The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Characterization of Spontaneous and Precipitated Nicotine Withdrawal in the Mouse
Abstract
The nicotine withdrawal syndrome was validated and characterized in the mouse using both somatic and affective measures after infusion with nicotine daily via subcutaneous minipumps. The influence of dose, duration of infusion, and repeated withdrawal as well as the contribution of genetic factors were investigated. We then characterized the contribution of nicotinic receptor and site mechanisms to withdrawal signs using various nicotinic antagonists. Our results showed that spontaneous nicotine withdrawal increased the number of somatic signs, decreased the time spent in open arms of the plus-maze test, and induced hyperalgesia. The effect was dose-dependent in all measures with no significant changes at the lowest dose of nicotine (6 mg/kg/day). Withdrawal signs were prominent shortly after pump removal and remained prominent through day 3 or 4. The results with the different antagonists (mecamylamine, dihydro-beta-erythroidine, and methyllycaconitine) suggest the involvement of several nicotinic subtypes such as alpha3beta4*, alpha4beta2*, and alpha7 in nicotine withdrawal. Increasing the duration of nicotine exposure (from 7 to 60 days) and the total nicotine exposure (increasing doses of infusing) augmented the severity of nicotine withdrawal signs. The withdrawal severity of nicotine differs between C57/BL and 129/SvEv inbred mice with nicotine withdrawal in C57 being more severe than in the 129 strain. In summary, our present results suggest that withdrawal from nicotine can be modulated by genetic factors, daily nicotine intake, duration of nicotine exposure, and withdrawal history. The present study demonstrates that our mouse nicotine withdrawal model will be useful for studying the pharmacological, biochemical, and genetic mechanisms involved in nicotine dependence.
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“Rodents chronically exposed to nicotine undergo a characteristic withdrawal syndrome which develops spontaneously, after removing the nicotine source, or can be precipitated by administration of a nAChR antagonist such as mecamylamine [7, 11, 81, 163–166].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [165]
In the citing paper
“Nicotine withdrawal can elicit anxiety-like behaviors in mice [190–192].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [191]
Citations
Cites
Dramatic decreases in brain reward function during nicotine withdrawal
Epping-Jordan, M. P., Watkins, S. S., Koob, G. F., & Markou, A. (1998) · Nature · doi:10.1038/30001 · Cited by 674
Reduced antinociception in mice lacking neuronal nicotinic receptor subunits
Marubio, L. M., Jiménez, M. D. M. A., Cordero‐Erausquin, M., Léna, C., Novère, N. G. L., d’Exaerde, A. D. K., Huchet, M., Damaj, M. I., & Changeux, J. (1999) · Nature · doi:10.1038/19756 · Cited by 538
Self-citationRodent model of nicotine abstinence syndrome
Malin, D. H., Lake, J. R., Newlin-Maultsby, P., Roberts, L. K., Lanier, J. G., Carter, V. A., Cunningham, J. S., & Wilson, O. B. (1992) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(92)90408-8 · Cited by 334
Analysis of Mecamylamine Stereoisomers on Human Nicotinic Receptor Subtypes
Papke, R. L., Sanberg, P. R., & Shytle, R. D. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29581-1 · Cited by 271
Smoking withdrawal dynamics in unaided quitters.
Piasecki, T. M., Niaura, R., Shadel, W. G., Abrams, D., Goldstein, M., Fiore, M. C., & Baker, T. B. (2000) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.109.1.74 · Cited by 262
Acute and chronic tolerance to nicotine measured by activity in rats
Stolerman, I. P., Fink, R. S., & Jarvik, M. E. (1973) · Psychopharmacology · doi:10.1007/bf00429192 · Cited by 246
Watkins, S. S., Stinus, L., Koob, G. F., & Markou, A. (2000) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35389-3 · Cited by 214
Cigarette smoking and nicotine addiction
Benowitz, N. L. (1992) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)30360-1 · Cited by 152
Cigarette withdrawal symptoms in adolescent smokers
McNeill, A. D., West, R., Jarvis, M. J., Jackson, P., & Bryant, A. (1986) · Psychopharmacology · doi:10.1007/bf00174074 · Cited by 142
RJR-2403: a nicotinic agonist with CNS selectivity I. In vitro characterization.
Bencherif, M., Lovette, M. E., Fowler, K., Arrington, S. R., Reeves, L., Caldwell, W. S., & Lippiello, P. M. (1996) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)21302-7 · Cited by 141
Cited by
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Guidelines on nicotine dose selection for in vivo research
Matta, S. G., Balfour, D. J., Benowitz, N. L., Boyd, R. T., Buccafusco, J. J., Caggiula, A. R., Craig, C. R., Collins, A. C., Damaj, M. I., Donny, E. C., et al. (2007) · Psychopharmacology · doi:10.1007/s00213-006-0441-0 · Cited by 824
Self-citationReward, addiction, withdrawal to nicotine
De Biasi, M., & Dani, J. A. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113734 · Cited by 366
“Mecamylamine, which has a slightly higher affinity for α3β4* nAChRs than for β2* receptors, is the best antagonist at precipitating nicotine withdrawal (Damaj et al. 2003).”
BackgroundSalas, R., Sturm, R., Boulter, J., & De Biasi, M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4934-08.2009 · Cited by 310
Salas, R., Pieri, F., & De Biasi, M. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1939-04.2004 · Cited by 226
Jackson, K. J., Martin, B. R., Changeux, J. P., & Damaj, M. I. (2008) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.132977 · Cited by 208
Self-citation
Metadata
- Authors
- Damaj, M. I., Kao, W., & Martin, B. R.
- Affiliations
- Virginia Commonwealth University (US)
- ORCID
- Damaj, M.I.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 307
- Issue
- 2
- Pages
- 526-534
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2112994833
- Cited by
- 222
- References
- 24
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 8 · 2023: 7 · 2022: 3 · 2021: 12 · 2020: 14 · 2019: 12 · 2018: 14 · 2017: 7 · 2016: 15 · 2015: 12 · 2014: 12 · 2013: 14 · 2012: 11
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (DA 05274)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- nicotine withdrawal, nicotine dependence, spontaneous withdrawal, nicotinic acetylcholine receptors, nicotinic receptor subtypes, alpha3beta4 nicotinic receptor, alpha4beta2 nicotinic receptor, alpha7 nicotinic acetylcholine receptor, nicotinic antagonists, mecamylamine, dihydro-beta-erythroidine, methyllycaconitine, hyperalgesia, anxiety-like behavior, inbred mouse strains
- MeSH terms
- Animals, Disease Models, Animal, Male, Mecamylamine, Mice, Inbred ICR, Nicotine, Substance Withdrawal Syndrome, Time Factors, Tobacco Use Disorder, Nicotinic Antagonists, Mice
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