Dissociation of the apparent relationship between nicotine tolerance and up-regulation of nicotinic receptors
Abstract
Saline or nicotine (0.8 mg/kg/hr) was administered chronically to rats via subcutaneous infusion for 7 days. After chronic treatment, the effects of a challenge dose of nicotine, injected subcutaneously, on open-field activity and body temperature were measured. Nicotine responses were measured 2 hours after infusion had been stopped (day 0) or 1, 2, 4, 8, or 21 days after cessation of treatment. Brain nicotinic receptors were measured using nicotine binding or bungarotoxin binding in six brain regions. Tolerance to nicotine's effects on open-field activity and body temperature were observed; this tolerance was lost before the fourth day of withdrawal. Both nicotine and BTX binding were increased after chronic nicotine treatment. The return of the receptors to control values was dependent on brain region, but in general receptors were still increased at 4 days after withdrawal. The half-lives for receptors returning to normal were greater for nicotine binding compared to BTX binding. These results suggest that a relatively short-lived tolerance results from chronic nicotine infusion and that alterations in nicotinic receptors can be dissociated from behavioral tolerance.
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Preclinical studies have demonstrated that nAChR levels return to control levels after termination of nicotine exposure, but with great variability in the time course.
“Preclinical studies have demonstrated that nAChR levels return to control levels after termination of nicotine exposure, but with great variability in the time course15-17.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [16]
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- Authors
- Collins, A. C., Romm, E., & Wehner, J. M.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Collins, Allan C.
- Venue
- Brain Research Bulletin
- Publisher
- Elsevier BV
- Published
- 1990-09
- Volume
- 25
- Issue
- 3
- Pages
- 373-379
- ISSN
- 0361-9230 (ISSN-L)
- OpenAlex
- W2024560338
- Cited by
- 79
- References
- 3
- Citations by year
- 2025: 1 · 2023: 1 · 2018: 1 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 2
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut de Recherche pour le Développement
- National Institutes of Health (5p50da005131-06)
- National Institute on Drug Abuse (DA05131, DA 03194, R01DA003194, DA00116)
- 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
- nicotine tolerance, nicotinic acetylcholine receptors, receptor up-regulation, nicotine withdrawal, bungarotoxin binding, nicotine binding, open field behavior, body temperature, receptor desensitization, receptor half-life
- MeSH terms
- Animals, Body Temperature, Bungarotoxins, Drug Tolerance, Female, Half-Life, Infusions, Intravenous, Iodine Radioisotopes, Kinetics, Motor Activity, Nicotine, Proteins, Rats, Inbred Strains, Receptors, Nicotinic, Substance Withdrawal Syndrome, Up-Regulation, Rats
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