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EVALUATION FOR ANIMAL MODEL OF WONDERER IN TRANSIENT ISCHEMIA-INDUCED ABNORMAL BEHAVIOR

Wonderer 动物模型短暂性缺血引起的异常行为的评估

基本信息

批准号：
11672262
负责人：
ARAKI Hiroaki
金额：
$ 2.18万
依托单位：
OKAYAMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

It is conceivable that the crisis and exacerbation of the psychiatric disorder is related to the occurrence of abnormality of some neurotransmitters in the brain, which are induced by stress, alcohol and so on. The depression has been supposed that the postsynaptic serotonin 2 receptor becomes for the supersensitivity, because of the decrease of serotonin in the brain as a disposition. It is suggested that when stresses are taken, serotonin over release is happened and the depression is induced. On the other hand, it is well known that the occlusion of bilateral carotid arteries for 5 min induces delayed neuronal death in the hippocampal CA1 neurons in Mongolian gerbils. In addition to this phenomenon, sustained hyperactivity (abnormal behavior) is happened prior to the neuronal death in gerbils. The abnormal release of some neurotransmitters are happened by the transient cerebral ischemia, and this seems to induce the sustained abnormal behavior disorder. It became clear that the dopa … More minergic neurotransmitter system was related to the sustained abnormal hyperactivity. Because, when dopaminergic receptor antagonists were administered 24 hr after transient ischemia, in which ischemia-induced hyperactivity was most remarkable period, ischemia-induced hyperactivity was inhibited significantly. The effect of repetitive administration of antidepressants and methamphetamine (MAP) on ischemia-induced hyperactivity was examined in Mongolian gerbils, because it is well known that the action of antidepressants and MAP is strengthened by the administration of these drugs repeatedly. Imipramine (5 and 10 mg/kg), desiramine (5 mg/kg), paroxetine (5 mg/kg), and MAP (1 and 3 mg/kg) were administered for 7 or 14 days once a day. Bilateral carotid arteries were occluded 30 min after the last administration of these drugs. The locomotor activity was measured 3 and 24 hr after ischemia. Though the hyperactivity induced by cerebral ischemia was suppressed by the administration of MAP dose dependently, imipramine, desipramine and paroxetine has no effect on it. From these results, it is conceivable that ischemia-induced hyperactivity is related to the dopaminergic neurotransmission. Dopaminergic nervous system blocking agents would seem to be the most effective for wandering which is one of the cerebrovascular disorders sequela. Less

可以想见，精神障碍的危机和恶化与大脑中某些神经递质的异常发生有关，这些神经递质是由压力、酒精等引起的。抑郁症被认为是由于脑内5-羟色胺的减少而引起的超敏反应，突触后5-羟色胺2受体起作用。提示在应激状态下，5-羟色胺过度释放，诱发抑郁。另一方面，沙土鼠双侧颈总动脉结扎5min可引起海马CA1区神经元迟发性死亡。除了这种现象外，持续的多动(异常行为)在沙土鼠神经元死亡之前发生。短暂性脑缺血引起某些神经递质的异常释放，可能导致持续性的异常行为障碍。很明显，多巴…矿化神经递质系统增多与持续性异常多动有关。因为在短暂性脑缺血后24小时给予多巴胺受体拮抗剂时，缺血诱导的多动反应最为显著，对缺血诱导的多动反应有明显的抑制作用。在蒙古沙土鼠中，反复给予抗抑郁药和甲基苯丙胺(MAP)对缺血引起的多动反应的影响进行了研究，因为众所周知，反复给药会增强抗抑郁药和MAP的作用。丙咪嗪(5 mg/kg和10 mg/kg)、地塞米松(5 mg/kg)、帕罗西汀(5 mg/kg)和MAP(1 mg/kg和3 mg/kg)，每日1次，共7~14d。最后一次给药后30min结扎双侧颈动脉。分别于缺血后3小时和24小时测定大鼠的运动能力。MAP剂量依赖性地抑制脑缺血所致的多动，但丙咪嗪、地塞帕明和帕罗西汀对其无影响。从这些结果可以想象，缺血引起的过度活动与多巴胺能神经传递有关。多巴胺能神经系统阻滞剂似乎是治疗游荡最有效的药物，游荡是脑血管疾病的后遗症之一。较少