Effects of minocycline on cocaine sensitization and phosphorylation of GluR1 receptors in 5-lipoxygenase deficient mice.
Effects of minocycline on cocaine sensitization and phosphorylation of GluR1 receptors in 5-lipoxygenase deficient mice.
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DOI：
10.1016/j.neuropharm.2010.09.006
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发表时间：
2011-06
影响因子：
4.7
通讯作者：
Manev, Hari
中科院分区：
文献类型：
--
作者：
Chen, Hu;Manev, Hari
在野生型（WT）小鼠中，抗生素米诺环素可抑制可卡因诱导的运动敏感性的发展。米诺环素的一些作用可能涉及5-脂氧合酶（5-LOX）途径。我们使用5-LOX缺陷小鼠模型来研究5-LOX是否参与米诺环素对可卡因作用的影响。运动致敏诱导4天可卡因注射和谷氨酸受体的磷酸化状态的GluR 1在脑样品中进行了测定。米诺环素未能影响5-LOX缺陷小鼠的可卡因致敏作用。在这些小鼠中，可卡因或米诺环素4天治疗均未改变GluR 1磷酸化。在米诺环素抑制可卡因致敏的WT小鼠中，4天可卡因治疗增加了额叶皮质中Ser 831和Ser 845位点的GluR 1磷酸化，而不是纹状体;此外，米诺环素阻止了这种作用。在基础条件下，并在一个单一的可卡因注射的GluR 1，GluR 2，和GluR 3 AMPA受体亚基的水平没有不同的野生型和5-LOX缺陷小鼠之间，但GluR 1磷酸化的反应，以一个单一的可卡因注射下5-LOX缺陷。因此，在野生型小鼠中，GluR 1磷酸化仅在额叶皮质和Ser 831位点增加。在5-LOX缺陷小鼠中，急性可卡因注射增加了额叶皮质和纹状体中Ser 831和Ser 845的磷酸化。我们认为，在研究米诺环素对可卡因的作用和/或成瘾的人类，这将是重要的是要考虑的主题的5-LOX系统的特性。
In wild-type (WT) mice, the antibiotic minocycline inhibits development of cocaine-induced locomotor sensitization. Some of the actions of minocycline may involve the 5-lipoxygenase (5-LOX) pathway. We used the model of 5-LOX-deficient mice to investigate whether 5-LOX participates in minocycline’s influence on the effects of cocaine. Locomotor sensitization was induced by 4 daily cocaine injections and the phosphorylation status of GluR1 glutamate receptors was assayed in brain samples. Minocycline failed to affect cocaine sensitization in 5-LOX-deficient mice. In these mice, neither cocaine nor minocycline 4-day treatment altered GluR1 phosphorylation. In WT mice in which minocycline inhibited development of cocaine sensitization, a 4-day cocaine treatment increased GluR1 phosphorylation at both Ser831 and Ser845 sites in the frontal cortex but not the striatum; further, this effect was prevented by minocycline. Under basal conditions and in response to a single cocaine injection the levels of GluR1, GluR2, and GluR3 AMPA receptor subunits did not differ between WT and 5-LOX-deficient mice, but the response of GluR1 phosphorylation to a single cocaine injection was greater under the 5-LOX deficiency. Hence, in WT mice GluR1 phosphorylation increased only in the frontal cortex and only at the Ser831 site. In 5-LOX-deficient mice, acute cocaine injection increased both Ser831 and Ser845 phosphorylation both in the frontal cortex and in the striatum. We suggest that in studying minocycline’s action on cocaine’s effects and/or addiction in humans, it would be important to consider the characterization of the subjects’ 5-LOX system.
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影响因子：
5.2
作者：
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通讯作者：
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