Cited by 231Neurotransmitter Receptor Influence on BehaviorNicotinic Acetylcholine Receptors StudySmoking Behavior and Cessation

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The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of nicotine dependence

Balfour, David J.K, Wright, Adèle E, Benwell, Maureen E.M, Birrell, Claire E·2000·Behavioural Brain Research

DOI 10.1016/s0166-4328(00)00202-3

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Abstract

A majority of habitual tobacco smokers find it very difficult to quit the habit because they become addicted to the nicotine present in tobacco smoke. Nicotine, like other psychostimulant drugs of abuse, increases dopamine release in the principal terminal field of the mesolimbic system, the nucleus accumbens, and there is evidence that this mediates the 'rewarding' properties of the drug, which reinforce its self-administration. This review focuses on the working hypothesis that addiction to nicotine, and other psychostimulant drugs, depends upon their ability to evoke a sustained increase in dopamine release directly into the extracellular space which lies between the cells in the nucleus accumbens where it stimulates extra-synaptic dopamine receptors. It is suggested that increased stimulation of these receptors is associated with increased incentive learning or the attribution of increased incentive salience to the cues associated with acquisition and delivery of the drug. The hypothesis proposes that these cues can become conditioned reinforcers of drug-taking behaviour. The receptors, which mediate the effects of nicotine on mesoaccumbens dopamine neurones, are desensitised by sustained exposure to nicotine at concentrations commonly found in the plasma of habitual smokers. It is proposed that, at times when the plasma nicotine concentration is sufficiently high to cause desensitisation of the receptors, tobacco smoking is maintained by the conditioned reinforcers present in the tobacco smoke. The hypothesis predicts, therefore, that conditioned reinforcement may play a more important role in the addiction to tobacco than for most other addictive behaviours. As a result, studies with nicotine have the potential to contribute to our understanding of the neurobiology of addiction which cannot easily be explored using drugs, such as cocaine and amphetamine, which invariably increase dopamine overflow in the forebrain.

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Authors: Balfour, D. J. K., Wright, A. E., Benwell, M. E. M., & Birrell, C. E.
Affiliations: University of Dundee (GB)
Corresponding author: Balfour, David J.K
ORCID: Balfour, David J.K
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2000-08
Volume: 113
Issue: 1-2
Pages: 73-83
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/s0166-4328(00)00202-3
OpenAlex: W2081491792
Cited by: 231
References: 83
Citations by year: 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 10 · 2015: 3 · 2014: 7 · 2013: 10 · 2012: 10
FWCI: 5.52
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Behavioural Brain Research (publishedVersion)
PubMed (publishedVersion)
Funders: Stiftung VERUM
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 › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
Keywords: nicotine dependence, mesolimbic dopamine system, nucleus accumbens, dopamine release, incentive salience, incentive learning, conditioned reinforcement, receptor desensitization, stimulant use disorder, smoking, self-administration
MeSH terms: Animals, Conditioning, Classical, Dopamine, Extracellular Space, Humans, Limbic System, Mesencephalon, Motivation, Synaptic Transmission, Nucleus Accumbens, Tobacco Use Disorder

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The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of nicotine dependence

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