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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Johnson, JE; Slade, S; Wells, C; Petro, A; Sexton, H; Rezvani, AH; Brown, ML; Paige, MA; McDowell, BE; Xiao, Y; Kellar, KJ; Levin, ED

Published Date

  • July 2012

Published In

Volume / Issue

  • 222 / 2

Start / End Page

  • 269 - 276

PubMed ID

  • 22297831

Pubmed Central ID

  • 22297831

Electronic International Standard Serial Number (EISSN)

  • 1432-2072

Digital Object Identifier (DOI)

  • 10.1007/s00213-012-2642-z

Language

  • eng

Conference Location

  • Germany