Nicotinic receptor subtypes and cognitive function
Open accessAbstract
Nicotinic receptor systems are involved in a wide variety of behavioral functions including cognitive function. Nicotinic medications may provide beneficial treatment for cognitive dysfunction such as Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Nicotine has been shown to improve attentional performance in all of these disorders. Better efficacy with fewer side effects might be achieved with novel nicotinic ligands selective for particular nicotinic subtypes. To develop these novel selective nicotinic ligands it is important to use animal models to determine the critical neurobehavioral bases for nicotinic involvement in cognitive function. Nicotine‐induced cognitive improvement in rats is most consistently seen in working memory tasks. We have found that both acute and chronic nicotine administration significantly improves working memory performance of rats in the radial‐arm maze. The pharmacologic and anatomic mechanisms for this effect have been examined in our laboratory in a series of local drug infusion studies. Both α4β2 and α7 nicotinic receptors in the ventral hippocampus and basolateral amygdala are involved in working memory function. Working memory impairments were caused by local infusion of either α4β2 or α7 antagonists. Ventral hippocampal α4β2 blockade‐induced working memory deficits are reversed by chronic systemic nicotine treatment, while ventral hippocampal α7 blockade‐induced working memory deficits were not found to be reversed by the same nicotine regimen. Interestingly, α4β2 and α7 induced deficits were not found to be additive in either the ventral hippocampus or the basolateral amygdala. In fact, in the amygdala, α7 antagonist cotreatment actually reversed the working memory impairment caused by α4β2 antagonist administration. These studies of the neural nicotinic mechanisms underlying cognitive function are key for opening avenues for development of safe and effective nicotinic treatments for cognitive dysfunction. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 633–640, 2002
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Lynx1 plays a critical role in maintaining a balance between the beneficial effects of short-term nAChR activation and the potentially devastating degenerative excitotoxic effects of chronic over-activation of nAChRs.
“We also conclude that lynx1 plays a critical role in maintaining a balance between the beneficial effects of short-term nAChR activation (117) and the potentially devastating degenerative excitotoxic effects of chronic over-activation of nAChRs (118,119).”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [117]
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- Authors
- Levin, E. D.
- Affiliations
- Duke University (US)
- Corresponding author
- Levin, Edward D.
- ORCID
- Levin, Edward D.
- Venue
- Journal of Neurobiology
- Publisher
- Wiley
- Published
- 2002-11-15
- Volume
- 53
- Issue
- 4
- Pages
- 633-640
- ISSN
- 0022-3034 (ISSN-L)
- 1097-4695
- OpenAlex
- W2025498694
- Cited by
- 354
- References
- 59
- Citations by year
- 2025: 6 · 2024: 8 · 2023: 5 · 2022: 11 · 2021: 6 · 2020: 7 · 2019: 8 · 2018: 8 · 2017: 1 · 2016: 10 · 2015: 15 · 2014: 18 · 2013: 16 · 2012: 27
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01da011943-03)
- National Institute of Mental Health (MH 64494, R01MH064494)
- National Institute on Drug Abuse (DA 11943)
- 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
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotinic acetylcholine receptors, nicotinic receptor subtypes, alpha4beta2 nicotinic receptor, alpha7 nicotinic acetylcholine receptor, working memory, nicotine, cognitive enhancement, ventral hippocampus, basolateral amygdala, nicotinic antagonists, Alzheimer's disease, schizophrenia, attention deficit hyperactivity disorder, radial maze
- MeSH terms
- Amygdala, Animals, Cognition, Hippocampus, Humans, Memory, Nicotine, Receptors, Nicotinic, Nicotinic Agonists, Nicotinic Antagonists, alpha7 Nicotinic Acetylcholine Receptor
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