Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming, People's Republic of China.
Hippocampus. 2010 Feb;20(2):335-43. doi: 10.1002/hipo.20638.
The formation of memory is believed to depend on experience- or activity-dependent synaptic plasticity, which is exquisitely sensitive to psychological stress since inescapable stress impairs long-term potentiation (LTP) but facilitates long-term depression (LTD). Our recent studies demonstrated that 4 days of opioid withdrawal enables maximal extents of both hippocampal LTP and drug-reinforced behavior; while elevated-platform stress enables these phenomena at 18 h of opioid withdrawal. Here, we examined the effects of low dose of morphine (0.5 mg kg(-1), i.p.) or the opioid receptor antagonist naloxone (1 mg kg(-1), i.p.) on synaptic efficacy in the hippocampal CA1 region of anesthetized rats. A form of synaptic depression was induced by low dose of morphine or naloxone in rats after 18 h but not 4 days of opioid withdrawal. This synaptic depression was dependent on both N-methyl-D-aspartate receptor and synaptic activity, similar to the hippocampal long-term depression induced by low frequency stimulation. Elevated-platform stress given 2 h before experiment prevented the synaptic depression at 18 h of opioid withdrawal; in contrast, the glucocorticoid receptor (GR) antagonist RU38486 treatment (20 mg kg(-1), s.c., twice per day for first 3 days of withdrawal), or a high dose of morphine reexposure (15 mg kg(-1), s.c., 12 h before experiment), enabled the synaptic depression on 4 days of opioid withdrawal. This temporal shift of synaptic depression by stress or GR blockade supplements our previous findings of potentially correlated temporal shifts of LTP induction and drug-reinforced behavior during opioid withdrawal. Our results therefore support the idea that stress experience during opioid withdrawal may modify hippocampal synaptic plasticity and play important roles in drug-associated memory. (c) 2009 Wiley-Liss, Inc.
记忆的形成被认为依赖于经验或活动依赖性的突触可塑性，而这种可塑性对心理应激非常敏感，因为不可避免的应激会损害长时程增强（LTP），但促进长时程抑制（LTD）。我们最近的研究表明，4 天的阿片类药物戒断使海马 LTP 和药物强化行为达到最大程度；而在阿片类药物戒断 18 小时时，高架平台应激可使这些现象发生。在这里，我们研究了低剂量吗啡（0.5 mg/kg，ip）或阿片受体拮抗剂纳洛酮（1 mg/kg，ip）对麻醉大鼠海马 CA1 区突触效能的影响。在阿片类药物戒断 18 小时后，低剂量吗啡或纳洛酮会在大鼠中诱导一种突触抑制，但在 4 天的阿片类药物戒断后则不会。这种突触抑制依赖于 N-甲基-D-天冬氨酸受体和突触活动，类似于低频刺激诱导的海马长时程抑制。实验前 2 小时给予高架平台应激可防止阿片类药物戒断 18 小时时的突触抑制；相反，糖皮质激素受体（GR）拮抗剂 RU38486 处理（戒断的前 3 天，每天两次，皮下注射 20 mg/kg）或高剂量吗啡再暴露（实验前 12 小时，皮下注射 15 mg/kg）可使阿片类药物戒断 4 天时发生突触抑制。应激或 GR 阻断对突触抑制的这种时间推移补充了我们之前的发现，即在阿片类药物戒断期间，LTP 诱导和药物强化行为的潜在相关时间推移。因此，我们的研究结果支持这样一种观点，即在阿片类药物戒断期间的应激体验可能会改变海马突触可塑性，并在药物相关记忆中发挥重要作用。（c）2009 年威利-利希特公司
