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Psychopharmacology (Berl). 2012 Jul;222(2):269-76. doi: 10.1007/s00213-012-2642-z.

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

Author information

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

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.

PMID:
22297831
[PubMed - indexed for MEDLINE]
PMCID:
PMC3426624
Free PMC Article

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