Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking

• DOI: 10.1111/j.1369-1600.2011.00314.x
• Publication Date: 2011-04-26T14:09:51Z
• Authors: Islam Gamaleddin; Carrie Wertheim; Andy Z.X. Zhu; Kathleen M. Coen; Kiran Vemuri; Alex Makryannis; Steven R. Goldberg; Bernard Le Foll
• Keywords: Male; Motivation; Nicotine; Behavior, Animal; Dose-Response Relationship, Drug; Morpholines; Feeding Behavior; Motor Activity; Naphthalenes; Benzoxazines; Extinction, Psychological; Rats; Analgesics, Opioid; Behavior, Addictive; 03 medical and health sciences; Discrimination, Psychological; 0302 clinical medicine; Piperidines; Animals; Conditioning, Operant; Pyrazoles; Cues

ABSTRACTThe 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.