Persistent proteomic alterations in the medial prefrontal cortex with abstinence from cocaine self-administration.
Persistent proteomic alterations in the medial prefrontal cortex with abstinence from cocaine self-administration.
复制标题
DOI：
10.1002/prca.200800055
复制
发表时间：
2009-03-17
影响因子：
2
通讯作者：
Freeman, Willard M.
中科院分区：
文献类型：
--
作者：
Lull, Melinda E.;Erwin, Mandi S.;Morgan, Drake;Roberts, David C. S.;Vrana, Kent E.;Freeman, Willard M.
药物滥用的神经蛋白质组学研究提供了一个系统水平的理解成瘾的潜力。了解可卡因对大脑蛋白质表达的反应性改变，即使延长戒断时间也会持续存在，这可能会提供对复发倾向的深入了解。在当前的研究中，通过2D-DIGE量化了强制戒酒1天和100天后可卡因自我给药大鼠内侧前额叶皮质的蛋白质变化。我们以前曾报道过，即使在强制禁欲100天后，这种模型中的药物寻求和药物服用以及mRNA和表观遗传变化也会增加。与突触功能和神经元重塑相关的蛋白质中的许多显著变化是明显的，包括神经丝介质和热休克蛋白73（Hsp 73），其在戒断1天时增加，但在戒断100天后恢复到正常水平。-1和突触体相关蛋白25 kDa（SNAP-25）在戒断1天时没有变化，但在100天后显著降低。这些数据表明，虽然一些蛋白质变化在强制可卡因戒断后恢复到正常水平，但在长达100天的可卡因戒断后，一些蛋白质仍然存在或发生变化。这些蛋白质表达的变化，不复位到前可卡因暴露水平可能有助于持续复发的潜力，发生在响应可卡因戒断。
Neuroproteomic studies of drug abuse offer the potential for a systems-level understanding of addiction. Understanding cocaine-responsive alterations in brain protein expression that persist even with extended abstinence may provide insight into relapse liability. In the current study, protein changes in the medial prefrontal cortex of cocaine self-administering rats following 1 and 100 days of enforced abstinence were quantified by 2D-DIGE. We have previously reported increased drug-seeking and drug-taking, as well as mRNA and epigenetic changes in this model even after 100 days of enforced abstinence. A number of statistically-significant changes in proteins relating to synapse function and neuronal remodeling were evident, including neurofilament medium and heat shock protein 73 (Hsp73) which increased at 1 day of abstinence, but returned to normal levels following 100 days of abstinence. −1 and synaptosome-associated protein 25 kDa (SNAP-25) were unchanged at 1 day of abstinence, but were significantly decreased after 100 days. These data demonstrate that while some protein changes return to normal levels following enforced cocaine abstinence, a number remain or become altered after long periods, up to 100 days, of cocaine abstinence. Those protein expression changes that do not reset to pre-cocaine exposure levels may contribute to the persistent relapse potential that occurs in response to cocaine abstinence.
登录
查看更多内容
影响因子：
3.2
作者：
Jing, H;Li, Y
通讯作者：
Li, Y
影响因子：
7.6
作者：
NESTLER, EJ
通讯作者：
NESTLER, EJ
影响因子：
7.6
作者：
Freeman, Willard M.;Patel, Kruti M.;Vrana, Kent E.
通讯作者：
Vrana, Kent E.
影响因子：
4.7
作者：
Hope, BT;Crombag, HS;Wise, RA
通讯作者：
Wise, RA
影响因子：
7
作者：
Moron, Jose A.;Abul-Husn, Noura S.;Devi, Lakshmi A.
通讯作者：
Devi, Lakshmi A.