Psychopharmacology

, Volume 222, Issue 2, pp 269–276 | Cite as

Assessing the effects of chronic sazetidine-A delivery on nicotine self-administration in both male and female rats

  • Joshua E. Johnson
  • Susan Slade
  • Corinne Wells
  • Ann Petro
  • Hannah Sexton
  • Amir H. Rezvani
  • Milton L. Brown
  • Mikell A. Paige
  • Brian E. McDowell
  • Yingxian Xiao
  • Kenneth J. Kellar
  • Edward D. Levin
Original Investigation

Abstract

Rationale

Sazetidine-A is a selective α4β2 nicotinic receptor desensitizing agent and partial agonist. It has been shown in previous studies to significantly reduce nicotine self-administration in rats after acute or repeated injections. However, the effects of continuous chronic infusions of sazetidine-A on maintenance of nicotine self-administration and relapse after abstinence have yet to be examined.

Objectives

This study evaluated the efficacy of continuous sazetidine-A infusions (sc) over a period of 4 weeks to reduce nicotine self-administration in male and female Sprague-Dawley rats.

Methods

Sazetidine-A was administered via Alzet osmotic minipumps to young adult female and male rats at doses of 0, 2 or 6 mg/kg/day for 4 weeks. The effects of sazetidine-A on IV nicotine self-administration were examined in repeated 3-h sessions over the first 2 weeks of infusion followed by 1 week of forced abstinence from nicotine and 1 week of resumed nicotine access.

Results

The 6 mg/kg/day sazetidine-A dose significantly reduced overall nicotine self-administration compared with vehicle control across the sessions for both male (p < 0.001) and female (p < 0.05) rats. The lower 2 mg/kg/day sazetidine-A infusion dose was effective in reducing nicotine self-administration for male (p < 0.001), but not female rats. No attenuation in sazetidine-A effectiveness was seen over the course of the 4-week treatment. In the vehicle control group, male rats self-administered significantly (p < 0.001) more nicotine than females.

Conclusions

The continuing effectiveness of sazetidine-A in reducing nicotine self-administration in both male and female rats supports its promise as a new treatment to help people successfully quit smoking.

Keywords

Nicotine Sazetidine-A Chronic Self-administration Sex differences 

Notes

Acknowledgments and disclosures

This study was supported by NIDA U19 grant DA027990. Co-authors Drs. Yingxian Xiao and Kenneth J Kellar and Georgetown University hold a patent for Sazetidine-A.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Joshua E. Johnson
    • 1
  • Susan Slade
    • 1
  • Corinne Wells
    • 1
  • Ann Petro
    • 1
  • Hannah Sexton
    • 1
  • Amir H. Rezvani
    • 1
  • Milton L. Brown
    • 2
  • Mikell A. Paige
    • 2
  • Brian E. McDowell
    • 2
  • Yingxian Xiao
    • 2
  • Kenneth J. Kellar
    • 2
  • Edward D. Levin
    • 1
  1. 1.Department of Psychiatry and Behavioral SciencesDuke University Medical CenterDurhamUSA
  2. 2.Department of Pharmacology and PhysiologyGeorgetown University School of MedicineWashingtonUSA

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