PUBLICATION
Determination of narcotic potency using a neurobehavioral assay with larval zebrafish
- Authors
- Broening, H.W., La Du, J., Carr, G.J., Nash, J.F., Truong, L., Tanguay, R.L.
- ID
- ZDB-PUB-190516-6
- Date
- 2019
- Source
- Neurotoxicology 74: 67-73 (Journal)
- Registered Authors
- La Du, Jane K., Tanguay, Robyn L.
- Keywords
- alcohols, ethanol, etomidate, locomotor activity, narcosis, neurobehavioral effects, surfactants, toxicity, zebrafish
- MeSH Terms
-
- Alcohols/chemistry
- Alcohols/toxicity
- Anesthetics, Intravenous/toxicity
- Animals
- Behavior, Animal/drug effects*
- Embryonic Development/drug effects
- Etomidate/toxicity
- Larva/drug effects*
- Motor Activity/drug effects
- Narcotics/pharmacology*
- Narcotics/toxicity
- Photic Stimulation
- Solvents/toxicity
- Structure-Activity Relationship
- Surface-Active Agents/toxicity
- Zebrafish*
- PubMed
- 31085211 Full text @ Neurotoxicology
Citation
Broening, H.W., La Du, J., Carr, G.J., Nash, J.F., Truong, L., Tanguay, R.L. (2019) Determination of narcotic potency using a neurobehavioral assay with larval zebrafish. Neurotoxicology. 74:67-73.
Abstract
Background Identifying chemicals with narcotic potency is an important aspect of assessing the safety of consumer products that may be accidentally ingested. A rapid and efficient assay of narcotic potency is desired for assessing chemicals with such suspected activity.
Objectives This purpose of this research was to develop a non-mammalian vertebrate, high throughput, neurobehavioral method to assess the narcotic potency of chemicals using larval zebrafish.
Methods Larval zebrafish were acutely exposed to chemicals beginning at 5 days post fertilization (5 dpf). Locomotor activity, elicited by regular, periodic photostimulation, was quantified using a video tracking apparatus. Narcotic potency was determined as the molar concentration at which photostimulated locomotor activity was reduced by 50% (IC50). Toxicity was assessed based on observations of morbidity or mortality. Recovery was assessed following removal of test material by serial dilution and reassessment of photostimulated behavior 24 hr later (6 dpf).
Results A total of 21 chemicals were assessed. Etomidate, a human narcotic analgesic agent, was used as a reference material. Investigating a series of eleven linear, primary alcohols (C6 to C16), a relationship between narcotic potency and carbon number was observed; narcotic potency increased with carbon number up to C12, consistent with historical studies. For a set of technical grade surfactants, nonionic surfactants (i.e., alcohol ethoxylates) were observed to be narcotic agents while anionic surfactants produced evidence of reduced locomotor activity only in combination with toxicity. Of the solvents evaluated, only ethanol exhibited narcotic activity with an IC50 of 261 mM and was the least potent of the chemicals investigated. Etomidate was the most potent material evaluated with an IC50 of 0.39 µM.
Conclusions The larval zebrafish neurobehavioral assay provides a method capable of estimating the narcotic potency of chemicals and can identify if toxicity contributes to observed neurobehavioral effects in the test organism.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping