Neuroimmunophilin GPI-1046 reduces ethanol consumption in part through activation of GLT1 in alcohol-preferring rats.
Neuroimmunophilin GPI-1046 reduces ethanol consumption in part through activation of GLT1 in alcohol-preferring rats.
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DOI：
10.1016/j.neuroscience.2012.10.007
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发表时间：
2012-12-27
期刊：
影响因子：
3.3
通讯作者：
Sreemantula, S. N.
中科院分区：
文献类型：
--
作者：
Sari, Y.;Sreemantula, S. N.
我们之前已经证明，头孢曲松，β-内酰胺抗生素已知上调谷氨酸转运蛋白1（GLT 1），减少乙醇偏好（P）大鼠的乙醇摄入量。GLT 1是一种神经胶质谷氨酸转运蛋白，调节大部分细胞外谷氨酸摄取。在这项研究中，我们测试了神经亲免疫素GPI-1046（3-（3-吡啶基）-1-丙基（2S）-1-（3，3-二甲基-1，2-二氧戊基）-2-吡咯烷羧酸酯）在P大鼠乙醇摄入中的作用，已知该物质也可上调GLT 1表达。雄性P大鼠同时获得自由选择的15%和30%的乙醇，水和食物五周。在第6周，P大鼠继续这种饮水和食物方案，并且它们被施用10或20 mg/kg GPI-1046（i. p.），或者连续五天都没有车从GPI-1046或溶媒腹膜内注射第1天开始，每天测量体重、乙醇摄入量和饮水量，持续8天。我们还测试了GPI-1046（20 mg/kg）对每日蔗糖（10%）摄入量的影响。数据显示，在整个治疗和治疗后阶段，在首次用GPI-1046治疗后48小时开始，乙醇摄入量的减少具有显著的剂量依赖性作用。饮水量也呈剂量依赖性增加。然而，GPI-1046处理不影响所有动物的体重和蔗糖摄入。重要的是，与所有组相比，GPI-1046（20 mg/kg）增加了脑桥核核心（NAc-核心）中的GLT 1水平。或者，与媒介物（未经乙醇处理）组相比，GPI-1046（10 mg/kg）上调NAC核心中的GLT 1水平。此外，与未经乙醇处理的媒介物组相比，两种剂量的GPI-1046均显著增加了前额叶皮层（PFC）中的GLT 1水平。与仅暴露于水和食物的未处理对照组相比，GPI-1046（20 mg/kg）增加PFC中的GLT 1水平。这些发现表明，神经亲免疫素GPI-1046部分通过上调PFC和NAC核心中的GLT 1来减弱乙醇摄入。
We have previously shown that ceftriaxone, β-lactam antibiotic known to upregulate glutamate transporter 1 (GLT1), reduced ethanol intake in alcohol-preferring (P) rats. GLT1 is a glial glutamate transporter that regulates the majority of extracellular glutamate uptake. We tested in this study the effects of neuroimmunophilin GPI-1046 (3-(3-pyridyl)-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidinecarboxylate), known also to upregulate GLT1 expression, in ethanol intake in P rats. Male P rats had concurrent access to free choice of 15% and 30% ethanol, water, and food for five weeks. On Week 6, P rats continued in this drinking and food regimen and they were administered either 10 or 20 mg/kg GPI-1046 (i.p.), or a vehicle for five consecutive days. Body weight, ethanol intake, and water consumption were measured daily for 8 days starting on Day 1 of GPI-1046 or vehicle i.p. injections. We have also tested the effect of GPI-1046 (20 mg/kg) on daily sucrose (10%) intake. The data revealed significant dose-dependent effects in the reduction of ethanol intake starting 48 h after the first treatment with GPI-1046 throughout treatment and post-treatment periods. There were also dose-dependent increases in water intake. However, GPI-1046 treatment did not affect the body weight of all animals nor sucrose intake. Importantly, GPI-1046 (20 mg/kg) increased GLT1 level compared to all groups in nucleus accumbens core (NAc-core). Alternatively, GPI-1046 (10 mg/kg) upregulated GLT1 level in NAc-core compared to vehicle (ethanol naïve) group. Moreover, both doses of GPI-1046 increased significantly GLT1 level in the prefrontal cortex (PFC) compared to ethanol naïve vehicle group. GPI-1046 (20 mg/kg) increased GLT1 level in PFC compared to naïve control group that was exposed to water and food only. These findings demonstrated that neuroimmunophilin GPI-1046 attenuates ethanol intake in part through the upregulation of GLT1 in PFC and NAc-core.
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影响因子：
3.3
作者：
Miller, B. R.;Dorner, J. L.;Rebec, G. V.
通讯作者：
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影响因子：
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作者：
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DOI：
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作者：
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DOI：
10.1111/j.1530-0277.2008.00620.x
发表时间：
2008-04-01
影响因子：
3.2
作者：
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通讯作者：
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