Psychopharmacology

, Volume 211, Issue 2, pp 161–174

Effects of sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor desensitizing agent on alcohol and nicotine self-administration in selectively bred alcohol-preferring (P) rats

Authors

    • Department of Psychiatry and Behavioral SciencesDuke University Medical Center
  • Susan Slade
    • Department of Psychiatry and Behavioral SciencesDuke University Medical Center
  • Cori Wells
    • Department of Psychiatry and Behavioral SciencesDuke University Medical Center
  • Ann Petro
    • Department of Psychiatry and Behavioral SciencesDuke University Medical Center
  • Lawrence Lumeng
    • Department of Internal MedicineUniversity of Indiana
  • Ting-Kai Li
    • Department of Psychiatry and Behavioral SciencesDuke University Medical Center
  • Yingxian Xiao
    • Department of PharmacologyGeorgetown University School of Medicine
  • Milton L. Brown
    • Department of Drug Discovery ProgramGeorgetown University School of Medicine
  • Mikell A. Paige
    • Department of Drug Discovery ProgramGeorgetown University School of Medicine
  • Brian E. McDowell
    • Department of Drug Discovery ProgramGeorgetown University School of Medicine
  • Jed E. Rose
    • Department of Psychiatry and Behavioral SciencesDuke University Medical Center
  • Kenneth J. Kellar
    • Department of PharmacologyGeorgetown University School of Medicine
  • Edward D. Levin
    • Department of Psychiatry and Behavioral SciencesDuke University Medical Center
Original Investigation

DOI: 10.1007/s00213-010-1878-8

Cite this article as:
Rezvani, A.H., Slade, S., Wells, C. et al. Psychopharmacology (2010) 211: 161. doi:10.1007/s00213-010-1878-8

Abstract

Rationale

Manipulations of nicotinic cholinergic receptors have been shown to influence both alcohol and nicotine intake. Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a novel compound that potently and selectively desensitizes α4β2 nicotinic receptors with only modest receptor activation.

Objectives

The goal of the present study was to examine the effects of sazetidine-A on alcohol and nicotine self-administration in alcohol-preferring (P) rats.

Methods

P rats were given the choice of water or alcohol. Once stable baselines were established, the acute (0, 0.1, 0.3, 1, and 3 mg/kg, s.c.) and chronic (3 mg/kg for 10 days) effects of sazetidine-A on alcohol intake were assessed. Naltrexone (2.5 mg/kg) served as a positive control. The effect of sazetidine-A (3 mg/kg) and naltrexone (4 mg/kg) on saccharin (0.2%) preference was also assessed. In addition, the acute effects of sazetidine-A (3 mg/kg) and naltrexone (4 mg/kg) on alcohol intake after alcohol deprivation were evaluated. In another experiment, the effects of sazetidine-A (0, 1, or 3 mg/kg) on IV nicotine self-administration in P and NP rats were assessed.

Results

Sazetidine-A caused a dose-dependent reduction in alcohol intake. Chronic sazetidine-A also effectively reduced alcohol intake until the seventh day of treatment, when partial tolerance appeared to develop. In the post-deprivation study, sazetidine-A significantly reduced alcohol intake and preference. Sazetidine-A at 3 mg/kg significantly reduced nicotine self-administration in both lines.

Conclusions

Sazetidine-A significantly reduced alcohol and nicotine intake in P rats that self-administer higher levels of both drugs. Sazetidine-A may hold promise for the treatment of alcohol and nicotine addiction.

Keywords

AlcoholismP ratsNicotinic agonistsAlcohol drinkingNaltrexoneTreatmentAnimal modelSaccharinNicotine addiction

Copyright information

© Springer-Verlag 2010