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Preclinical studies on the therapy of epilepsy and epileptic psychosis.

Research Project

Project/Area Number 08671125
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionNational Institute of Neuroscience

Principal Investigator

MINABE Yoshio  Chief, National Institute of Neuroscience, NCNP, 精神研究所第7部, 室長 (60181947)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsEpilepsy / Excitatory Amino Acids / Heat Shock Protain / Hippocampus / Dopamine / Serotonin / Neuropeptides / Sigma receptor
Research Abstract

1. Using an animal model of partial hippocampal seizure, we investigated the effects of verious drogs on seizure parameters. AMPA receptor antagonists showed a similar profile with carbamazepine by increasing the seizure threshold. NMDA receptor antagonists also increased the seizure threshold and GABA agonists decreased the duration of seizure. K^+-channel openers showed a similar profile with Ca^<++>-channel blockers by decreasing the seizure duration. Antisense c-fos ODN also decreased the seizure duration.
2. Heat shock protain (HSP) was introduced by only 10-min duration seizure after the application of adenosin I receptor antagonist plus electrical stimulation into the hippocampus. The epileptic status by kainic acid i.p.introduced HSP,BDNF and COX-2 mRNA expression.
3. The expression of HSP protain, but not of necrotic change in the rat cortex caused by NMDA receptor antagonists was blocked by AMPA receptor antagonists, muscarinic receptor antagonists and cAMP phosphodiesterase inhibitors.
4. Using the in vivo extracellular single-unit recording technipue, we examined the effect of various drugs on the spontaneously active dopamine cells of A9, A10 area. Serotonin Ia agonists or IIa, IIc antagonists showed a similar profile with antipsychotics. Sigma receptor agonists showed a similar profile with antidepressants. During the withdrawal period after cocaine or MDMA chronic injection, dopamine cell function of A10 area was suppressed.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Minabe Y., et al.: "Acute effect of c-fos antisense cligodeoxynucleotide on hippocampal partial seizures elicited by electrical stimulation in rats." Neuroscience Letters. 225. 149-152 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minabe Y., et al.: "Rolipram,a selective phosphodiesterase type-4 inhibitor,prevents induction of heat shock protein HSP-70 and hsp-70 mRNA in rat retrosplenial cortex by NMDA receptor antagonist dizoclpine." European Journal of Neuroscience. 9. 1891-1901 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minabe Y., et al.: "The acute effects of various GABA receptor agonists and glutamate receptor antagonists on focal hippocampal seizures in freely moving rats elicited by low-frequency stimulation." Synapse. 28. 103-109 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minabe Y., et al.: "The depletion of brain serotonin levels by PCPA administration significantly alters the actigity of midbrain dopamine cells in rats:An extracellular single cell recording study." Synapse. 22. 46-53 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minabe Y., et al.: "Anti-and Pro-convulsive actions of levcromakalim.an opner of ATP-sensitive K channel,in the model of hippocampus-generating partial seizures in rats." European Journal of Pharmacology. 311. 37-44 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minabe Y., et al.: "Memantine induces heat shock protein HSP70 in the posterior cingulate cortex,retrosplenial cortex and dentate gyrus of rat brain." Brain Research. 746. 1-5 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minabe Y., et al.: "Acute effect of c-fos antisense oligodeoxynucleotide on hippocampal partial seizures elictited by electrical stimulation in rats." Neuroscience Letters. 225. 149-152 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minabe Y., et al.: "Rolipram, a selective phosphodiesterase type-4 inhibitor, prevents induction of heat shock protein HSP-70 and hsp-70 mRNA in rat retrosplenial cortex by NMDA receptor antagonist dizocilpine." European Journal of Neuroscience. 9. 1891-1901 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minabe Y., et al.: "The acute effects of various GABA receptor agonists and glutamate receptor antagonists on focal hippocampal seizures in freely moving rats elicited by low-frequency stimulation" Synapse. 28. 103-109 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minabe Y., et al.: "The depletion of brain serotonin levels by PCPA administration significantly alters the activity of midbrain dopamine cells in rats : An extracellular single cell recording" Synapse. 22. 46-53 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minabe Y., et al.: "Anti-and Pro-convulsive actions of levcromakalim, an opener of ATP-sensitive K channel, in the model of hippocampus-generating partial seizures in rats" European Journal of Pharmacology. 311. 37-44 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minabe Y., et al.: "Memantine induces heat shock protein HSP70 in the posterior cinulate cortex, retrosplenial cortex and dentate gyrus of rat brain" Brain Research. 746. 1-5 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minabe Y.,et al.: "The effect of acute and chronic administration of the selective neurokinin2 receptor antagonist SR48968 on midbrain dopamine neurons in the rat:an in Vivo extracellular single cell study." Synapse. 25. 196-204 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Minabe Y.,et al.: "YM90K,a selective a-amino-3-hydroxy-5methy-4isoxazole propinate(AMPA)receptor antagonist,preven induction of heat shock protein HSP-70 and hsp-70 mRNA in rat retrosplenial cortex by phencyclidine." Addiction Biology. 2. 47-56 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Minabe Y.,et al.: "Acute effect of c-fos antisense oligodexynucleotide on hippocampal partial seizures elicited by electrical stimulation in rats." Neuroscience Letters. 225. 149-152 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Minabe Y.,et al.: "Ragionally different effects of scopolamine on NMDA antagonist-induced heat shock protein HSP70." Brain Research. 763. 255-258 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Minabe Y.,et al.: "Rolipram,a selective phosphodiesterase type-4 inhibitor,prevents induction of heat shock protein HSP-70 and hsp-70 mRNA in rat retrosplenial cortex by NMDA receptor antagonist dizocilpine." European Journal of Neuroscience. 9. 1891-1901 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Minabe Y.,et al.: "The acute effects of various GABA receptor agonists and glutamate receptor antagonists on focal hippocampal seizures in freely moving rats elicited by low-frequency stimulation." Synapse. 28. 103-109 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Minabe Y.: "The effect of acute and chronic administration of on midbrain dopamine neurons" Synapse. 22. 35-45 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Minabe Y.: "The depletion of brain serotonin levels by PCPA significantly alters the activity of midbrain dopamine cells" Synapse. 22. 46-53 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hashimoto K.: "Induction of HSP-70 in posterior cingulate and retrosplenial cortex by dizocilpine and phencyclidne" Addiction Biology. 1. 61-70 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hashimoto K.: "Induction of HSP-70 in rat retrosplenial cortex following administration of dextromethorphan" Environmental Toxicology and pharmacology. 1. 235-239 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Katzumori H.: "Anti and proconvulsive actions of levcromakalim in the model of hippocampus generating seizures" European J.pharmacology. 311. 37-44 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tomitaka S.: "Memantine induces HSP70 in the posterior cingulate cortex of rat brain" Brain Research. 740. 1-5 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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