Study on the role of emotional stress on the pathogenesis of endogenous psychiatric diseases. ---To clarify the molecular biological and neurochemical mechanism in the amygdala.

情绪应激在内源性精神疾病发病机制中的作用研究。

基本信息

批准号：
17591191
负责人：
INOUE Takeshi
金额：
$ 2.24万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

The purpose of this study is to examine the molecular biological and neurochemical mechanism of emotional stress in the amygdala, using freezing behavior induced by conditioned fear stress (CFS) as an index of anxiety.1) The first study examined CFS-associated genes in the amygdala using DNA microarray (GeneChip Rat Genome 230 2.0 Array including 28000 genes). We detected 18 genes in the amygdala, whose expressions were changed by CFS. Among these genes, only one gene, neurotensin, is an SSRI-CFS associated gene, whose change by CFS is cancelled by SSRI treatment. This result suggests that neurotensin is associated with the mechanism of anxiolytic action of SSRIs.2) Local infusion of citalopram, a selective serotonin reuptake inhibitor (SSRI), into the amygdala increased extracellular serotonin (5-HT) levels in the amygdala of fear幼onditioned rats and inhibited freezing behavior simultaneously. This result indicates that increased 5-HT induced by SSRI in the amygdala causes an anxiolyt … More ic effect of SSRI.3) Although one day after fear conditioning, tandospirone, a 5-HT_<1A> agonist, and SSRIs inhibited conditioned freezing significantly in a dose-dependent manner, 14 days after fear conditioning, the anxiolytic effects of these drugs were weakened, suggesting that a 14-days model has validity as an animal model of clinical anxiety disorders. Fourteen days after fear conditioning, co-administration of tandospirone and SSRIs given at subeffective doses enhanced anxiolytic effects. This combination thearapy is a promising strategy for the treatment of anxiety and mood disorders.4) A selective glycine transporterl inhibitor stimulated NMDA receptor, a subtype of glutamate receptor, via the stimulation of glycine site. Administration of a glycine transporterl inhibitor inhibited both the acquisition and expression of conditioned freezing (in the acquisition experiment, drugs are administered before fear conditioning by footshock, and in the expression experiment, drugs are administered after footshock and before conditioned fear test, re-exposure to shock-chamber). Less

这项研究的目的是检查杏仁核中情绪压力的分子生物学和神经化学机制，使用条件恐惧应激（CFS）作为焦虑指标诱导的冻结行为。1）第一项研究研究了使用DNA Microarray的杏仁核中CFS相关基因的CFS相关基因（包括Genecharay cenecphray cenecphare cenecthere cenececty norame cenecy norame cenecy norame cenecy cenecy nore）。我们在杏仁核中检测到了18个基因，其表达方式是由CFS改变的。在这些基因中，只有一个基因神经素，是SSRI-CFS相关的基因，其CFS的变化被SSRI处理取消。该结果表明，神经素与SSRIS的抗焦虑作用的机制相关。2）局部输注Citalopram（一种选择性的5-羟色胺再生抑制剂（SSRI））在杏仁核外血清素血清素（5-HT）水平延伸到乳腺乳 - 乳腺乳乳蛋白（5-HT）水平的恐惧和free freezing freezing和bastive freezing的恐惧。该结果表明，杏仁核中SSRI诱导的5-HT增加会引起抗焦虑……SSRI的更大影响。 14天模型作为临床动画障碍动物模型的有效性。恐惧调理后的十四天，以亚表现剂量给予的tandospirone和SSRI的共同给药增强了抗焦虑作用。这种组合挑战是治疗焦虑和情绪障碍的有希望的策略。4）选择性甘氨酸转运蛋白抑制剂刺激的NMDA受体，NMDA受体，谷氨酸受体的亚型，通过刺激甘氨酸位点。甘氨酸转运蛋白抑制剂的给药抑制了条件冻结的采集和表达（在采集实验中，在恐惧通过脚垫调理之前对药物进行给药，在表达实验中，在脚丝和脚部后和调节性恐惧测试后，对药物进行了药物，重新暴露于休克室）。

项目成果

期刊论文数量（26）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effect of the protein kinase C inhibitor, staurosporine, on the high dose of methamphetamine-induced behavioral sensitization to dizocilpine (MK-801)

DOI：
10.1007/s00213-005-2145-2
发表时间：
2005-06-01
期刊：
PSYCHOPHARMACOLOGY
影响因子：
3.4
作者：
Fang, YR;Abekawa, T;Koyama, T
通讯作者：
Koyama, T

on the high dose of methamphetamine-induced behavioral sensitization to dizocilpine (MK-801).

高剂量甲基苯丙胺诱导的地佐西平 (MK-801) 行为过敏。

DOI：
发表时间：
2005
期刊：
Psychopharmacology 180(1)
影响因子：
0
作者：
Fang YR;Abekawa T;Li XB;Wang ZC;Inoue T;Koyama T.Effect of the protein kinase C inhibitor;staurosporine
通讯作者：
staurosporine

Target brain sites of the anxiolytic effect of citalopram, a selective serotonin reuptake inhibitor