1. Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking.
- Author
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Gamaleddin I, Wertheim C, Zhu AZ, Coen KM, Vemuri K, Makryannis A, Goldberg SR, and Le Foll B
- Subjects
- Analgesics, Opioid pharmacology, Animals, Behavior, Addictive chemically induced, Behavior, Animal, Benzoxazines pharmacology, Conditioning, Operant drug effects, Cues, Discrimination, Psychological drug effects, Dose-Response Relationship, Drug, Extinction, Psychological drug effects, Feeding Behavior drug effects, Male, Morpholines pharmacology, Motor Activity drug effects, Naphthalenes pharmacology, Piperidines pharmacology, Pyrazoles pharmacology, Rats, Rats, Long-Evans, Rats, Sprague-Dawley, Reinforcement, Psychology, Rimonabant, Self Administration statistics & numerical data, Motivation drug effects, Nicotine administration & dosage, Receptor, Cannabinoid, CB1 antagonists & inhibitors, Tobacco Use Disorder
- Abstract
The cannabinoid system appears to play a critical facilitative role in mediating the reinforcing effects of nicotine and relapse to nicotine-seeking behaviour in abstinent subjects based on the actions of cannabinoid (CB) receptor antagonists. However, the effects of CB receptor stimulation on nicotine self-administration and reinstatement have not been systematically studied. Here, we studied the effects of WIN 55,212-2, a CB1/2 agonist, on intravenous nicotine self-administration under fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement in rats. The effects of WIN 55,212-2 on responding for food under similar schedules were also studied. In addition, the effects of WIN 55,212-2 on nicotine- and cue-induced reinstatement of nicotine seeking were also studied, as well as the effects of WIN 55,212-2 on nicotine discrimination. WIN 55,212-2 decreased nicotine self-administration under the FR schedule. However, co-administration of WIN 55,212-2 with nicotine decreased responding for food, which suggests that this effect was non-selective. In contrast, WIN 55,212-2 increased both nicotine self-administration and responding for food under the PR schedule, produced dose-dependent reinstatement of nicotine seeking, and enhanced the reinstatement effects of nicotine-associated cues. Some of these effects were reversed by the CB1 antagonist rimonabant, but not by the CB2 antagonist AM630. In the drug discrimination tests between saline and 0.4 mg/kg nicotine, WIN 55,212-2 produced no nicotine-like discriminative effects but significantly potentiated discriminative stimulus effects of nicotine at the low dose through a CB1-receptor-dependent mechanism. These findings indicate that cannabinoid CB1-receptor stimulation increases the reinforcing effects of nicotine and precipitates relapse to nicotine-seeking behaviour in abstinent subjects. Thus, modulating CB1-receptor signalling might have therapeutic value for treating nicotine dependence., (© 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.)
- Published
- 2012
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