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---

本研究的目的是探讨不同脑区在焦虑中的功能作用以及谷氨酸/单胺神经传递与情绪行为之间的关系。1）丘脑背内侧核和杏仁核的损伤干扰了情境恐惧条件反射的获得和表达。隔核损伤只减少了条件性恐惧的表达。2）杏仁基底外侧核微量注射选择性5-羟色胺再摄取抑制剂（SSRI）减少了条件性恐惧诱导的冻结行为。3）杏仁核和丘脑背内侧核微量注射NMDA受体拮抗剂减少了条件性恐惧诱导的冻结行为。4）条件性恐惧诱导的c-羟色胺再摄取抑制剂（SSRI）减少了条件性恐惧诱导的冻结行为。Fos在杏仁核中的表达和这种增加的c-Fos表达被SSRI给药和消退试验减弱。c-Fos表达减少伴随着作为恐惧指数的冻结行为减少。这些结果表明，SSRIs诱导的血清素增加抑制了杏仁核中的神经元活动，减少了恐惧。这种血清素假说可以解释SSRIs抗焦虑作用的机制。

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.