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Histamine and learning-memory and convulsion

Research Project

Project/Area Number 05454663
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTohoku University Medical School

Principal Investigator

WATANABE Takehiko  Tohoku Univ.Pharmacology Prof, 医学部, 教授 (70028356)

Co-Investigator(Kenkyū-buntansha) OHTSU Hiroshi  Tohoku Univ.Pharmacology Assoc.Prof., 医学部, 助手 (60250742)
YANAI Kazuhiko  Tohoku Univ.Pharmacology Assoc.Prof., 医学部, 講師 (50192787)
ONODERA Kinji  Tohoku Univ.Pharmacology Assoc.Prof., 歯学部, 講師 (40133988)
MAEYAMA Kazutaka  Ehime Univ.Pharmacology Prof., 医学部, 教授 (00157158)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1994: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1993: ¥5,000,000 (Direct Cost: ¥5,000,000)
KeywordsHistamine / Learning-Memory / Convulsion / PET / Aging
Research Abstract

Our major findings of the studies are as follows.
(1) When the histaminergic neuron system is activated pharmacologically, the duration periods of electroconvulsion are shortened. On the other hand, when the neuron is inactivated, the duration periods are prolonged. Thus, histamine is anticonvulsant.
(2) The threshold of electroconvulsion is lower in young mice (3 weeks) than in adult mice (>6 weeks), and the value is decreased further by an H1 antagonist, pyrilamine, but not by terfenadine, a non-sedative antihistaminic. These findings are consistnet with our clinical observation that the symptoms of some patients of epilepsy became worse when ketotifen was prescribed for allergic diseases, but they are well controlled when terfenadine was used.
(3) Thioperamide, an H3 antagonist, shoretend the latency in passive avoidance test of senescence accelerated mice. When the brain histamine level was decreased by treatment with an inhibitor of histidine decarboxylase, the death of neural cells … More in CA 2 region of the hippocampus of gerbils subjected to ischemia by a transient occlusion of the carotid arteries was promoted compared to control group. These findings suggest that the histaminergic system is involved in learning and memory processes.
(4) The double label autoradiography of a brain section was developed by taking advantage of the difference in the half-lives of 3H and 11C.The application of the method showed that H3 receptros are modulated by dopaminergic neurons through D1 receptors.
(5) The distribution of H1 receptors in the living human brain was mapped by PET with [11C] doxepin as a tracer. Its density decreased by aging in the ratio of 13 % per a decade. The density was higher in the foci of abnormal discharge of patients with complex partial seizure than in the opposite side, showing that the H1 receptors are up-regulated in the foci. The observation is in good agreement with the idea that brain histamine is anticonvulsant, which was obtained by pharmacological studies described above. The density was significantly lower in the cerebral cortices of patients of Alzheimer'disease or multiinfarct dementia than the age- and sex-matched normal controls. Less

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] K.Iinuma: "Histamine H1 receptors in complex partial seizures." Lancet. 341. 238-238 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Onodera: "Effects of α-fluoromethylhistidine on brain histamine and noradrenaline in muricidal rats." Meth.Find.Fxp.Clin.Pharmacol.15. 423-427 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Sakai: "Effects of (R)-α-methylhistamine and (S)-α-fluoromethyl histidine on the locomotor activity of W/W^V mice." Pharmacol.Biochem.Behav.46. 95-99 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Yokoyama: "The proconvulsive effects of pyrilamine on electrically-induced seizure in mice of developing period." Psychopharmacology. 112. 199-203 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Yokoyama: "Effect of thiopermide, a histamine H3-antagonist, on electrically-induced convulsions in mice." Eur.J.Pharmacol.234. 129-133 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Yokohama: "A histamine H1-antagonist,ketotifen produced seizures in an epileptic child activation study of d-chlorpheniramine on EEG." Meth.Find.Exp.Clin.Pharmacol.15. 183-188 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.H.Ryu: "Heteronenous distributions of of histamine H3,dopamine D1 and D2 receptors demonstrated by double labeled autoradiography in rat brain." NeuroReport,. 5. 621-624 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.H.Ryu: "Marked increase in nistamine H3 receptors on the striato nigral neurons after 6-hydroxydopamine-induced denervation of nigrrostriatal dopaminergic neurons demonstrated by autoradiography." Neurosci.Lett.178. 19-22 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Sugimoto: "Histamine depletion in brain caused by treatment woth (S)-α-fluoro methyl-histidine enhances ischemic damage of gerbil hippocampal CA2 neurons." Brain Res.666. 279-283 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Yanai: "Binding characteristics of a new histamineH3 receptor antagonist,[^3H]S-methylthioperamide:Comparison with[^3H](R)-α-methylhistamine binding to rat tissues." Jap.J.Pharmacol.65. 107-112 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Yokoyama: "2-Thiozolylethylamine, a selective H1 antagonist decreases seizure susceptibility." Pharmacol.Biochem.Behav.47. 503-507 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Yokoyama: "Clobenproprit, a new histamine H3 receptor antgonist, and electrically-induced convulsions." Eur.J.Pharmacol.260. 23-28 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 谷内一彦: "ポジトロン(β^+)標識受容体リガンドを用いた神経受容体の画像化" 日本薬理学雑誌. 103. 49-58 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Onodera: "Neuropharmacology of the histaminergic neuron system in the brain and its relationship with behavioral disorders.21GC14:Prog.Neurobiol." 42. 685-702 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Sakai: "Effect of L-histidine with or without thioperramide on locomotion of mice." Anuatio Psychiatrico. (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Sakai: "Long-term depletion of brain histamine induced by α-fluoromethy1-histidine increases feeding-associated locomotor activity in mice with a modolation of barin amino acid levels." Behav.Brain.Res.(1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Meguro: "Effects of thioperamide,a histamine H3-antagonist,on the step-through passive avoidance reponse in senescence accelerated mice." Pharmac.Biochem.Behav.(1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 谷内一彦: "PET/SPECTによる神経伝達・受容体機能の測定" BME. 8. 26-35 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Yokoyama: "Quantification of Brain Function. Tracer Kinetics and Image Analysis in Brain PET" Elsevier, 4 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 渡邊建彦: "神経伝達物質・受容体アトラス" 医学書院, 10 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 谷内一彦: "脳の神経伝達機能イメージング" 金芳堂, 20 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Yanai: "Clinical PET in Oncology" World Scientific, 4 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K,Iinuma: "Histamine H1 receptors in complex partial seizures." Lancet. 341. 238 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Onodera: "Effects of alpha-fluoromethylhistidine on brain histamine and noradrenaline in muricidal rats." Meth.Find.Exp.Clin.Pharmacol.15. 423-427 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Sakai: "Effects of (R) -alpha-methylhistamine and (S) -alpha-fluorometyhlhistidine on the locomotor activity of W/W^V mice." Pharmacol.Biochem.Behav.46. 95-99 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Yokoyama: "The proconvulsive effects of pyrilamine on electrically-induced seizure in mice of developing period." Psychopharmacology. 112. 199-203 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Yokoyama: "Effect of thioperamide, a histamine H3-antagonist, on electrically-induced convulsions in mice." Eur.J.Pharmacol.234. 129-133 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Yokoyama: "A histamine H1-antagonist, ketotifen produced seizures in an epileptic child activation study of d-chlorphenimine on EEG." Meth.Find.Exp.Clin.Pharmacol.15. 183-188 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Meguro: "Effects of thioperamide, a histamine H3-antagonist, on the step-through passive avoidance response in senescence accelerated mice." Pharmac.Biochem.Behav.(in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.H.Ryu: "Heteronenous distributions of histamine H3, dopamine D1 and D2 receptors demonstrated by double labeled autoradiography in rat barin." NeuroReport. 5. 621-624 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.H.Ryu: "Marked increase in histamine H3 receptors on the striatonigral neurons after 6-hydroxydopamineinduced denervation of nigrrostriatal dopaminergic neurons demonstratd by autoradiography." Neurosci, Lett.178. 19-22 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Sugimoto: "Histamine depletion in brain caused by treatment woth (S) -alpha-fluoromethyl-histidine enhances ischemic damage of gerbil hippocampal CA2 neurons." Brain Res.666. 279-283 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Yanai: "Binding characterisrtics of a new histamine H3 recepter antagonist, [^3H] S-methylthioperamide : Comparison with [^3H] (R) -alpha-methylhistamine binding to rat tissues." Jap.J.Pharmacol.65. 107-112 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Yokoyama: "2-Thiozolylethylamine, a selective H1 antagonist decreases seizure susceptibility." Pharmacol.Biochem.Behav.47. 503-507 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Yokoyama: "Clobenproprit, a new histamine H3 receptor antagonist, and electrically-incuced convulsions." Eur.J.Pharmacol.260. 23-28 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Onodera: "Neuropharmacology of the histaminergic neuron system in the brain and its relationship with behavioral disorders." Prog, Neurobiol.42. 685-702 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Sakai: "Effect of L-histidine with or without thioperamide on locomotion of mice." Anuario Psychiatrico. (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Sakai: "Long-term depletion of brain histamine induced by alpha-fluoromethylhistidine increases feeding-associated locomotor activity in mice with a modulation of barin amino acid levels." Submitted to Behav.Brain.Res.(1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.H.Ryu: "Ontogenetic development of histamine receptor subtypes in rat brain demonstrated by quantitative autoradiography." Submitted to Dev.Brain.Res.(1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Yokoyama: "Mapping of histamine H1-receptors in patients with complex partial seizure with PET and 11C-doxepin." Quantification of Brain Function Tracer Kinetics and Image Analysis in Brain PET. 297-301 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Yanai: "Labelling of histamine H1, H2 and H3 antagonists with carbon-11 : Radiopharmaceuticals for PET studies." Clinical PET in Oncology. 367-370 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.H.Ryu: "Heteronenous distributions of histamine H3,dopamine D1 and D2 receptors demonstrated by double labeled autoradiography in rat barin." NeuroReport. 5. 621-624 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] J.H.Ryu: "Marked increase in histamine H3 receptors on the striatonigral neurons after 6-hydroxydopamine-induced denervation of nigrrostriatal dopaminergic neurons demonstrated by autoradiography." Neurosci.Lett.178. 19-22 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Sugimoto: "Histamine depletion in brain caused by treatment woth(S)-α-fluoro-methyl-histidine enhances ischemic damage of gerbil hippocampal CA2 neurons." Brain Res.666. 279-283 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Yokoyama: "2-Thiozolylethylamine,a selective H1 antagonist decreases seizure susceptibility." Pharmacol.Biochem.Behav.47. 503-507 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Yokoyama: "Clobenproprit,a new histamine H3 receptor antagonist,and electrically-incuced convulsions." Eur.J.Pharmacol.260. 23-28 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Onodera: "Neuropharmacology of the histaminergic neuron system in the brain and its relationship with behavioral disorders." Prog.Neurobiol.42. 685-702 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 谷内一彦: "脳の神経伝達機能イメージング" 金芳堂, 20

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Yanai: "Clinical PET in Oncology" World Scientific,

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Iinuma: "Histamine H1 receptors in complex partial seizures." Lancet. 341. 238-238 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] N.Sakai: "Effects of (R)-α-methylhistamine and (S)-α-fluoromethylhistidine on the locomotor activity of W/W^V mice." Pharmacol.Biochem.Behav.46. 95-99 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Yokoyama: "The proconvulsive effects of pyrilamine on electrically-induced seizure in mice of developing period." Psychopharmacology. 112. 199-203 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Yokoyama: "Effect of thioperamide,a histamine H3-antagonist,on electrically-induced convulsions in mice." Eur.J.Pharmacol.234. 129-133 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Yokoyama: "A histamine H1-antagonist,ketotifen produced seizures in an epileptic child activation study of d-chlorpheniramine on EEG." Meth.Find.Exp.Clin.Pharmacol.15. 183-188 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Hayashi: "Methods in Neurotransmitter and Neuropeptide Research(Eds.S.H.Parvez,M.Naoi,T.Nagatsu)" Elsevier, 29 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 渡邉建彦: "神経伝達物質・受容体アトラス(遠山正弥 編)" 医学書院, 10 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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