Cited by 130Nicotinic Acetylcholine Receptors StudyNeurotransmitter Receptor Influence on BehaviorSmoking Behavior and Cessation

Cholinergic modulation of dopaminergic reward areas: upstream and downstream targets of nicotine addiction

Mansvelder, Huibert D., De Rover, Mischa, McGehee, Daniel S., Brussaard, Arjen B.·2003·European Journal of Pharmacology

Abstract

Nicotine reinforces smoking behaviour by activating nicotinic acetylcholine receptors in the midbrain dopaminergic reward centres. Upstream of the dopaminergic neurons nicotine induces long-term potentiation of the excitatory input to dopamine cells in the ventral tegmental area, and depresses inhibitory inputs. Both effects of nicotine were shown to last much longer than the nicotine exposure and together will activate the dopaminergic ventral tegmental area projection toward the nucleus accumbens. However, downstream of dopamine, effects of nicotine are also likely to occur. Cholinergic interneurons within the nucleus accumbens are important in the tonic control of the gamma-amino buteric acid (GABA) nucleus accumbens output neurons, which project back to the ventral tegmental area. The nicotinic acetylcholine receptors that mediate this control are likely to desensitise upon preexposure to the nicotine concentrations found in the blood of smokers. Thus, synaptic mechanisms both upstream and downstream of dopamine release are potentially important factors contributing to the etiology of nicotine addiction.

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Crossref · 10.1016/j.ejphar.2003.08.099

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Authors
Mansvelder, H. D., De Rover, M., McGehee, D. S., & Brussaard, A. B.
Affiliations
  • Vrije Universiteit Amsterdam (NL)
  • University of Chicago (US)
Corresponding author
Brussaard, Arjen B.
Venue
European Journal of Pharmacology
Publisher
Elsevier BV
Published
2003-11
Volume
480
Issue
1-3
Pages
117-123
ISSN
0014-2999 (ISSN-L)
OpenAlex
W2062697629
Cited by
130
References
46
Citations by year
2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 5 · 2018: 4 · 2016: 8 · 2015: 4 · 2014: 4 · 2013: 8 · 2012: 4
FWCI
0.65
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • VU Research Portal (publishedVersion)
  • Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
Keywords
nicotine dependence, nicotinic acetylcholine receptors, cholinergic modulation, dopaminergic reward, ventral tegmental area, nucleus accumbens, long-term potentiation, GABAergic interneurons, synaptic plasticity, smoking behavior
MeSH terms
Animals, Cholinergic Fibers, Dopamine, Humans, Interneurons, Nicotine, Receptors, Nicotinic, Reward, Substance-Related Disorders

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