Study on the role of emotional stress on the pathogenesis of schizophrenia and mood disorder.---To clarify the relationship between emotional stress and central neural systems of monoamine and glutamate by using animal models of psychiatric disorders---

本研究的目的是研究大脑不同区域对焦虑的功能作用，以及谷氨酸/单胺类神经传递与情绪行为的关系。1)丘脑和杏仁内侧核的损伤干扰了背景恐惧条件反射的获得和表达。2)杏仁核底外侧核微量注射选择性5-羟色胺再摄取抑制剂(SSRI)可减少条件性恐惧引起的冰冻行为。3)杏仁核和丘脑内侧核微量注射NMDA受体拮抗剂可减少条件性恐惧引起的冰冻行为。4)条件性恐惧诱导杏仁核c-Fos表达，这种增加的c-Fos表达可被SSRI应用和消退实验所减弱。C-Fos表达减少伴随着冻结行为的减少，这是恐惧的一个指标。这些结果表明，SSRIs诱导的5-羟色胺增加抑制了杏仁核中的神经元活动，减少了恐惧。这种5-羟色胺假说可以解释SSRIs的抗焦虑作用机制。

The purpose of this study is to examine the functional role of various brain regions for anxiety and the relationship between glutamate/monoamine neurotransmission and emotional behavior.1)Damages to the mediodorsal nucleus of the thalamus and the amygdale interfered with both the acquisition and expression of contextual fear conditioning. Septal lesions reduced only the expression of contextual fear conditioning.2)Microinjection of a selective serotonin reuptake inhibitor (SSRI) into the basolateral nucleus of the amygdala reduces freezing behavior induced by conditioned fear.3)Microinjection of NMDA receptor antagonists into the amygdale and mediodorsal nucleus of the thalamus reduces freezing behavior induced by conditioned fear.4)Conditioned fear induced c-Fos expression in the amygdala and this increased c-Fos expression was attenuated by SSRI administration and extinction trials. Reduced c-Fos expression was accompanied by reduced freezing behavior as an index of fear. These results suggest that increased serotonin induced by SSRIs inhibits neuronal activities in the amygdala and reduces fear. This serotonin hypothesis may explain the mechanism of anxiolytic action of SSRIs.