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

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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.

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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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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 104790, Durham, NC, 27710, USA

    Joshua E. Johnson, Susan Slade, Corinne Wells, Ann Petro, Hannah Sexton, Amir H. Rezvani & Edward D. Levin

  2. Department of Pharmacology and Physiology, Georgetown University School of Medicine, 3900 Reservoir Road NW, Medical Dental Building, Washington, DC, 20057, USA

    Milton L. Brown, Mikell A. Paige, Brian E. McDowell, Yingxian Xiao & Kenneth J. Kellar

Authors
  1. Joshua E. Johnson
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  2. Susan Slade
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  3. Corinne Wells
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  4. Ann Petro
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  5. Hannah Sexton
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  6. Amir H. Rezvani
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  7. Milton L. Brown
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  8. Mikell A. Paige
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  9. Brian E. McDowell
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  10. Yingxian Xiao
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  11. Kenneth J. Kellar
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  12. Edward D. Levin
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Corresponding author

Correspondence to Edward D. Levin.

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Johnson, J.E., Slade, S., Wells, C. et al. Assessing the effects of chronic sazetidine-A delivery on nicotine self-administration in both male and female rats. Psychopharmacology 222, 269–276 (2012). https://doi.org/10.1007/s00213-012-2642-z

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  • DOI: https://doi.org/10.1007/s00213-012-2642-z

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