Zebrafish: A Pharmacogenetic Model for Anesthesia

• Published in: Methods in enzymology Vol. 602; p. 189
• Main Authors: Bedell, Victoria, Buglo, Elena, Marcato, Daniel, Pylatiuk, Christian, Mikut, Ralf, Stegmaier, Johannes, Scudder, Will, Wray, Maxwell, Züchner, Stephan, Strähle, Uwe, Peravali, Ravindra, Dallman, Julia E
• Format: Journal Article
• Language: English
• Published: United States 2018
• Subjects: Anesthesia - adverse effects; Anesthesia - methods; Anesthetics - administration & dosage; Anesthetics - adverse effects; Anesthetics - pharmacokinetics; Animals; Animals, Genetically Modified - genetics; Behavior, Animal - drug effects; Biotransformation - genetics; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Discovery - methods; Gene Editing - methods; Gene Knockdown Techniques - instrumentation; Gene Knockdown Techniques - methods; High-Throughput Screening Assays - instrumentation; High-Throughput Screening Assays - methods; Humans; Mutation; Pharmacogenetics - methods; Pharmacogenomic Variants - genetics; Propofol - administration & dosage; Propofol - adverse effects; Propofol - pharmacokinetics; Zebrafish - genetics; Zebrafish Proteins - genetics; Anesthesia; Zebrafish; Genome editing; Behavior; Propofol
• ISSN: 1557-7988
• DOI: 10.1016/bs.mie.2018.02.004

General anesthetics are small molecules that interact with and effect the function of many different proteins to promote loss of consciousness, amnesia, and sometimes, analgesia. Owing to the complexity of this state transition and the transient nature of these drug/protein interactions, anesthetics can be difficult to study. The zebrafish is an emerging model for the discovery of both new genes required for the response to and side effects of anesthesia. Here we discuss the tools available to manipulate the zebrafish genome, including both genetic screens and genome engineering approaches. Additionally, there are various robust behavior assays available to study anesthetic and other drug responses. These assays are available for single-gene study or high throughput for genetic or drug discovery. Finally, we present a case study of using propofol as an anesthetic in the zebrafish. These techniques and protocols make the zebrafish a powerful model to study anesthetic mechanisms and drug discovery.