The cannabinoid antagonist AM251 attenuates nicotine self-administration and nicotine-seeking behaviour in rats.
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.
Shoaib
Mohammed
M
Psychobiology Research Laboratories, Newcastle Medical School, Newcastle University, Newcastle, NE2 4HH, UK. mohammed.scoaid@newcastle.ac.uk
D000818:Animals; D002186:Cannabinoids / Q000037:antagonists & inhibitors*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004305:Dose-Response Relationship, Drug; D005502:Food; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D012054:Reinforcement, Psychology; D055502:Secondary Prevention; D012646:Self Administration; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000523:psychology*
D002186:Cannabinoids; D018722:Nicotinic Agonists; D010880:Piperidines; D011720:Pyrazoles; C103505:AM 251; D009538:Nicotine