Selective, retrieval-independent disruption of methamphetamine-associated memory by actin depolymerization.
Selective, retrieval-independent disruption of methamphetamine-associated memory by actin depolymerization.
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DOI：
10.1016/j.biopsych.2013.07.036
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发表时间：
2014-01-15
影响因子：
10.6
通讯作者：
Miller, Courtney A.
中科院分区：
文献类型：
--
作者：
Young, Erica J.;Aceti, Massimiliano;Griggs, Erica M.;Fuchs, Rita A.;Zigmond, Zachary;Rumbaugh, Gavin;Miller, Courtney A.
与滥用药物有关的记忆，如甲基苯丙胺（METH），增加了对物质使用障碍的复发脆弱性。越来越多的人认为，记忆是由兴奋性突触突触后树突棘中的F-肌动蛋白聚合驱动的结构和功能可塑性支持的。然而，在巩固发生后，负责长期维持记忆的机制在很大程度上是未知的。条件性位置偏爱（N=112）和上下文诱导的自我管理恢复（N=19）被用来评估的作用F-肌动蛋白聚合和肌球蛋白II，分子马达驱动记忆促进树突棘肌动蛋白聚合，在维护的甲基-相关的记忆和相关的结构可塑性。通过与甲基苯丙胺（METH），但不与足休克或食物奖励协会，形成的记忆被破坏时，注入杏仁核巩固后的维持阶段高度特异性肌动蛋白循环抑制剂。这种选择性的解聚作用对甲基苯丙胺相关记忆是即时的，持久的，并不依赖于检索或强度的协会。非肌肉肌球蛋白II的抑制也导致了甲基苯丙胺相关记忆的破坏。因此，药物相关记忆似乎是由肌球蛋白II驱动的一种独特的F-肌动蛋白循环形式积极维持的。这一发现为选择性治疗与精神疾病相关的不想要的记忆提供了一种潜在的治疗方法，该方法既具有选择性，又不依赖于记忆的检索。结果进一步表明，记忆的维持取决于聚合肌动蛋白的保存。
Memories associated with drugs of abuse, such as methamphetamine (METH), increase relapse vulnerability to substance use disorder. There is a growing consensus that memory is supported by structural and functional plasticity driven by F-actin polymerization in postsynaptic dendritic spines at excitatory synapses. However, the mechanisms responsible for the long-term maintenance of memories, after consolidation has occurred, are largely unknown. Conditioned place preference (N=112) and context-induced reinstatement of self-administration (N=19) were used to assess the role of F-actin polymerization and myosin II, a molecular motor that drives memory-promoting dendritic spine actin polymerization, in the maintenance of METH-associated memories and related structural plasticity. Memories formed through association with methamphetamine (METH), but not associations with foot shock or food reward, were disrupted by a highly-specific actin cycling inhibitor when infused into the amygdala during the post-consolidation maintenance phase. This selective effect of depolymerization on METH-associated memory was immediate, persistent and did not depend upon retrieval or strength of the association. Inhibition of non-muscle myosin II also resulted in a disruption of METH-associated memory. Thus, drug-associated memories appear to be actively maintained by a unique form of cycling F-actin driven by myosin II. This finding provides a potential therapeutic approach for the selective treatment of unwanted memories associated with psychiatric disorders that is both selective and does not rely on retrieval of the memory. The results further suggest that memory maintenance depends upon the preservation of polymerized actin.
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