Intra-hippocampal administration of ZIP alleviates depressive and anxiety-like responses in an animal model of posttraumatic stress disorder.
Intra-hippocampal administration of ZIP alleviates depressive and anxiety-like responses in an animal model of posttraumatic stress disorder.
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海马内注射 ZIP 可减轻创伤后应激障碍动物模型的抑郁和焦虑样反应
DOI：
10.1186/1744-9081-10-28
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发表时间：
2014-09-01
期刊：
影响因子：
--
通讯作者：
Wang ZY
中科院分区：
文献类型：
--
作者：
Ji LL;Tong L;Xu BK;Fu CH;Shu W;Peng JB;Wang ZY
鉴于恐惧消退障碍与创伤后应激障碍（PTSD）的发病机制有关，促进恐惧消退的有效药物干预可能为传统治疗提供替代策略。人们普遍认为，zeta抑制肽（ZIP）是一种有争议的蛋白激酶M zeta （PKMζ）抑制剂，可以消除某些类型的先前建立的长期记忆。然而，目前尚不清楚ZIP是否可以减轻ptsd相关的抑郁和焦虑样异常。在这里，我们建立了一个再应激单延长应激（SPS）范式，一个改进的PTSD流行动物模型，并分析了SPS过程后海马中PKMζ的表达。再次应激前7天，将ZIP注射到海马中，随后通过强迫游泳（FS）、开放场和升高迷宫（EPM）测试检测抑郁和焦虑样行为。在FS前给予ZIP的大鼠在FS测试中静止时间减少，EPM中张开臂（OA）次数增加，OA持续时间延长。他们在空地中央待的时间也更长。我们的研究结果表明，应激后的SPS可以重现与PTSD患者相似的行为改变，并且这些与PTSD共病的行为症状可以通过海马内给药ZIP有效缓解。
Given that impairment of fear extinction has been implicated in the pathogenesis of posttraumatic stress disorder (PTSD), effective pharmacological interventions that facilitate fear extinction may provide alternative strategies to conventional treatment. It is generally accepted that the zeta inhibitory peptide (ZIP), a controversial inhibitor of protein kinase M zeta (PKMζ), could erase certain types of previously established long-term memories. However, it is unclear whether ZIP administration may alleviate PTSD-associated depressive and anxiety-like abnormalities. Here we developed a re-stressed single-prolonged stress (SPS) paradigm, a modified prevalent animal model of PTSD, and assayed the expressions of PKMζ in the hippocampus after SPS procedure. Next, Seven days prior to re-stress, ZIP was injected into the hippocampus, and the depressive and anxiety-like behavior was examined by the subsequent forced swim (FS), open-field and elevated plus maze (EPM) test. Rats given ZIP prior to FS exhibited a reduction of immobility time in FS test, and more open arms (OA) entries and longer OA duration in EPM. They also spent longer time in the center of the open field. Our results suggested that re-stressed SPS could reproduce behavioral alteration similar to that observed in patients with PTSD, and these behavioral symptoms co-morbid with PTSD could be effectively alleviated by the intro-hippocampal administration of ZIP.
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DOI：
10.1523/jneurosci.5884-10.2011
发表时间：
2011-04-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Li YQ;Xue YX;He YY;Li FQ;Xue LF;Xu CM;Sacktor TC;Shaham Y;Lu L
通讯作者：
Lu L
影响因子：
4.8
作者：
Hernandez, AI;Blace, N;Sacktor, TC
通讯作者：
Sacktor, TC
影响因子：
25
作者：
Gilbertson, MW;Shenton, ME;Pitman, RK
通讯作者：
Pitman, RK
影响因子：
56.9
作者：
Li, Xiang-Yao;Ko, Hyoung-Gon;Zhuo, Min
通讯作者：
Zhuo, Min
影响因子：
56.9
作者：
KIM, JJ;FANSELOW, MS
通讯作者：
FANSELOW, MS