【摘要】：精神分裂癥是一種嚴(yán)重而復(fù)雜的精神疾病,認(rèn)知障礙是其核心癥狀之一。己知乙酰膽堿系統(tǒng)是參與認(rèn)知調(diào)節(jié)的中樞神經(jīng)遞質(zhì)系統(tǒng)之一,且與目前公認(rèn)的與精神分裂癥關(guān)系密切的多巴胺系統(tǒng)有一定的相互作用。本研究通過青春期MK-801注射和青春期社會隔離兩種建模方式,采用Morris水迷宮和前脈沖抑制兩種行為檢測方法,觀察了乙酰膽堿激動劑加蘭他敏對大鼠擬精神分裂癥認(rèn)知功能障礙的影響,并進(jìn)一步探討了其與中樞多巴胺神經(jīng)遞質(zhì)系統(tǒng)的相互作用。 研究結(jié)果發(fā)現(xiàn),青春期MK-801注射及社會隔離均能誘導(dǎo)成年大鼠前脈沖抑制的缺失,并顯著降低了前額葉多巴胺D2受體的蛋白含量,但不影響青春期大鼠的前脈沖抑制。乙酰膽堿激動劑加蘭他敏可以逆轉(zhuǎn)上述擬精神分裂癥動物模型的前脈沖抑制缺失,以及前額葉多巴胺D2受體蛋白含量的異常降低。 以上研究結(jié)果表明,通過對青春期動物進(jìn)行MK-801注射和社會隔離,可以成功建立擬精神分裂癥前脈沖抑制的動物模型,從而為進(jìn)一步研究精神分裂癥的神經(jīng)機(jī)制奠定了基礎(chǔ)。加蘭他敏對前脈沖抑制缺失的逆轉(zhuǎn)證實(shí)了乙酰膽堿激動劑對于精神分裂癥認(rèn)知障礙的治療效果,為精神分裂癥認(rèn)知障礙神經(jīng)機(jī)制研究以及相關(guān)新藥的研發(fā)提供了基礎(chǔ)。此外,加蘭他敏對前額葉多巴胺D2受體蛋白含量異常降低的逆轉(zhuǎn)以及這種逆轉(zhuǎn)與前脈沖抑制逆轉(zhuǎn)的一致性表明,乙酰膽堿激動劑對于前脈沖抑制的影響與前額葉多巴胺D2受體相關(guān),二者之間的相互作用為進(jìn)一步研究精神分裂癥的發(fā)病機(jī)制提供了實(shí)驗(yàn)依據(jù)。
[Abstract]:Schizophrenia is a serious and complex mental disease, cognitive impairment is one of its core symptoms. Acetylcholine system is known to be one of the central neurotransmitter systems involved in cognitive regulation and has a certain interaction with the current recognized dopamine system which is closely related to schizophrenia. In this study, two modeling methods, MK-801 injection and social isolation, were used to detect the behavior of Morris water maze and pre-pulse suppression. The effects of acetylcholine agonist galantamine on cognitive dysfunction in rats with schizophrenia were observed and its interaction with central dopamine neurotransmitter system was further investigated. The results showed that MK-801 injection and social isolation could induce the absence of prepulse inhibition in adult rats, and significantly decreased the protein content of dopamine D2 receptor in prefrontal lobe, but had no effect on prepulse inhibition in adolescent rats. The acetylcholine agonist galantamine can reverse the prepulse inhibition deletion and the abnormal decrease of dopamine D2 receptor protein content in the prefrontal lobe of the above schizophrenic animal model. These results suggest that the animal model of prepulse suppression of schizophrenia can be successfully established by MK-801 injection and social isolation in adolescent animals, thus laying a foundation for further study of the neuromechanism of schizophrenia. The reversal of prepulse inhibition by galantamine confirms the efficacy of acetylcholine agonists in the treatment of cognitive disorders in schizophrenia and provides a basis for the study of the neuromechanism of cognitive disorders in schizophrenia and the development of related new drugs. In addition, galantamine reversed the abnormal decrease in dopamine D2 receptor protein content in prefrontal lobe and the consistency of this reversal with that of prepulse suppression. The effect of acetylcholine agonist on prepulse inhibition is related to dopamine D2 receptor in prefrontal lobe. The interaction between them provides experimental evidence for further study of the pathogenesis of schizophrenia.
【學(xué)位授予單位】：北京大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R749.3;R96

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