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

通过同时应激暴露来阻断吗啡耐受性和依赖性的发展

基本信息

批准号：
02671003
负责人：
TAKAHASHI Masakatsu
金额：
$ 0.32万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

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

已经进行了研究，以阐明通过同时暴露于脚印（FS）或心理（PSY）应力的耐耐受性抗伤害感受的阻碍中所强调的可能机制。1。研究了抑制作用的主要作用部位。伴随的应力或U-50，488h导致抑制对鞘内（i。t。）吗啡的耐受性；然而，这种治疗未能抑制对脑室内（I.C.V.）吗啡的耐受性的发展。 Norbinaltorphimine通过PSY应力和U-50，488H的抑制作用，但没有通过FS应力来抑制。这是这些应力通过作用在脊髓上抑制吗啡耐受性的发展，并且在PSY胁迫的情况下，K-阿片受体机制也可能参与抑制。 2。对药物的耐受性是一种自适应反应，学习和记忆过程基本上是对环境变化和暴露于药物的适应性的赋予功能……更多。这就是研究精氨酸加压素（AVP）在应力抑制中的作用。 FS和PSY应力后，小鼠脑下丘脑中降低了可放射免疫的AVP含量。相反，SW应力不会影响水平。由于暴露于压力降低AVP水平抑制了耐受性的发展，因此AVP可能在该机制中起关键作用。通过使用V_1受体拮抗剂和V_2受体拮抗剂i。 c。 v。3。FS和PSY应力未能阻止可乐定的耐受性的发展，而SW应力导致了可乐定耐受性的抑制。 4。地西p和丁螺酮消除了PSY胁迫抑制吗啡耐受性的抑制，Panax Ginseng提取物因FS应力消除了封锁。为了评估压力消除抑制作用可能会为评估具有抗焦虑或抗压力特性的化合物提供一种简单而新的筛选方法。较少的