Protein phosphatase 2A deficiency in hippocampal CA1 inhibits priming effect of morphine on conditioned place preference in mice.
Protein phosphatase 2A deficiency in hippocampal CA1 inhibits priming effect of morphine on conditioned place preference in mice.
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DOI：
10.1093/cercor/bhac527
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发表时间：
2023-01
期刊：
影响因子：
3.7
通讯作者：
J. Dai;Ran Xie;Zhou-Na Sun;Xiaolin Kou;Jia-qi Zhang;Cui Qi;Rui Liu;Xiang Gao;Jing Wang;Jun Gao
中科院分区：
文献类型：
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作者：
J. Dai;Ran Xie;Zhou-Na Sun;Xiaolin Kou;Jia-qi Zhang;Cui Qi;Rui Liu;Xiang Gao;Jing Wang;Jun Gao
研究表明，蛋白质磷酸化在吗啡滥用中起着重要作用。然而，蛋白磷酸酶2A（PP 2A）的神经生物学机制的吗啡启动过程仍然不清楚。在此，我们构建了T29-2-Cre; PP 2Afl/fl条件性敲除小鼠（KO），并研究了海马PP 2A在吗啡引发中的作用。我们观察到，PP 2A缺陷抑制吗啡的启动行为，阻断启动诱导的KO小鼠海马长时程增强（LTP）。此外，与对照组相比，KO小鼠中脑核Rack 1和膜GluN 2B的表达水平显著降低，这可能与KO小鼠海马HDAC 4的表达水平降低有关。与此一致，类似的抑制启动效应也观察到在野生型小鼠与丁酸钠（NaB）-组蛋白脱乙酰酶的非特异性抑制剂-吗啡给药后3小时。综上所述，我们的研究结果表明，海马PP 2A可能通过PP 2A/HDAC 4/Rack 1通路参与吗啡引发。
Studies have shown that protein phosphorylation plays an important role in morphine abuse. However, the neurobiological mechanism of protein phosphatase 2A (PP2A) underlying the morphine-priming process is still unclear. Here we constructed T29-2-Cre; PP2Afl/fl conditional knockout mice (KO) and investigated the role of hippocampal PP2A in morphine priming. We observed that the deficit of PP2A inhibited the priming behavior of morphine and blocked the priming-induced long-term potentiation (LTP) in the hippocampus of KO mice. Moreover, the expression levels of Rack1 and the membrane GluN2B were significantly reduced in the nucleus accumbens of KO mice compared with those in the control mice, which may be attributed to the decreased HDAC4 in the hippocampus of KO mice. Consistent with it, the similar inhibited priming effects were also observed in the wild-type mice treated with sodium butyrate (NaB)-a nonspecific inhibitor of histone deacetylases-3 h after morphine administration. Taken together, our results suggest that hippocampal PP2A may be involved in morphine priming through the PP2A/HDAC4/Rack1 pathway.