Improvement of pentylenetetrazol-induced learning deficits by valproic acid in the adult zebrafish.
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.
Lee
Yunkyoung
Y
Department of Biological Sciences, Institute of Molecular and Cellular Biology, Inha University, Incheon, Republic of Korea.
Kim
Dohee
D
Kim
Yeon-Hwa
YH
Lee
Hansol
H
Lee
Chang-Joong
CJ
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004409:Dyskinesia, Drug-Induced / Q000517:prevention & control; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007859:Learning Disabilities / Q000139:chemically induced / Q000517:prevention & control*; D008124:Locomotion / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000633:toxicity; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D010433:Pentylenetetrazole / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D012601:Scopolamine / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013997:Time Factors; D014635:Valproic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D015027:Zebrafish
D000927:Anticonvulsants; D018840:HSP70 Heat-Shock Proteins; D018727:Muscarinic Antagonists; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D014635:Valproic Acid; D012601:Scopolamine; D010433:Pentylenetetrazole