苯甲酸鈉改善K他命誘發之行為異常

Sodium benzoate ameliorates ketamine-induced behavioral disturbances

劉奕賢(none)

指導教授 ： 陳慧諴、詹銘煥

國立政治大學/理學院/神經科學研究所/碩士(2018年)

https://doi.org/10.6814/THE.NCCU.IN.004.2018.C05

摘要

K他命 (Ketamine)是一種合成的解離型麻醉劑，具有快速啟動抗憂鬱效果的作用。近年來，它成為了一種常見的濫用藥物。長期使用K他命會造成突觸功能損傷與行為異常，如 : 社交互動缺陷、認知功能障礙以及憂鬱症傾向的情形發生，亦會降低突觸相關蛋白的表現量。越來越多的研究發現，藉由增強NMDA受體的功能可以改善K他命誘導的行為異常與神經化學變化。苯甲酸鈉 (sodium benzoate)是一種右旋胺基酸氧化酵素酶抑制劑，透過增加D-serine間接增強NMDA受體功能，臨床研究顯示對思覺失調症或憂鬱症患者皆有良好的治療效果。本研究的目標在於檢測sodium benzoate是否可以保護或改善小鼠急性或重複暴露K他命情況下所導致的行為與突觸蛋白異常。結果發現，sodium benzoate在強迫游泳試驗中具有抗憂鬱效果，然而與K他命並不會產生加成的作用。Sodium benzoate增強了K他命在失去翻正反射試驗中的麻醉反應，但減弱了K他命誘導在社交互動行為與新物體辨識能力測試中的擬精神病行為。同時重複給予sodium benzoate與K他命14天顯著地減弱K他命誘導的持續性行為異常，包括社交退縮、認知障礙、類憂鬱症行為與5-HT2A受體介導頭部抽蓄反應的敏感性。此外，透過後給予sodium benzoate方式也能改善重複暴露K他命後的異常行為表現及海馬迴中突觸蛋白表現異常的影響。這些結果推測sodium benzoate可能有助於減緩使用K他命所造成的負面行為影響。

關鍵字

K他命 ； 苯甲酸鈉 ； 抗憂鬱效果 ； 擬精神病行為 ； 麻醉反應

並列摘要

Ketamine is a synthetic dissociative anesthetic and has rapid onset antidepressant effect. It has become a common abused substance, recently. Heavy ketamine use often results in synaptic dysfunction and behavioral disturbances including depression, social deficits, cognitive impairments and decrease synapse-associated protein expression. Growing evidence shows that enhancement of NMDA receptor function can ameliorate the effects of ketamine-induced behavioral and neurochemical responses. Sodium benzoate, an inhibitor of D-amino acid oxidase, can indirectly increase the NMDA receptor function through increasing the levels of D-serine and is also beneficial to the patients with depression or schizophrenia in the clinical study. The present study examined whether sodium benzoate could protect or reverse the behavioral dysfunction and synaptic dysfunction in mice exposed to ketamine acutely or repeatedly. Our results showed that sodium benzoate has antidepressant-like responses in the forced swimming test, whereas it did not produce additive effect with ketamine. Sodium benzoate enhanced the anesthetic responses of ketamine in the loss of righting reflex test, but attenuated the ketamine-induced psychotomimetic behaviors in the social interaction test and novel object recognition test. Repeated cotreatment of sodium benzoate and ketamine for 14 days significantly attenuated ketamine-induced persistent behavioral abnormalities including social withdrawal, recognition impairment, depression-like behaviors and hypersensitiveness of 5-HT2A receptor-mediated head twitch response. Moreover, the behavioral manifestation and lower level of synaptic protein PSD-95 after repeated ketamine exposure could be ameliorated by post-treatment of sodium benzoate. These findings suggest that sodium benzoate might have potential to reduce negative behavioral consequences of heavy ketamine use.

並列關鍵字

Ketamine ； Sodium benzoate ； Antidepressant-like responses ； Psychotomimetic behaviors ； Anesthetic responses

參考文獻

中文部分

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英文部分

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