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

frontiers
Pharmacological profiling of zebrafish behavior using chemical and genetic classification of sleep-wake modifiers
Yuhei Nishimura, Shiko Okabe, Shota Sasagawa, Soichiro Murakami, Yoshifumi Ashikawa, Mizuki Yuge, Koki Kawaguchi, Reiko Kawase, Toshio Tanaka

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. Towards 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.