Activation of p38 signaling in the microglia in the nucleus accumbens contributes to the acquisition and maintenance of morphine-induced conditioned place preference
Activation of p38 signaling in the microglia in the nucleus accumbens contributes to the acquisition and maintenance of morphine-induced conditioned place preference
复制标题
伏隔核小胶质细胞中p38信号的激活有助于吗啡诱导的条件性位置偏好的获得和维持
DOI：
10.1016/j.bbi.2011.09.017
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发表时间：
2012-02-01
影响因子：
15.1
通讯作者：
Xin, Wen-Jun
中科院分区：
文献类型：
--
作者：
Zhang, Xue-Qin;Cui, Yu;Xin, Wen-Jun
多项证据表明，激活的神经胶质细胞有助于吗啡诱导的奖赏（条件性位置偏好，CPP）。与星形胶质细胞在吗啡 CPP 中明确的作用相比，小胶质细胞在伏隔核 (NAc) 中的作用仍然知之甚少。本研究的目的是探讨小胶质细胞在吗啡诱导的 CPP 中的独特作用。吗啡的全身给药（7.5 mg/kg，持续5天）诱导大鼠对吗啡配对区室的显着偏好，这种偏好在吗啡治疗停止后持续至少6天。免疫组织化学结果显示，慢性吗啡治疗诱导的 NAc 小胶质细胞中 p38 的激活持续到第 11 天。在给予吗啡之前，在 NAc 内双侧注射米诺环素（一种推定的小胶质细胞抑制剂）或 SB203580（一种 p38 抑制剂），不仅抑制小胶质细胞中 p38 的激活，而且损害 CPP 的获得。在获得吗啡CPP的第二天，单次注射米诺环素或SB203580未能阻断CPP的表达。值得注意的是，在获得吗啡 CPP 后用米诺环素或 SB203580 预处理 5 天，显着抑制了 p38 的激活并减弱了吗啡 CPP 的维持。总的来说，我们目前的研究表明，NAc 小胶质细胞中的 p38 信号传导可能在吗啡 CPP 的获得和维持中发挥重要作用，但在吗啡 CPP 的表达中没有发挥重要作用，并提供了新的证据，表明小胶质细胞可能是吗啡成瘾治疗的潜在靶点。 (C) 2011 Elsevier Inc. 保留所有权利。
Several lines of evidence have suggested that activated glia contributes to morphine-induced reward (conditioned place preference, CPP). Compared to well-defined roles of astrocyte in morphine CPP, the role of microglia in the nucleus accumbens (NAc) remains poorly characterized. The aim of the present study was to investigate the distinct role of microglia in morphine-induced CPP. Systemic administration of morphine (7.5 mg/kg for 5 days) induced significant preference for the morphine-paired compartment in rats, which lasted for at least 6 days after cessation of morphine treatment. Immunohistochemistry results showed that activation of p38 in the NAc microglia induced by chronic morphine treatment maintained on day 11. Bilateral intra-NAc injection of minocycline, a putative microglia inhibitor, or SB203580, an inhibitor of p38, prior to morphine administration not only inhibited p38 activation in the microglia but impaired the acquisition of CPP. On the day following the acquisition of morphine CPP, a single injection of minocycline or SB203580 failed to block the expression of CPP. Notably, pretreatment with minocycline or SB203580 for 5 days following the acquisition of morphine CPP significantly suppressed the activation of p38 and attenuated the maintenance of morphine CPP. Collectively, our present study indicates that the p38 signaling in the NAc microglia may play an important role in the acquisition and maintenance but not the expression of morphine CPP, and provides new evidence that microglia might be a potential target for the therapy of morphine addiction. (C) 2011 Elsevier Inc. All rights reserved.