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

本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，使用条件性恐惧应激（CFS）诱导的冻结行为作为焦虑指标。1）第一项研究检查了杏仁核中与 CFS 相关的基因。使用DNA微阵列（GeneChip Rat Genome 230 2.0 Array，包含28000个基因）检测杏仁核，我们检测到杏仁核中的18个基因，其表达发生了改变。 CFS。在这些基因中，只有一个基因，神经降压素，是SSRI-CFS相关基因，其由CFS引起的改变被SSRI治疗所抵消。这一结果表明神经降压素与SSRIs的抗焦虑作用机制相关。2)局部输注。将西酞普兰（一种选择性血清素再摄取抑制剂（SSRI））注入杏仁核，会增加杏仁核中的细胞外血清素（5-HT）水平恐惧幼鼠并同时抑制冻结行为。该结果表明，杏仁核中 SSRI 诱导的 5-HT 增加会导致 SSRI 的抗焦虑作用。3) 尽管在恐惧调节后一天，tandospirone 的 5-HT_< 1A >激动剂和SSRIs以剂量依赖的方式显着抑制条件性冻结，在条件性恐惧后14天，这些药物的抗焦虑作用减弱，这表明 14 天的模型作为临床焦虑症的动物模型是有效的，在恐惧调节后 14 天，联合给予亚有效剂量的坦度螺酮和 SSRI 可以增强抗焦虑作用，这种联合疗法是治疗焦虑症的一种有前途的策略。 4)选择性甘氨酸转运蛋白1抑制剂通过甘氨酸转运蛋白1抑制剂的刺激来刺激NMDA受体(谷氨酸受体的亚型)。抑制条件性冻结的获得和表达（在获得实验中，在通过足部电击进行恐惧条件化之前施用药物，而在表达实验中，在足部电击之后和条件性恐惧测试之前，重新暴露于电击室之前施用药物）。较少的

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