EVALUATION FOR ANIMAL MODEL OF WONDERER IN TRANSIENT ISCHEMIA-INDUCED ABNORMAL BEHAVIOR
| Project/Area Number |
11672262
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
ARAKI Hiroaki MEDICAL SCHOOL HOSPITAL, OKAYAMA UNIVERSITY, ASSOCIATE PROFESSOR, 医学部・附属病院, 助教授 (50294450)
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| Co-Investigator(Kenkyū-buntansha) |
GOMITA Yutaka MEDICAL SCHOOL HOSPITAL, OKAYAMA UNIVERSITY, PROFESSOR, 医学部・附属病院, 教授 (00088709)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | transient ischemia / dopaminergic neuronal system / wondering / methamphetamine / antidepressants / hyperactivity / Mongolian gerbil / methamphetamine / 薬物反応性 |
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| Research Abstract |
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
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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
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Report
(3 results)
Research Products
(6 results)
