Molecular substrates for retrieval and reconsolidation of cocaine-associated contextual memory
Molecular substrates for retrieval and reconsolidation of cocaine-associated contextual memory
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DOI：
10.1016/j.neuron.2005.08.006
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发表时间：
2005-09-15
期刊：
影响因子：
16.2
通讯作者：
Marshall, JF
中科院分区：
文献类型：
--
作者：
Miller, CA;Marshall, JF
成瘾者重新吸毒通常取决于药物配对线索与这些药物（如可卡因（COC））的奖励效应之间的习得性关联。对药物配对线索的记忆抵抗消退，并导致高复发率;然而，这些关联的分子机制尚不清楚。我们发现，COC条件性位置偏爱（CPP）激活ERK，CREB，Elk-1，和Fos在核内的丘脑核心（AcbC），但不壳。AcbC内输注U 0126（ERK激酶MEK的抑制剂）阻止ERK、CREB、Elk-1和Fos的活化以及COC-CPP的恢复。当在AcbC内输注U 0126或另一种MEK抑制剂PD 98059后24小时或14天再次测试时，CPP恢复和伴随的蛋白质活化显著减弱。总之，这些发现表明AcbC ERK信号通路对药物配对的上下文线索记忆的必要性，并表明这些强大的记忆可能变得容易受到治疗剂的破坏。
Relapse into drug taking among addicts often depends on learned associations between drug-paired cues and the rewarding effects of these drugs, such as cocaine (COC). Memory for drug-paired cues resists extinction and contributes to the high rate of relapse; however, the molecular mechanisms underlying these associations are not understood. We show that COC-conditioned place preference (CPP) activates ERK, CREB, Elk-1, and Fos in the nucleus accumbens core (AcbC) but not shell. Intra-AcbC infusions of U0126, an inhibitor of the ERK kinase MEK, prevent both the activation of ERK, CREB, Elk-1, and Fos and retrieval of COC-CPP. When tested again 24 hr or 14 days after intra-AcbC infusions of U0126 or another MEK inhibitor, PD98059, CPP retrieval and concomitant protein activation were significantly attenuated. Together, these findings indicate the necessity of the AcbC ERK signaling pathway for drug-paired contextual cue memories and suggest that these strong memories can become susceptible to disruption by therapeutic agents.