Nicotine-induced upregulation of nicotinic receptors: Underlying mechanisms and relevance to nicotine addiction

Govind, Anitha P.; Vezina, Paul; Green, William N.

doi:10.1016/j.bcp.2009.06.011

Cited by 338Nicotinic Acetylcholine Receptors StudySmoking Behavior and CessationNeuroscience and Neuropharmacology Research

Nicotine-induced upregulation of nicotinic receptors: Underlying mechanisms and relevance to nicotine addiction

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Govind, Anitha P., Vezina, Paul, Green, William N.·2009·Biochemical Pharmacology

DOI 10.1016/j.bcp.2009.06.011PMC PMC2728164

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Abstract

A major hurdle in defining the molecular biology of nicotine addiction has been characterizing the different nicotinic acetylcholine receptor (nAChR) subtypes in the brain and how nicotine alters their function. Mounting evidence suggests that the addictive effects of nicotine, like other drugs of abuse, occur through interactions with its receptors in the mesolimbic dopamine system, particularly ventral tegmental area (VTA) neurons, where nicotinic receptors act to modulate the release of dopamine. The molecular identity of the nicotinic receptors responsible for drug seeking behavior, their cellular and subcellular location and the mechanisms by which these receptors initiate and maintain addiction are poorly defined. In this commentary, we review how nicotinic acetylcholine receptors (nAChRs) are upregulated by nicotine exposure, the potential posttranslational events that appear to cause it and how upregulation is linked to nicotine addiction.

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Multiple cellular processes influence nAChR upregulation.
“A variety of cellular processes influence receptor upregulation (Govind et al. 2009; Rezvani et al. 2009, 2010; Henderson et al. 2014).”
From Nicotine Withdrawal (2015) · cites this paper as Govind et al. 2009
Sensitization caused by repeated drug use has been observed with many drugs of abuse, including alcohol and nicotine.
“Sensitization caused by repeated drug use has been observed with many drugs of abuse, including alcohol and nicotine (Benwell & Balfour, 1992; Cadoni & Di Chiara, 2000; Govind, Vezina, & Green, 2009; Laviolette & van der Kooy, 2004).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Govind, Vezina, & Green, 2009

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Nicotine addiction
Benowitz, N. L. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0809890 · Cited by 1,508 · see citing works
Nicotine 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
Nicotine Withdrawal
McLaughlin, I., Dani, J. A., & De Biasi, M. (2015) · Current Topics in Behavioral Neurosciences · doi:10.1007/978-3-319-13482-6_4 · Cited by 173 · see citing works
“A variety of cellular processes influence receptor upregulation (Govind et al. 2009; Rezvani et al. 2009, 2010; Henderson et al. 2014).”
Background
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
Nicotine Addiction and Intensity of e-Cigarette Use by Adolescents in the US, 2014 to 2021
Glantz, S., Jeffers, A., & Winickoff, J. P. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.40671 · Cited by 117 · 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
Development of the motivational system during adolescence, and its sensitivity to disruption by nicotine
Counotte, D. S., Smit, A. B., Pattij, T., & Spijker, S. (2011) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2011.05.010 · Cited by 77 · see citing works
Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior
Hellberg, S. N., Russell, T. I., & Robinson, M. J. F. (2019) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/s13415-018-00662-3 · Cited by 65 · see citing works
Nicotine exposure during adolescence alters the rules for prefrontal cortical synaptic plasticity during adulthood
Goriounova, N. A., & Mansvelder, H. D. (2012) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2012.00003 · Cited by 65 · 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
A Comparative Study of the Effects of the Intravenous Self-Administration or Subcutaneous Minipump Infusion of Nicotine on the Expression of Brain Neuronal Nicotinic Receptor Subtypes
Moretti, M., Mugnaini, M., Tessari, M., Zoli, M., Gaimarri, A., Manfredi, I., Pistillo, F., Clementi, F., & Gotti, C. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.064071 · Cited by 58 · see citing works
Adolescent nicotine exposure transiently increases high-affinity nicotinic receptors and modulates inhibitory synaptic transmission in rat medial prefrontal cortex
Counotte, D. S., Goriounova, N. A., Moretti, M., Smoluch, M. T., Irth, H., Clementi, F., Schoffelmeer, A. N. M., Mansvelder, H. D., Smit, A. B., Gotti, C., et al. (2012) · The FASEB Journal · doi:10.1096/fj.11-198994 · Cited by 44 · see citing works
Intermittent nicotine exposure upregulates <scp>nAChR</scp>s in VTA dopamine neurons and sensitises locomotor responding to the drug
Baker, L. K., Mao, D., Chi, H., Govind, A. P., Vallejo, Y. F., Iacoviello, M., Herrera, S., Cortright, J. J., Green, W. N., McGehee, D. S., et al. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12114 · Cited by 39 · see citing works
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Nicotinic alteration of decision-making
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Authors: Govind, A. P., Vezina, P., & Green, W. N.
Affiliations: University of Chicago (US)
Corresponding author: Green, William N.
ORCID: Govind, Anitha P.
Green, William N.
Venue: Biochemical Pharmacology
Publisher: Elsevier BV
Published: 2009-10
Volume: 78
Issue: 7
Pages: 756-765
ISSN: 0006-2952 (ISSN-L)
DOI: 10.1016/j.bcp.2009.06.011
PMC: PMC2728164
OpenAlex: W1980253122
Cited by: 338
References: 157
Citations by year: 2026: 15 · 2025: 16 · 2024: 14 · 2023: 11 · 2022: 15 · 2021: 25 · 2020: 37 · 2019: 21 · 2018: 17 · 2017: 25 · 2016: 19 · 2015: 25 · 2014: 18 · 2013: 20 · 2012: 24
FWCI: 1.53
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biochemical Pharmacology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Drug Abuse (R01DA013602, DA-019695, P01DA019695)
National Institute of Neurological Disorders and Stroke (R56NS043782, NS 043782, R01NS043782)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: nicotinic acetylcholine receptors, nicotine, receptor up-regulation, nicotine dependence, ventral tegmental area, mesolimbic dopamine system, dopamine release, drug-seeking behavior, post-translational modification, receptor subtypes
MeSH terms: Action Potentials, Animals, Dopamine, Humans, Neurons, Nicotine, Nucleus Accumbens, Protein Conformation, Protein Processing, Post-Translational, Receptors, Nicotinic, Tobacco Use Disorder, Up-Regulation, Ventral Tegmental Area, Protein Subunits, Protein Transport

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Nicotine-induced upregulation of nicotinic receptors: Underlying mechanisms and relevance to nicotine addiction

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