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研究生(外文):Shii-Yi Yang
論文名稱(外文):Effect of the Sarcosine, a Glycine Transporter Type I Inhibitor, on Ketamine-induced Schizophrenia-Like Symptoms in Rats
指導教授(外文):Yn-Ho Huang
外文關鍵詞:ketamineschizophreniaratprepulse inhibition
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精神分裂症是一種包含精神、認知以及情感面的複雜神經精神異常,一般學者認為精神分裂症的肇因之一是前額腦中的麩氨酸過低(hypoglutamatergia)所引起,確實原因仍在研究中。K他命是一種NMDA受器通道的阻斷劑,在人體使用會產生類似精神分裂症的行為反應,因此成為研究精神分裂症的動物模式之一。而肌胺酸(sarcosine),一種第一型甘膠酸轉運子(glycine transporter type I)抑制劑,具有活化NMDA受器的功用,可能具有改善精神分裂症症狀的效果。
在本篇報告中,我們使用K他命(30mg/kg)在大白鼠身上誘導出類似精神分裂症的行為表現,然後使用clozapine(10 or 15mg/kg)作為正向控制組,來測試肌胺酸(100mg/kg)對ketamine類精神症動物的作用。我們也應用前脈衝抑制反射(PPI),一種認知感覺運動調控的反應,來測試並當作精神分裂症的表徵指數。結果發現肌胺酸處理組顯著的改善K他命引發的高運動量、刻板性行為以及PPI功能缺失。免疫組織染色的結果顯示肌胺酸處理組在嗅球的c-Fos與酪氨酸氫氧化酶(TH)表現與K他命組比較都有顯著性降低(p<0.05),但在內側前額葉與下視丘室旁核則顯著的提高。依據上述結果推論肌胺酸對於K他命造成的精神症狀可能具有改善的效果。
Schizophrenia is a complex neuropsychiatric disorder with psychotic, cognitive and affective features. Animal models are critical in pursuit of knowledge and better treatments about schizophrenia. In animal studies, the disruption of prepulse inhibition (PPI), a sign of sensorimotor gating abnormality, is believed to be a symptom of schizophrenia. Sarcosine, an glycine Transporter Type 1 Inhibitor, act as a N-methyl-D- aspartate (NDMA) receptor glycine site co-agonist, have been proposed to have beneficial effect on symptoms of schizo- phrenia. Ketamine is a NMDA receptor antagonist known to produce schizophrenia-like behavior in human beings as well as in animal.
In this study, we used ketamine (30mg/kg, IP) to induce schizophrenia-like behaviors in Spague-Dawley rats, and clozapine (15 mg/kg) for positive control, to test if sarcosine (100mg/kg) have effects on ketamine psychosis. Prepulse Inhibition (PPI) was used as an index for rating deficits in sensory-motor gating. The result showed that sarcosine (sarcosine/ketamine) treatment significantly reduced hyperlocomotion, stereotypy, and PPI deficit induced by ketamine (saline/ketamine). Immunohistochemistry results also showed that sarcosine treatment significantly reduced numbers of c-Fos and tyrosine hydroxylase (TH) expressive cells in the olfactory bulb as compared with the ketamine alone group, but c-Fos positive cells were significantly raised in the medial prefrontal cortex and the hypothalamic paraventricular nucleus. The number of the TH positive cells did not show significant change in the ventral tegmental area and the substantia nigra. The results showed that sarcosine may have beneficial effect on ketamine-induced psychosis.
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