PUBLICATION
Improvement of pentylenetetrazol-induced learning deficits by valproic acid in the adult zebrafish
- Authors
- Lee, Y., Kim, D., Kim, Y.H., Lee, H., and Lee, C.J.
- ID
- ZDB-PUB-100719-7
- Date
- 2010
- Source
- European Journal of Pharmacology 643(2-3): 225-231 (Journal)
- Registered Authors
- Keywords
- Danio rerio, Seizure, Pentylenetetrazol, Valproic acid, Avoidance learning
- MeSH Terms
-
- Animals
- Anticonvulsants/administration & dosage
- Anticonvulsants/therapeutic use*
- Avoidance Learning/drug effects
- Behavior, Animal/drug effects
- Brain/metabolism
- Dose-Response Relationship, Drug
- Drug Evaluation, Preclinical/methods
- Dyskinesia, Drug-Induced/prevention & control
- Gene Expression Regulation/drug effects
- HSP70 Heat-Shock Proteins/genetics
- HSP70 Heat-Shock Proteins/metabolism
- Learning Disabilities/chemically induced
- Learning Disabilities/prevention & control*
- Locomotion/drug effects
- Muscarinic Antagonists/toxicity
- Neuroprotective Agents/administration & dosage
- Neuroprotective Agents/therapeutic use*
- Pentylenetetrazole/toxicity*
- RNA, Messenger/metabolism
- Scopolamine/toxicity
- Seizures/chemically induced
- Seizures/prevention & control
- Time Factors
- Valproic Acid/administration & dosage
- Valproic Acid/therapeutic use*
- Zebrafish
- PubMed
- 20599908 Full text @ Eur. J. Pharmacol.
- CTD
- 20599908
Citation
Lee, Y., Kim, D., Kim, Y.H., Lee, H., and Lee, C.J. (2010) Improvement of pentylenetetrazol-induced learning deficits by valproic acid in the adult zebrafish. European Journal of Pharmacology. 643(2-3):225-231.
Abstract
Pentylenetetrazol (PTZ) has been shown to induce seizure-like behavior, learning deficits in passive avoidance response test, and an increase in hsp70 (heat shock protein 70) mRNA expression in the adult zebrafish; PTZ has been increasingly appreciated as an excellent model system for the study of seizures. In this study, we demonstrate that valproic acid (VPA), an antiepileptic drug, suppresses seizure-like behavior and improves learning ability in adult zebrafish treated with PTZ. Pretreatment with VPA significantly reduces rapid involuntary movement and abrupt changes in moving direction in the PTZ-treated zebrafish. PTZ-induced learning impairments were also improved in the zebrafish pretreated with 200 or 500muM VPA. However, the scopolamine-induced impairments of learning ability were not improved by VPA pretreatment. It is worth noting that while the zebrafish treated with 500muM VPA for 1-3weeks learned the passive avoidance response, those treated with 1 or 2mM VPA for 3h didn't. Furthermore, the increased level of hsp70 expression induced by PTZ, a stress marker protein, was significantly reduced in the VPA-pretreated zebrafish brains. Collectively, our data show the antiepileptic effects of VPA in the adult zebrafish, which coincides with reduced hsp70 mRNA expression, rescued learning impairment under PTZ-treated conditions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping