PUBLICATION

Pharmacological profiling of zebrafish behavior using chemical and genetic classification of sleep-wake modifiers

Authors
Nishimura, Y., Okabe, S., Sasagawa, S., Murakami, S., Ashikawa, Y., Yuge, M., Kawaguchi, K., Kawase, R., Tanaka, T.
ID
ZDB-PUB-151119-3
Date
2015
Source
Frontiers in pharmacology   6: 257 (Journal)
Registered Authors
Tanaka, Toshio
Keywords
behavior, hypnotics, hypocretin, profiling, psychostimulants, zebrafish
MeSH Terms
none
PubMed
26578964 Full text @ Front Pharmacol
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes