Evidence map›Paper›PMID 28555315›Full record

ArticlePsychopharmacology2017

Differential efficacies of the nicotinic α4β2 desensitizing agents in reducing nicotine self-administration in female rats.

Amir H Rezvani, Susan Slade, Corinne Wells, Venkata M Yenugonda, Yong Liu, Milton L Brown, Yingxian Xiao, Kenneth J Kellar, Edward D Levin

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Article in Psychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Amir H RezvaniDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 104790, Durham, NC, 27710, USA. Azadi@duke.edu.
Susan SladeDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 104790, Durham, NC, 27710, USA.
Corinne WellsDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 104790, Durham, NC, 27710, USA.
Venkata M YenugondaDrug Discovery Program, Georgetown University School of Medicine, Washington, DC, 20057, USA.
Yong LiuDrug Discovery Program, Georgetown University School of Medicine, Washington, DC, 20057, USA.
Milton L BrownDrug Discovery Program, Georgetown University School of Medicine, Washington, DC, 20057, USA.
Yingxian XiaoDepartment of Pharmacology and Physiology, Georgetown University School of Medicine, Washington, DC, 20057, USA.
Kenneth J KellarDrug Discovery Program, Georgetown University School of Medicine, Washington, DC, 20057, USA.
Edward D LevinDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 104790, Durham, NC, 27710, USA.

Funding

NIH HHS NIDA DA027990
6 · The paper itself

Abstract

RATIONALE AND

objectivesDesensitization of neuronal nicotinic acetylcholine receptors holds promise as an effective treatment of tobacco addiction. Previously, we found that sazetidine-A (Saz-A), which selectively desensitizes α4β2 nicotinic receptors, significantly decreased intravenous (IV) nicotine self-administration (SA) in rats with an effective dose of 3 mg/kg in acute and repeated injection studies. We also found that chronic infusions of Saz-A at doses of 2 and 6 mg/kg/day significantly reduced nicotine SA in rats. In continuing studies, we have characterized other Saz-A analogs, YL-2-203 and VMY-2-95, to determine their efficacies in reducing nicotine SA in rats.

methodsYoung adult female Sprague-Dawley rats were fitted with IV catheters and were trained for nicotine SA (0.03 mg/kg/infusion) on a fixed ratio 1 schedule for ten sessions. The same rats were also implanted subcutaneously with osmotic minipumps to continually deliver 2 or 6 mg/kg body weight YL-2-203, VMY-2-95, or saline for four consecutive weeks.

resultsChronic administration of VMY-2-95 at doses of 2 and 6 mg/kg/day caused significant (p < 0.01) decreases in nicotine SA over the 2 weeks of continued nicotine SA and for the 1-week period of resumed access after a week of enforced abstinence, whereas chronic administration of YL-2-203 at the same doses was not found to be effective.

conclusionsThese studies, together with our previous studies of Saz-A, revealed a spectrum of efficacies for these α4β2 nicotinic receptor desensitizing agents and provide a path forward for the most effective compounds to be further developed as possible aids to smoking cessation.

Indexed as

Receptors, NicotinicAnimalsAzetidinesBehavior, AnimalDose-Response Relationship, DrugFemaleNicotineNicotinic AgonistsNicotinic AntagonistsPyridinesRatsRats, Sprague-DawleySelf Administration3-(azetidin-2-ylmethoxy)-5-(phenylethynyl)pyridineAzetidinesNicotineNicotinic AgonistsNicotinic Antagonistsnicotinic receptor alpha4beta2PyridinesReceptors, NicotinicNicotine addictionNicotinic receptorsSazetidine-ATreatmentVMY-2-95YL-2-203

Identifiers

PMID28555315

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