Han Huili, Dong Zhifang, Jia Yunfang, Mao Rongrong, Zhou Qixin, Yang Yuexiong, Wang Liping, Xu Lin, Cao Jun
1] Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China [2] Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China [3] Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
Sci Rep. 2015 May 5;5:9666. doi: 10.1038/srep09666.
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.
成瘾行为越来越被认为是一种与药物相关的病理性记忆，其中海马体深度参与其中。已有充分的文献证明，海马体中兴奋性传递的突触可塑性适应可能导致阿片类药物成瘾。然而，在阿片类药物滥用期间，海马体中抑制性传递的突触可塑性是否以及如何发生适应性变化仍不清楚。在此，我们报告，与生理盐水对照相比，单次体内吗啡暴露（SM）不影响海马体中的抑制性长时程抑制（I-LTD）；而重复吗啡暴露（RM）则消除了这种I-LTD。有趣的是，重复吗啡暴露后3至5天的阿片类药物戒断（RMW），而非单次吗啡暴露（SMW），在很大程度上增强了I-LTD。更重要的是，单次吗啡治疗中的I-LTD依赖于突触前机制，因为它可被选择性大麻素受体1拮抗剂AM251阻断。而RMW组中的大量I-LTD依赖于突触前和突触后组合机制，因为它可被AM251和L型钙通道阻滞剂LaCl3共同应用所阻断。因此，这些结果表明，阿片类药物的使用和戒断驱动海马体中突触前和突触后I-LTD表达的动态变化，这可能导致阿片类药物滥用期间持续的行为改变。
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