Modulation of Hippocampus-Dependent Learning and Synaptic Plasticity by Nicotine
Open accessAbstract
A long-standing relationship between nicotinic acetylcholine receptors (nAChRs) and cognition exists. Drugs that act at nAChRs can have cognitive-enhancing effects and diseases that disrupt cognition such as Alzheimer's disease and schizophrenia are associated with altered nAChR function. Specifically, hippocampus-dependent learning is particularly sensitive to the effects of nicotine. However, the effects of nicotine on hippocampus-dependent learning vary not only with the doses of nicotine used and whether nicotine is administered acutely, chronically, or withdrawn after chronic nicotine treatment but also vary across different hippocampus-dependent tasks such as the Morris water maze, the radial arm maze, and contextual fear conditioning. In addition, nicotine has variable effects across different types of hippocampal long-term potentiation (LTP). Because different types of hippocampus-dependent learning and LTP involve different neural and molecular substrates, comparing the effects of nicotine across these paradigms can yield insights into the mechanisms that may underlie the effects of nicotine on learning and memory and aid in understanding the variable effects of nicotine on cognitive processes. This review compares and contrasts the effects of nicotine on hippocampus-dependent learning and LTP and briefly discusses how the effects of nicotine on learning could contribute to nicotine addiction.
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Craving and cognitive impairments are reliable markers of nicotine withdrawal.
“Although craving and cognitive impairments are reliable markers of nicotine withdrawal (Kenney and Gould, 2008; Levin et al, 2006; McClernon et al, 2004; Rezvani and Levin, 2001), anxiety has been shown to impact relapse rate as well (Dani and Harris, 2005; DiMatteo et al, 2000).”
From Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal (2013) · cites this paper as Kenney and Gould, 2008
This hyperexcitability may underlie many of the nicotine withdrawal symptoms.
“This hyperexcitability may underlie many of the nicotine withdrawal symptoms (Kenney et al, 2008).”
From Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal (2013) · cites this paper as Kenney et al, 2008
The C57BL/6J mouse strain performs well in fear conditioning and is sensitive to nicotine effects on learning.
“This strain was chosen because it performs well in fear conditioning (Owen et al., 1997) and is sensitive to the effects of nicotine on learning (Kenney and Gould, 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 Kenney and Gould, 2008
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Self-citationNicotine enhances both foreground and background contextual fear conditioning
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Alzheimer's disease amyloid β-protein and synaptic function
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Nicotine modulation of fear memories and anxiety: Implications for learning and anxiety disorders
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Self-citationNicotinic mechanisms influencing synaptic plasticity in the hippocampus
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“the effects of nicotine on learning (Kenney and Gould, 2008).”
Self-citationNicotinic receptor activation in perirhinal cortex and hippocampus enhances object memory in rats
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Nicotine and extinction of fear conditioning
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Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal
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Self-citationAdolescent nicotine exposure disrupts context conditioning in adulthood in rats
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Nakauchi, S., Malvaez, M., Su, H., Kleeman, E., Dang, R., Wood, M. A., & Sumikawa, K. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2014.12.007 · Cited by 27 · see citing works
Stojanovic, T., Velarde Gamez, D., Schuld, G. J., Bormann, D., Cabatic, M., Uhrin, P., Lubec, G., & Monje, F. J. (2022) · Cells · doi:10.3390/cells11020261 · Cited by 8 · see citing works
- Authors
- Kenney, J. W., & Gould, T. J.
- Affiliations
- Temple University (US)
- Corresponding author
- Gould, Thomas J.
- Venue
- Molecular Neurobiology
- Published
- 2008-08
- Volume
- 38
- Issue
- 1
- Pages
- 101-121
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- PMC
- PMC2683366
- OpenAlex
- W2130009335
- Cited by
- 242
- References
- 230
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 10 · 2022: 5 · 2021: 12 · 2020: 11 · 2019: 6 · 2018: 9 · 2017: 9 · 2016: 24 · 2015: 15 · 2014: 34 · 2013: 21 · 2012: 23
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA015515, R03AA015515)
- National Institute on Drug Abuse (DA017949, R01DA017949, DA 07237, T32DA007237)
- 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 › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- nicotine, nicotinic acetylcholine receptors, hippocampus-dependent learning, synaptic plasticity, long-term potentiation, learning and memory, nicotine withdrawal, cognitive enhancement, nicotine dependence, Alzheimer's disease, schizophrenia, contextual fear conditioning, Morris water maze, radial maze
- MeSH terms
- Animals, Hippocampus, Humans, Learning, Memory, Neuronal Plasticity, Nicotine, Receptors, Nicotinic, Long-Term Potentiation, Substance-Related Disorders
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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.
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