紐約西奈山醫(yī)療中心一項(xiàng)新的研究表明：反復(fù)接觸可卡因會(huì)降低大腦中樞系統(tǒng)的正常運(yùn)作所必需的蛋白質(zhì)的活性,，從而提高了中樞對(duì)可卡因的依賴性,，從而導(dǎo)致成癮發(fā)生,。相關(guān)研究論文發(fā)表在4月22日的Nature Neuroscience雜志上,，該研究揭示了可卡因是如何改變小鼠模型中大腦神經(jīng)元中樞形狀和大小的。
反復(fù)接觸可卡因會(huì)降低大腦中樞系統(tǒng)的正常運(yùn)作所必需的蛋白質(zhì)的表達(dá),，從而提高了中樞對(duì)可卡因的利用率,，刺激成癮性的產(chǎn)生。使用蛋白質(zhì)的實(shí)時(shí)光活化形式光即遺傳學(xué)技術(shù),，研究者發(fā)現(xiàn)阻止大腦中樞中心反復(fù)暴露于可卡因環(huán)境下,。盡管將研究結(jié)果從動(dòng)物模型上開展到人身上有許多步驟要完成，但研究人員表示這一發(fā)現(xiàn)為治療可卡因成癮提供了一個(gè)新的研究方向,。
西奈山醫(yī)學(xué)院大腦研究所Eric Nestler博士表示：可卡因成癮沒有實(shí)質(zhì)性的藥物治療方案,，只有心理治療和一些疫苗等。Rac1存在于小鼠,、大鼠,，猴子和人體內(nèi)的許多細(xì)胞中，它參與控制神經(jīng)細(xì)胞的生長(zhǎng),。
研究者敲除或“刪除”調(diào)控Rac1生成的基因,，或注射病毒以提高Rac1的表達(dá)。
Nestler博士說：這項(xiàng)研究為我們了解可卡因如何影響大腦中樞,，以及大腦中樞是如何被修復(fù)的提供了新的思路,。（生物谷：Bioon.com）
doi:10.1038/nn.3094
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PMID:
Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons
David M Dietz,Haosheng Sun,Mary Kay Lobo,Michael E Cahill,Benjamin Chadwick,Virginia Gao,Ja Wook Koo,Michelle S Mazei-Robison,Caroline Dias,Ian Maze,et al.
Repeated cocaine administration increases the dendritic arborization of nucleus accumbens neurons, but the underlying signaling events remain unknown. Here we show that repeated exposure to cocaine negatively regulates the active form of Rac1, a small GTPase that controls actin remodeling in other systems. Further, we show, using viral-mediated gene transfer, that overexpression of a dominant negative mutant of Rac1 or local knockout of Rac1 is sufficient to increase the density of immature dendritic spines on nucleus accumbens neurons, whereas overexpression of a constitutively active Rac1 or light activation of a photoactivatable form of Rac1 blocks the ability of repeated cocaine exposure to produce this effect. Downregulation of Rac1 activity likewise promotes behavioral responses to cocaine exposure, with activation of Rac1 producing the opposite effect. These findings establish that Rac1 signaling mediates structural and behavioral plasticity in response to cocaine exposure.
