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Attenuation by baclofen of nicotine rewarding properties and nicotine withdrawal manifestations

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Abstract

Rationale

Nicotine is a major active ingredient in tobacco and plays a major role in tobacco addiction. In rodents, repeated nicotine administration produces behavioral responses related to its addictive properties, such as reinforcing effects and physical dependence.

Objectives

The aim of the present study was to evaluate the possible role of GABAB receptor in responses induced by repeated nicotine administration in Swiss Webster mice.

Results

Nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.) administration induced rewarding properties in the conditioning place preference test. The GABAB receptor agonist, baclofen (3 mg/kg, i.p.) abolished the rewarding properties induced by nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.). In addition, naloxone-precipitated nicotine withdrawal induced somatic manifestations, anxiety-like effects in the elevated plus maze test and dysphoric manifestations in the conditioned place aversion paradigm. Baclofen (2 and 3 mg/kg, i.p.) prevented the somatic manifestations and the anxiety-like effects associated with naloxone-precipitated nicotine withdrawal but not the dysphoric manifestations.

Conclusions

These results showed that nicotine rewarding properties and negative aspects of nicotine withdrawal, such as anxiety-like effects and somatic manifestations, can be modulated by the GABAB receptor activity. This study now reveals a novel possible application of baclofen to develop new therapeutic strategies to achieve smoking cessation.

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Acknowledgments

This work has been supported by grants from University of Buenos Aires (UBACyT B016 and UBACyT 2013-2016 Nº 20020120100244), CONICET (PIP 11420090100303), Spanish “Ministerio de Ciencia e Innovación” (#SAF2011-29864), “Instituto de Salud Carlos III” (RETICS: #RD06/0001/0001, #RD06/0001/1004), Plan Nacional sobre Drogas (PNSD #2009/026), the Catalan Government (SGR2009-00131), and the ICREA Foundation (ICREA Academia-2008). Andrés P. Varani is a doctoral fellow of the University of Buenos Aires (677/10). The organizations have no further role in study design; in the collection, analysis, and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication. The experiments comply with the current laws of the country in which they were performed. The authors declare they have no a financial relationship with the organizations that supported the research.

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  1. Ester Aso

    Present address: Institut de Neuropatologia, Servei d’Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain

Authors and Affiliations

  1. Instituto de Investigaciones Farmacológicas (CONICET), Junín 956 5° Piso, Buenos Aires, C1113AAD, Argentina

    Andrés P. Varani, Lirane Machado Moutinho & Graciela N. Balerio

  2. Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, C/Dr. Aiguader, 88, 08003, Barcelona, Spain

    Ester Aso & Rafael Maldonado

  3. Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 5° Piso, Buenos Aires, C1113AAD, Argentina

    Graciela N. Balerio

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  1. Andrés P. Varani
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Correspondence to Graciela N. Balerio.

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Varani, A.P., Aso, E., Moutinho, L.M. et al. Attenuation by baclofen of nicotine rewarding properties and nicotine withdrawal manifestations. Psychopharmacology 231, 3031–3040 (2014). https://doi.org/10.1007/s00213-014-3469-6

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