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Role of the cannabinoid system in the effects induced by nicotine on anxiety-like behaviour in mice

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Abstract

Rationale

Acute behavioural effects and motivational responses induced by nicotine can be modulated by the endocannabinoid system supporting the existence of a physiological interaction between these two systems.

Objectives

The present study was designed to examine the possible involvement of the cannabinoid system in the anxiolytic- and anxiogenic-like responses induced by nicotine in mice.

Methods

Animals were only exposed once to nicotine. The acute administration of low (0.05) or high (0.8 mg/kg, s.c.) doses of nicotine produced opposite effects in the elevated plus-maze, i.e. anxiolytic- and anxiogenic-like responses, respectively. The effects of the pretreatment with the CB1 cannabinoid receptor antagonist, rimonabant (0.25, 0.5 and 1 mg/kg, i.p.), and the cannabinoid agonist, Δ9-tetrahydrocannabinol (Δ9-THC, 0.1 mg/kg, ip), were evaluated on the anxiolytic- and anxiogenic-like responses induced by nicotine.

Results

Rimonabant completely abolished nicotine-induced anxiolytic-like effects and increased the anxiogenic-like responses of nicotine, suggesting an involvement of CB1 receptors in these behavioural responses. On the other hand, Δ9-THC failed to modify nicotine anxiolytic-like responses but attenuated its anxiogenic-like effects. In addition, the association of non-effective doses of Δ9-THC and nicotine produced clear anxiolytic-like responses.

Conclusions

These results demonstrate that the endogenous cannabinoid system is involved in the regulation of nicotine anxiety-like behaviour in mice and provide new findings to support the use of cannabinoid antagonists in the treatment of tobacco addiction.

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Acknowledgements

This work has been supported by grants from National Institutes of Health (1R01-DA016768-0111), Ministerio de Educación y Ciencia (BFU 2004-00920/BFI), Marató TV3, Redes de Centros y Grupos del Instituto de Salud Carlos III (C03/06 and G03/005), Generalitat de Catalunya (2002 SGR00193) and the European Comission (Quality of Life and Management of Living Resources QLRT-2001-01691 LSHM-CT 2004-005166). Graciela Balerio is a postdoctoral fellow supported by “Fundación Carolina”. We thank the helpful assistance of Ms. Andreea Bura.

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  1. Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, C/ Doctor Aiguader 80, 08003, Barcelona, Spain

    Graciela N. Balerio, Ester Aso & Rafael Maldonado

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  1. Graciela N. Balerio
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  2. Ester Aso
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  3. Rafael Maldonado
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Correspondence to Rafael Maldonado.

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Balerio, G.N., Aso, E. & Maldonado, R. Role of the cannabinoid system in the effects induced by nicotine on anxiety-like behaviour in mice. Psychopharmacology 184, 504–513 (2006). https://doi.org/10.1007/s00213-005-0251-9

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  • DOI: https://doi.org/10.1007/s00213-005-0251-9

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