Opioid addiction and withdrawal differentially drive long-term depression of inhibitory synaptic transmission in the hippocampus.
Opioid addiction and withdrawal differentially drive long-term depression of inhibitory synaptic transmission in the hippocampus.
复制标题
阿片类药物成瘾和戒断不同程度地驱动海马抑制性突触传递的长期抑制
DOI：
10.1038/srep09666
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发表时间：
2015-05-05
影响因子：
4.6
通讯作者：
Cao J
中科院分区：
文献类型：
--
作者：
Han H;Dong Z;Jia Y;Mao R;Zhou Q;Yang Y;Wang L;Xu L;Cao J
成瘾行为越来越被认为是一种与药物相关的病理记忆，海马体在其中起着深刻的作用。已有文献表明，海马兴奋性传递突触可塑性的适应可能有助于阿片类药物成瘾。然而，在阿片类药物滥用过程中，海马抑制性传递突触可塑性是否以及如何发生适应性变化尚不清楚。在这里，我们报道了与生理盐水对照相比，单次体内吗啡暴露（SM）不影响海马的抑制性长期抑郁（I-LTD）；而重复吗啡暴露（RM）则消除了这种I-LTD。有趣的是，重复（RMW）后3-5天的阿片类药物戒断，而不是单次吗啡暴露（SMW），在很大程度上增强了I-LTD。更重要的是，单一吗啡治疗中的I-LTD依赖于突触前机制，因为它可以被AM251（一种选择性大麻素受体1拮抗剂）阻断。而RMW组的大I-LTD依赖于突触前和突触后的组合机制，因为它可以通过AM251和l型钙通道阻滞剂LaCl3共同应用来阻断。因此，这些结果表明，阿片类药物使用和戒断驱动突触前和突触后海马I-LTD表达的动态，这可能有助于阿片类药物滥用期间持续的行为改变。
Addictive behavior is increasingly accepted as a drug-associated pathological memory in which the hippocampus is profoundly engaged. It has been well documented that adaptations of synaptic plasticity of excitatory transmission in the hippocampus may contribute to opioid addiction. However, it remains unknown whether and how adaptive changes of synaptic plasticity of inhibitory transmission in the hippocampus occurs during opioid abuse. Here, we reported that a single in vivo morphine exposure (SM) did not affect inhibitory long-term depression (I-LTD) in the hippocampus, compared with saline control; while repeated morphine exposure (RM) abolished this I-LTD. Interestingly, opioid withdrawal for 3-5 days after repeated (RMW), but not a single morphine exposure (SMW), largely enhanced I-LTD. More importantly, the I-LTD in single morphine treatment is dependent on presynaptic mechanism since it can be blocked by AM251, a selective cannabinoid receptor 1 antagonist. While the large I-LTD in RMW group is dependent on combinatorial presynaptic and postsynaptic mechanisms since it can be blocked by co-application of AM251 and L-type calcium channel blocker LaCl3. Thus, these results demonstrate that opioid use and withdrawal drive the dynamics of presynaptic and postsynaptic I-LTD expression in the hippocampus that may contribute to the persistent behavioral changes during opioid abuse.