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

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
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1016/s0166-4328(00)00202-3

Cites

82 of 82 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

  • Both bupropion and nicotine increase catecholamine concentrations in midbrain limbic regions.

    “both increase catecholamine concentrations in midbrain limbic regions [214, 227].”

    From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [227]

Cites

Flagged first, then by citations

1 of the 83 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

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 › Physiology › 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

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