Dong Zhifang, Zhong Weixia, Tian Meng, Han Huili, Cao Jun, Xu Tianle, Luo Jianhong, Xu Lin
Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People's Republic of China.
Hippocampus. 2006;16(12):1017-25. doi: 10.1002/hipo.20234.
Stress impairs hippocampal long-term potentiation (LTP), but it is unknown whether the stress evoked by opiate withdrawal has the same effect. Here the authors report that opiate withdrawal for 4 days does not influence basal synaptic transmission, but results in a greatly increased LTP in hippocampal CA1 area in anesthetized rats. Elevated-platform stress enabled a large LTP in rats withdrawn for only 18 h, but the glucocorticoid receptor antagonist RU38486 (twice per day for 3 days) prevented the large LTP on 4 days withdrawal. Moreover, 4 days withdrawal enhanced the NMDAR-mediated EPSCs, in which the NR2A-containing NMDAR-mediated EPSC was increased but the NR2B-containing NMDAR-mediated EPSC was decreased. These results suggest that adaptive changes of the NMDAR and glucocorticoid receptor functions during 4 days of opiate withdrawal may enable stress to facilitate hippocampal LTP, potentially contributing to the opiate withdrawal experience-dependent modifications of hippocampal functions.
应激会损害海马体的长时程增强效应（LTP），但阿片类药物戒断所引发的应激是否具有同样的作用尚不清楚。在此，作者报告称，4天的阿片类药物戒断并不影响基础突触传递，但会导致麻醉大鼠海马CA1区的LTP大幅增加。高架平台应激在仅戒断18小时的大鼠中引发了较大的LTP，但糖皮质激素受体拮抗剂RU38486（每天两次，共3天）可在戒断4天时阻止这种较大的LTP。此外，4天的戒断增强了NMDAR介导的兴奋性突触后电流（EPSCs），其中含NR2A的NMDAR介导的EPSC增加，而含NR2B的NMDAR介导的EPSC减少。这些结果表明，在4天的阿片类药物戒断过程中，NMDAR和糖皮质激素受体功能的适应性变化可能使应激促进海马LTP，这可能有助于阿片类药物戒断经历依赖的海马功能改变。
