The cannabinoid antagonist AM251 attenuates nicotine self-administration and nicotine-seeking behaviour in rats

Neuropharmacology. 2008 Feb;54(2):438-44. doi: 10.1016/j.neuropharm.2007.10.011. Epub 2007 Dec 3.


The cannabinoid receptor subtype (CB1) antagonist rimonabant (SR141716) has been shown to decrease nicotine self-administration and attenuate nicotine-evoked dopamine release in the nucleus accumbens; effects that support recent findings on its clinical efficacy as a smoking cessation aid. The present experiments aim to advance our understanding on the role of CB1 receptors in rodent models of nicotine dependence. AM251, a selective antagonist at CB1 receptors dose-dependently (1, 3 and 10mg/kg IP) suppressed intravenous nicotine (0.03mg/kg per infusion) self-administration in rats during three successive days of pre-treatment. This reduction was short lasting since behaviour was reinstated by suspending AM251 pre-treatment. This was relatively specific to nicotine self-administration since the profile of these reductions produced by AM251 was significantly different from the responses maintained by food pellets. In a model of nicotine-seeking behaviour, rats that had been extinguished by removal of nicotine and associated cues, and presented with a priming dose of nicotine (0.2mg/kg SC) with the cues, showed robustly reinstated responses to nicotine-seeking behaviour. Acute pre-treatment with AM251 (1-10mg/kg IP) dose-dependently attenuated the reinstatement effects produced by nicotine and the contingently presented cues. These preclinical findings support the use of rimonabant as a smoking cessation aid and highlight the CB1 receptor as a viable target to control intake of nicotine and prevent relapse.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cannabinoids / antagonists & inhibitors*
  • Conditioning, Operant / drug effects
  • Cues
  • Dose-Response Relationship, Drug
  • Food
  • Male
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Piperidines / pharmacology*
  • Pyrazoles / pharmacology*
  • Rats
  • Reinforcement, Psychology
  • Secondary Prevention
  • Self Administration
  • Tobacco Use Disorder / drug therapy*
  • Tobacco Use Disorder / psychology*


  • Cannabinoids
  • Nicotinic Agonists
  • Piperidines
  • Pyrazoles
  • AM 251
  • Nicotine