Hakami Alqassem Y, Alshehri Fahad S, Althobaiti Yusuf S, Sari Youssef
Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
Behav Brain Res. 2017 Mar 1;320:316-322. doi: 10.1016/j.bbr.2016.12.016. Epub 2016 Dec 16.
Alcohol dependence is associated with deficits in glutamate uptake and impairment of glutamate homeostasis in different brain reward regions. Glutamate transporter subtype 1 (GLT-1), cystine-glutamate exchanger (xCT) and glutamate/aspartate transporter (GLAST) are one of the key players in regulating extracellular glutamate concentration in the brain. Parenteral treatment with ceftriaxone, β-lactam antibiotic, has been reported to attenuate ethanol consumption and reinstatement to cocaine-seeking behavior, in part, by restoring the expression of GLT-1 and xCT in mesocorticolimbic brain regions in rats. In this study, we focused to test Augmentin (amoxicillin/clavulanate), which can be administered orally to subjects. Therefore, we examined the effects of orally administered Augmentin on ethanol intake as well as GLT-1, xCT and GLAST expression in male alcohol-preferring (P) rats. We found that orally administered Augmentin significantly attenuated ethanol consumption in P rats as compared to the vehicle-treated group. Importantly, the attenuation in ethanol consumption was associated with a significant upregulation of GLT-1 and xCT expression in nucleus accumbens (NAc) and prefrontal cortex (PFC). There was no effect of orally administered Augmentin on GLAST expression in either NAc or PFC. These findings present strong evidence that oral administration of Augmentin can be used as an alternative to parenteral treatment.
酒精依赖与不同脑奖赏区域中谷氨酸摄取缺陷及谷氨酸稳态受损有关。谷氨酸转运体亚型1（GLT-1）、胱氨酸-谷氨酸交换体（xCT）和谷氨酸/天冬氨酸转运体（GLAST）是调节大脑细胞外谷氨酸浓度的关键因素之一。据报道，静脉注射头孢曲松（一种β-内酰胺类抗生素）可部分通过恢复大鼠中脑边缘脑区GLT-1和xCT的表达来减少乙醇消耗及恢复对可卡因觅药行为。在本研究中，我们着重测试可口服给药的阿莫西林/克拉维酸（Augmentin）。因此，我们研究了口服阿莫西林/克拉维酸对雄性嗜酒（P）大鼠乙醇摄入量以及GLT-1、xCT和GLAST表达的影响。我们发现，与给予赋形剂处理的组相比，口服阿莫西林/克拉维酸可显著减少P大鼠的乙醇消耗。重要的是，乙醇消耗的减少与伏隔核（NAc）和前额叶皮质（PFC）中GLT-1和xCT表达的显著上调有关。口服阿莫西林/克拉维酸对NAc或PFC中的GLAST表达均无影响。这些发现提供了强有力的证据，表明口服阿莫西林/克拉维酸可作为静脉注射治疗的替代方法。
