Effects of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline on glutamate transporter 1 and cysteine/glutamate exchanger as well as ethanol drinking behavior in male, alcohol-preferring rats.
Effects of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline on glutamate transporter 1 and cysteine/glutamate exchanger as well as ethanol drinking behavior in male, alcohol-preferring rats.
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DOI：
10.1002/jnr.23554
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发表时间：
2015-06
影响因子：
4.2
通讯作者：
Sari, Youssef
中科院分区：
文献类型：
--
作者：
Aal-Aaboda, Munaf;Alhaddad, Hasan;Osowik, Francis;Nauli, Surya M.;Sari, Youssef
饮酒很大程度上与几个大脑奖赏区域的细胞外谷氨酸浓度的变化有关。我们最近发现，嗜酒大鼠长期接触乙醇五周后，谷氨酸转运蛋白 1 (GLT-1) 下调，伏核和前额皮质中 GLT-1 水平的上调在一定程度上导致了乙醇消耗量的减少。还发现 P 大鼠慢性乙醇暴露后半胱氨酸谷氨酸逆向转运蛋白 (xCT) 下调，其上调可能对减少乙醇饮酒有价值。在这项研究中，我们检测了合成化合物 (R)-(−)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153) 对乙醇饮用以及 P 大鼠杏仁核和海马中 GLT-1 和 xCT 表达的影响。 P 大鼠连续自由选择接触水、15% 和 30% 乙醇和食物五周，然后接受 MS-153 或媒介物治疗五天。结果表明，MS-153治疗显着降低了P大鼠的乙醇消耗量。结果表明，与水对照动物相比，乙醇载体处理的大鼠（乙醇载体组）的杏仁核和海马中 GLT-1 和 xCT 表达均下调。重要的是，MS-153 治疗上调了这些大脑区域的 GLT-1 和 xCT 表达。这些发现表明 MS-153 对这些谷氨酸转运蛋白在减弱乙醇饮用行为方面发挥着重要作用。
Alcohol consumption is largely associated with alterations in the extracellular glutamate concentrations in several brain reward regions. We have recently found that glutamate transporter 1 (GLT-1) is downregulated following chronic exposure to ethanol for five weeks in alcohol-preferring rats, and upregulation of the GLT-1 levels in nucleus accumbens and prefrontal cortex resulted, in part, in attenuating ethanol consumption. Cysteine glutamate antiporter (xCT) was also found to be downregulated after chronic ethanol exposure in P rats, and its upregulation could be valuable in attenuating ethanol drinking. In this study, we examined the effect of a synthetic compound, (R)-(−)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), on ethanol drinking and expression of GLT-1 and xCT in the amygdala and hippocampus of P rats. P rats were exposed to continuous free-choice access to water, 15% and 30% ethanol, and food for five weeks, and then after which they received treatments of MS-153 or vehicle for five days. The results showed that MS-153 treatment significantly reduced ethanol consumption in P rats. It was revealed that GLT-1 and xCT expressions were downregulated in both the amygdala and hippocampus of ethanol-vehicle treated rats (ethanol vehicle group) as compared to water control animals. Importantly, MS-153 treatment upregulated GLT-1 and xCT expression in these brain regions. These findings provide important role of MS-153 on these glutamate transporters for the attenuation of ethanol drinking behavior.
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影响因子：
3.4
作者：
Chefer V;Meis J;Wang G;Kuzmin A;Bakalkin G;Shippenberg T
通讯作者：
Shippenberg T
影响因子：
16.2
作者：
MURPHY, TH;MIYAMOTO, M;COYLE, JT
通讯作者：
COYLE, JT
DOI：
10.1097/01.alc.0000156086.65665.4d
发表时间：
2005-03-01
影响因子：
3.2
作者：
Melendez, RI;Hicks, MP;Kalivas, PW
通讯作者：
Kalivas, PW
影响因子：
3
作者：
Lalumiere RT
通讯作者：
Lalumiere RT
影响因子：
3.4
作者：
Alhaddad, Hasan;Das, Sujan C.;Sari, Youssef
通讯作者：
Sari, Youssef