吸毒成癮是一種慢性疾病，往往長(zhǎng)時(shí)間戒毒后仍然會(huì)復(fù)發(fā),。該疾病的神經(jīng)生物學(xué)的依據(jù)目前還不清楚,，不過(guò)，大腦中的突觸聯(lián)系持續(xù)變化的區(qū)域可能與毒癮相關(guān),。在8月28日的《神經(jīng)元》（Neuron）雜志上,，Pulipparacharuvil等人的研究表明，肌細(xì)胞增強(qiáng)因子-2的轉(zhuǎn)錄因子是體內(nèi)控制可卡因誘導(dǎo)結(jié)構(gòu)性突觸的可塑性的關(guān)鍵蛋白質(zhì),。
反復(fù)接觸可卡因會(huì)引起敏感的行為反應(yīng)，并在增加伏核紋狀體（NAc）棘狀神經(jīng)元樹(shù)突狀刺,。Pulipparacharuvil等發(fā)現(xiàn),，可卡因可以在體內(nèi)通過(guò)調(diào)節(jié)心肌細(xì)胞增強(qiáng)因子-2（MEF2）的轉(zhuǎn)錄因子來(lái)控制上述兩個(gè)過(guò)程；可卡因抑制紋狀體MEF2活動(dòng)的部分作用機(jī)制涉及環(huán)磷酸腺苷,、鈣調(diào)蛋白信號(hào)傳導(dǎo)器和神經(jīng)鈣蛋白,；減少體內(nèi)Nac中MEF2的活動(dòng)，需要在樹(shù)突狀刺密度中可卡因誘導(dǎo)的增加,。
但令人驚訝的是,，阻止這種結(jié)構(gòu)性突觸的可塑性的條件是提高反復(fù)接觸可卡因的行為反應(yīng)。這表明在神經(jīng)元結(jié)構(gòu)中,，長(zhǎng)期的可卡因誘導(dǎo)變化可能是限制上癮有關(guān)行為一個(gè)補(bǔ)償機(jī)制,，而不是維持毒癮。（生物谷Bioon.com）
生物谷推薦原始出處：
Neuron,，Vol 59, 621-633, 28 August 2008,，Suprabha Pulipparacharuvil, Christopher W. Cowan
Cocaine Regulates MEF2 to Control Synaptic and Behavioral Plasticity
Suprabha Pulipparacharuvil,1,7 William Renthal,1,2,7 Carly F. Hale,1 Makoto Taniguchi,1Guanghua Xiao,3 Arvind Kumar,1,2 Scott J. Russo,1,2,8 Devanjan Sikder,4 Colleen M. Dewey,1,2Maya M. Davis,6 Paul Greengard,5 Angus C. Nairn,5,6 Eric J. Nestler,1,2,8 and Christopher W. Cowan1
Repeated exposure to cocaine causes sensitized behavioral responses and increased dendritic spines on medium spiny neurons of the nucleus accumbens (NAc). We find that cocaine regulates myocyte enhancer factor 2 (MEF2) transcription factors to control these two processes in vivo. Cocaine suppresses striatal MEF2 activity in part through a mechanism involving cAMP, the regulator of calmodulin signaling (RCS), and calcineurin. We show that reducing MEF2 activity in the NAc in vivo is required for the cocaine-induced increases in dendritic spine density. Surprisingly, we find that increasing MEF2 activity in the NAc, which blocks the cocaine-induced increase in dendritic spine density, enhances sensitized behavioral responses to cocaine. Together, our findings implicate MEF2 as a key regulator of structural synapse plasticity and sensitized responses to cocaine and suggest that reducing MEF2 activity (and increasing spine density) in NAc may be a compensatory mechanism to limit long-lasting maladaptive behavioral responses to cocaine.
