title: Pharmacological profiling of zebrafish behavior using chemical and genetic classification of sleep-wake modifiers.
abstract: Sleep-wake states are impaired in various neurological disorders. Impairment of sleep-wake states can be an early condition that exacerbates these disorders. Therefore, treating sleep-wake dysfunction may prevent or slow the development of these diseases. Although many gene products are likely to be involved in the sleep-wake disturbance, hypnotics and psychostimulants clinically used are limited in terms of their mode of action and are not without side effects. Therefore, there is a growing demand for developing new hypnotics and psychostimulants with high efficacy and few side effects. Toward this end, animal models are indispensable for use in genetic and chemical screens to identify sleep-wake modifiers. As a proof-of-concept study, we performed behavioral profiling of zebrafish treated with chemical and genetic sleep-wake modifiers. We were able to demonstrate that behavioral profiling of zebrafish treated with hypnotics or psychostimulants from 9 to 10 days post-fertilization was sufficient to identify drugs with specific modes of action. We were also able to identify behavioral endpoints distinguishing GABA-A modulators and hypocretin (hcrt) receptor antagonists and between sympathomimetic and non-sympathomimetic psychostimulants. This behavioral profiling can serve to identify genes related to sleep-wake disturbance associated with various neuropsychiatric diseases and novel therapeutic compounds for insomnia and excessive daytime sleep with fewer adverse side effects.
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan ; Mie University Medical Zebrafish Research Center Tsu, Japan ; Department of Systems Pharmacology, Mie University Graduate School of Medicine Tsu, Japan ; Department of Omics Medicine, Mie University Industrial Technology Innovation Institute Tsu, Japan ; Department of Bioinformatics, Mie University Life Science Research Center Tsu, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Shiko
authors.initials: S
authors.lastname: Okabe
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Sasagawa
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Murakami
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ashikawa
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Yuge
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kawase
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan ; Mie University Medical Zebrafish Research Center Tsu, Japan ; Department of Systems Pharmacology, Mie University Graduate School of Medicine Tsu, Japan ; Department of Omics Medicine, Mie University Industrial Technology Innovation Institute Tsu, Japan ; Department of Bioinformatics, Mie University Life Science Research Center Tsu, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
keywords: behavior; hypnotics; hypocretin; profiling; psychostimulants; zebrafish