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2001 Fiscal Year Final Research Report Summary

Cloning of rat sigma-1 receptor cDNA and its roles for psychoses

Research Project

Project/Area Number 10670901
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

UJIKE Hiroshi  okayama univ., Graduate School of Medicine and Dentistry, Associate Professor, 大学院・医歯学総合研究科, 助教授 (90213420)

Project Period (FY) 1998 – 2000
Keywordsrat / brain / sigma receptor type 1 / cloning / messenger RNA / autoradiography / methamphetamine-psychosis / behavioral senstization
Research Abstract

Although central sigma receptors has been proposed to play roles for various neurological and psychiatric functions, those mechanisms is not well understood. Cloning of cDNA of sigma receptor type 1 of human and guinea-pig have been reported, however, that of rat was not yet. Based on homologous sequence search of amino acids between human and guinea pig, I produced degenerated primer sets encoding 30-37th and 166-173 amino acids of sigma receptor type 1. Using the primer set, I have cloned a cDNA of rat sigma receptor type 1 from rat brain cDNA library using PCR technique. The rat cDNA sequence of sigma receptor type 1 showed 90% and 87% homology to that of human and guinea pig, respectively.
From the sequence of the rat cDNA of sigma receptor type 1, three kinds of 45mer antisense oligonucleotides complementary to cording region, 3' and 5' untranslated region were produced, and in situ hybridization was performed using rat brain. However, any probe showed a significant signals in rat … More brain. Neither northern blotting from whole rat brain showed signals. These results indicated that expression of sigma receptor type 1 mRNA should be very low. To examine protein levels of rat sigma receptors, an autoradiography study was performed using rat brain. So far, there was no suitable and enough strong ligands for sigma receptor autoradiography. However, I found that [^3H]YM-09151-2, usually used as D2 dopamine receptors, is a potent ligand for sigma receptors under Na^+ free condition with no binding to D2 receptors. Using this ligand and the condition, the autoradiography showed that sigma receptors are rich in cortex, hippocampus and red nucleus, whereas those intensity was quite less than that in guinea pig brain. The results indicated that not only mRNA and also protein expression of sigma receptor in rat is quite less than that of guinea pig brain. Behavioral sensitization was an animal model for human psychoses. Rats received intermittent methamphetamine injection developed sensitization. In sensitized brain to methamphetamine showed increased binding of sigma receptors in prefrontal cortex, hippocampus, substantia nigra and cerebellum. The two former brain region showed a sustained increase of sigma receptor binding at least 3 weeks after discontinuation of methamphetamine treatment.
As to human methamphctamine-induced psychosis, I examined two kinds of polymorphisms in promoter regions in the sigma receptor type 1 gene compared with normal controls. It was revealed that there was no significant difference in genotypic or allelic distribution between the patients with methamphetamine-induced psychoses and normal controls. This finding showed that sigma receptor gene polymorphisms did not confer susceptibility to methamphetamine-precipitated psychoses. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 氏家 寛: "神経系に作用する薬物マニュアル1998,シグマ受容体"生体の科学. 49. 412-416 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 氏家 寛: "薬物・アルコール関連障害、神経化学的側面"臨床精神医学講座(松下正明編集)中山書店. 8巻. 55-73 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 氏家 寛: "中枢興奮薬による精神障害の生物学的機序"薬物依存研究の最前線(加藤 信, 鈴木 勉, 高田孝二編)星和書店. 31-55 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 氏家 寛: "薬物依存を誘導する遺伝子群の研究"脳の科学. 22. 679-684 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 氏家 寛: "薬物依存と脳内報酬系"薬物依存(精神医学レビュー)、ライフサイエンス社. 34巻. 36-44 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takaki M., et al.: "Increased expression of synaptophysin and stathmin mRNAs after methamphetamin administration in rat brain"Neuroreport. 12. 1055-1060 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. UJIKE: "Drug manual acting in CNS 1998, sigma receptors"Seitai No Kagaku. 49. 412-416 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. UJIKE: "Drug and alchohol related disorders, Neurochemistry"Rinsho-Seisin Igaku Koza. Vol.8. 55-73 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. UJIKE: "Biological basis for psychostimulants-induced mental disorders"Yakubutu Izon Kenkyu No Saizensen. 31-55 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. UJIKE: "A set of genes leading to drug dependence"Nou No Kagaku. 22. 679-684 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. UJIKE: "Drug dependence and rearding systems"Drug dependence, A psychiatric review. Vol.34. 36-44 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Takaki: "Increased expression of synaptophysin and stathmin mRNAs after methamphetamine administration in rat brain"Neuroreport. 12. 1055-1060 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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