Rodent model of nicotine abstinence syndrome

Malin, David H.; Lake, J.Ronald; Newlin-Maultsby, Paige; Roberts, Linda K.; Lanier, Jacqueline G.; Carter, Victoria A.; Cunningham, J.Scott; Wilson, Owen B.

doi:10.1016/0091-3057(92)90408-8

Cited by 334Smoking Behavior and CessationNicotinic Acetylcholine Receptors StudyPrenatal Substance Exposure Effects

Rodent model of nicotine abstinence syndrome

Malin, David H., Lake, J.Ronald, Newlin-Maultsby, Paige, Roberts, Linda K., Lanier, Jacqueline G., Carter, Victoria A., Cunningham, J.Scott, Wilson, Owen B.·1992·Pharmacology Biochemistry and Behavior

DOI 10.1016/0091-3057(92)90408-8

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Abstract

Few animals models are currently in use for the recognized clinical problem of nicotine dependence and abstinence. This study introduces a rapid and convenient model using the rat. Sixteen male rats were rendered nicotine dependent by 7 days of continuous subcutaneous infusion of either 3 mg/kg/day (n = 8) or 9 mg/kg/day (n = 8) nicotine tartrate salt; 8 control rats were infused with saline alone. Rats were observed for 15 min before, during, and after the drug infusion period using a tally sheet modified from a standard checklist of opiate abstinence signs. There were few signs observed in any group at baseline and at the end of the infusion period. However, nicotine-infused rats showed a significant, dose-related increase over the control group at 16 h after the end of infusion, largely subsiding by 40 h. The most frequently observed signs during withdrawals included: teeth-chattering/chews, writhes/gasps, ptosis, tremors/shakes, and yawns. A significant drop in locomotor activity and increase in weight gain following termination of nicotine infusion provided additional evidence of an abstinence syndrome. This syndrome was alleviated by SC administration of 0.4 mg/kg nicotine tartrate.

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Rodents chronically exposed to nicotine undergo a characteristic withdrawal syndrome that can occur spontaneously or be precipitated by mecamylamine.
“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 [163]

The Health consequences of smoking: nicotine addiction: a report of the Surgeon General
(1989) · Choice Reviews Online · doi:10.5860/choice.27-1560 · Cited by 882 · see citing works
Smoking withdrawal symptoms in two weeks of abstinence
Shiffman, S. M., & Jarvik, M. E. (1976) · Psychopharmacology · doi:10.1007/bf00634151 · Cited by 548 · see citing works
Symptoms of Tobacco Withdrawal: A Replication and Extension
Hughes, J. R. (1991) · Archives of General Psychiatry · doi:10.1001/archpsyc.1991.01810250054007 · Cited by 449 · see citing works
Absorption and metabolism of nicotine from cigarettes.
ARMITAGE, A. K., Dollery, C. T., George, C. F., Houseman, T. H., Lewis, P. J., & Turner, D. M. (1975) · BMJ · doi:10.1136/bmj.4.5992.313 · Cited by 293 · see citing works
Tobacco withdrawal symptoms: An experimental analysis
Hatsukami, D. K., Hughes, J. R., Pickens, R. W., & Svikis, D. S. (1984) · Psychopharmacology · doi:10.1007/bf00427451 · Cited by 217 · see citing works
The Health Consequences of Smoking: Nicotine Addiction: A Report of the Surgeon General
Education. Office on Smoking (1988) · Cited by 178 · see citing works
Nicotine protects against μ-opioid receptor antagonism by β-funaltrexamine: Evidence for nicotine-induced release of endogenous opioids in brain
Davenport, K. E., Houdi, A. A., & Loon, G. R. V. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90491-q · Cited by 145 · see citing works
FMRF-NH2-like mammalian octapeptide: Possible role in opiate dependence and abstinence
Malin, D. H., Lake, J. R., Hammond, M. V., Fowler, D. E., Rogillio, R. B., Brown, S. L., Sims, J. L., Leecraft, B. M., & Yang, H. T. (1990) · Peptides · doi:10.1016/0196-9781(90)90018-z · Cited by 144 · see citing works
Self-citation
Chronic nicotine and withdrawal effects on body weight and food and water consumption in female rats
Levin, E. D., Morgan, M. M., Galvez, C., & Ellison, G. D. (1987) · Physiology & Behavior · doi:10.1016/0031-9384(87)90370-2 · Cited by 102 · see citing works
Quantitative Electroencephalogram in Smoking and Smoking Deprivation
Ulett, J. A., & Itil, T. M. (1969) · Science · doi:10.1126/science.164.3882.969 · Cited by 93 · see citing works
EEG Changes During Tobacco Withdrawal
Herning, R. I., Jones, R. T., & Bachman, J. (1983) · Psychophysiology · doi:10.1111/j.1469-8986.1983.tb03004.x · Cited by 89 · see citing works
Nicotine-induced alterations in brain regional concentrations of native and cryptic Met- and Leu-enkephalin
Pierzchała, K., Houdi, A. A., & Loon, G. R. V. (1987) · Peptides · doi:10.1016/0196-9781(87)90133-1 · Cited by 76 · see citing works
Effects of nicotine on behavioral arousal and brain 5-Hydroxytryptamine function in female rats selected for differences in activity
Rosecrans, J. A. (1971) · European Journal of Pharmacology · doi:10.1016/0014-2999(71)90119-1 · Cited by 57 · see citing works
Evidence for a behavioral deficit during withdrawal from chronic nicotine treatment
Corrigall, W. A., Herling, S., & Coen, K. M. (1989) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(89)90387-0 · Cited by 44 · see citing works
Auricular microelectrostimulation: Naloxone-reversible attenuation of opiate abstinence syndrome
Malin, D. H., Murray, J. B., Crucian, G. P., Schweitzer, F. C., Cook, R. E., & Skolnick, M. H. (1988) · Biological Psychiatry · doi:10.1016/0006-3223(88)90223-5 · Cited by 41 · see citing works
Self-citation
A psychological and behavioural comparison of ex-smokers and smokers
Pederson, L. L., & Lefcoe, N. M. (1976) · Journal of Chronic Diseases · doi:10.1016/0021-9681(76)90083-7 · Cited by 41 · see citing works
Nicotine dependence in rats
Carroll, M. E., Lac, S. T., Asencio, M., & Keenan, R. M. (1989) · Life Sciences · doi:10.1016/0024-3205(89)90025-8 · Cited by 37 · see citing works

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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 · see citing works
Neurobiological similarities in depression and drug dependence: a self-medication hypothesis
Markou, A. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00113-9 · Cited by 767 · see citing works
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 · see citing works
Neural mechanisms underlying nicotine addiction: acute positive reinforcement and withdrawal
S. Watkins, G. F. K. (2000) · Nicotine & Tobacco Research · doi:10.1080/14622200050011277 · Cited by 424 · see citing works
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 · see citing works
“In rats, somatic signs of physical dependency include teethchattering, chewing, gasps, palpebral ptosis, tremors, shakes, and yawns (Malin et al. 1992).”
Background
Nicotinic receptors in the brain. Links between molecular biology and behavior
Picciotto, M. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00146-3 · Cited by 354 · see citing works
Nicotine withdrawal versus other drug withdrawal syndromes: similarities and dissimilarities
HUGHES, J. R., HIGGINS, S. T., & BICKEL, W. K. (1994) · Addiction · doi:10.1111/j.1360-0443.1994.tb03744.x · Cited by 312 · see citing works
Neurobiology of the nicotine withdrawal syndrome
Kenny, P. J., & Markou, A. (2001) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00651-7 · Cited by 310 · see citing works
The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of nicotine dependence
Balfour, D. J. K., Wright, A. E., Benwell, M. E. M., & Birrell, C. E. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00202-3 · Cited by 231 · see citing works
Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat
Cryan, J. F., Bruijnzeel, A. W., Skjei, K. L., & Markou, A. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1445-7 · Cited by 223 · see citing works
Characterization of spontaneous and precipitated nicotine withdrawal in the mouse
Damaj, M. I., Kao, W., & Martin, B. R. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.054908 · Cited by 222 · see citing works
Reward and Somatic Changes during Precipitated Nicotine Withdrawal in Rats: Centrally and Peripherally Mediated Effects
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 · see citing works
Differential Role of Nicotinic Acetylcholine Receptor Subunits in Physical and Affective Nicotine Withdrawal Signs
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 · see citing works
Reduced dopamine output in the nucleus accumbens but not in the medial prefrontal cortex in rats displaying a mecamylamine-precipitated nicotine withdrawal syndrome
Hildebrand, B. E., Nomikos, G. G., Hertel, P., Schilström, B., & Svensson, T. H. (1998) · Brain Research · doi:10.1016/s0006-8993(97)01135-9 · Cited by 200 · see citing works
Effects of abstinence from tobacco: Etiology, animal models, epidemiology, and significance: A subjective review
Hughes, J. (2007) · Nicotine & Tobacco Research · doi:10.1080/14622200701188927 · Cited by 173 · see citing works
The nicotinic antagonist mecamylamine precipitates nicotine abstinence syndrome in the rat
Malin, D. H., Ronald Lake, J., Carter, V. A., Scott Cunningham, J., Hebert, K. M., Conrad, D. L., & Wilson, O. B. (1994) · Psychopharmacology · doi:10.1007/bf02244770 · Cited by 165 · see citing works
Self-citation
Nicotine dependence
Malin, D. H. (2001) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00699-2 · Cited by 167 · see citing works
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Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system
Berrendero, F., Robledo, P., Trigo, J. M., Martín-García, E., & Maldonado, R. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.02.006 · Cited by 140 · see citing works
Behavioral manifestations of the nicotine abstinence syndrome in the rat: peripheral versus central mechanisms
Hildebrand, B. E., Nomikos, G. G., Bondjers, C., Nisell, M., & Svensson, T. H. (1997) · Psychopharmacology · doi:10.1007/s002130050200 · Cited by 122 · see citing works
Common aspects of the action of nicotine and other drugs of abuse
Picciotto, M. R. (1998) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(98)00074-x · Cited by 117 · see citing works
How does bupropion work as a smoking cessation aid?
Warner, C., & Shoaib, M. (2005) · Addiction Biology · doi:10.1080/13556210500222670 · Cited by 115 · see citing works
Neuroadaptive changes in the mesoaccumbens dopamine system after chronic nicotine self-administration: a microdialysis study
Rahman, S., Zhang, J., Engleman, E. A., & Corrigall, W. A. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.08.010 · Cited by 110 · see citing works
The Neuronal Pathways Mediating the Behavioral and Addictive Properties of Nicotine
Balfour, D. J. K. (2009) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-540-69248-5_8 · Cited by 99 · see citing works
Dissociation of physical abstinence signs from changes in extracellular dopamine in the nucleus accumbens and in the prefrontal cortex of nicotine dependent rats
Carboni, E., Bortone, L., Giua, C., & Di Chiara, G. (2000) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(99)00064-2 · Cited by 96 · see citing works
Influence of Neuronal Nicotinic Receptors over Nicotine Addiction and Withdrawal
De Biasi, M., & Salas, R. (2008) · Experimental Biology and Medicine · doi:10.3181/0712-mr-355 · Cited by 95 · see citing works
Rodent models of nicotine withdrawal syndrome
Malin, D. H., & Goyarzu, P. (2009) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-69248-5_14 · Cited by 89 · see citing works
Self-citation
Deficits in a sustained attention task following nicotine withdrawal in rats
Shoaib, M., & Bizarro, L. (2005) · Psychopharmacology · doi:10.1007/s00213-004-2004-6 · Cited by 87 · see citing works
Nicotine and endogenous opioids: neurochemical and pharmacological evidence
Hadjiconstantinou, M., & Neff, N. H. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.11.010 · Cited by 81 · see citing works
Mechanistic insights into nicotine withdrawal
Paolini, M., & De Biasi, M. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.07.075 · Cited by 66 · see citing works
Varenicline ameliorates nicotine withdrawal-induced learning deficits in C57BL/6 mice.
Raybuck, J. D., Portugal, G. S., Lerman, C., & Gould, T. J. (2008) · Behavioral Neuroscience · doi:10.1037/a0012601 · Cited by 62 · see citing works
Strain-dependent effects of acute, chronic, and withdrawal from chronic nicotine on fear conditioning
Portugal, G. S., Wilkinson, D. S., Kenney, J. W., Sullivan, C., & Gould, T. J. (2012) · Behavior Genetics · doi:10.1007/s10519-011-9489-7 · Cited by 58 · see citing works
Nicotine coregulates multiple pathways involved in protein modification/degradation in rat brain
Kane, J. K., Konu, Ö., Ma, J. Z., & Li, M. D. (2004) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.09.010 · Cited by 61 · see citing works
Nicotine and Hippocampus-Dependent Learning: Implications for Addiction
Gould, T. J. (2006) · Molecular Neurobiology · doi:10.1385/mn:34:2:93 · Cited by 61 · see citing works
Addiction‐related neuroadaptations following chronic nicotine exposure
Wills, L., & Kenny, P. J. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15356 · Cited by 61 · see citing works
Interactions between age and the aversive effects of nicotine withdrawal under mecamylamine-precipitated and spontaneous conditions in male Wistar rats
Shram, M. J., Siu, E. C. K., Li, Z., Tyndale, R. F., & Lê, A. D. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1115-x · Cited by 60 · see citing works
Exposure to passive nicotine vapor in male adolescent rats produces a withdrawal-like state and facilitates nicotine self-administration during adulthood
Kallupi, M., de Guglielmo, G., Larrosa, E., & George, O. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2019.08.299 · Cited by 25 · see citing works
Behavioral effects of nicotine withdrawal differ by genetic strain in male and female adolescent rats
Hamilton, K. R., Perry, M. E., Berger, S. S., & Grunberg, N. E. (2010) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntq179 · Cited by 27 · see citing works
Enhanced dopamine transporter function in striatum during nicotine withdrawal
Hadjiconstantinou, M., Duchemin, A., Zhang, H., & Neff, N. H. (2011) · Synapse · doi:10.1002/syn.20820 · Cited by 20 · see citing works

Authors: Malin, D. H., Lake, J. R., Newlin-Maultsby, P., Roberts, L. K., Lanier, J. G., Carter, V. A., Cunningham, J. S., & Wilson, O. B.
Affiliations: University of Houston (US)
University of Houston - Clear Lake (US)
Baylor College of Medicine (US)
Corresponding author: Malin, David H.
ORCID: Malin, David H.
Lake, J.Ronald
Venue: Pharmacology Biochemistry and Behavior
Publisher: Elsevier BV
Published: 1992-11
Volume: 43
Issue: 3
Pages: 779-784
ISSN: 0091-3057 (ISSN-L)
DOI: 10.1016/0091-3057(92)90408-8
OpenAlex: W2083993994
Cited by: 334
References: 17
Citations by year: 2026: 2 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 12 · 2020: 9 · 2019: 12 · 2018: 11 · 2017: 4 · 2016: 16 · 2015: 6 · 2014: 10 · 2013: 12 · 2012: 8
FWCI: 1.73
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacology Biochemistry and Behavior (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › 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 dependence, nicotine withdrawal, withdrawal syndrome, rat model, withdrawal signs, locomotor activity, weight gain, nicotine self-administration
MeSH terms: Animals, Behavior, Animal, Body Weight, Disease Models, Animal, Male, Motor Activity, Nicotine, Substance Withdrawal Syndrome, Rats, Sprague-Dawley, Rats

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Rodent model of nicotine abstinence syndrome

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