The α4β2 nicotinic acetylcholine-receptor partial agonist varenicline inhibits both nicotine self-administration following repeated dosing and reinstatement of nicotine seeking in rats
Abstract
Introduction The alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline has greater efficacy than other pharmacotherapeutic aids for smoking cessation. This presents an opportunity to evaluate the predictive validity of rat models of nicotine taking and relapse. The aim of this study was to evaluate the ability of varenicline to attenuate nicotine self-administration and relapse, as modelled by the reinstatement model of nicotine relapse in rats.Materials and methods Rats were trained to respond for intravenous nicotine under a fixed ratio schedule of reinforcement. The effects of varenicline (0.3-3.0 mg/kg s.c.) on both nicotine and food self-administration and reinstatement of nicotine seeking were evaluated.Results and discussion Varenicline dose-dependently reduced nicotine self-administration and attenuated both nicotine prime and combined nicotine prime plus nicotine-paired cue-induced reinstatement. Varenicline had no effect on cue-induced reinstatement in the absence of a nicotine prime nor did it induce reinstatement when given alone.Conclusion The effects of varenicline on nicotine-induced reinstatement of drug-seeking are consistent with the demonstrated clinical efficacy of varenicline for smoking cessation.
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Both sazetidine-A and varenicline reduce nicotine self-administration.
“reduce nicotine self-administration (Levin et al, 2010; O'Connor et al, 2010; Rezvani et al, 2010).”
From Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal (2013) · cites this paper as O'Connor et al, 2010
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- Authors
- O’Connor, E. C., Parker, D., Rollema, H., & Mead, A. N.
- Affiliations
- University of Sussex (GB)
- Pfizer (United Kingdom) (GB)
- Pfizer (United States) (US)
- Corresponding author
- Mead, Andy N.
- Venue
- Psychopharmacology
- Published
- 2009-12-05
- Volume
- 208
- Issue
- 3
- Pages
- 365-376
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2019718444
- Cited by
- 118
- References
- 57
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 6 · 2021: 1 · 2020: 6 · 2019: 10 · 2018: 7 · 2017: 5 · 2016: 13 · 2015: 9 · 2014: 10 · 2013: 9 · 2012: 12
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- varenicline, α4β2 nicotinic acetylcholine receptor, nicotine self-administration, smoking cessation, cue-induced reinstatement, food self-administration, rat model
- MeSH terms
- Varenicline, Animals, Association Learning, Behavior, Animal, Benzazepines, Conditioning, Operant, Cues, Dose-Response Relationship, Drug, Exploratory Behavior, Food, Male, Nicotine, Quinoxalines, Receptors, Nicotinic, Recurrence, Reinforcement, Psychology, Self Administration, Tobacco Use Disorder, Nicotinic Agonists, Models, Animal, Rats
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