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Involvement of the opioid system in the effects induced by nicotine on anxiety-like behaviour in mice

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Abstract

Rationale

Recent studies have revealed the participation of the endogenous opioid system in several behavioural responses induced by nicotine including antinociception, rewarding properties, and physical drug dependence.

Objectives

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

Methods

The acute administration of low (0.05) or high (0.8 mg/kg) doses of nicotine subcutaneously produced opposite effects in the elevated plus maze, i.e. anxiolytic- and anxiogenic-like responses, respectively. Animals were only exposed once to nicotine. The effects of the pretreatment with the μ-opioid receptor antagonist, β-funaltrexamine (5 mg/kg), the δ-opioid antagonist, naltrindole (2.5 mg/kg) and the κ-opioid antagonist, nor-binaltorphimine (2.5 mg/kg) intraperitoneally were evaluated on the anxiolytic- and anxiogenic-like responses induced by nicotine.

Results

β-funaltrexamine, but not nor-binaltorphimine or naltrindole, abolished nicotine-induced anxiolytic-like effects, suggesting an involvement of μ-opioid receptors in this behavioural response. On the other hand, naltrindole, but not nor-binaltorphimine or β-funaltrexamine, increased the anxiogenic-like responses of nicotine, suggesting an involvement of δ-receptors in this behavioural effect.

Conclusions

These results demonstrate that the endogenous opioid system is involved in the effects induced by nicotine on anxiety-like behaviour and provide new findings to further clarify the interaction between these two neurochemical systems.

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Acknowledgements

This work has been supported by grants from National Institutes of Health (1R01-DA016768-0111), Human Frontier Science Program Organisation (RG0077/2000-B), Marató TV3, Redes de Centros y Grupos del Instituto de Salud Carlos III (C03/06 and G03/005), Generalitat de Catalunya (Research Distinction and 2002 SGR00193), and the European Commission (Quality of Life and Management of Living Resources QLRT-2001-01691). Graciela Balerio is a postdoctoral fellow supported by “Fundación Carolina”. We thank the helpful assistance of Ms. Kaja Beate Nyquist and Ms. Núria Gresa.

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Correspondence to Rafael Maldonado.

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Balerio, G.N., Aso, E. & Maldonado, R. Involvement of the opioid system in the effects induced by nicotine on anxiety-like behaviour in mice. Psychopharmacology 181, 260–269 (2005). https://doi.org/10.1007/s00213-005-2238-y

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  • DOI: https://doi.org/10.1007/s00213-005-2238-y

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