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Neuroadaptive changes in the mesoaccumbens dopamine system after chronic nicotine self-administration: A microdialysis study
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 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]
In the citing paper
“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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Metadata
- 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)
- 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
- 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 › Public Health, Environmental and Occupational Health › 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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