Control of the reinforcing effects of nicotine by associated environmental stimuli in animals and humans

Trends Pharmacol Sci. 2005 Jun;26(6):287-93. doi: 10.1016/


Tobacco dependence through cigarette smoking is the leading preventable cause of death in the world and kills nearly 4 million people annually. Nicotine, a psychoactive component of tobacco, is thought to have a major role in tobacco dependence by acting directly as a reinforcer of drug-seeking and drug-taking behavior. However, recent findings obtained with two procedures that are used widely to assess reinforcing effects of drugs in experimental animals, intravenous drug self-administration and conditioned place-preference procedures, demonstrate that environmental factors have a major influence on the reinforcing effects of nicotine. Under some experimental conditions, nicotine is also self-administered reliably by humans. Environmental stimuli that have been associated previously with the self-administration of nicotine can reinstate extinguished drug-seeking behavior in animals and precipitate relapse to smoking behavior in ex-smokers. Innovative medications that target cannabinoid CB(1) and dopamine D(3) receptors and might block specifically the influence of such conditioned environmental stimuli in smokers are in development.

Publication types

  • Review

MeSH terms

  • Animals
  • Conditioning, Psychological
  • Humans
  • Nicotine / pharmacology*
  • Receptor, Cannabinoid, CB1 / drug effects
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D3
  • Reinforcement, Psychology*
  • Self Administration


  • DRD3 protein, human
  • Receptor, Cannabinoid, CB1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Nicotine