Binding and functional activity of nicotinic cholinergic receptors in selected rat brain regions are increased following long‐term but not short‐term nicotine treatment
Abstract
Chronic nicotine exposure up‐regulates neuronal nicotinic receptors, but the functional consequences for these receptors is less well understood. Following 2 weeks of nicotine or saline treatment by osmotic minipump, the functional activity of nicotinic receptors was measured by concentration–response curves for epibatidine‐stimulated 86 Rb efflux. Nicotine‐treated animals had a significantly higher maximal efflux in cerebral cortex and superior colliculus, but not in thalamus or interpeduncular nucleus plus medial habenula. This increase was confirmed in a separate experiment with stimulation by single concentrations of epibatidine (cortex, superior colliculus) or nicotine (cortex only). Chronic nicotine did not alter 86 Rb efflux stimulated by cytisine, an α3β4‐selective agonist, or by potassium chloride, in any region. Short‐term (16 h) nicotine exposure caused no changes in either 86 Rb efflux or receptor binding measured with [3 H]epibatidine. Binding was significantly increased after 2 weeks nicotine exposure in cortex, superior colliculus and thalamus, but not in interpeduncular nucleus plus medial habenula. The increases in epibatidine‐stimulated 86 Rb efflux in the four regions tested was linearly correlated with the increases in [3 H]epibatidine binding in these regions (R2 = 0.91), suggesting that rat brain receptors up‐regulated by chronic nicotine are active. These results have important consequences for understanding nicotinic receptor neurobiology in smokers and users of nicotine replacement therapy.
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The nAChRs upregulated by chronic nicotine are probably active rather than desensitized.
“that the upregulated receptors are probably active rather than desensitized (4,5);”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [4]
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- Authors
- Nguyen, H. N., Rasmussen, B. A., & Perry, D. C.
- Affiliations
- George Washington University (US)
- Corresponding author
- Perry, David C.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2004-05-25
- Volume
- 90
- Issue
- 1
- Pages
- 40-49
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1585413892
- Cited by
- 83
- References
- 47
- Citations by year
- 2023: 2 · 2021: 1 · 2019: 1 · 2018: 2 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 7
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 056920, R01DK056920)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- nicotinic acetylcholine receptors, chronic nicotine exposure, receptor up-regulation, epibatidine, 86Rb efflux, receptor binding, cerebral cortex, superior colliculus, thalamus, interpeduncular nucleus, medial habenula, alpha3beta4 nicotinic receptor, cytisine, nicotine replacement therapy, smoking
- MeSH terms
- Animals, Autoradiography, Binding, Competitive, Brain, Cotinine, Dose-Response Relationship, Drug, Ligands, Male, Nicotine, Protein Binding, Pyridines, Receptors, Nicotinic, Rubidium Radioisotopes, Time Factors, Up-Regulation, Infusion Pumps, Implantable, Rats, Sprague-Dawley, Nicotinic Agonists, Bridged Bicyclo Compounds, Heterocyclic, Rats
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