Characterization of Nicotinic Receptor‐Mediated [3H]Dopamine Release from Synaptosomes Prepared from Mouse Striatum
Abstract
This study establishes that presynaptic nicotinic receptors modulate dopamine release in the mouse striatum. Nicotinic agonists elicit a dose-dependent increase in the release of [3H]dopamine from synaptosomes prepared from mouse striatum. At low concentrations, this release is Ca2+ dependent, whereas at higher concentrations Ca(2+)-independent, mecamylamine-insensitive release was also observed. The Ca(2+)-dependent nicotine-evoked release was not blocked by alpha-bungarotoxin but was effectively blocked by neuronal bungarotoxin as well as several other nicotinic receptor antagonists. The relationship between potency for stimulation of release for agonists and potency for inhibition of release for antagonists was compared to the affinity of these compounds for the [3H]nicotine binding site. The overall correlation between release and binding potency was not high, but the drugs may be classified into separate groups, each of which has a high correlation with binding. This finding suggests either that more than one nicotinic receptor regulates dopamine release or that not all agonists interact with the same receptor in an identical fashion.
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Lower doses of nicotine, consistent with those in the blood of human smokers, result in desensitization rather than activation of nAChRs as measured by nicotine-dependent dopamine release in striatal synaptosomes.
“Studies in striatal synaptosomes, however, show that lower doses of nicotine, consistent with those in the blood of human smokers, result in desensitization rather than activation of nAChRs as measured by nicotine-dependent dopamine release (Grady et al., 1992; Grady et al., 1994; Rowell and Duggan, 1998; Rowell and Hillebrand, 1994).”
From It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood (2008) · cites this paper as Grady et al., 1992
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- Authors
- Grady, S., Marks, M. J., Wonnacott, S., & Collins, A. C.
- Affiliations
- University of Colorado Boulder (US)
- University of Bath (GB)
- Corresponding author
- Collins, Allan C.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1992-09
- Volume
- 59
- Issue
- 3
- Pages
- 848-856
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2005274709
- Cited by
- 350
- References
- 1
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 2 · 2015: 9 · 2014: 5 · 2013: 4 · 2012: 2
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (DA 03194, R01DA003194, DA00116)
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotinic acetylcholine receptors, presynaptic dopamine release, striatum, synaptosomes, calcium-dependent release, mecamylamine, alpha-bungarotoxin, nicotinic antagonists, nicotinic agonists, receptor heterogeneity
- MeSH terms
- Animals, Corpus Striatum, Dopamine, Dose-Response Relationship, Drug, Female, Ganglionic Stimulants, Mice, Inbred C57BL, Nicotine, Osmolar Concentration, Receptors, Nicotinic, Synaptosomes, Tritium, Mice
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