Morphine-Associated Contextual Cues Induce Structural Plasticity in Hippocampal CA1 Pyramidal Neurons
Morphine-Associated Contextual Cues Induce Structural Plasticity in Hippocampal CA1 Pyramidal Neurons
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DOI：
10.1038/npp.2016.69
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发表时间：
2016-10-01
影响因子：
7.6
通讯作者：
Moron, Jose A.
中科院分区：
文献类型：
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作者：
Fakira, Amanda K.;Massaly, Nicolas;Moron, Jose A.
在有阿片类药物滥用史的人中，即使在多年的禁欲之后，与先前药物摄入相关的线索也可能引发复发。检查导致线索/背景和阿片类药物之间记忆形成和维持的过程可能有助于发现新的治疗药物来治疗药物寻求行为。海马体是学习和记忆必不可少的大脑区域，它参与了阿片类药物渴望的机制。记忆和联想的形成被认为依赖于与树突棘的结构可塑性相关的突触强化。在这里，我们评估海马CA 1区的树突棘是如何受到吗啡条件训练的影响。我们的研究结果表明，吗啡与环境线索（即条件性位置偏爱（CPP）装置）配对触发海马中细树突棘数量的显着减少。有趣的是，当小鼠使用未配对的吗啡CPP设计进行训练时，无论条件反应的表达如何，都会观察到这种效应，而当在饲养笼中给予吗啡时，这种效应就不存在了。为了研究这种结构可塑性的机制，我们研究了Rho GTdR在树突棘重塑中的作用。我们发现，突触表达的RhoA增加与吗啡条件和阻断RhoA信号阻止吗啡诱导的CPP的表达。我们的研究结果揭示了吗啡相关的环境线索和脊柱可塑性的潜在改变的新机制。
In people with a prior history of opioid misuse, cues associated with previous drug intake can trigger relapse even after years of abstinence. Examining the processes that lead to the formation and maintenance of the memories between cues/context and the opioid may help to discover new therapeutic candidates to treat drug-seeking behavior. The hippocampus is a brain region essential for learning and memory, which has been involved in the mechanisms underlying opioid cravings. The formation of memories and associations are thought to be dependent on synaptic strengthening associated with structural plasticity of dendritic spines. Here, we assess how dendritic spines in the CA1 region of the hippocampus are affected by morphine-conditioning training. Our results show that morphine pairing with environmental cues (ie, the conditioned place preference (CPP) apparatus) triggers a significant decrease in the number of thin dendritic spines in the hippocampus. Interestingly, this effect was observed regardless of the expression of a conditioned response when mice were trained using an unpaired morphine CPP design and was absent when morphine was administered in the home cage. To investigate the mechanism underlying this structural plasticity, we examined the role of Rho GTPase in dendritic spine remodeling. We found that synaptic expression of RhoA increased with morphine conditioning and blocking RhoA signaling prevented the expression of morphine-induced CPP. Our findings uncover novel mechanisms in response to morphine-associated environmental cues and the underlying alterations in spine plasticity.