Validation of the Zebrafish Pentylenetetrazol Seizure Model: Locomotor versus Electrographic Responses to Antiepileptic Drugs
| Autor: | Camila V. Esguerra, Alexander D. Crawford, Ralph Clinckers, Tatiana Afrikanova, Ann-Sophie K. Serruys, Ilse Julia Smolders, Peter de Witte, Olivia Erin M Buenafe |
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| Přispěvatelé: | Pharmaceutical Chemistry, Drug Analysis and Drug Information |
| Rok vydání: | 2013 |
| Předmět: |
Central Nervous System
Drugs and Devices Drug Research and Development Science medicine.medical_treatment Neurophysiology Biology Pharmacology Behavioral Neuroscience Epilepsy Model Organisms Neuropharmacology Seizures In vivo medicine Animals Pentylenetetrazol Zebrafish Multidisciplinary GABAA receptor fungi Antagonist Animal Models medicine.disease biology.organism_classification Anticonvulsant Neurology Behavioral Pharmacology Toxicity Pentylenetetrazole Medicine Anticonvulsants Locomotion Research Article Neuroscience medicine.drug |
| Zdroj: | PLoS ONE, Vol 8, Iss 1, p e54166 (2013) PLoS ONE Vrije Universiteit Brussel |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0054166 |
| Popis: | Zebrafish have recently emerged as an attractive in vivo model for epilepsy. Seven-day-old zebrafish larvae exposed to the GABAA antagonist pentylenetetrazol (PTZ) exhibit increased locomotor activity, seizure-like behavior, and epileptiform electrographic activity. A previous study showed that 12 out of 13 antiepileptic drugs (AEDs) suppressed PTZ-mediated increases in larval movement, indicating the potential utility of zebrafish as a high-throughput in vivo model for AED discovery. However, a question remained as to whether an AED-induced decrease in locomotion is truly indicative of anticonvulsant activity, as some drugs may impair larval movement through other mechanisms such as general toxicity or sedation. We therefore carried out a study in PTZ-treated zebrafish larvae, to directly compare the ability of AEDs to inhibit seizure-like behavioral manifestations with their capacity to suppress epileptiform electrographic activity. We re-tested the 13 AEDs of which 12 were previously reported to inhibit convulsions in the larval movement tracking assay, administering concentrations that did not, on their own, impair locomotion. In parallel, we carried out open-field recordings on larval brains after treatment with each AED. For the majority of AEDs we obtained the same response in both the behavioral and electrographic assays. Overall our data correlate well with those reported in the literature for acute rodent PTZ tests, indicating that the larval zebrafish brain is more discriminatory than previously thought in its response to AEDs with different modes of action. Our results underscore the validity of using the zebrafish larval locomotor assay as a rapid firstpass screening tool in assessing the anticonvulsant and/or proconvulsant activity of compounds, but also highlight the importance of performing adequate validation when using in vivo models. ispartof: PLoS One vol:8 issue:1 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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