The DOI matches its Crossref record; 260 of the 264 references it cites were found in a registry or an index.
Neurobiology of the nicotine withdrawal syndrome
Abstract
The aversive aspects of withdrawal from chronic nicotine exposure are thought to be an important motivational factor contributing to the maintenance of the tobacco habit in human smokers. Much emphasis has been placed on delineating the underlying neurobiological mechanisms mediating different components of the nicotine withdrawal syndrome. Recent studies have shown that both central and peripheral populations of nicotinic acetylcholine receptors (nAChRs) are involved in mediating somatic signs of nicotine withdrawal as measured by the rodent nicotine abstinence scale. However, only central populations of nAChRs are involved in mediating affective aspects of nicotine withdrawal, as measured by elevations in brain-stimulation reward thresholds and conditioned place aversion. Nicotine interacts with several neurotransmitter systems, including acetylcholine, dopamine, opioid peptides, serotonin, and glutamate systems. Evidence so far suggests that these neurotransmitters play a role in nicotine dependence and withdrawal processes. The available evidence also suggests that different underlying neurochemical deficits mediate somatic and affective components of nicotine withdrawal. The aim of the present review is to discuss preclinical findings concerning the neuroanatomical and neurochemical substrates involved in these different aspects of nicotine withdrawal.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Dependence on tobacco smoking depends not only on the balance between the rewarding and aversive action of nicotine described above, but also on escape from the aversive consequences of nicotine withdrawal (Doherty et al. 1995;Kenny and Markou 2001).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Kenny and Markou 2001
In the citing paper
“The most common somatic symptoms include bradycardia, gastrointestinal discomfort, and increased appetite.”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Kenny and Markou 2001
In the citing paper
“Affective symptoms primarily include depressed mood including anhedonia, dysphoria, anxiety, irritability, difficulty concentrating, and craving (Parrott 1993;Doherty et al. 1995;Kenny and Markou 2001).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Kenny and Markou 2001
In the citing paper
“The nicotine withdrawal syndrome in abstinent smokers is comprised of”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Kenny and Markou 2001
In the citing paper
“The neuroadaptations arising from chronic nicotine exposure cause widespread alterations in brain neurotransmission that promote and sustain the use of tobacco [21–24].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [22]
Citations
Cites
Items 201–260 of 260
Locomotor activity in morphine-dependent and post-dependent rats
Brady, L. S., & Holtzman, S. G. (1981) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(81)90403-2 · Cited by 71
Use of ganglionic blockers to assess neurogenic pressor activity in conscious rats
Santajuliana, D., Hornfeldt, B. J., & Osborn, J. W. (1996) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/1056-8719(95)00132-8 · Cited by 70
NKP608, an NK1 receptor antagonist, has an anxiolytic action in the social interaction test in rats
File, S. E. (2000) · Psychopharmacology · doi:10.1007/s002130000513 · Cited by 70
Macey, D. J., Koob, G. F., & Markou, A. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02229-0 · Cited by 69
Self-citationWest, R., Hájek, P., & McNeill, A. D. (1991) · Psychopharmacology · doi:10.1007/bf02244560 · Cited by 68
Iorio, P. D., Battaglia, G., Ciccarelli, R., Ballerini, P., Giuliani, P., Poli, A., Nicoletti, F., & Caciagli, F. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.67010302.x · Cited by 66
In vivo pharmacological effects of dihydro-β-erythroidine, a nicotinic antagonist, in mice
Damaj, M. I., Welch, S. P., & Martin, B. R. (1995) · Psychopharmacology · doi:10.1007/bf02245100 · Cited by 65
Chen, D., Dang, H., & Patrick, J. W. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70010349.x · Cited by 65
Fu, Y., Matta, S. G., Gao, W., & Sharp, B. M. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00371-7 · Cited by 64
Nicotine regulates 5‐HT1A receptor gene expression in the cerebral cortex and dorsal hippocampus
Kenny, P. J., File, S. E., & Rattray, M. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01501.x · Cited by 63
Self-citationModulation of opioidergic system on mecamylamine-precipitated nicotine-withdrawal aversion in rats
Ise, Y., Narita, M., Nagase, H., & Suzuki, T. (2000) · Psychopharmacology · doi:10.1007/s002130000482 · Cited by 63
Mecamylamine does not precipitate withdrawal in cigarette smokers
Eissenberg, T., Griffiths, R. R., & Stitzer, M. L. (1996) · Psychopharmacology · doi:10.1007/s002130050094 · Cited by 62
Efficacy of nicotine chewing gum: a review.
Fagerström, K. O. (1988) · PubMed · Cited by 62
Effect of Buspirone on Withdrawal Symptoms Associated With Smoking Cessation
Hilleman, D. E. (1992) · Archives of Internal Medicine · doi:10.1001/archinte.1992.00400140096021 · Cited by 60
Milanés, M. V., Laorden, M. L., Chapleur-Château, M., & Burlet, A. J. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37420-8 · Cited by 60
Does switching to an ultra-low nicotine cigarette induce nicotine withdrawal effects?
West, R., Russell, M. A., Jarvis, M. J., & Feyerabend, C. (1984) · Psychopharmacology · doi:10.1007/bf00432039 · Cited by 58
Rasmussen, K., Calligaro, D. O., Czachura, J. F., Dreshfield, L. J., Evans, D. C., Hemrick-Luecke, S. K., Kallman, M. J., Kendrick, W. T., Leander, J. D., Nelson, D. L. G., et al. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39123-2 · Cited by 58
The effects of nicotine administration on 5-HT uptake and biosynthesis in rat brain
Benwell, M. E. M., & Balfour, D. J. K. (1982) · European Journal of Pharmacology · doi:10.1016/0014-2999(82)90158-3 · Cited by 56
Depression After Smoking Cessation
Stage, K. B., Glassman, A. H., & Covey, L. S. (1996) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v57n1005 · Cited by 54
Cigarette smoking: Effects upon self-rated stress and arousal over the day
Parrott, A. C. (1993) · Addictive Behaviors · doi:10.1016/0306-4603(93)90055-e · Cited by 53
Bassareo, V., Tanda, G., & Chiara, G. D. (1995) · Psychopharmacology · doi:10.1007/bf02246097 · Cited by 51
Stimulatory role of dopamine on fibroblast growth factor‐2 expression in rat striatum
Roceri, M., Molteni, R., Fumagalli, F., Racagni, G., Gennarelli, M., Corsini, G. U., Maggio, R., & Riva, M. A. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00088.x · Cited by 50
Malin, D. H. (1998) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(98)00028-8 · Cited by 50
α3, β2, and β4 Form Heterotrimeric Neuronal Nicotinic Acetylcholine Receptors in Xenopus Oocytes
Colquhoun, L. M., & Patrick, J. W. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69062355.x · Cited by 49
Effect of dose on nicotine's reinforcing, withdrawal-suppression and self-reported effects.
Hughes, J. R., Gust, S. W., Keenan, R. M., & Fenwick, J. W. (1990) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)20177-x · Cited by 48
Almeida, L. E. F., Pereira, E. F. R., Alkondon, M., Fawcett, W. P., Randall, W. R., & Albuquerque, E. X. (2000) · Neuropharmacology · doi:10.1016/s0028-3908(00)00157-x · Cited by 47
Efficacy of buspirone in smoking cessation: A placebo-controlled trial*
Schneider, N. G., Olmstead, R. E., Steinberg, C., Sloan, K., Daims, R. M., & Brown, H. V. (1996) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(96)90153-8 · Cited by 46
Hilleman, D. E., Mohiuddin, S. M., & DelCore, M. G. (1994) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1994.tb03989.x · Cited by 46
Rasmussen, K., & Czachura, J. F. (1997) · Psychopharmacology · doi:10.1007/s002130050411 · Cited by 45
Could Nicotine Antagonists be Used in Smoking Cessation?
Stolerman, I. P. (1986) · British Journal of Addiction · doi:10.1111/j.1360-0443.1986.tb00292.x · Cited by 45
Nicotine withdrawal in the rat: role of α7 nicotinic receptors in the ventral tegmental area
Nomikos, G. G., Hildebrand, B. E., Panagis, G., & Svensson, T. H. (1999) · Neuroreport · doi:10.1097/00001756-199903170-00007 · Cited by 45
Dopaminergic mediation of the discriminative stimulus effects of bupropion in rats
Terry, P., & Katz, J. L. (1997) · Psychopharmacology · doi:10.1007/s002130050443 · Cited by 43
Nicotine Abstinence Syndrome Precipitated by Central But Not Peripheral Hexamethonium
Malin, D. H. (1997) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(97)90006-x · Cited by 43
Depression following smoking cessation in women
Bock, B. C., Goldstein, M. G., & Marcus, B. H. (1996) · Journal of Substance Abuse · doi:10.1016/s0899-3289(96)90151-0 · Cited by 42
Maldonado, R. J., Girdlestone, D., & Roques, B. P. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90457-v · Cited by 42
Molander, L., Lunell, E., & Fagerström, K. O. (2000) · Nicotine & Tobacco Research · doi:10.1080/713688123 · Cited by 41
Baldinger, B. (1995) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(94)00302-y · Cited by 39
Effects of intra-amygdalar dopamine agonists and antagonists on gastric stress lesions in rats
Ray, A., Henke, P. G., & Sullivan, R. M. (1988) · Neuroscience Letters · doi:10.1016/0304-3940(88)90525-3 · Cited by 37
Clonidine blocks acquisition but not expression of conditioned opiate withdrawal in rats
Schulteis, G. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00036-0 · Cited by 37
Belluardo, N., Mudò, G., Blum, M., Cheng, Q., Caniglia, G., Dell’Albani, P., & Fuxé, K. (1999) · Molecular Brain Research · doi:10.1016/s0169-328x(99)00266-1 · Cited by 34
Nicotine abstinence syndrome precipitated by an analog of neuropeptide FF
Malin, D. H. (1996) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)02279-1 · Cited by 32
Clonidine for smoking cessation
Gourlay, S., Stead, L., & Benowitz, N. (1999) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd000058 · Cited by 32
Mecamylamine Blockade of Both Positive and Negative Effects of IV Nicotine in Human Volunteers
Lundahl, L. H., Henningfield, J. E., & Lukas, S. E. (2000) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(00)00252-5 · Cited by 31
A Dopamine D1 Agonist Elevates Self-Stimulation Thresholds
Baldo, B. A., Jain, K., Veraldi, L., Koob, G. F., & Markou, A. (1999) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(98)00206-8 · Cited by 30
Self-citationSuzuki, T., Ise, Y., Mori, T., & Misawa, M. (1997) · Life Sciences · doi:10.1016/s0024-3205(97)00745-5 · Cited by 30
Léna, C., & Changeux, J. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb11333.x · Cited by 30
Broersen, L. M., Abbate, F., Feenstra, M. G. P., de Bruin, J. P. C., Heinsbroek, R. P. W., & Olivier, B. (2000) · Psychopharmacology · doi:10.1007/s002130000390 · Cited by 29
Mecamylamine-precipitated nicotine-withdrawal aversion in Lewis and Fischer 344 inbred rat strains
Suzuki, T., Ise, Y., Maeda, J., & Misawa, M. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00086-2 · Cited by 28
Effect of nicotine on the level of extracellular amino acids in the hippocampus of rat
Tóth, E. (1996) · Neurochemical Research · doi:10.1007/bf02532339 · Cited by 27
Central dopamine involvement in experimental gastrointestinal injury
Glavin, G. B. (1992) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(92)90073-n · Cited by 27
NMDA receptor antagonists inhibit ethanol-produced locomotor stimulation in NMRI mice
Liljequist, S. (1991) · Alcohol · doi:10.1016/0741-8329(91)90449-7 · Cited by 27
The CCK-B antagonist LY288513 blocks the effects of nicotine withdrawal on auditory startle
Rasmussen, K., Czachura, J. F., Kallman, M. J., & Helton, D. R. (1996) · Neuroreport · doi:10.1097/00001756-199604100-00019 · Cited by 26
Tomé, Â. R., Izaguirre, V., Rosário, L. M., Ceña, V., & Gonzalez-Garcia, C. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02388-5 · Cited by 24
Pharmacologic approaches to smoking cessation.
Sachs, D. P. L., & Leischow, S. J. (1991) · PubMed · Cited by 22
GOSLING, J. A., & LU, T. C. (1969) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)28253-2 · Cited by 20
Abdel‐Rahman, A. A. (1989) · PubMed · Cited by 20
Parrott, S., Godfrey, C., Raw, M., West, R., & McNeill, A. D. (1998) · UCL Discovery (University College London) · Cited by 17
Effect of buspirone on withdrawal symptoms associated with smoking cessation
Hilleman, D. E. (1992) · Archives of Internal Medicine · doi:10.1001/archinte.152.2.350 · Cited by 12
Pandey, S. C., Xu, T., & Zhang, D. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00172-x · Cited by 9
Fagerström, K. O., Ramström, L., & Svensson, T. H. (1992) · The Lancet · doi:10.1016/0140-6736(92)90974-8 · Cited by 4
Research works printed but not linked: 3
- Paterson, 2001, Nicotine self-administration in rats: short-term abstinence, progressive ratio schedule, and extinction with or without conditioned stimuli, Drug Alcohol Depend, 63, S120
- Ridley, 1997, The influence of nicotine on 5-HT overflow in the dorsal hippocampus of the rat, Br J Pharmacol, 112, 301P
- Wonnacott, 1993, Methyllycaconitine: a new probe that discriminates between nicotinic acetylcholine receptor subclasses, Methods Neurosci, 12, 263
Cited by
Sorted by citations
Tzschentke, T. M. (2007) · Addiction Biology · doi:10.1111/j.1369-1600.2007.00070.x · Cited by 1,336
The dynamic effects of nicotine on the developing brain
Dwyer, J. B., McQuown, S. C., & Leslie, F. M. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.02.003 · Cited by 559
Cue dependency of nicotine self-administration and smoking
Caggiula, A. R., Donny, E. C., White, A. R., Chaudhri, N., Booth, S., Gharib, M. A., Hoffman, A., Perkins, K. A., & Sved, A. F. (2001) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00676-1 · Cited by 425
Reward, 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
“In the conditioned place-aversion paradigm, the animal learns to avoid the compartment in which nicotine withdrawal is experienced (Jackson et al. 2009, Kenny & Markou 2001).”
BackgroundWhat Keeps Us Awake: the Neuropharmacology of Stimulants and Wakefulness Promoting Medications
Boutrel, B., & Koob, G. F. (2004) · SLEEP · doi:10.1093/sleep/27.6.1181 · Cited by 310
Metadata
- Authors
- Kenny, P. J., & Markou, A.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Markou, Athina
- ORCID
- Kenny, Paul J.
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2001-12
- Volume
- 70
- Issue
- 4
- Pages
- 531-549
- ISSN
- 0091-3057 (ISSN-L)
- OpenAlex
- W2020567468
- Cited by
- 310
- References
- 264
- Citations by year
- 2025: 9 · 2024: 7 · 2023: 10 · 2022: 7 · 2021: 10 · 2020: 12 · 2019: 11 · 2018: 7 · 2017: 11 · 2016: 8 · 2015: 17 · 2014: 12 · 2013: 19 · 2012: 18
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (DA 11946, R56DA011946)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine withdrawal, nicotine dependence, nicotinic acetylcholine receptors, somatic withdrawal signs, conditioned place aversion, dopamine, opioid peptides, serotonin, glutamate, acetylcholine, neuroanatomical substrates
- MeSH terms
- Animals, Humans, Nicotine, Substance Withdrawal Syndrome, Nicotinic Agonists
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 ›
Are you an author, or do you see a problem with this page? Request a review
