Behavioral pharmacological and molecular biological study on the emotional symptoms of schizophrenia for the pathogenesis of psychiatric disorders. ---The relationship between aggression/anxiety and excitatory amino acid in the chronic

精神分裂症情绪症状与精神疾病发病机制的行为药理学和分子生物学研究。

• 批准号: 11670924
• 负责人: TAKESHI Inoue
• 金额: $ 2.18万
• 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670924/
• 关键词: Methamphetamine; Schizophrenia; excitatory amino acid; emotion; anxiety; aggression

The purpose of this study is to clarify the effect of chronic methamphetamine treatment on aggressive behavior and anxiety and to examine the functional role of various brain regions for aggression and anxiety and the relationship between glutamate neurotransmission and emotional behavior.1) Repeated methamphetamine treatment increased aggressive behavior and anxiety, which was antagonized by the pretreatment with the dopamine2 receptor antagonist as shown in our previous study.2) MS-153, an inhibitor for glutamate release, inhibited both the acquisition and expression of conditioned freezing, an index of anxiety/fear. Repeated MS-153 pretreatment enhanced the inhibitory effect of MS-153 on the acquisition of conditioned fear. These indicate that endogenous glutamate is related to the acquisition and expression of anxiety or fear.3) The radiofrequency lesions of the amygdala and the mediodorsal nuleus of the thalamus inhibited both the acquisition and expression of conditioned fear. These results suggest that both brain regions play an important role for the development and expression of anxiety.4) Chronic treatment with staurosporine, a protein kinase C inhibitor, reduced the acquisition, but not expression, of conditioned fear.

本研究的目的是阐明慢性甲基苯丙胺治疗对攻击行为和焦虑的影响，并检查各个脑区对攻击和焦虑的功能作用以及谷氨酸神经传递与情绪行为之间的关系。1）重复甲基苯丙胺治疗增加了攻击行为和焦虑，2）谷氨酸释放抑制剂MS-153抑制条件性冻结的获得和表达，焦虑/恐惧的表现重复MS-153预处理增强了MS-153对条件性恐惧获得的抑制作用。说明内源性谷氨酸与焦虑或恐惧的获得和表达有关。3）射频毁损杏仁核和丘脑背内侧核可抑制条件性恐惧的获得和表达。这些结果表明，这两个大脑区域的发展和表达的焦虑发挥了重要作用。4）staurosporine，蛋白激酶C抑制剂，慢性治疗，减少收购，但不表达，条件性恐惧。

项目成果

Tomohiro Abekawa: "Effects of MS-153 on the development of behavioral sensitization to locomotion-and ataxia-inducing effects of phencyclidine"Psychopharmacology. 160. 122-131 (2002)

Tomohiro Abekawa：“MS-153 对苯环己哌啶的运动和共济失调诱导作用的行为敏感性发展的影响”精神药理学。

Takeshi Inoue: "Serotonergic neurotransmission and defensive freezing in the conditioned fear stress paradigm"In : Affective Minds, Elsevier Science, Amsterdam. 91-100 (2000)

Takeshi Inoue：“条件性恐惧压力范式中的血清素神经传递和防御性冻结”，载于：情感思维，爱思唯尔科学，阿姆斯特丹。

Takeshi Inoue: "Effect of the dopamine D1/5 antagonist SCH 23390 on the acquisition of conditioned fear"Pharmacology, Biochemistry and Behavior. 66. 573-578 (2000)

Takeshi Inoue：“多巴胺 D1/5 拮抗剂 SCH 23390 对获得条件性恐惧的影响”药理学、生物化学和行为。

Muraki I.: "Effect of sub chronic lithium treatment on c, talopran-induced increases in extracellular conontrations of sewtonin in the medial prefrontal cirtea"Journal of Neurochemistry. 76(2). 490-497 (2001)

Muraki I.：“亚慢性锂治疗对 c，talopran 诱导的内侧前额叶环中 sewtonin 细胞外浓度增加的影响”神经化学杂志。

井上 猛: "人の不安・恐怖における扁桃体の役割"脳の科学. 21(9). 1011-1015 (1999)

Takeshi Inoue：“杏仁核在人类焦虑和恐惧中的作用”《脑科学》21(9)。