  • Varenicline