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The roles of central neurotransmitters in the mechanism of action of psychotropic drugs.

Research Project

Project/Area Number 60480129
Research Category

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

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionKyushu University

Principal Investigator

UEKI Showa  Fa. of Pharmceutical Sci., Kyushu Univ., Professor, 薬学部, 教授 (80037564)

Co-Investigator(Kenkyū-buntansha) KATAOKA Yasufumi  Fa. of Pharmceutical Sci., Kyushu Univ., Instructor, 薬学部, 助手 (70136513)
SHIBATA Shigenobu  Fac. of Pharmceutical Sci., Kyushiu Univ., Instructor, 薬学部, 助手 (10162629)
YAMAMOTO Tsuneyuki  Fa. of Pharmceutical Sdi., Kyushu Univ., Instructor, 薬学部, 助手 (20091332)
Project Period (FY) 1985 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1987: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1986: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1985: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsAnxiolytics / Antidepressants / Antidementia drug / Conflict behavior / Muricide of the rat / Hypothalamus / Amygdala / 脳内アミン / ニューロペプチドY / ノルアドレナリン / セロトニン
Research Abstract

The mechanisms of action of antidepressants, anxiolytics and antidementia drugs were investigated by using relevant models of brain dysfunction in rats.
1. Muricide of the rat is selectively suppressed by antidepressants. In olfactory bulbectomized (OB) rats exhibiting muricide, noradrenaline (NA) content increased and NA turnover decreased in the lateral hypothalamus (LH), ventromedial hypothalamus (VMH), mammillary body (MB) and medial amygdala (AME), and serotonin (5-HT) turnover also decreased in LH and MB. In midbrain raphe-lesioned (Raphe) rats, 5-HT and its metabolites markedly decreased, but NA content in LH and VMH significantly increased, in accordance with the development of muricide. In nucleus accumbens-lesiond (Acc) rats exhibiting muricide, NA content significantly increased in LH, VMH and MB, 5-HT content decreased in LH and 5-HT turnover also decreased in MB. All these changes of brain monoamines in muricidal rats were mormalized with muricide suppressed by antidepressants.
2. The antimuricide effect of NA microinjected into AME of OB rats was potentiated by neuropeptide Y (NPY). In OB rats exhibiting muricide, NPY content significantly increased in LH, VMH and the amygdala. This increase of NPY was reduced to the normal level with muricide inhibited by antideppressants.
3. In the rats exhibiting muricide, the number of 5-HT_2 receptor but not of 5-HT_1 receptor significantly increased in the amygdala in OB rats and in the hypothalamus in Raphe rats. NAergic <alpha>2 receptors decreased in LH and VMH in OB rats.
4. The central amygdala (ACE) and MB are the important sites of anticonflict action of benzodiazepines (BDZ), but the mechanism of action of BDZ was different in ACE and MB. The distribution of BDZ receptor subtypes was also different between ACE and MB.
5. Relevant dementia models were provided and useful methods to quantitatively measure memory deficits were establishedfor evaluatiang antidementia drugs in rats.

Report

(2 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Shyh Yuh Liou: Japan. J. Pharmacol.37. 167-172 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Shyh Yuh Liou: Pharmacol. Biochem. Behav.23. 65-70 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tsuneyuki Yamamoto: Pharmacol. Biochem. Behav.22. 559-563 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Katsunori Iwasaki: Pharmacol. Biochem. Behav.24. 1715-1720 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kazuhiko Shibata: Brain Res.372. 159-162 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Izaldin M. H. Al-Khatib: Asia Pacific J. Pharmacol.1. 79-85 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tsuneyuki Yamamoto: Pharmacol. Biochem. Behav.26. 111-117 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Izaldin M. H. Al-Khatib: Pharmacol. Biochem. Behav.26. 351-355 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tsuneyuki Yamamoto: Japan. J. Pharmacol.43. 165-171 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Showa Ueki: Japan. J. Pharmacol.43. 309-326 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Takao Shimazoe: J. Pharmacobio-Dyn.10. 639-643 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yasufumi Kataoka: Brain Res.416. 243-247 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yoshihiro Tani: Pharmacol. Biochem. Behav.26. 725-729 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yasufumi Kataoka: Pharmacol. Biochem. Behav.28. 101-103 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tadashi Nagatani: European J. Pharmacol.142. 17-22 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tsuneyuki Yamamoto: Neuropharmacology. 27. 123-127 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yoshiaki Furuya: Japan. J. Pharmacol.46. 183-188 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tadashi Nagatani: Japan. J. Pharmacol.46. 267-274 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] R. Takahashi Ed.;Showa Ueki: "Psychotropic and Neurotropic drugs and neurotransmitter receptor" Excepta Medica, 11 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Shy Yun Liou: "Differential effects of electroconvlulsive shock on four models of experimentally induced aggression in rats" Japan. J. Pharmacol.37. 167-172 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Shyh Yun Liou: "The role of central noradrenergic neurons in electroconvulsive shock-induced muricide inhibition in olfactory bulbectomized rats" Pharmacol. Biochem. Behav.23. 65-70 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tsuneyuki Yamamoto: "Effects of chronic LiCl and RbCl on muricide induced by midbrain raphe lesions in rats" Pharmacol. Biochem. Behav.22. 559-563 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Katsunori Iwasaki: "Changes in brain catecholamine levels following olfactory bulbectomy and the effect of acute and chronic administration of desipramne in rats" Pharmacol. Biochem. Behav.24. 1715-1720 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kazuhiko Shibata: "An important role of the central amygdaloid nucleus and mammillary body in the mediation of conflict behavior in rats" Brain Res.372. 159-162 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tsuneyuki Yamamoto: "A new method for screening anxiolytic drugs in rats" Pharmacol. Biochem. Behav.26. 111-117 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Izaldin M.H. Al-Khatib: "The role of brain catecholamines in the exhibition of muricide induced by nucleus accumbens lesions and the effect of antidepressants in rats" Pharmacol. Biochem. Behav.26. 351-355 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tsuneyuki Yamamoto: "Rolipram as a discriminative stimuli; transfer to phosphodiesterase inhibitors" Japan. J. Pharmacol.43. 165-171 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Showa Ueki: "Behavioral and electroencephalographic effects of zopiclone, a cyclopyrrolone derivative" Japan. J. Pharmacol.43. 309-326 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Takao Shimazoe: "A new forced swimming test for the evaluation of antidepressants in rats by recording vibration of a water tank" J. Pharmacobio-Dyn.10. 639-643 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yasufumi Kataoka: "Differential mechanisms involved in the anticonflict action of benzodiazepines injected into the central amygdala and mammillary body" Brain Res.416. 243-247 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yoshihiro Tani: "Changes of brain monoamine contents in three models of experimentally induced muricide in rats" Pharmacol. Biochem. Behav.26. 725-729 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yasufumi Kataoka: "The involvement of neuropeptide Y in the antimuricide action of noradrenaline injected into the medial amygdala of olfactory bulbectomized rats" Pharmacol. Biochem. Behav.28. 101-103 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tadashi Nagatani: "The effect of agonists at the GABA-benzodiazepine receptor complex on the duration of immobility of mice in the forced swimming test" European J. Pharmcol.142. 17-22 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tsuneyuki Yamamoto: "Anti-serotonin action in combination with noradrenaline-stimulating action is important for inhibiting muricide in midbrain raphe-lesioned rats" Neuropharmacology. 27. 123-127 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yoshiaki Furuya: "A new method for studying working memory by using the three-panel runway apparatus in rats" Japan. J. Pharmacol.46. 183-188 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tadashi Nagatani: "The effect of agonists at the GABA-benzodiazepine-receptor-complex on the proconflict effect induced by <beta>-CCM and pentetrazol in rats" Japan. J. Pharmacol.46. 267-274 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Showa Ueki: Excepta Medica. Psychotropic and Neurotropic drugs and neurotransmitter receptor, 11 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Katsunori Iwasaki: Pharmacol.Biochem.Behav.24. 1715-1719 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Al-Khatib,I.M.H: Asia Pacific Journal of Pharmacology. 1(2). 79-85 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 岩崎克典: 薬物・精神・行動. 6. 45-46 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 島添隆雄: 薬物・精神・行動. 6. 47-48 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Showa Ueki,Ed by R.Takahashi: "Psychotropic and Neurotropic Drugs and Neurotransmitter Receptors" Excepta Medica, 85 (1986)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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