Study on the role of emotional stress for the pathogenesis of psychiatric disorders. -To clarify the relationship between emotional stress and central monoaminergic/peptidergic neural systems using animal models-

本研究的目的是利用体内微透析、放射免疫测定、原位杂交和Northern Blot在离散脑区阐明条条性恐惧应激对中枢单胺能和多肽能系统的影响，并检查神经系统的功能定位。1)选择性5 -羟色胺再摄取抑制剂（SSRIs）降低了条件冻结（一项焦虑指标），亚慢性锂预处理在治疗血浆锂水平下增强了这些抗焦虑作用。亚慢性锂预处理也增强了5 -羟色胺1a激动剂的抗焦虑作用。体内微透析研究表明，亚慢性锂治疗增加了细胞外血清素的基础水平，并诱导了ssri诱导的细胞外血清素增加的附加效应。2)在条件恐惧模型中检验单胺氧化酶抑制剂（MAOIs）的抗焦虑作用。MAO-A抑制剂或MAO-B抑制剂不产生抗焦虑作用，但非选择性mao - is以及MAO-A和MAO-B抑制剂联合使用具有抗焦虑作用。体内微透析研究表明，MAO-A和MAO-B抑制剂联合使用比单独使用任何一种抑制剂更能诱导细胞外血清素的增加。3)锂和SSRI处理可提高大鼠纹状体多巴胺2受体mRNA水平和多巴胺2受体基因转录率。

The purpose of this study is to clarify the effect of conditioned fear stress on central monoaminergic and peptidergic systems using in vivo microdialysis, radioimmunoassay, in situ hybridization, and Northern Blot in discrete brain regions and to examine functional localization of neural systems.1) Selective serotonin reuptake inhibitors (SSRIs) reduced conditioned freezing, an index of anxiety, and these anxiolytic effects were enhanced by subchronic lithium pretreatment at the therapeutic plasma lithium levels.The anxiolytic effects of serotonin1A agonists were also enhanced by subchronic lithium pretreatment. In vivo microdialysis studies showed that subchronic lithium treatment increased basal levels of extracellular serotonin and induced additive effects on SSRI-induced increases in extracellular serotonin.2) The anxiolytic effects of monoamine oxidase inhibitors (MAOIs) were tested in the conditioned fear model. MAO-A inhibitors or MAO-B inhibitors did not induce anxiolytic effects, but non-selective MAOIs and the combination of MAO-A and MAO-B inhibitors were anxiolytic. In vivo microdialysis studies showed that the combination of MAO-A and MAO-B inhibitors induced more increases in extracellular serotonin than either inhibitor alone did.3) Lithium and SSRI treatment increased the level of dopamine2 receptor mRNA and the transcription rate of the dopamine2 receptor gene in the rat striatum.