Presynaptic Nicotinic Modulation of Dopamine Release in the Three Ascending Pathways Studied by In Vivo Microdialysis: Comparison of Naive and Chronic Nicotine‐Treated Rats
Abstract
Abstract: The modulation of dopamine release by presynaptic nicotinic receptors in vitro is well established, but the significance of this effect in vivo is unclear. We have characterised the effect of nicotine, locally applied via a microdialysis probe, on dopamine release from the terminal regions of three ascending dopaminergic pathways in conscious, freely moving rats. Nicotine caused a dose‐dependent increase in dopamine release in the striatum, the nucleus accumbens, and, to a lesser extent, the frontal cortex. Metabolite levels were unaltered by any concentration of nicotine. Prior administration of mecamylamine via the probe abolished the nicotine‐evoked increase in dopamine release, confirming the mediation of nicotinic receptors. The dose dependence of mecamylamine‐sensitive, nicotine‐evoked dopamine release was similar in all three brain regions. However, 10−5M tetrodotoxin totally blocked nicotine‐stimulated dopamine release in the striatum and the accumbens but not the cortex. Daily subcutaneous injections of nicotine (0.4 mg kg−1 for 7 days) increased the response to a subsequent local application of nicotine in the striatum, and a similar trend was found in the other brain areas. The same daily dose of nicotine given as a continuous infusion had no effect, whereas infusion of 4 mg kg−1 day−1 increased the response to a subsequent nicotine challenge. The localisation and regulation of nicotinic receptors in the terminal fields of dopaminergic pathways are discussed.
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These effects on dopaminergic terminals extend and confirm other reports that chronic nicotine increases nicotine-induced dopamine release and upregulates receptors in striatum.
“These effects on dopaminergic terminals extend and confirm other reports that chronic nicotine increases nicotine-induced dopamine release (25,26) and upregulates receptors in striatum (5).”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [25]
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- Authors
- Marshall, D. L., Redfern, P. H., & Wonnacott, S.
- Affiliations
- University of Bath (GB)
- Corresponding author
- Wonnacott, Susan
- ORCID
- Wonnacott, Susan
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1997-04
- Volume
- 68
- Issue
- 4
- Pages
- 1511-1519
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2090796082
- Cited by
- 284
- References
- 0
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 7 · 2018: 8 · 2017: 1 · 2016: 7 · 2015: 9 · 2014: 3 · 2013: 13 · 2012: 10
- FWCI
- 5.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- presynaptic nicotinic acetylcholine receptors, dopamine release, nicotine, striatum, nucleus accumbens, frontal cortex, mecamylamine, tetrodotoxin, chronic nicotine treatment, nicotine tolerance, dopamine metabolites, in vivo microdialysis
- MeSH terms
- Animals, Dopamine, Male, Mecamylamine, Neurons, Nicotine, Tetrodotoxin, Time Factors, Rats, Sprague-Dawley, Microdialysis, Presynaptic Terminals, Nicotinic Agonists, Nicotinic Antagonists, Rats
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 ›
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