Nicotine induces conditioned place preferences over a large range of doses in rats

Psychopharmacology (Berl). 2005 Apr;178(4):481-92. doi: 10.1007/s00213-004-2021-5. Epub 2004 Nov 18.


Rationale: Conditioned place preference (CPP) procedures provide one measure of potential rewarding effects of abused drugs. Many attempts to induce CPP with nicotine have been unsuccessful.

Objectives: To assess the influence of nicotine dose and stimulus assignment procedure on development of nicotine-induced CPP.

Methods: Initial preferences for one side of a two-compartment apparatus were first determined in Sprague-Dawley rats. In subsequent conditioning trials, the compartment paired with nicotine was the initially preferred side for half of the rats, and the initially non-preferred side for the other half. Rats received either an injection of nicotine (0.01-2 mg/kg SC) before being placed in one compartment (three trials) or saline before being placed in the other compartment (three trials). Control rats had saline injections associated with both compartments. A final test trial with no injection assessed final place preference.

Results: Significant CPP were induced by 0.1-1.4 mg/kg doses of nicotine. Nicotine-induced CPP were only apparent when nicotine was paired with the initially non-preferred side. Moreover, a very high dose of nicotine (2 mg/kg) induced conditioned place aversion when paired with the initially preferred side of the apparatus.

Conclusions: Nicotine induced significant CPP across a wide range of doses, in accordance with its role as the primary addictive component of tobacco. Small preferences for one side of the apparatus played a major role in the development of nicotine-induced CPP. These findings suggest that biased procedures may be more suitable than unbiased procedures for evaluation of rewarding effects of nicotine using CPP paradigms.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Animals
  • Ataxia / chemically induced
  • Conditioning, Operant / drug effects*
  • Dose-Response Relationship, Drug*
  • Hypokinesia / chemically induced
  • Injections, Subcutaneous
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Nicotine / administration & dosage
  • Nicotine / adverse effects
  • Nicotine / pharmacokinetics*
  • Psychopharmacology / instrumentation
  • Psychopharmacology / methods
  • Rats
  • Rats, Inbred Strains
  • Rats, Sprague-Dawley
  • Reinforcement, Psychology
  • Time Factors
  • Tobacco Use Disorder / physiopathology


  • Nicotine