ArticleAnesthesiology2019
Drug-selective Anesthetic Insensitivity of Zebrafish Lacking γ-Aminobutyric Acid Type A Receptor β3 Subunits.
Article in Anesthesiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Glabridin Hypnosis in Zebrafish Larvae Is Associated With Effects on Multiple Anesthetic Target Receptors.Anesthesia and analgesia · 2025Article
- The Serotonergic Dorsal Raphe Promotes Emergence from Propofol Anesthesia in Zebrafish.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Systematized Serendipity: Fishing Expeditions for Anesthetic Drugs and Targets.Anesthesiology · 2024Review
- Antagonism of propofol anesthesia by alkyl-fluorobenzene derivatives.Scientific reports · 2024Article
- The role of anesthesia in peri‑operative neurocognitive disorders: Molecular mechanisms and preventive strategies.Fundamental research · 2024Review
- Comparison of Behavioral Effects of GABAergic Low- and High-Efficacy Neuroactive Steroids in the Zebrafish Larvae Assay.ACS chemical neuroscience · 2024Article
- Antagonism of Propofol Anesthesia by Alkyl-fluorobenzene Derivatives.Research square · 2024Article
- Substituted Cysteine Modification and Protection with n-Alkyl-MTS Reagents Quantifies Steric Changes Induced by a Mutation in Anesthetic Binding Sites on GABA Type A Receptors.Molecular pharmacology · 2023Article
- Article
- Photomotor Responses in Zebrafish and Electrophysiology Reveal Varying Interactions of Anesthetics Targeting Distinct Sites on γ-Aminobutyric Acid Type A Receptors.Anesthesiology · 2022Article
- Article
- Zebrafish Is a Powerful Tool for Precision Medicine Approaches to Neurological Disorders.Frontiers in molecular neuroscience · 2022Review
- Characterization of zebrafish GABAScientific reports · 2021Article
- Respiratory depression and analgesia by opioid drugs in freely behaving larval zebrafish.eLife · 2021Article
- A vertebrate model to reveal neural substrates underlying the transitions between conscious and unconscious states.Scientific reports · 2020Article
- A Guide to Understanding "State-of-the-Art" Basic Research Techniques in Anesthesiology.Anesthesia and analgesia · 2020Review
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Authors and funding
7 authors at 1 institution in 4 countries.
Funding
Abstract
backgroundTransgenic mouse studies suggest that γ-aminobutyric acid type A (GABAA) receptors containing β3 subunits mediate important effects of etomidate, propofol, and pentobarbital. Zebrafish, recently introduced for rapid discovery and characterization of sedative-hypnotics, could also accelerate pharmacogenetic studies if their transgenic phenotypes reflect those of mammals. The authors hypothesized that, relative to wild-type, GABAA-β3 functional knock-out (β3) zebrafish would show anesthetic sensitivity changes similar to those of β3 mice.
methodsClustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 mutagenesis was used to create a β3 zebrafish line. Wild-type and β3 zebrafish were compared for fertility, growth, and craniofacial development. Sedative and hypnotic effects of etomidate, propofol, pentobarbital, alphaxalone, ketamine, tricaine, dexmedetomidine, butanol, and ethanol, along with overall activity and thigmotaxis were quantified in 7-day postfertilization larvae using video motion analysis of up to 96 animals simultaneously.
resultsXenopus oocyte electrophysiology showed that the wild-type zebrafish β3 gene encodes ion channels activated by propofol and etomidate, while the β3 zebrafish transgene does not. Compared to wild-type, β3 zebrafish showed similar morphology and growth, but more rapid swimming. Hypnotic EC50s (mean [95% CI]) were significantly higher for β3 versus wild-type larvae with etomidate (1.3 [1.0 to 1.6] vs. 0.6 [0.5 to 0.7] µM; P < 0.0001), propofol (1.1 [1.0 to 1.4] vs. 0.7 [0.6 to 0.8] µM; P = 0.0005), and pentobarbital (220 [190 to 240] vs. 130 [94 to 179] μM; P = 0.0009), but lower with ethanol (150 [106 to 213] vs. 380 [340 to 420] mM; P < 0.0001) and equivalent with other tested drugs. Comparing β3 versus wild-type sedative EC50s revealed a pattern similar to hypnosis.
conclusionsGlobal β3 zebrafish are selectively insensitive to the same few sedative-hypnotics previously reported in β3 transgenic mice, indicating phylogenetic conservation of β3-containing GABAA receptors as anesthetic targets. Transgenic zebrafish are potentially valuable models for sedative-hypnotic mechanisms research.
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