Zebrafish Sleep Disorders Assays

Sleep disturbances can be caused by a variety of drugs, including beta-blockers, benzodiazepines, opioids, and amphetamines. Understanding the nature and severity of sleep disturbances is necessary to assess drug safety, and sleep deprivation is detrimental to human health and can lead to diabetes, hormone deficiencies, and neurological disorders. In any case, it is important to understand the effects on sleep early in the developmental process.

Like humans, zebrafish are diurnal, showing peak activity during the light phase and more calm during the dark phase. Zebrafish have been shown to exhibit sleep-characterized behaviors, including quiescence regulated by circadian rhythms, reduced sensory responsiveness, and homeostatic regulation. In zebrafish and humans, melatonin produced by the pineal organ regulates the circadian regulation of sleep, downstream of the light-carried circadian clock. Furthermore, clinically used hypnotics and stimulants have similar effects on the sleep/wake cycle in zebrafish as in humans. Multiple studies have now demonstrated that zebrafish larvae can be successfully used to identify the effects of known target drugs on sleep/wake behavior, suggesting that this system could be used in preclinical screening to identify potential sleep-disrupting effects of new drugs.

Fig. 1 Characterization of Rest in Zebrafish as a Sleep-Like State.

Our Zebrafish Sleep Disorders Assays

Our behavioral analysis of zebrafish can be used to assess the effects of pharmaceutical and genetic interventions on sleep-wake states, and in addition, fine-grained analysis of motor behavior allows us to tease out the relatively subtle effects of compounds on sleep/wake behavior. We used automated rest/wake behavioral assays to monitor activity in zebrafish treated with small molecules, and behavioral analysis revealed conserved functions of psychotropic molecules and predicted mechanisms of action of poorly characterized compounds. In addition, our behavioral analysis of zebrafish can also be used to classify neuroactive compounds according to their mechanism of action, using the zebrafish response to light motion for high-throughput screening of compounds.

Our Advantages

• Motor activity-based sleep/wake behavior can be easily determined in a high-throughput manner
• Allows non-invasive observation of toxicity and possible recovery
• Rapid identification of toxic drug candidates, uncovering conserved functions of psychotropic molecules and predicting mechanisms of action of poorly characterized compounds

Contact us to learn more about our zebrafish sleep disorders assays services. 

References

1. Yokogawa T, et al. Characterization of sleep in zebrafish and insomnia in hypocretin receptor mutants. PLoS Biol. 2007, 5(10):e277.
2. Rihel J, et al. Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation. Science. 2010, 327(5963):348-351.
3. Nishimura Y, et al. Pharmacological profiling of zebrafish behavior using chemical and genetic classification of sleep-wake modifiers. Front Pharmacol. 2015, 6:257.
4. Cassar S, et al. Use of Zebrafish in Drug Discovery Toxicology. Chem Res Toxicol. 2020, 33(1):95-118.
5. Prober DA, et al. Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. J Neurosci. 2006, 26:13400-13410.

For research use only. Not intended for any clinical use.