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Varenicline and cytisine: two nicotinic acetylcholine receptor ligands reduce ethanol intake in University of Chile bibulous rats

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Abstract

Rationale

Neuronal nicotinic acetylcholine receptors (nAChRs) are pharmacological targets that have recently been implicated in the reinforcing effects of many drugs of abuse, including ethanol. Varenicline and cytisine are nAChR partial agonists in clinical use as smoking cessation aids. However, their efficacies to reduce alcohol consumption have not been fully studied.

Objectives

This study aims to compare the effects of varenicline and cytisine on ethanol consumption by rats bred for many generations as high ethanol drinkers (UChB).

Results

Repeated dosing (0.5 or 1.0 mg/kg/day i.p.) of varenicline or cytisine, for three consecutive days, to male UChB rats pre-exposed to 10 % (v/v) ethanol and water 24 h/day for 4 weeks, significantly reduced alcohol intake and preference of ethanol over water during 1- and 24-h ethanol access periods. This effect was specific for ethanol intake and was not observed for 0.2 % saccharin or water consumption. Varenicline appears to be more effective than cytisine, probably due to its more favorable pharmacokinetic and pharmacodynamic properties. Long-term use of both nAChRs ligands for more than 8–10 days induced tolerance to their effects on ethanol consumption.

Conclusions

This preclinical study in UChB rats demonstrated that both varenicline and cytisine reduce alcohol intake, with varenicline producing a greater and longer-lasting reduction than cytisine. However, dose adjustment will have to be considered as a possible way to counter tolerance arising after continued use.

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Acknowledgments

This work was funded by MSI Grants Nº P10/063-F and P05/001-F, and FONDECYT Grant N° 111-0392. The authors thank Dr. Patricio Iturriaga-Vásquez for a generous gift of cytisine.

Disclosure/Conflict of interest

The authors of this paper declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Departamento de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Av. Gran Bretaña 1111, Playa Ancha, Valparaíso, Chile

    Ramón Sotomayor-Zárate

  2. Millennium Science Nucleus in Stress and Addiction (NEDA) and Center for Addiction Studies (CEDA-UC), Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile

    Ramón Sotomayor-Zárate & Katia Gysling

  3. Centre for Addiction and Mental Health and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

    Usoa E. Busto

  4. Millennium Institute for Cell Dynamics and Biotechnology and Department of Chemistry, Faculty of Sciences, University of Chile, Santiago, Chile

    Bruce K. Cassels

  5. Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile

    Lutske Tampier & María Elena Quintanilla

  6. Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Casilla 70.000, Santiago 7, Chile. Av. Independencia 1027, Santiago, Chile

    María Elena Quintanilla

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  1. Ramón Sotomayor-Zárate
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  2. Katia Gysling
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  3. Usoa E. Busto
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Correspondence to Ramón Sotomayor-Zárate or María Elena Quintanilla.

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Sotomayor-Zárate, R., Gysling, K., Busto, U.E. et al. Varenicline and cytisine: two nicotinic acetylcholine receptor ligands reduce ethanol intake in University of Chile bibulous rats. Psychopharmacology 227, 287–298 (2013). https://doi.org/10.1007/s00213-013-2974-3

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