Presynaptic nicotinic receptors modulating dopamine release in the rat striatum
Abstract
The modulation of striatal dopamine release by presynaptic nicotinic acetylcholine receptors is well documented for both synaptosomes and slices. Because the latter retain local anatomical integrity, we have compared [3H]dopamine release evoked by the nicotinic receptor agonists (-)-nicotine and (+/-)-anatoxin-a from striatal synaptosome and slice preparations in parallel. At higher agonist concentrations, mecamylamine-sensitive [3H]dopamine release was greater from slices, indicative of an additional component, and this increase was abolished by glutamate receptor antagonists. To begin to examine the localisation of specific nicotinic acetylcholine receptor subtypes in the striatum, immunogold electron microscopy was undertaken with the beta2-specific monoclonal antibody 270. In striatal sections, gold particles were associated with symmetric synapses (dopaminergic) but were absent from asymmetric synapses (glutamatergic). Surface labelling of striatal synaptosomes with gold particles was also demonstrated. Taken together, these results are consistent with dopamine release mediated by beta2-containing nicotinic acetylcholine receptors on dopamine terminals, while non-beta2-containing nicotinic acetylcholine receptors may enhance dopamine release indirectly by releasing glutamate from neighbouring terminals.
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Nicotine has a cascading effect on central neurotransmission resulting in the release of norepinephrine, histamine, GABA and glutamate.
“In addition, nicotine has a cascading effect on central neurotransmission also resulting in the release of norepinephrine and histamine as well as GABA and glutamate (28, 29).”
From The detrimental effects of smoking on the course and outcome in adults with bipolar disorder—A narrative review (2023) · cites this paper as [29]
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- Authors
- Wonnacott, S., Kaiser, S., Mogg, A., Soliakov, L., & Jones, I. W.
- Affiliations
- University of Bath (GB)
- Corresponding author
- Wonnacott, Susan
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2000-03
- Volume
- 393
- Issue
- 1-3
- Pages
- 51-58
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2023915778
- Cited by
- 232
- References
- 36
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 9 · 2021: 3 · 2020: 7 · 2019: 6 · 2018: 18 · 2017: 3 · 2016: 5 · 2015: 7 · 2014: 8 · 2013: 6 · 2012: 8
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Oxford
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- presynaptic nicotinic acetylcholine receptors, dopamine release, striatum, anatoxin-a, mecamylamine, synaptosomes, brain slices, glutamate release, glutamate receptor antagonists, dopaminergic terminals, immunogold electron microscopy, nicotinic receptor subtypes
- MeSH terms
- Animals, Corpus Striatum, Dopamine, Immunohistochemistry, Male, Receptors, Nicotinic, Synaptosomes, Tritium, Rats, Sprague-Dawley, Receptors, Presynaptic, Nicotinic Agonists, Rats, In Vitro Techniques
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