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Cited by 110Neurotransmitter Receptor Influence on BehaviorNicotinic Acetylcholine Receptors StudySmoking Behavior and Cessation

Neuroadaptive changes in the mesoaccumbens dopamine system after chronic nicotine self-administration: a microdialysis study

Rahman, S., Zhang, J., Engleman, E.A., Corrigall, W.A.·2004·Neuroscience
DOI 10.1016/j.neuroscience.2004.08.010
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Abstract

There is little evidence to date to indicate if mesoaccumbens dopamine function at the neurochemical level is altered during early abstinence from chronic i.v. nicotine self-administration. Thus, a quantitative microdialysis (no-net-flux) approach was used to measure basal extracellular concentrations and extraction fractions of dopamine in the nucleus accumbens (ACB) of rats that self-administered nicotine i.v. for 25 days, as well as in rats serving as yoked comparison groups (yoked nicotine and yoked saline). After 24-48 h of the final self-administration session, there was a significant reduction in basal extracellular dopamine levels in the ACB of the self-administration group compared with the yoked saline group (1.35+/-0.15 nM versus 3.70+/-0.28 nM). The basal extracellular dopamine levels in the yoked nicotine group (1.46+/-0.20 nM) were not significantly different compared with the nicotine self-administration group. The in vivo extraction fraction of dopamine, an indirect measure of dopamine uptake, was significantly increased in the nicotine self-administration (86%) and yoked nicotine (91%) groups compared with the yoked saline group (77%). In addition, a marked reduction in the elevation of extracellular dopamine levels in the ACB occurred after a nicotine challenge as measured by conventional microdialysis in the self-administration (112% of basal) and yoked nicotine (121% of basal) groups as compared with a yoked saline (154% of basal) group. The reduced basal ACB dopamine levels in the nicotine groups during early abstinence appears to be due to increased clearance, suggesting increased dopamine uptake is occurring as a result of the chronic nicotine treatment. The reduced elevation of extracellular dopamine levels in the ACB upon nicotine challenge suggests a functional desensitization or downregulation phenomenon involving acetylcholine receptors (nicotinic nAChRs). Overall, these results provide clear evidence for a neuroadaptive change that alters dopamine transmission in the ACB during abstinence from chronic i.v. nicotine exposure.

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  • The hypodopaminergic state during withdrawal is produced by reduced DA release and increased DA re-uptake due to DAT upregulation.

    “The hypodopaminergic state associated with withdrawal is produced by both a reduction in DA release and an increase in DA re-uptake [140]. Increased DA re-uptake is due to upregulation of the DA transporter (DAT) [137, 141].”

    From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [137]

  • Acute withdrawal from major drugs of abuse including nicotine decreases mesolimbic DAergic activity.

    “Acute withdrawal from all major drugs of abuse, including nicotine, decreases activity of the mesolimbic DAergic system, [135–139]”

    From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [137]

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Authors
Rahman, S., Zhang, J., Engleman, E. A., & Corrigall, W. A.
Affiliations
  • Centre for Addiction and Mental Health (CA)
  • Indiana University Indianapolis (US)
Corresponding author
Rahman, S.
ORCID
Rahman, S.
Venue
Neuroscience
Publisher
Elsevier BV
Published
2004-01
Volume
129
Issue
2
Pages
415-424
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2004.08.010
OpenAlex
W2033657283
Cited by
110
References
64
Citations by year
2025: 1 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 2 · 2018: 3 · 2017: 1 · 2016: 5 · 2015: 6 · 2014: 11 · 2013: 5 · 2012: 10
FWCI
2.11
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01da009577-06)
  • National Institute on Drug Abuse (DA 09577)
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 self-administration, nicotine abstinence, nucleus accumbens, extracellular dopamine, dopamine uptake, extraction fraction, acetylcholine receptor, nicotinic receptor desensitization, neural adaptation, chronic nicotine exposure
MeSH terms
Adaptation, Physiological, Animals, Chromatography, High Pressure Liquid, Conditioning, Operant, Dopamine, Extracellular Space, Infusions, Intravenous, Male, Synaptic Transmission, Nicotine, Nucleus Accumbens, Self Administration, Substance Withdrawal Syndrome, Microdialysis, Nicotinic Agonists, Rats, Long-Evans, Rats

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