吸毒成瘾是一种慢性疾病，往往长时间戒毒后仍然会复发。该疾病的神经生物学的依据目前还不清楚，不过，大脑中的突触联系持续变化的区域可能与毒瘾相关。在8月28日的《神经元》（Neuron）杂志上，Pulipparacharuvil等人的研究表明，肌细胞增强因子-2的转录因子是体内控制可卡因诱导结构性突触的可塑性的关键蛋白质。
反复接触可卡因会引起敏感的行为反应，并在增加伏核纹状体（NAc）棘状神经元树突状刺。Pulipparacharuvil等发现，可卡因可以在体内通过调节心肌细胞增强因子-2（MEF2）的转录因子来控制上述两个过程；可卡因抑制纹状体MEF2活动的部分作用机制涉及环磷酸腺苷、钙调蛋白信号传导器和神经钙蛋白；减少体内Nac中MEF2的活动，需要在树突状刺密度中可卡因诱导的增加。
但令人惊讶的是，阻止这种结构性突触的可塑性的条件是提高反复接触可卡因的行为反应。这表明在神经元结构中，长期的可卡因诱导变化可能是限制上瘾有关行为一个补偿机制，而不是维持毒瘾。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
