中文摘要：

学习和记忆的依赖和缺陷是象 opioids 那样的滥用的药引起的二 well-establishedfeatures。马头鱼尾的怪兽是与两药依赖联系的一个重要区域并且学习并且记忆。然而，在到象 opioids 那样的滥用的药的马头鱼尾的怪兽追随者暴露的分子的事件很好没被理解。这里，我们由 proteomic 分析在海马趾的蛋白质表示上检验了长期的吗啡处理的效果。 Wefound 到为 10 天的吗啡的老鼠的那长期的暴露生产了柔韧的吗啡退却跳和记忆缺陷，并且也导致了三新陈代谢的酶的海马趾的蛋白质层次的一条重要down 规定包括 Fe-S 蛋白质 1 NADH 脱氢酶， pyruvate 建筑群和乳酸脱氢酶的 dihydrolipoamide acetyltransferase 或 E2 部件 2 。进一步即时的量的 PCR 分析证实相应 mRNAs 的层次显著地也被减少。与这些调查结果，更低的 ATP 层次和把葡萄糖变换成 ATP 的一个损害能力一致也在长期地对待的老鼠的马头鱼尾的怪兽被观察。显著地与吗啡附随地管理的 Opioid 对手 naltrexone 压制了吗啡退却跳并且颠倒了这些蛋白质的 down 规定。到吗啡的尖锐暴露也生产了跳的柔韧的吗啡退却和重要存储器缺陷，但是在吗啡管理显著地提高了 ATPlevels 并且压制了吗啡退却不在长期的对待吗啡的鼠标在尖锐 morphine-treatedbut 跳和存储器缺陷以前，没有通过 D 葡萄糖的这三 proteins.Intrahippocampal 注射的表达式到减少。D 葡萄糖的高剂量的 Intraperitoneal 注射在作为中央处理跳的导致吗啡的退却上显示出类似的效果。总起来说，我们的结果建议在由于长期的吗啡处理的马头鱼尾的怪兽的三新陈代谢的酶的那减少的表情贡献象吗啡退却跳和记忆缺陷那样的导致药的症状的发展。

英文摘要：

Dependence and impairment of learning and memory are two well-established features caused by abused drugs such as opioids. The hippocampus is an important region associated with both drug dependence and learning and memory. However, the molecular events in hippocampus following exposure to abused drugs such as opioids are not well understood. Here we examined the effect of chronic morphine treatment on hippocampal protein expression by proteomic analyses. We found that chronic exposure of mice to morphine for 10 days produced robust morphine withdrawal jumping and memory impairment, and also resulted in a significant downregulation of hippocampal protein levels of three metabolic enzymes, including Fe-S protein 1 ofNADH dehydrogenase, dihydrolipoamide acetyltransferase or E2 component of the pyruvate dehydrogenase complex and lactate dehydrogenase 2. Further real-time quantitative PCR analyses confirmed that the levels of the corresponding mRNAs were also remarkably reduced. Consistent with these findings, lower ATP levels and an impaired ability to convert glucose into ATP were also observed in the hippocampus of chronically treated mice. Opioid antagonist naltrexone administrated concomitantly with morphine significantly suppressed morphine withdrawal jumping and reversed the downregulation of these proteins. Acute exposure to morphine also produced robust morphine withdrawal jumping and significant memory impairment, but failed to decrease the expression of these three proteins. Intrahippocampal injection of D-glucose before morphine administration significantly enhanced ATP levels and suppressed morphine withdrawal jumping and memory impairment in acute morphine-treated but not in chronic morphine-treated mice. Intraperitoneal injection of high dose of D-glucose shows a similar effect on morphine-induced withdrawal jumping as the central treatment. Taken together, our results suggest that reduced expression of the three metabolic enzymes in the hippocampus as a result of chronic morphine treatment contributes