Sazetidine-A, a Selective α4β2 Nicotinic Receptor Desensitizing Agent and Partial Agonist, Reduces Nicotine Self-Administration in Rats
Abstract
Adequate treatment of tobacco addiction remains problematic. Part of the problem with treatment is a poor understanding of the pharmacologic aspects of nicotine contributing to addiction. In addition to activating nicotinic acetylcholine receptors, nicotine also desensitizes them. It is currently not known how much of each of nicotine's actions contribute to its particular behavioral effects. Sazetidine-A (saz-A) is a novel nicotinic receptor-desensitizing agent and partial agonist with high selectivity for alpha4beta2 receptors. The current experiments were conducted to determine whether saz-A would reduce nicotine self-administration in rats and to characterize its ancillary effects. Adult male Sprague-Dawley rats were allowed to self-administer nicotine. After initial food pellet training followed by 10 sessions of nicotine self-administration training, the rats were administered saz-A (0.1-3 mg/kg s.c.) or the saline vehicle in a repeated-measures counterbalanced design. Saz-A at the 3 mg/kg dose significantly decreased nicotine self-administration relative to performance of the same rats after saline injections. In a second study, long-term administration of this dose of sazetidine-A over the course of 10 sessions significantly reduced nicotine self-administration with no apparent diminution of effect. Saz-A in this dose range had only modest effects on locomotor activity, without any overall decrease in activity over a 1-h-long session. Saz-A significantly reduced food self-administration, but this effect was smaller than its effect on nicotine self-administration. Saz-A, which is a selective alpha4beta2-desensitizing agent and partial agonist, effectively reduces nicotine self-administration. This type of treatment holds promise for a new therapy to aid 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 Levin et al, 2010
Sazetidine-A has antidepressant-like activity and utility as a smoking cessation therapy.
“sazetidine-A, which has antidepressant-like activity and utility as a smoking cessation therapy (Levin et al., 2010)”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Levin et al., 2010
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- Authors
- Levin, E. D., Rezvani, A. H., Xiao, Y., Slade, S., Cauley, M., Wells, C., Hampton, D., Petro, A., Rose, J. E., Brown, M. L., Paige, M. A., McDowell, B. E., & Kellar, K. J.
- Affiliations
- Duke University (US)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 332
- Issue
- 3
- Pages
- 933-939
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2007447520
- Semantic Scholar
- 3f60bc259b16ec906360f3dbee77294391716228
- Cited by
- 65
- References
- 25
- Citations by year
- 2021: 1 · 2019: 5 · 2018: 6 · 2017: 2 · 2016: 8 · 2015: 6 · 2014: 9 · 2013: 9 · 2012: 9
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- α4β2 nicotinic acetylcholine receptor, receptor desensitization, partial agonists, nicotine self-administration, nicotine dependence, smoking cessation, locomotor activity, food self-administration
- MeSH terms
- Animals, Azetidines, Conditioning, Operant, Dose-Response Relationship, Drug, Food, Male, Motivation, Motor Activity, Nicotine, Pyridines, Receptors, Nicotinic, Self Administration, Rats, Sprague-Dawley, Nicotinic Agonists, Rats, Drug Partial Agonism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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