Oral sazetidine-A, a selective α4β2* nicotinic receptor desensitizing agent, reduces nicotine self-administration in rats.

Journal Article (Journal Article)

Sazetidine-A selectively desensitizes α4β2 nicotinic receptors and also has partial agonist effects. We have shown that subcutaneous acute and repeated injections as well as chronic infusions of sazetidine-A significantly reduce intravenous (IV) nicotine self-administration in rats. To further investigate the promise of sazetidine-A as a smoking cessation aid, it is important to determine sazetidine-A effects with oral administration and the time-effect function for its action on nicotine self-administration. Young adult female Sprague-Dawley rats were trained to self-administer IV nicotine at the benchmark dose of 0.03 mg/kg/infusion dose in an operant FR1 schedule in 45-min sessions. After five sessions of training, they were tested for the effects of acute oral doses of sazetidine-A (0, 0.3, 1 and 3 mg/kg) given 30 min before testing. To determine the time-effect function, these rats were administered 0 or 3 mg/kg of sazetidine-A 1, 2, 4 or 23 h before the onset of testing. Our previous study showed that with subcutaneous injections, only 3 mg/kg of sazetidine-A significantly reduced nicotine self-administration, however, with oral administration of sazetidine-A lower dose of 1 mg/kg was also effective in reducing nicotine intake. A similar effect was seen in the time-effect study with 3 mg/kg of oral sazetidine-A causing a significant reduction in nicotine self-administration across all the time points of 1, 2, 4 or 23 h after oral administration. These results advance the development of sazetidine-A as a possible aid for smoking cessation by showing effectiveness with oral administration and persistence of the effect over the course of a day.

Full Text

Duke Authors

Cited Authors

  • Rezvani, AH; Wells, C; Slade, S; Xiao, Y; Kellar, KJ; Levin, ED

Published Date

  • April 2019

Published In

Volume / Issue

  • 179 /

Start / End Page

  • 109 - 112

PubMed ID

  • 30794849

Pubmed Central ID

  • PMC6570822

Electronic International Standard Serial Number (EISSN)

  • 1873-5177

Digital Object Identifier (DOI)

  • 10.1016/j.pbb.2019.02.007


  • eng

Conference Location

  • United States