title: Insights About Striatal Circuit Function and Schizophrenia From a Mouse Model of Dopamine D2Receptor Upregulation.
abstract: The dopamine hypothesis of schizophrenia is supported by a large number of imaging studies that have identified an increase in dopamine binding at the D2receptor selectively in the striatum. We review a decade of work using a regionally restricted and temporally regulated transgenic mouse model to investigate the behavioral, molecular, electrophysiological, and anatomical consequences of selective D2receptor upregulation in the striatum. These studies have identified new and potentially important biomarkers at the circuit and molecular level that can now be explored in patients with schizophrenia. They provide an example of how animal models and their detailed level of neurobiological analysis allow a deepening of our understanding of the relationship between neuronal circuit function and symptoms of schizophrenia, and as a consequence generate new hypotheses that are testable in patients.
authors.affiliation: Departments of Psychiatry, Columbia University, New York, New York; Center for Neurobiology and Behavior, New York State Psychiatric Institute, New York, New York. Electronic address: Es534@columbia.edu.
authors.forename: Eleanor H
authors.initials: EH
authors.lastname: Simpson
authors.affiliation: Pharmacology, Columbia University, New York, New York; Division of Molecular Therapeutics (CK), New York State Psychiatric Institute, New York, New York.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kellendonk
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D015854:Up-Regulation
chemical_list: D017448:Receptors, Dopamine D2
keywords: D(2) receptor; Dopamine; Mouse model, Negative symptoms; Schizophrenia; Striatal circuit function