PUBLICATION
The opioid antagonist naltrexone decreases seizure-like activity in genetic and chemically induced epilepsy models
- Authors
- Sturgeon, M.L., Langton, R., Sharma, S., Cornell, R.A., Glykys, J., Bassuk, A.G.
- ID
- ZDB-PUB-211022-32
- Date
- 2021
- Source
- Epilepsia open 6: 528-538 (Journal)
- Registered Authors
- Cornell, Robert
- Keywords
- scn1Lab, Zebrafish, drug repurpose, mice, naltrexone, pentylenetetrazole
- MeSH Terms
-
- Animals
- Epilepsy*
- Humans
- Mice
- Naltrexone*/adverse effects
- Narcotic Antagonists/adverse effects
- Seizures/chemically induced
- Seizures/drug therapy
- Seizures/genetics
- Zebrafish
- PubMed
- 34664432 Full text @ Epilepsia Open
Citation
Sturgeon, M.L., Langton, R., Sharma, S., Cornell, R.A., Glykys, J., Bassuk, A.G. (2021) The opioid antagonist naltrexone decreases seizure-like activity in genetic and chemically induced epilepsy models. Epilepsia open. 6:528-538.
Abstract
Objective A significant number of epileptic patients fail to respond to available anticonvulsive medications. To find new anticonvulsive medications, we evaluated FDA-approved drugs not known to be anticonvulsants. Using zebrafish larvae as an initial model system, we found that the opioid antagonist naltrexone exhibited an anticonvulsant effect. We validated this effect in three other epilepsy models and present naltrexone as a promising anticonvulsive candidate.
Methods Candidate anticonvulsant drugs, determined by our prior transcriptomics analysis of hippocampal tissue, were evaluated in a larval zebrafish model of human Dravet syndrome (scn1Lab mutants), in wild-type zebrafish larvae treated with the pro-convulsant drug pentylenetetrazole (PTZ), in wild-type C57bl/6J acute brain slices exposed to PTZ, and in wild-type mice treated with PTZ in vivo. Abnormal locomotion was determined behaviorally in zebrafish and mice and by field potential in neocortex layer IV/V and CA1 stratum pyramidale in the hippocampus.
Results The opioid antagonist naltrexone decreased abnormal locomotion in the larval zebrafish model of human Dravet syndrome (scn1Lab mutants) and wild-type larvae treated with the pro-convulsant drug PTZ. Naltrexone also decreased seizure-like events in acute brain slices of wild-type mice, and the duration and number of seizures in adult mice injected with PTZ.
Significance Our data reveal that naltrexone has anticonvulsive properties and is a candidate drug for seizure treatment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping