欠神発作モデルマウスにおける核内転写調節因子の挙動とGABA<SUB>B</SUB>受容体拮抗薬の抗てんかん作用

• 伊藤 芳久

  日本大学薬学部薬理学教室

• 石毛 久美子

  日本大学薬学部薬理学教室

• 愛澤 昌宏

  日本大学薬学部薬理学教室

• 福田 英臣

  日本大学薬学部薬理学教室

書誌事項

タイトル別名

• Induction of transcription factors and antiepileptic effect of GABA<SUB>B</SUB> anatagonists in absence seizure model mice

抄録

Pharmacological profiles of generalized absence-like seizures in animal models were studied. Selective GABA_B antagonists, CGP 35348 and CGP 46381, suppressed absence seizure behavior and spike and wave discharges (SWD_s) in lethargic (1h/1h) and γ-butyrolactone (GBL)-treated mice but not in stargazer (stg/stg) mice. Administration of GBL increased nuclear CRE- and AP-1 DNA-binding activities in mouse whole brain. CGP 35348 suppressed the increases in DNA-binding activities. It has been shown that the cortical and thalamic circuitry plays an important role in the genesis and spreading of absence seizures. Gel-shift assays in various brain regions revealed that administration of GBL increased nuclear CRE- and AP-1 DNA-binding activities significantly in the thalamus + midbrain and cerebral cortex but not in the hippocampus, cerebellum or pons-medulla. The region-specific increases in nuclear DNA-binding activities were also suppressed by CGP 35348. These results suggest that GABA_B receptors play a significant role in generalized absence seizures in lethargic and GBL-treated mice and that the increases in nuclear CRE- and AP-1 DNA-binding activities are correlated with the GBL-induced absence seizures. It is also suggested that different mechanisms are involved in absence seizures in stargazer mice.

収録刊行物

• 日本薬理学雑誌

  日本薬理学雑誌 106 (supplement), 172-176, 1995

  公益社団法人 日本薬理学会

キーワード

• Pharmacology

詳細情報

• CRID: 1390282679247488384
• NII論文ID: 10008631422
• NII書誌ID: AN00198335
• DOI: 10.1254/fpj.106.supplement_172
• ISSN: 13478397
• ISSN: 00155691
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可