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Withdrawal from Chronic Nicotine Administration Impairs Contextual Fear Conditioning in C57BL/6 Mice
Open accessAbstract
The effects of acute nicotine administration (0.09 mg/kg nicotine), chronic nicotine administration (6.3 mg/kg/d nicotine for 14 d), and withdrawal from chronic nicotine administration on fear conditioning in C57BL/6 mice were examined. Mice were trained using two coterminating conditioned stimulus (30 s; 85 dB white noise)–unconditioned stimulus (2 s; 0.57 mA foot shock) pairings and tested 24 h later for contextual and cued fear conditioning. Acute nicotine administration enhanced contextual fear conditioning, chronic nicotine administration had no effect on contextual fear conditioning, and withdrawal from chronic nicotine administration impaired contextual fear conditioning. Plasma nicotine concentrations were similar after acute and chronic treatment and were within the range reported for smokers. During withdrawal, concentrations of nicotine were undetectable. An acute dose of nicotine (0.09 mg/kg) during withdrawal from chronic nicotine treatment reversed withdrawal-associated deficits in contextual fear conditioning. The results suggest that tolerance to the effects of nicotine on contextual fear conditioning develops with chronic nicotine treatment at a physiologically relevant dose, and withdrawal from this chronic nicotine treatment is associated with impairments in contextual fear conditioning. These findings provide a model of how the effects of nicotine on learning may contribute to the development and maintenance of nicotine addiction.
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“Contextual FC is dependent upon hippocampal signaling (Davis et al. 2005)”
From Nicotine Withdrawal (2015) · cites this paper as Davis et al. 2005
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“Administration of nicotine to mice undergoing withdrawal ameliorates this deficit (Davis et al. 2005).”
From Nicotine Withdrawal (2015) · cites this paper as Davis et al. 2005
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“and during spontaneous withdrawal from nicotine, mice exhibit deficient contextual FC relative to saline-treated controls (Davis et al. 2005).”
From Nicotine Withdrawal (2015) · cites this paper as Davis et al. 2005
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“This effect was not attributable simply to a lowered threshold of fear responses inherent to the effects of nicotine because cued FC was equivalent between nicotine-treated and nicotine-naïve groups.”
From Nicotine Withdrawal (2015) · cites this paper as Davis et al. 2005
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“It has been shown that nicotine, varenicline, and bupropion ameliorate nicotine withdrawal-associated deficits in hippocampus-dependent learning (Davis et al., 2005; Portugal and Gould, 2007; Raybuck et al., 2008).”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Davis et al., 2005
In the citing paper
“Withdrawal from chronic nicotine disrupts contextual learning in mice and this deficit is mediated by direct effects of nicotine in the hippocampus.”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Davis et al., 2005
In the citing paper
“The dose of nicotine was chosen based on our prior research demonstrating that it produced withdrawal deficits in contextual fear conditioning (André et al., 2008; Davis and Gould, 2007b) with plasma nicotine levels of approximately 13.00 ng/ml (Davis et al., 2005), which is within the range seen in smokers (Henningfield and Keenan, 1993).”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Davis et al., 2005
In the citing paper
“acute nicotine ameliorates withdrawal-related deficits in hippocampus-dependent learning (Davis et al., 2005).”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Davis et al., 2005
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Metadata
- Authors
- Davis, J. A., James, J. R., Siegel, S. J., & Gould, T. J.
- Affiliations
- Temple University (US)
- Virginia Commonwealth University (US)
- University of Pennsylvania (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-09-21
- Volume
- 25
- Issue
- 38
- Pages
- 8708-8713
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2697573
- OpenAlex
- W2088102722
- Cited by
- 146
- References
- 45
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 15 · 2015: 14 · 2014: 17 · 2013: 8 · 2012: 8
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pennsylvania Department of Health
- Temple University
- National Institutes of Health (DA017949)
- U.S. Public Health Service (P5084718)
- National Institute on Drug Abuse (DA017949, R01DA017949, T32DA 07237, P5084718, T32DA007237)
- National Cancer Institute (P5084718)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Keywords
- nicotine, nicotine withdrawal, contextual fear conditioning, cued fear conditioning, chronic nicotine administration, acute nicotine administration, tolerance (pharmacology and immunology), nicotine dependence, C57BL/6 mice, plasma nicotine concentration, learning deficits
- MeSH terms
- Animals, Conditioning, Psychological, Fear, Male, Mice, Inbred C57BL, Nicotine, Substance Withdrawal Syndrome, Mice
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