, Volume 227, Issue 2, pp 287–298

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

  • Ramón Sotomayor-Zárate
  • Katia Gysling
  • Usoa E. Busto
  • Bruce K. Cassels
  • Lutske Tampier
  • María Elena Quintanilla
Original Investigation



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.


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).


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.


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.


Varenicline Cytisine Alcohol High-alcohol-drinking UChB rats Ethanol preference 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Ramón Sotomayor-Zárate
    • 1
    • 2
  • Katia Gysling
    • 2
  • Usoa E. Busto
    • 3
  • Bruce K. Cassels
    • 4
  • Lutske Tampier
    • 5
  • María Elena Quintanilla
    • 5
    • 6
  1. 1.Departamento de Fisiología, Facultad de CienciasUniversidad de ValparaísoValparaísoChile
  2. 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 SciencesPontificia Universidad Católica de ChileSantiagoChile
  3. 3.Centre for Addiction and Mental Health and Department of Pharmacology and ToxicologyUniversity of TorontoTorontoCanada
  4. 4.Millennium Institute for Cell Dynamics and Biotechnology and Department of Chemistry, Faculty of SciencesUniversity of ChileSantiagoChile
  5. 5.Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, Faculty of MedicineUniversity of ChileSantiagoChile
  6. 6.Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de MedicinaUniversidad de ChileSantiagoChile

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