Phenotypic Characterization of an α4 Neuronal Nicotinic Acetylcholine Receptor Subunit Knock-Out Mouse
Open accessAbstract
Neuronal nicotinic acetylcholine receptors (nAChR) are present in high abundance in the nervous system (Decker et al., 1995). There are a large number of subunits expressed in the brain that combine to form multimeric functional receptors. We have generated an α4nAChR subunit knock-out line and focus on defining the behavioral role of this receptor subunit. Homozygous mutant mice (Mt) are normal in size, fertility, and home-cage behavior. Spontaneous unconditioned motor behavior revealed an ethogram characterized by significant increases in several topographies of exploratory behavior in Mt relative to wild-type mice (Wt) over the course of habituation to a novel environment. Furthermore, the behavior of Mt in the elevated plus-maze assay was consistent with increased basal levels of anxiety. In response to nicotine, Wt exhibited early reductions in a number of behavioral topographies, under both unhabituated and habituated conditions; conversely, heightened levels of behavioral topographies in Mt were reduced by nicotine in the late phase of the unhabituated condition. Ligand autoradiography confirmed the lack of high-affinity binding to radiolabeled nicotine, cytisine, and epibatidine in the thalamus, cortex, and caudate putamen, although binding to a number of discrete nuclei remained. The study confirms the pivotal role played by the α4 nAChR subunit in the modulation of a number of constituents of the normal mouse ethogram and in anxiety as assessed using the plus-maze. Furthermore, the response of Mt to nicotine administration suggests that persistent nicotine binding sites in the habenulo-interpeduncular system are sufficient to modulate motor activity in actively exploring mice.
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α4 knockout mice showed increased anxiety in the elevated plus maze.
“α4 KO mice showed increased anxiety in the same paradigm (Labarca et al., 2001; Ross et al., 2000).”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Ross et al., 2000
Alterations in the activation of the a4 nAChR subunit result in heightened anxiety.
“For example, alterations in the activation of the a4 nAChR subunit result in heightened anxiety (Ross et al., 2000;Labarca et al., 2001).”
From Activation of α4β2*/α6β2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors (2014) · cites this paper as Ross et al., 2000
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- Authors
- Ross, S. A., Wong, J. Y. F., Clifford, J. J., Kinsella, A., Massalas, J. S., Horne, M. K., Scheffer, I. E., Kola, I., Waddington, J. L., Berkovic, S. F., & Drago, J.
- Affiliations
- Monash University (AU)
- Royal College of Surgeons in Ireland (IE)
- Dublin Institute of Technology (IE)
- The University of Melbourne (AU)
- Monash Medical Centre (AU)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-09-01
- Volume
- 20
- Issue
- 17
- Pages
- 6431-6441
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W4320577279
- Cited by
- 204
- References
- 42
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 7 · 2016: 9 · 2015: 13 · 2014: 6 · 2013: 7 · 2012: 5
- FWCI
- 5.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Funders
- Brain Research Foundation
- Royal College of Surgeons in Ireland
- Epilepsy Society of Australia
- Higher Education Authority
- Monash University
- Epilepsy Society
- Medical Research Council
- National Health and Medical Research Council
- 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
- anxiety, nicotine, ethogram, exploratory behavior, elevated plus maze, thalamus, caudate-putamen
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