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1991 Fiscal Year Final Research Report Summary

Blockade by Concurrent Stress Exposure of the Development of Tolerance to and Dependence on Morphine

Research Project

Project/Area Number 02671003
Research Category

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

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionNagasaki University

Principal Investigator

TAKAHASHI Masakatsu  Faculty of Pharmaceutical Sciences, Nagasaki University Associate Professor, 薬学部, 助教授 (90112383)

Project Period (FY) 1990 – 1991
KeywordsPsychological Stress / Footshock Stress / Opioid Receptors / Stress-Induced Analgesia / Morphine Tolerance and Dependence / Forced Swim / Antianxietic Drugs / Arginine Vasopressin Receptors
Research Abstract

Studies have been carried out to clarify the possible mechanism underlined in the blockade of the development of tolerance to morphine antinociception by concurrent exposure to footshock (FS) or Psychological (PSY) stress.
1. The main site of action involved in the suppression was investigated. Concomitant stresk or U-50, 488H resulted in the suppression of tolerance to intrathecal (i. t.) morphine ; however, such treatment failed to suppress the development of tolerance to intracerebroventricular (i. c. v.) morphine. Norbinaltorphimine abolished the suppression by PSY stress and U-50, 488H but not that by FS stress. Thus, these stresses suppress the development of morphine tolerance by acting on the spinal cord, and also that K-opioid receptor mechanisms could be involved in the suppression in case of PSY stress. 2. Tolerance to a drug is an adaptive response and learning and memory processes essentially endowed functions in the adaptation to environmental changes and exposure to drugs … More . Thus, the role of arginine vasopressin (AVP) in the suppression by stresses was examined. Radioimmunoassayable AVP content was decreased in mouse brain hypothalamus after FS and PSY stresses. In contrast, SW stress did not affect the level. Since the exposure to stress lowing AVP levels suppress the development of tolerance, AVP may play a critical role in this mechanism. The development of tolerance to morphine was prevented by pretreatment with V_1 receptor antagonist and likewise with V_2 receptor antagonist, i. c. v. 3. FS and PSY stress failed to block the development of tolerance to clonidine, whilst SW stress resulted in the suppression of clonidine tolerance. 4. Diazepam and buspirone abolished the suppression of the development of morphine tolerance by PSY stress, and Panax ginseng extracts abolished the blockade by FS stress. To assess the abolishment of suppression by stresses may provide a simple and new screening method for the evaluation of compounds possessing antianxiety or anti-stress properties. Less

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Masakatsu Takahashi: "Further evidence for the implication of a κ-opioid receptor mechanism in the production of psychological stress-induced analgesia" Japan.J.Pharmacol.53. 487-494 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Osamu Yamashiro: "Role of vasopressin in the blockade of the development of morphine tolerance by footshock and psychological stress" Arch.int.Pharmacodyn.Ther.307. 60-70 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masakatsu Takahashi: "Differential roles of adrenal gland in the suppression of the development of morphine antinociceptive tolerance by α-and β-adrenergic blockers" Japan.J.Pharmacol.55. 555-558 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masakatsu Takahashi: "Footshock-and psychological-stress prevent the development of tolerance to spinal but not supraspinal morphine" Japan.J.Pharmacol.56. 121-126 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masakatsu Takahashi: "Spinal κ-opioid receptors in the blockade of development of analgesic tolerance to morphine" Eur.J.Pharmacol.200. 293-297 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shogo Tokuyama: "Participation of an α_2-mediated mechanism in the production of forced swimming-stress induced analgesia in mice" J.Pharmacobio-Dyn.14. 357-361 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shogo Tokuyama: "Further evidence for the participation of an α_2-adrenoceptor mediated mechanism in the production of forced swimming-stress induced analgesia in mice" J.Pharmacobio-Dyn.14. 637-641 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高橋 正克: "ストレス誘発鎮痛" 薬物・精神・行動(Jpn.J.Psychopharmacol.). 11. (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Qiang Xu: "Dependency on the brain function of arginine vasopressin system of the development to and recovery from analgesic tolerance to morphine" Brain Res.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi, M. et al.: "Further evidence for the implication of a kappa-opioid receptor mechanism in the production of psychological stress-induced analgesia." Japan. J. Pharmacol.53 (4). 487-494 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamashiro, O. et al.: "Role of vasopressin in the blockade of the development of morphine tolerance by footshock and psychological stress." Arch. int. Pharmacodyn. Ther.307 (1-2). 60-70 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, M. et al.: "Differential roles of adrenal gland in the suppression of the development of morphine antinociceptive tolerance to alpha- and beta-adrenergic blockers." Japan. J. Pharmacol.55 (4). 555-558 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, M. et al.: "Footshock- and psychological stress prevent the development of tolerance to spinal but not supraspinal morphine." Japan. J. Pharmacol.56 (2). 121-126 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, M. et al.: "Spinal kappa-opioid receptors in the blockade of development of analgesic tolerance to morphine." Eur. J. Pharmacol.200 (2-3). 293-297 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tokuyama, S. et al.: "Participation of an alpha_2 - mediated mechanism in the production of forced swimming-stress induced analgesia in mice." J. Pharmacobio-Dyn.14 (6). 357-361 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tokuyama, S. et al.: "Further evidence for the participation of an alpha_2-adrenoceptor mediated mechanism in the production of forced swimming-stress induced analgesia in mice." J. Pharmacobio-Dyn.14 (11). 637-641 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, M.: "Stress-induced analgesia." Japan. J. Psychopharmacol.11 (5). (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Xu, Q. et al.: "Dependence on the brain function of arginine vasopressin system of the development to and recovery from analgesic tolerance to morphine." Brain Res.(1992)

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

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Published: 1993-03-16  

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