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Calcium-dependent mechanisms underlying methamphetamine-induced behavioral sensitization - an animal model of schizophrenia

Research Project

Project/Area Number 10670900
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionOkayama University

Principal Investigator

AKIYAMA Kazufumi  OKAYAMA UNIVERSITY, MEDICAL SCHOOL, ASSOCIATE PROFESSOR, 医学部, 助教授 (40150990)

Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsMethamphetamine / Behavioral sensitization / Reverse Tolerance / Calmodulin / Calcium-calmodulin-dependent protein kinase II / Dopamine D1 receptor / NMDA recepor / Neuroleptics / クロザピン / オランザピン / CaM-Kinase II / カルシウム
Research Abstract

Using antisense oligonucleotides to three distinct rat calmodulin genes (CaM I, CaM II, CaM III), CaM I mRNA was reduced in the striatum and nucleus accumbens within 2 h of acute administration of 4 mg/kg methamphetamine (METH), but returned to the control level by 6 h, The calmodulin contentin both the cytosolic and membrane fractions of the striatum was reduced 0.5, 2, and 6 h after acute administration of METH. In the chronic experiments, rats were treated with either 4 mg/kg METH or saline once daily for 14 days. Following a 4-week abstinence period, rats were challenged with either METH (4mg/kg) or saline. The calmodulin content in the membrane fraction was significantly increased in the mesolimbic area, medial prefrontal cortex and hippocampus of the rats that underwent the chronic METH administration and a challenge with METH. These results suggest that chronic METH administration leads to a translocation of calmodulin from the cytosolic to membrane fractions.
Ca^<2+>/calmodulin- … More dependent protein kinase II (CaM-kinase II) activity was decreased in five regions of the rat brain (parietal cortex, frontal cortex, hippocampus, striatum and nucleus accumbens) after a single injection of METH. Pretreatment with the selective dopamine D1 receptor antagonist SCH 23390 prevented the acute METH-induced decrease in CaM-kinase II activity in the parietal cortex, striatum, nucleus accumbens and substantia nigra/ventral tegmental area.(SN/VTA) Pretreatment with the N-methyl-D-aspartate receptor antagonist MK-801 significantly restored the acute METH-induced decrease in CaM-kinase II activity in the parietal cortex, nucleus accumbens and SN/VTA. Striatal CaM-kinase II activity was still significantly lower than that of the chronic saline-treated controls after a 1-week, but not a 4-week, abstinence from chronic administration of METH. A METH challenge after a 4-week abstinence period induced a more pronounced decrease in CaM-kinase II activity in rats chronically injected with METH than in rats chronically injected with saline. Western blot analysis revealed that the amount of CaM-kinase II protein was not altered after a single METH injection or after chronic METH injections, compared with saline-treated controls. These results suggest that chronic treatment with METH leads to an enhanced capacity of METH to decrease CaM-kinase II activity after an extended withdrawal period. Less

Report

(4 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Akiyama K, Suemaru J: "Effect of acute and chronic administration of methamphetamine on calcium-calmodulin dependent protein kinase II activity in the rat brain"Annals of the New York Academy of Sciences. 914. 263-274 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suemaru J, Akiyama K, Tanabe Y, Kuroda S: "Methamphetamine decreases calcium-calmodulin dependent protein kinase II activity in discrete rat brain regions"Synapse. 36. 155-166 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 秋山一文: "1矯正施設に於ける覚せい剤精神病"精神医学. 42. 1143-1151 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kodama M, Akiyama K, Ujike H, Shimizu Y, Tanaka Y, Kuroda S: "A robust increase in expression of arc gene, an effector immediate early gene, in the rat brain after acute and chronic methamphetamine administration"Brain Research. 796. 273-283 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishihara T, Akiyama K, Kashihara K: "Enhanced AP-1 binding in brain induced by D1 and D2 agonists in methamphetamine-sensitized rats"Neuro Report. 9. 3913-3917 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akiyama K, Ujike H, Sakai K, Shimizu Y, Kodama M, Kuroda S: "Effect of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline on methamphetamine-and cocaine-induced behavioral sensitization"Pharmacology Biochemistry and Behavior. 61. 419-426 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 秋山一文: "臨床精神医学講座 第24巻,精神医学研究方法(分担執筆:精神医学における動物モデル)"中山書店. 26 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akiyama K and Suemaru J: "Effect of acute and chronic administration of methamphetamine on calcium-calmodulin dependent protein kinase II activity in the rat brain."Annals of the New York Academy of Sciences. 914. 263-274 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suemaru J, Akiyama K, Tanabe Y and Kuroda S: "Methamphetamine decreases calcium-caimodulin dependent protein kinase II activity in discrete rat brain regions."Synapse. 36(3). 155-166 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kazufumi Akiyama: "Methamphetamine psychosis in a Japanese prison."Clinical Psychiatry. 42(11)(in Japanese). 1143-1151 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kodama M, Akiyama K, Ujike H, Shimizu Y, Tanaka Y and Kuroda S: "A robust increase in expression of arc gene, an effector immediate early gene, in the rat brain after acute and chronic methamphetamine admmistration."Brain Research. 796. 273-283 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishihara T, Akiyama K and Kashihara K: "Enhanced AP-1 binding in brain induced by D1 and D2 agonists in methamphetamine-sensitized rats."Neuro Report. 9. 3913-3917 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akiyama K, Ujike H, Sakai K, Shimizu Y, Kodama M and Kuroda S: "Effect of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (f)quinoxaline on methamphetamine and cocaine-induced behavioral sensitization"Pharmacology Biochemistry and Behavior. 61. 419-426 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akiyama K: "Animal models in psychiatry., In: Encyclopedia of clinical psychiatry, vol 24"Nakayama- shoten, Tokyo, (in Japanese). 317-342 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akiyama K: "Treatment algorithm for neuroleptic-induced tardive extrapyramidal symptoms., In: The treatment algorithm for schizophrenia and mood disorder"Seiwa-shoten, Tokyo, (in Japanese). 3450 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akiyama K and Suemaru J: "Effect of Acute and Chronic Administration of methamphetamine on calcium-calmodulin dependent protein kinase II activity in the rat brain."Annals of the New York Academy of Sciences. 914. 263-274 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suemaru J,Akiyama K,Tanabe Y and Kuroda S: "Methamphetamine decreases calcium-calmodulin dependent protein kinase II activity in discrete rat brain regions."Synapse. 36(3). 155-166 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 秋山一文: "1矯正施設に於ける覚せい剤精神病"精神医学. 42(11). 1143-1151 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akiyama K: "Serum levels of soluble IL-2 receptor α, IL-6, and IL-1 receptor antagonist in schizophrenia before and during neuroleptic administration"Schizophrenia Research. 37. 97-106 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suemaru J, Akiyama K, Tanabe Y and Kuroda S: "Methamphetamine decreases calcium-calmodulin dependent protein Kinase II activity in discrete rat brain regions"Synapse. 36(in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 秋山 一文: "精神分裂病に於ける遺伝子発現"脳の科学. 21. 389-395 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 秋山 一文: "薬による精神障害"今日の治療指針 1999(多賀須幸雄 尾形悦郎 総編集、倉知正佳 編)医学書院. 287-288 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 秋山 一文: "精神医学研究における動物モデル"臨床精神医学講座 第24巻、精神医学研究法(融直男、南光進一郎編),中山書店. 317-342 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 秋山 一文: "一矯正施設に於ける覚せい剤精神病"精神医学. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 秋山一文: "質疑応答 「覚醒剤による逆耐性現象」-その発生機序・フラッシュバック" 日本医事新報. 3891. 113-114 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kodama,M.: "A robustincreuse in expression of arc gene,an effector immediare early in the rat brain after acute and clwcnic methamphetamire adminisnarion." Brain Research. 796. 273-283 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ishihara,T.: "Enhanced AP-1 binding in brain induced by D_1 and D_2 agchists in mcthamphetaminc-sensitized vars." Neuroreport. 9. 3913-3917 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akiyama,K.: "Effect of 2,3-dihydraxy-6-nitro-7-sultamoyl-benzo(t) quinoraline on methamphetamire-and cocaine-induced behaviaral sensitization." Pharmacology Biochemistry and Behavior. 61. 419-426 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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