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Establishment of Animal Models of Dementia with Neuropeptides and Development Study of Anti-Dementia Drugs

Research Project

Project/Area Number 09672261
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionMeijo University

Principal Investigator

UKAI Makoto  Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Associate Professor, 薬学部, 助教授 (80131209)

Co-Investigator(Kenkyū-buntansha) KAMEYAMA Tsutomu  Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Professor, 薬学部, 教授 (10076698)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsNeuropeptide / Alzheimer's disease / Dynorphin / Galanin / Passive avoidance learning / Tachykinin / Anti-dementia drug / δ-Opioid receptor / 自発的交替行動 / サブスタンスP / ニューロキニンA / スコポラミン / オピオイド受容体 / オピオイドペプチド
Research Abstract

1.Galanin shortened step-down latency of passive avoidance learning, while the dopamine DィイD21ィエD2 receptor agonist SKF38393, the dopamine DィイD22ィエD2 receptor agonist RU24213, the dopamine DィイD21ィエD2 receptor antagonist SCH23390 or the dopamine DィイD22ィエD2 receptor antagonist S(-)-sulpiride failed to influence it. Dynorphin A-(1-13) and SKF38393 markedly improved the galanin-induced shortening of step-down latency. However, RU24213, SCH23390 or S(-)-sulpiride did not affect the galanin-induced shortening of step-down latency.
The effects of intracerebroventricular administration of δィイD21ィエD2- and δィイD22ィエD2-selective opioid receptor agonists on spontaneous alternation performance, elevated plus-maze behavior and passive avoidance learning including step-down and step-through types were examined in mice. Although the δィイD21ィエD2-selective opioid receptor agonist, [D-PenィイD12ィエD1, L-PenィイD15ィエD1] enkephalin (DPLPE) or the δィイD22ィエD2-selective opioid receptor agonist, [D-AlaィイD12ィエD1] delto … More rphin II (deltorphin) did not markedly affect spontaneous alternation performance or elevated plus-maze behavior, DPLPE and deltorphin inhibited passive avoidance learning including step-down and step-through types. The δィイD21ィエD2-selective opioid receptor antagonist, 7-benzylidenenaltrexone, and the δィイD22ィエD2-selective opioid receptor antagonist, naltriben, significantly antagonized the inhibitory effects of DPLPE and deltorphin on passive avoidance learning, respectively. In contrast, DPLPE or deltorphin did not markedly influence behavioral responses induced by electroshocks during training of passive avoidance learning.
3.The present study was designed to clarify whether opioid neuronal systems are involved in the beneficial effects of tachykinins such as the neurokinin NKィイD21ィエD2 receptor agonist, substance P(SP), the neurokinin NKィイD22ィエD2 receptor agonist, neurokinin A(NKA), and the neurokinin NKィイD23ィエD2 receptor agonist, senktide, on the scopolamine-induced impairment of spontaneous alternation performance in mice. Intracerebroventricular injections of SP, NKA and senktide inhibited the scopolamine-induced impairment of spontaneous alternation performance without influencing total arm entries, indicating the antiamnesic effects of tachykinins. Furthermore, the inhibitory effects of SP, but not those of NKA or senktide, were almost completely reversed by pretreatment with naloxone. However, the effects of SP on the scopolamine-induced impairment of spontaneous alternation performance were not influenced by pretreatment with the μ-opioid receptor antagonist, β-funaltrexamine, the δ-opioid receptor antagonist, naltrindole, and the κ-opioid receptor antagonist, nor-binaltorphimine. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Makoto Ukai: "Effects of the κ-opioid dynorphin A-(1-13) on learning and memory in mice"Behavioral Brain Research. 83. 169-172 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Makoto Ukai: "Effects of the dopamine D_3 receptor agonist R(+)-7-hydroxy-N, N-di-n-propyl-2-aminotetralin on memory processes in mice"European Journal of Pharmacology. 324. 147-151 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Makoto Ukai: "Stimulation of δ_1-andδ_2 -opioid receptors produces amnesia in mice"European Journal of Pharmacology. 338. 1-6 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Makoto Ukai: "Effects of Tyr-D-Arg-Phe-β-Ala-NH_2, a novel dermorphin analog, on elevated plusmaze learning and spontaneous alternation performance in mice"General Pharmacology. 29. 453-456 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Makoto Ukai: "Dopaminergic involvement in improving effects of dynorphin A-(1-13) on galanin-induced impairment of passive avoidance learning in mice"Human Psychopharmacology. 12. 243-248 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Makoto Ukai: "Involvement of dopamine receptors in beneficial effects of tachykinins on scopolamine-induced impairment of alternation performance in mice"European Journal of Pharmacology. 350. 39-45 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 鵜飼 良: "神経行動薬理学研究の最前線"J. R. Prous S. A. Publishers. 7 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 鵜飼 良: "疼痛治療の現状と展望"ミクス. 12 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Makoto Ukai, Jiro Itoh, Tetsuya Kobayashi, Norihiro Shinkai and Tsutomu Kameyama: "Effects of the κ-opioid dynorphin A-(1-13) on learning and memory in mice."Behav.Brain Res.. 83. 169-172 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Makoto Ukai, Tomoko Tanaka and Tsutomu Kameyama: "Effects of the dopamine DィイD23ィエD2 receptor agonist R(+)-7-hydroxy-N, N-di-n-propyl-2-aminotetralin on memory processes in mice."Eur. J. Pharmacol.. 324. 147-151 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Makoto Ukai, Akio Takada and Tsutomu Kameyama: "Stimulation of δィイD21ィエD2- and δィイD22ィエD2-opioid receptors produces amnesia in mice."Eur. J. Pharmacol.. 338. 1-6 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Makoto Ukai, Jun Monma, Norihiro Shinkai, Yusuke Sasaki and Tsutomu Kameyama: "Effects of Tyr-D-Arg-Phe-β-Ala-NHィイD22ィエD2, a novel dermorphin analog, on elevated plus-maze learning and spontaneous alternation performance in mice."Gen. Pharmacol.. 29. 453-456 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Makoto Ukai, Masataka Miura and Tsutomu Kameyama: "Dopaminergic involvement in improving effects of dynorphin A-(1-13) on galanin-induced impairment of passive avoidance learning in mice."Hum. Psychopharmacol.. 12. 243-248 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Makoto Ukai, Norihiro Shinkai and Tsutomu Kameyama: "Involvement of dopamine receptors in beneficial effects of tachykinins on scopolamine-induced impairment of alternation performance in mice."Eur. J. Pharmacol.. 350. 39-45 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsutomu Kameyama, Makoto Ukai and Norihiro Shinkai: "Ameliorative effects of tachykinins on scopolamine-induced impairment of spontaneous alternation performance in mice."Meth. Find. Exp. Clin. Pharmacol.. 20. 555-560 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Makoto Ukai: "Effects of intracerebroventricular injection of opioid peptides selective for μ, δ and κ receptors on discriminative stimulus properties of pentazocine in the rat" Human Psychopharmacology. 13. 171-176 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Makoto Ukai: "Beneficial effects of acute and repeated administrations of σ receptor agonists on behavioral despair in mice exposed to tail suspension" Pharmacology Biochemistry and Behavior. 61. 247-252 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsutomu Kameyama: "Ameliorative effects of tachykinins on scopolamine-induced impairment of spontaneous alternation performance in mice" Methods and Findings in Experimental and Clinical Pharmacology. 20. 555-560 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Makoto Ukai: "Involvement of dopamine receptors in beneficial effects of tachykinins on scopolamine-induced impairment of alternation performance in mice" European Journal of Pharmacology. 350. 39-45 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 鵜飼 良: "疼痛治療の現状と展望-臨床および基礎の立場から" ミクス, 12 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Makoto Ukai: "Effects of the κ-opioid dynorphin A-(1-13) on learning and memory in mice" Behavioral Brain Research. 83. 169-172 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Makoto Ukai: "Dopaminergic involvement in improving effects of dynorphin A-(1-13) on galanin-induced impairment of passive avoidance learning in mice" Human Psychopharmacology. 12. 243-248 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Makoto Ukai: "Effects of Tyr-D-Arg-Phe-β-Ala-NH_2,a novel dermorphin analog,on elevated plus-maze learning and spontaneous alternation performance in mice" General Pharmacology. 29. 453-456 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Makoto Ukai: "Effects of the dopamine D_3 receptor agonist R(+)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin on memory processes in mice" European Journal of Pharmacology. 324. 147-151 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Makoto Ukai: "Stimulation of δ_1-and δ_2-opioid receptors produces amnesia in mice" European Journal of Pharmacology. 338. 1-6 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 鵜飼 良: "生理活性ペプチドによるアルツハイマー型痴呆治療薬の開発研究" 名城大学総合研究所紀要. 2. 75-79 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 鵜飼 良: "神経行動薬理学研究の最前線" J.R.Prous S.A.Publishers, 7 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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