Desensitization of the nicotine-induced mesolimbic dopamine responses during constant infusion with nicotine
Open accessAbstract
1. The effects of constant nicotine infusions (0.25, 1.0 and 4.0 mg kg-1 day-1) on extracellular dopamine levels in the nucleus accumbens (NAc) and on locomotor activity have been compared with the changes evoked by repeated daily injections (0.4 mg kg-1 day-1 for 5 days) of the drug. 2. The extracellular dopamine concentration in the NAc was significantly increased (P < 0.05) following a challenge dose of nicotine (0.4 mg kg-1, s.c.) in animals which had been pretreated with daily injections of the drug. This effect was accompanied by an enhanced locomotor response to nicotine. 3. The stimulant effects of nicotine on mesolimbic dopamine secretion and on locomotor activity were significantly inhibited (P < 0.01) by the prior administration of mecamylamine (2.0 mg kg-1, s.c.) but not by hexamethonium (2.0 mg kg-1, s.c.). 4. The constant infusion of nicotine at a rate of 1 and 4 but not 0.25 mg kg-1 day-1 abolished the sensitized dopamine response in the NAc to an injection of nicotine in animals pretreated with the drug. The locomotor responses to nicotine in the nicotine-pretreated rats were significantly attenuated by the infusion of nicotine at all 3 doses, although the nicotine induced locomotor activity, in the rats infused with 0.25 mg kg-1 day-1 was also significantly (P < 0.05) higher than that observed in the rats treated acutely with nicotine. 5. Significantly (P<0.01) enhanced mesolimbic dopamine responses, to a challenge injection of nicotine(0.4 mg kg-1, s.c.), were observed 2 and 7 days after termination of the infusion of nicotine (4 mg kg-1 day-1 for 14 days); locomotor responses were enhanced (P<0.01) 1, 2 and 7 days after termination of the infusion.6. The results suggest that sensitized mesolimbic dopamine responses to nicotine occur as a result of stimulation of centrally located nicotinic receptors but that these receptors may be desensitized during periods of chronic exposure to nicotine at doses which may be relevant to smoking.
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After chronic nicotine treatment, increased responses that reflect the higher receptor numbers are usually observed later.
“Subsequently, however, increased responses reflecting the increased receptors are usually found (Rowell and Wonnacott, 1990;Benwell et al., 1995;Gopalakrishnan et al., 1996Gopalakrishnan et al., , 1997;;Buisson and Bertrand, 2001;Avila et al., 2003)”
From Chronic Sazetidine-A at Behaviorally Active Doses Does Not Increase Nicotinic Cholinergic Receptors in Rodent Brain (2012) · cites this paper as Benwell et al., 1995
Nicotine administration increases extracellular noradrenaline in various parts of the brain.
“Nicotine administration also increases the extracellular noradrenaline in various parts of the brain (32–35);”
From Tobacco addiction (2008) · cites this paper as [34]
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Cites
Di Chiara, G., & Imperato, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.14.5274 · Cited by 4,733 · see citing works
Bardo, M. T., & Hammer, R. P. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90226-e · Cited by 3,229 · see citing works
A psychomotor stimulant theory of addiction.
Wise, R. A., & Bozarth, M. A. (1987) · Psychological Review · doi:10.1037/0033-295x.94.4.469 · Cited by 2,747 · see citing works
The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine
Corrigall, W. A., Franklin, K. B. J., Coen, K. M., & Clarke, P. B. S. (1992) · Psychopharmacology · doi:10.1007/bf02245149 · Cited by 829 · see citing works
Nicotine preferentially stimulates dopamine release in the limbic system of freely moving rats
Imperato, A., Mulas, A., & Di Chiara, G. (1986) · European Journal of Pharmacology · doi:10.1016/0014-2999(86)90629-1 · Cited by 693 · see citing works
Benwell, M. E. M., Balfour, D. J. K., & Anderson, J. M. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb10600.x · Cited by 551 · see citing works
Self-citationClarke, P. B. S., & Pert, A. (1985) · Brain Research · doi:10.1016/0006-8993(85)90456-1 · Cited by 527 · see citing works
Nisell, M., Nomikos, G. G., & Svensson, T. H. (1994) · Synapse · doi:10.1002/syn.890160105 · Cited by 510 · see citing works
Benwell, M. E. M., & Balfour, D. J. K. (1992) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1992.tb09067.x · Cited by 426 · see citing works
Self-citationHigher levels of nicotine in arterial than in venous blood after cigarette smoking
Henningfield, J. E. (1993) · Drug and Alcohol Dependence · doi:10.1016/0376-8716(93)90030-t · Cited by 370 · see citing works
Clarke, P. B., Fu, D. S., Jakubovic, A., & Fibiger, H. C. (1988) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22152-8 · Cited by 318 · see citing works
In Vivo Regulation of [3H]Acetylcholine Recognition Sites in Brain by Nicotinic Cholinergic Drugs
Schwartz, R. D., & Kellar, K. J. (1985) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1985.tb04005.x · Cited by 282 · see citing works
Time course study of the effects of chronic nicotine infusion on drug response and brain receptors
Marks, M. J., Stitzel, J. A., & Collins, A. C. (1985) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24213-6 · Cited by 265 · see citing works
Cigarette Smoking: A Dependence on High-Nicotine Boli
Russell, M. A. H., & Feyerabend, C. (1978) · Drug Metabolism Reviews · doi:10.3109/03602537808993776 · Cited by 253 · see citing works
Lack of tolerance to nicotine-induced dopamine release in the nucleus accumbens
Damsma, G., Day, J. C., & Fibiger, H. C. (1989) · European Journal of Pharmacology · doi:10.1016/0014-2999(89)90798-x · Cited by 169 · see citing works
Locomotor activity in rats after administration of nicotinic agonists intracerebrally
Reavill, C. A., & Stolerman, I. P. (1990) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1990.tb14693.x · Cited by 158 · see citing works
Janson, A. M., Fuxé, K., Agnati, L. F., Kitayama, I. T., Härfstrand, A., Andersson, K., & Goldstein, M. (1988) · Brain Research · doi:10.1016/0006-8993(88)90092-3 · Cited by 114 · see citing works
Kirch, D. G., Gerhardt, G. A., Shelton, R. C., Freedman, R., & Wyatt, R. J. (1987) · Clinical Neuropharmacology · doi:10.1097/00002826-198708000-00009 · Cited by 89 · see citing works
Effects of nicotine on biological systems
(1990) · Toxicology Letters · doi:10.1016/0378-4274(90)90259-o · Cited by 82 · see citing works
Singer, G., Wallace, M., & Hall, R. (1982) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(82)90321-5 · Cited by 79 · see citing works
Nicotine psychopharmacology; molecular, cellular and behavioural aspects
Wonnacott, S. (1991) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(91)90222-x · Cited by 68 · see citing works
Cardiovascular and subjective effects of smoking before and after 24 h of abstinence from cigarettes
West, R., & Russell, M. A. (1987) · Psychopharmacology · doi:10.1007/bf00215491 · Cited by 67 · see citing works
Benwell, M. E. M., Balfour, D. J. K., & Lucchi, H. M. (1993) · Psychopharmacology · doi:10.1007/bf02244896 · Cited by 66 · see citing works
Self-citationSeelye, E. E. (1991) · American Journal of Psychotherapy · doi:10.1176/appi.psychotherapy.1991.45.1.131 · Cited by 63 · see citing works
Fuxé, K., Andersson, K., H�rfstrand, A., et al. (1986) · Journal of Neural Transmission · doi:10.1007/bf01243356 · Cited by 51 · see citing works
Chronic and acute tolerance to subjective effects of nicotine
Perkins, K. A., Grobe, J. E., Epstein, L. H., Caggiula, A. R., Stiller, R. L., & Jacob, R. G. (1993) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(93)90254-q · Cited by 51 · see citing works
Fung, Y. K. (1989) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1989.tb06334.x · Cited by 35 · see citing works
Janson, A. M., Fuxé, K., Agnati, L. F., Jansson, A., Bjelke, B., Sundström, E., Andersson, K., Härfstrand, A., Goldstein, M., & Owmand, C. (1989) · Progress in brain research · doi:10.1016/s0079-6123(08)62485-1 · Cited by 33 · see citing works
Naoi, M., Nomura, Y., Ishiki, R., et al. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb13256.x · Cited by 25 · see citing works
Aversive environmental stimuli as a factor in the psychostimulant response to nicotine
Vale, A. L., & Balfour, D. J. K. (1989) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(89)90048-8 · Cited by 19 · see citing works
Self-citationStudies on the Role of Mesolimbic Dopamine in Behavioural Responses to Chronic Nicotine
Balfour, D. J. K., Benwell, M. E. M., & Vale, A. L. (1991) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-7457-1_54 · Cited by 8 · see citing works
Self-citationWarburton, D. M. (1991) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-7457-1_62 · Cited by 4 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- Balfour, D.J.K. pp. 453-481. Oxford, New York: Pergamon Press.
- Adlkofer, F. & Thurau, K. pp. 406-416. Basel: Birkhiuser.
- Wonnacott, S., Russell, M.A.H. & Stolerman, I.P. pp. 112-157. Oxford: Univ. Press.
- RANG, H. & DALE, M.M. (1992). In Pharmacology (2nd edition) pp. 142-181. Edinburgh, London: Churchill Livingston.
- Wonnacott, S., Russell, M.A.H. & Stolerman, I.P. pp. 374-418. Oxford: Univ. Press.
Cited by
Sorted by citations
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
Self-citationNicotine addiction and nicotinic receptors: lessons from genetically modified mice
Changeux, J.-P. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2849 · Cited by 453 · see citing works
Chronic Exposure to Nicotine Upregulates the Human α4β2 Nicotinic Acetylcholine Receptor Function
Buisson, B., & Bertrand, D. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-06-01819.2001 · Cited by 361 · see citing works
One Is Not Enough: Understanding and Modeling Polysubstance Use
Crummy, E. A., O’Neal, T. J., Baskin, B. M., & Ferguson, S. M. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00569 · Cited by 351 · see citing works
Govind, A. P., Vezina, P., & Green, W. N. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.06.011 · Cited by 338 · see citing works
Nicotinic acetylcholine receptors as targets for antidepressants
Shytle, R. D., Silver, A. A., Lukas, R. J., Newman, M. B., Sheehan, D. V., & Sanberg, P. R. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001035 · Cited by 279 · 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
Hatsukami, D. K., Stead, L. F., & Gupta, P. C. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60871-5 · Cited by 227 · see citing works
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
Nicotinic receptors in human brain: topography and pathology
Court, J. A., Martin-Ruiz, C., Graham, A., & Perry, E. (2000) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(00)00110-1 · Cited by 180 · see citing works
Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Korpi, E. R., den Hollander, B., Farooq, U., Vashchinkina, E., Rajkumar, R., Nutt, D. J., Hyytiä, P., & Dawe, G. S. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010967 · Cited by 148 · see citing works
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
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
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
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
Nguyen, H. N., Rasmussen, B. A., & Perry, D. C. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02482.x · Cited by 83 · 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
Chronic nicotine administration in the drinking water affects the striatal dopamine in mice
Pietilä, K., & Ahtee, L. (2000) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(00)00235-5 · Cited by 50 · see citing works
Hussmann, G. P., Turner, J. R., Lomazzo, E., Venkatesh, R., Cousins, V., Xiao, Y., Yasuda, R. P., Wolfe, B. B., Perry, D. C., Rezvani, A. H., et al. (2012) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.198085 · Cited by 34 · see citing works
- Authors
- Benwell, M. E. M., Balfour, D. J. K., & Birrell, C. E.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Benwell, Maureen E.M.
- ORCID
- Balfour, David J.K.
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 1995-01
- Volume
- 114
- Issue
- 2
- Pages
- 454-460
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1510263
- OpenAlex
- W2155263358
- Cited by
- 169
- References
- 32
- Citations by year
- 2025: 2 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 8 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotine, nicotinic receptor desensitization, mesolimbic dopamine system, nucleus accumbens, locomotor activity, nicotine sensitization, mecamylamine, hexamethonium, smoking
- MeSH terms
- Animals, Dopamine, Extracellular Space, Homovanillic Acid, Limbic System, Male, Mecamylamine, Motor Activity, Nicotine, 3,4-Dihydroxyphenylacetic Acid, Infusion Pumps, Implantable, Rats, Sprague-Dawley, Microdialysis, Hexamethonium, Rats
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