Effects of sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor desensitizing agent on alcohol and nicotine self-administration in selectively bred alcohol-preferring (P) rats
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Rationale Manipulations of nicotinic cholinergic receptors have been shown to influence both alcohol and nicotine intake. Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a novel compound that potently and selectively desensitizes alpha4beta2 nicotinic receptors with only modest receptor activation.Objectives The goal of the present study was to examine the effects of sazetidine-A on alcohol and nicotine self-administration in alcohol-preferring (P) rats.Methods P rats were given the choice of water or alcohol. Once stable baselines were established, the acute (0, 0.1, 0.3, 1, and 3 mg/kg, s.c.) and chronic (3 mg/kg for 10 days) effects of sazetidine-A on alcohol intake were assessed. Naltrexone (2.5 mg/kg) served as a positive control. The effect of sazetidine-A (3 mg/kg) and naltrexone (4 mg/kg) on saccharin (0.2%) preference was also assessed. In addition, the acute effects of sazetidine-A (3 mg/kg) and naltrexone (4 mg/kg) on alcohol intake after alcohol deprivation were evaluated. In another experiment, the effects of sazetidine-A (0, 1, or 3 mg/kg) on i.v. nicotine self-administration in P and NP rats were assessed.Results Sazetidine-A caused a dose-dependent reduction in alcohol intake. Chronic sazetidine-A also effectively reduced alcohol intake until the seventh day of treatment, when partial tolerance appeared to develop. In the post-deprivation study, sazetidine-A significantly reduced alcohol intake and preference. Sazetidine-A at 3 mg/kg significantly reduced nicotine self-administration in both lines.Conclusions Sazetidine-A significantly reduced alcohol and nicotine intake in P rats that self-administer higher levels of both drugs. Sazetidine-A may hold promise for the treatment of alcohol and nicotine addiction.
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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 Rezvani et al, 2010
Saz-A reduces alcohol consumption.
“reduces alcohol consumption (Rezvani et al., 2010)”
From Chronic Sazetidine-A at Behaviorally Active Doses Does Not Increase Nicotinic Cholinergic Receptors in Rodent Brain (2012) · cites this paper as Rezvani et al., 2010
Saz-A decreases nicotine self-administration in rodents.
“In behavioral studies, saz-A decreases nicotine self-administration and increases performance on tasks of attention.”
From Chronic Sazetidine-A at Behaviorally Active Doses Does Not Increase Nicotinic Cholinergic Receptors in Rodent Brain (2012) · cites this paper as Rezvani et al., 2010
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“Other mechanisms that likely contribute to upregulation are decreased surface receptor turnover (Peng et al. 1997) and increased receptor assembly at the endoplasmic reticulum (Corringer et al. 2006; Darsow et al. 2005; Rezvani et al. 2007, 2010; Sallette et al. 2005).”
BackgroundRezvani, A. H., Cauley, M., Sexton, H., Xiao, Y., Brown, M. L., Paige, M. A., McDowell, B. E., Kellar, K. J., & Levin, E. D. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2161-8 · Cited by 50 · see citing works
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Self-citationDivergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal
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- Authors
- Rezvani, A. H., Slade, S., Wells, C., Petro, A., Lumeng, L., Li, T.-K., Xiao, Y., Brown, M. L., Paige, M. A., McDowell, B. E., Rose, J. E., Kellar, K. J., & Levin, E. D.
- Affiliations
- Duke University (US)
- Indiana University (US)
- Georgetown University (US)
- Corresponding author
- Rezvani, Amir H.
- Venue
- Psychopharmacology
- Published
- 2010-06-10
- Volume
- 211
- Issue
- 2
- Pages
- 161-174
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC3695635
- OpenAlex
- W1985530197
- Cited by
- 88
- References
- 65
- Citations by year
- 2023: 2 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 9 · 2017: 4 · 2016: 7 · 2015: 9 · 2014: 8 · 2013: 16 · 2012: 12
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Georgetown University
- National Institute on Drug Abuse (P50DA027840, U19DA027990)
- Topics
- 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
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- alpha4beta2 nicotinic receptor, alcohol self-administration, nicotine self-administration, alcohol-preferring rats, alcohol preference, saccharin preference, alcohol deprivation, naltrexone, tolerance (pharmacology and immunology), alcoholism treatment, tobacco dependence treatment
- MeSH terms
- Ethanol, Animals, Azetidines, Dose-Response Relationship, Drug, Drug Administration Schedule, Male, Naltrexone, Narcotic Antagonists, Nicotine, Pyridines, Receptors, Nicotinic, Reward, Saccharin, Self Administration, Nicotinic Agonists, Rats
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