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Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking.
Addict Biol. 2012 Jan; 17(1):47-61.AB

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.

Authors+Show Affiliations

Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21521420

Citation

Gamaleddin, Islam, et al. "Cannabinoid Receptor Stimulation Increases Motivation for Nicotine and Nicotine Seeking." Addiction Biology, vol. 17, no. 1, 2012, pp. 47-61.
Gamaleddin I, Wertheim C, Zhu AZ, et al. Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking. Addict Biol. 2012;17(1):47-61.
Gamaleddin, I., Wertheim, C., Zhu, A. Z., Coen, K. M., Vemuri, K., Makryannis, A., Goldberg, S. R., & Le Foll, B. (2012). Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking. Addiction Biology, 17(1), 47-61. https://doi.org/10.1111/j.1369-1600.2011.00314.x
Gamaleddin I, et al. Cannabinoid Receptor Stimulation Increases Motivation for Nicotine and Nicotine Seeking. Addict Biol. 2012;17(1):47-61. PubMed PMID: 21521420.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking. AU - Gamaleddin,Islam, AU - Wertheim,Carrie, AU - Zhu,Andy Z X, AU - Coen,Kathleen M, AU - Vemuri,Kiran, AU - Makryannis,Alex, AU - Goldberg,Steven R, AU - Le Foll,Bernard, Y1 - 2011/04/26/ PY - 2011/4/28/entrez PY - 2011/4/28/pubmed PY - 2012/5/15/medline SP - 47 EP - 61 JF - Addiction biology JO - Addict Biol VL - 17 IS - 1 N2 - 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. SN - 1369-1600 UR - https://www.unboundmedicine.com/medline/citation/21521420/Cannabinoid_receptor_stimulation_increases_motivation_for_nicotine_and_nicotine_seeking_ L2 - https://doi.org/10.1111/j.1369-1600.2011.00314.x DB - PRIME DP - Unbound Medicine ER -