Schizophrenia modifies the action of general anesthetics: Neuroscientific approach in amygdala/hippocampal preparation

2018 Fiscal Year Final Research Report

• Project/Area Number: 26462333
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: University of Toyama
• Principal Investigator: Koki Hirota 富山大学, 大学院医学薬学研究部(医学), 准教授 (30218854)
• Research Collaborator: Sasaki Rika 富山大学 ; Roth Sheldon H. University of Calgary
• Project Period (FY): 2014-04-01 – 2019-03-31
• Keywords: 統合失調症 / 扁桃体 / 海馬 / シナプス伝達 / 全身麻酔薬 / 静脈麻酔薬

Outline of Final Research Achievements

We have examined effects of general anesthetics on amygdala/hippocampal synaptic transmission in the absence and presence of schizophrenia. Schizophrenia model rats were produced with methylazoxymethanol acetate（MAM）administration. Stimulating electrodes were placed in radiatum stratum (Rad) to stimulate CA1, and in amygdala-hippocampal area (AH) to simulate amygdala inputs to hippocampus. Two sets of extracellular recording microelectrodes were positioned in cell bodies and dendrites of CA1 to record population spikes (PSs) and excitatory post-synaptic potentials (EPSPs), respectively.
The train induced disinhibition (TID) protocol demonstrated that GABA recruitments schizophrenia model rats were deteriorated, suggesting that schizophrenia can modify anesthetic actions. The modification might explain delirium, excitation, or unexpected unstableness during genenal anesthesia.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

精神疾患が全身麻酔薬作用に及ぼす影響に関する基礎的知見は乏しく，臨床における精神疾患症例の麻酔において，麻酔科医は限られた臨床経験をもとに手探りで麻酔管理を施行しているのが現状である．統合失調症の発症原因は不明であるが，最新の知見によると扁桃体/海馬などの感情回路の発達障害がその誘因の１つと考えられている（発達障害仮説）．
今回我々は，統合失調症モデルラットの扁桃体/海馬標本における全身麻酔薬の作用を検討した結果，抑制性伝達物質GABAの放出/再取り込みが障害されていることが明らかとなった．この知見は，今後臨床における統合失調症患者の麻酔管理に有用なエビデンスになると考えられる．