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Neuropsychopharmacology (2005) 30, 145155

in Rats Several Weeks after Nicotine Withdrawal: Reversal by

the Cannabinoid (CB1) Receptor Antagonist, Rimonabant

(SR141716)[notdef]

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[notdef][notdef]Caroline Cohen*,1, Ghislaine Perrault1, Guy Griebel1 and Philippe Soubrie11Sanofi-synthelabo Recherche, Bagneux, FranceConditioned stimuli are important for nicotine dependence and may trigger craving and relapse after prolonged nicotine abstinence.However, little is known about the pharmacology of this process. Among the systems that have been shown to play a role in drugseeking behavior is the endocannabinoid transmission. Therefore, the present study examined the resistance to extinction of drugseeking behavior elicited by nicotine-associated environmental stimuli and the effects of the selective CB1 cannabinoid antagonist

rimonabant (SR141716) on the reinforcing effects of nicotine-related stimuli. Rats were trained to self-administer nicotine (0.03 mg/kg/injection, i.v.) under conditions in which responding was reinforced jointly by response-contingent nicotine injections and stimuli (light andtone). After self-administration acquisition, nicotine was withdrawn and lever pressing was only reinforced by contingent presentation ofthe audiovisual stimuli. Under such a condition, responding persisted for 3 months, following which nonpresentation of the cuesproduced a progressive extinction of responding. As expected, rats trained to lever-press for saline injections paired with the audiovisualstimuli did not acquire the self-administration. These findings indicate that the cues required learned association with nicotine to acquirereinforcing properties and to function as conditioned reinforcers. When administered 1 month following nicotine withdrawal, rimonabant(1 mg/kg, i.p.) decreased conditioned behavior. These results showing the persistence of a nicotine-conditioned behavior are congruentwith the role of nicotine-related environmental stimuli in nicotine craving in abstinent smokers. Rimonabant, which has been shownpreviously to reduce nicotine self-administration, may be effective not only as an aid for smoking cessation but also in the maintenance ofabstinence.Neuropsychopharmacology (2005) 30, 145155, advance online publication, 4 August 2004; doi:10.1038/sj.npp.1300541Keywords: nicotine-seeking behavior; conditioned stimuli; cannabinoid antagonistINTRODUCTIONThe high rates of relapse commonly observed during the

first 6 months following smoking cessation have encouraged a search for treatment strategies that integrate

prevention of relapse...

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Nicotine-Associated Cues Maintain Nicotine-Seeking Behavior in Rats Several Weeks after Nicotine Withdrawal: Reversal by the Cannabinoid (CB1) Receptor Antagonist, Rimonabant (SR141716)

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Nicotine-Associated Cues Maintain Nicotine-Seeking Behavior in Rats Several Weeks after Nicotine Withdrawal: Reversal by the Cannabinoid (CB1) Receptor Antagonist, Rimonabant (SR141716)

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