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The Journal of Neuroscience, September 1, 2000, 20(17):6431-6441
Phenotypic Characterization of an
4 Neuronal Nicotinic Acetylcholine Receptor Subunit Knock-Out Mouse
Shelley A. Ross1, John Y. F. Wong1, Jeremiah J. Clifford3, Anthony Kinsella4, Jim S. Massalas1, Malcolm K. Horne1, Ingrid E. Scheffer1, 5, Ismail Kola2, John L. Waddington3, Samuel F. Berkovic5, and John Drago1 1 Neurosciences Group, Monash University Department of Medicine and 2 Institute of Reproduction and Development, Monash Medical Centre, Clayton, Victoria, 3168, Australia, 3 Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin 2, Ireland, 4 Department of Mathematics, Dublin Institute of Technology, Dublin 8, Ireland, and 5 Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria, 3084, Australia
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
4 nAChR 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
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Copyright © 2000 Society for Neuroscience 0270-6474/00/20176431-11$05.00/0
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