Reward and Somatic Changes during Precipitated Nicotine Withdrawal in Rats: Centrally and Peripherally Mediated Effects
Abstract
The negative affective aspects of nicotine withdrawal have been hypothesized to contribute to tobacco dependence. In the present studies in rats, brain stimulation reward thresholds, conditioned place aversions, and somatic signs of withdrawal were used to investigate the role of central and peripheral nicotinic acetylcholine and opioid receptors in nicotine withdrawal. Rats prepared with s.c. osmotic mini-pumps delivering 9.0 mg/kg/day nicotine hydrogen tartrate or saline were administered various doses of the nicotinic antagonists mecamylamine (s.c.), chlorisondamine (s. c. or i.c.v.), dihydro-beta-erythroidine (s.c.), or the opiate antagonist naloxone (s.c.). Nicotine-treated rats receiving mecamylamine or i.c.v. chlorisondamine exhibited elevated thresholds and more somatic signs than saline-treated rats. Nicotine-treated rats receiving s.c. chlorisondamine, at doses that do not readily cross the blood-brain barrier, exhibited more somatic signs than saline-treated rats with no threshold elevations. Naloxone administration produced threshold elevations and somatic signs only at high doses that induced similar magnitude effects in both nicotine- and saline-treated subjects. Mecamylamine or dihydro-beta-erythroidine administration induced conditioned place aversions in nicotine-treated rats but required higher doses than those needed to precipitate threshold elevations. In contrast, naloxone administration induced conditioned place aversions at lower doses than those required to precipitate threshold elevations and somatic signs. These data provide evidence for a dissociation between centrally mediated elevations in reward thresholds and somatic signs that are both centrally and peripherally mediated. Furthermore, threshold elevations and somatic signs of withdrawal appear to be mediated by cholinergic neurotransmission, whereas conditioned place aversions appear to be primarily mediated by the opioid system.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Both spontaneous and mecamylamine-precipitated nicotine withdrawal increase self-stimulation thresholds.
“Both spontaneous (Epping-Jordan et al. 1998, Harrison et al. 2001) and mecamylamine-precipitated (Watkins et al. 2000) nicotine withdrawal induce increases in self-stimulation thresholds.”
From Reward, addiction, withdrawal to nicotine (2011) · cites this paper as Watkins et al. 2000
The citation lists haven’t been fetched yet
References 42 · Cited by 214
- Authors
- Watkins, S. S., Stinus, L., Koob, G. F., & Markou, A.
- Affiliations
- Scripps Research Institute (US)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2000-03
- Volume
- 292
- Issue
- 3
- Pages
- 1053-1064
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1933095040
- Cited by
- 214
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 6 · 2021: 7 · 2020: 3 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 9 · 2014: 6 · 2013: 7 · 2012: 8
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Institutes of Health (5f31da005898-02)
- National Institute on Drug Abuse (DA04398, DA05898, R01DA004398)
- 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 › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine withdrawal, nicotine reward, conditioned place aversion, somatic withdrawal signs, nicotinic acetylcholine receptors, opioid receptors, mecamylamine, chlorisondamine, dihydro-beta-erythroidine, naloxone, cholinergic neurotransmission, opioid system, tobacco dependence, blood-brain barrier
- MeSH terms
- Animals, Brain, Chlorisondamine, Injections, Intraventricular, Male, Mecamylamine, Naloxone, Nicotine, Receptors, Nicotinic, Reward, Substance Withdrawal Syndrome, Rats, Wistar, 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 ›
Are you an author, or do you see a problem with this page? Request a review
