Role of protein kinase C epsilon (PKCvarepsilon) in the reduction of ethanol reinforcement due to mGluR5 antagonism in the nucleus accumbens shell.
Role of protein kinase C epsilon (PKCvarepsilon) in the reduction of ethanol reinforcement due to mGluR5 antagonism in the nucleus accumbens shell.
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DOI：
10.1007/s00213-009-1490-y
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发表时间：
2009-07
影响因子：
3.4
通讯作者：
Olive, M. Foster
中科院分区：
文献类型：
--
作者：
Gass, Justin T.;Olive, M. Foster
关键词：
5型代谢型谷氨酸受体（mGluR5）和蛋白激酶C的ε亚型（PKCε）调节乙醇摄入，并且我们先前已经证明mGluR5受体拮抗作用通过一种PKCε依赖性机制减少乙醇消耗。
我们通过将这些蛋白质的选择性抑制剂注入伏隔核（NAc）的壳区或核心区，探索了这种mGluR5 - PKCε信号通路对乙醇强化调节的神经解剖学基础。
雄性Wistar大鼠被训练进行静脉内乙醇自我给药，并在伏隔核内接受溶媒或选择性mGluR5拮抗剂3 - ((2 - 甲基 - 1,3 - 噻唑 - 4 - 基)乙炔基)吡啶（MTEP）单独以及与PKCε转位抑制剂（εV1 - 2）或乱序对照肽（sεV1 - 2）联合的灌注。还测定了伏隔核内MTEP对食物强化反应和旷场运动活动的影响。
当灌注到伏隔核核心区时，MTEP（1μg/μl）对乙醇或食物强化或运动活动没有影响。当灌注到伏隔核壳区而不是核心区时，MTEP（3μg/μl）减少了乙醇强化，并且这种作用被εV1 - 2（1μg/μl）而不是sεV1 - 2（1μg/μl）逆转。在这两个区域，此浓度的MTEP都没有改变食物强化反应或运动活动，并且单独灌注εV1 - 2没有改变乙醇强化。当灌注到壳区时，MTEP（10μg/μl）减少了运动活动，因此这个浓度没有进一步在乙醇或食物反应上进行测试。
伏隔核壳区的mGluR5受体阻断通过一种PKCε依赖性机制减少乙醇强化。
The type 5 metabotropic glutamate receptor (mGluR5) and the epsilon isoform of protein kinase C (PKCε) regulate ethanol intake, and we have previously demonstrated that mGluR5 receptor antagonism reduces ethanol consumption via a PKCε-dependent mechanism. We explored the neuroanatomical substrates of the regulation of ethanol reinforcement by this mGluR5-PKCε signaling pathway by infusing selective inhibitors of these proteins into the shell or core region of the nucleus accumbens (NAc). Male Wistar rats were trained to self-administer ethanol intravenously and received intra-NAc infusions of vehicle or the selective mGluR5 antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) alone and in combination with a PKCε translocation inhibitor (εV1-2) or a scrambled control peptide (sεV1-2). The effects of intra-NAc MTEP on food-reinforced responding and open-field locomotor activity were also determined. MTEP (1 μg/μl) had no effect on ethanol or food reinforcement or locomotor activity when infused into the NAc core. MTEP (3 μg/μl) reduced ethanol reinforcement when infused into the NAc shell but not the core, and this effect was reversed by εV1-2 (1 μg/μl) but not sεV1-2 (1 μg/μl). In both regions, this concentration of MTEP did not alter food-reinforced responding or locomotor activity, and infusion of εV1-2 alone did not alter ethanol reinforcement. MTEP (10 μg/μl) reduced locomotor activity when infused into the shell, and therefore this concentration was not further tested on responding for ethanol or food. Blockade of mGluR5 receptors in the NAc shell reduces ethanol reinforcement via a PKCε-dependent mechanism.
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影响因子：
2.5
作者：
GROENEWEGEN, HJ;RUSSCHEN, FT
通讯作者：
RUSSCHEN, FT
DOI：
10.1124/jpet.105.090449
发表时间：
2005-11-01
影响因子：
3.5
作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
25
作者：
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Conn, PJ