1. Improvement of pentylenetetrazol-induced learning deficits by valproic acid in the adult zebrafish.
- Author
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Lee Y, Kim D, Kim YH, Lee H, and Lee CJ
- Subjects
- Animals, Anticonvulsants administration & dosage, 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, Locomotion drug effects, Muscarinic Antagonists toxicity, Neuroprotective Agents administration & dosage, RNA, Messenger metabolism, Scopolamine toxicity, Seizures chemically induced, Seizures prevention & control, Time Factors, Valproic Acid administration & dosage, Zebrafish, Anticonvulsants therapeutic use, Learning Disabilities prevention & control, Neuroprotective Agents therapeutic use, Pentylenetetrazole toxicity, Valproic Acid therapeutic use
- 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 500 microM 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 500 microM VPA for 1-3 weeks 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., (2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
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