Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, United States.
Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, United States; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, United States.
Alcohol. 2021 May;92:1-9. doi: 10.1016/j.alcohol.2021.01.004. Epub 2021 Jan 16.
Repeated cycles of chronic intermittent ethanol (CIE) exposure increase voluntary consumption of alcohol (ethanol) in mice. Previous reports from our laboratory show that CIE increases extracellular glutamate in the nucleus accumbens (NAc) and that manipulating accumbal glutamate concentrations will alter ethanol drinking, indicating that glutamate homeostasis plays a crucial role in ethanol drinking in this model. A number of studies have shown that ceftriaxone increases GLT-1 expression, the major glutamate transporter, and that treatment with this antibiotic reduces ethanol drinking. The present studies examined the effects of ceftriaxone on ethanol drinking and GLT-1 in a mouse model of ethanol dependence and relapse drinking. The results show that ceftriaxone did not influence drinking at any dose in either ethanol-dependent or non-dependent mice. Further, ceftriaxone did not increase GLT-1 expression in the accumbens core or shell, with the exception of the ethanol-dependent mice receiving the highest dose of ceftriaxone. Interestingly, ethanol-dependent mice treated with only vehicle displayed reduced expression of GLT-1 in the accumbens shell and of the presynaptic mGlu2 receptor in the accumbens core. The reduced expression of the major glutamate transporter (GLT-1), as well as a receptor that regulates glutamate release (mGlu2), may help explain, at least in part, increased glutamatergic transmission in this model of ethanol dependence and relapse drinking.
反复的慢性间歇性乙醇（CIE）暴露会增加小鼠对酒精（乙醇）的自愿摄入。我们实验室的先前报告表明，CIE 会增加伏隔核（NAc）中的细胞外谷氨酸，并且操纵伏隔核谷氨酸浓度会改变乙醇的摄入，这表明谷氨酸稳态在该模型的乙醇摄入中起着至关重要的作用。许多研究表明头孢曲松会增加 GLT-1 的表达，即主要的谷氨酸转运蛋白，并且这种抗生素的治疗会减少乙醇的摄入。本研究在乙醇依赖和复发饮酒的小鼠模型中检查了头孢曲松对乙醇摄入和 GLT-1 的影响。结果表明，头孢曲松在任何剂量下都不会影响乙醇依赖或非依赖小鼠的饮酒。此外，头孢曲松除了在接受最高剂量头孢曲松的乙醇依赖小鼠中，不会增加伏隔核核心或壳中的 GLT-1 表达。有趣的是，仅用载体治疗的乙醇依赖小鼠在伏隔核壳中显示出 GLT-1 的表达减少，以及伏隔核核心中调节谷氨酸释放的突触前 mGlu2 受体的表达减少。主要谷氨酸转运蛋白（GLT-1）和调节谷氨酸释放的受体（mGlu2）的表达减少，至少可以部分解释在这种乙醇依赖和复发饮酒的模型中谷氨酸能传递的增加。
