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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

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 neurotoxin 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 juvenile 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

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）

5-HT_<1A> receptor agonist affects fear conditioning throng stimulations of the postsynaptic 5-HT_<1A> receptors in the hippocampus and amygdala.

5-HT_ 1A 受体激动剂影响海马和杏仁核中突触后5-HT_ 1A 受体的恐惧调节群体刺激。

DOI：
发表时间：
2006
期刊：
European Journal of Pharmacology 532
影响因子：
0
作者：
Kondo M;Nakano N;Shiraki Y;Hiruma M;Ikeda S;et al.;Ozdemir V;Kato C;Li XB
通讯作者：
Li XB

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

Subchronic milnacipran treatment increases basal extracellular noradrenaline concentrations in the medial prefrontal cortex of rats

亚慢性米那普仑治疗增加大鼠内侧前额皮质的基础细胞外去甲肾上腺素浓度

DOI：
发表时间：
2005
期刊：
European Journal of Pharmacology 520(1-3)
影响因子：
0
作者：
Inoue T;Nakagawa S;Izumi T;Kitaichi Y;Koyama T;櫻井高太郎;Kitaichi Y;Tanaka N;Izumi T;Izumi T;Kitaichi Y
通讯作者：
Kitaichi Y

Effects of co-administration of antidepressants and monoamine oxidase inhibitors on 5-HT-related behavior in rats.

抗抑郁药和单胺氧化酶抑制剂共同给药对大鼠 5-HT 相关行为的影响。