AIM Glutamate has been considered as neurotransmitter that is critical in triggering relapse to drugs of abuse, including ethanol and cocaine. Extracellular glutamate concentrations are tightly regulated by several mechanisms, including reuptake through glutamate transporters. Glutamate transporter type 1 (GLT-1) is responsible for clearing the majority of extracellular glutamate. The astrocytic cystine/glutamate antiporter (xCT) regulates also glutamate homeostasis. In this study, we investigated the effects of cocaine exposure and ampicillin/sulbactam (AMP/SUL), a β-lactam antibiotic known to upregulate GLT-1 and xCT, on relapse-like ethanol intake and the expression of astrocytic glutamate transporters in mesocorticolimbic brain regions. METHODS Male alcohol-preferring (P) rats had free access to ethanol for 5 weeks. On Week 6, rats were exposed to either cocaine (20 mg/kg, i.p.) or saline for 12 consecutive days. Ethanol bottles were then removed for 7 days; during the last 5 days, either AMP/SUL (100 or 200 mg/kg, i.p.) or saline was administered to the P rats. Ethanol bottles were reintroduced, and ethanol intake was measured for 4 days. RESULTS Cocaine exposure induced an alcohol deprivation effect (ADE), which was associated in part by a decrease in the expression of GLT-1 and xCT in the nucleus accumbens (NAc) core. AMP/SUL (100 mg/kg, i.p.) attenuated the ADE, while AMP/SUL (200 mg/kg, i.p.) reduced ethanol intake during 4 days of ethanol re-exposure and upregulated GLT-1 and xCT expression in the NAc core, NAc shell and dorsomedial prefrontal cortex (dmPFC). CONCLUSION This study suggests that these astrocytic glutamate transporters might be considered as potential targets for the treatment of polysubstance abuse.

中文翻译：

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可卡因暴露对星形胶质细胞谷氨酸转运蛋白和雄性酒精偏好大鼠的复发样乙醇饮酒行为的影响。


AIM 谷氨酸被认为是一种神经递质，对于引发滥用药物（包括乙醇和可卡因）的复发至关重要。细胞外谷氨酸浓度受到多种机制的严格调节，包括通过谷氨酸转运蛋白的再摄取。 1 型谷氨酸转运蛋白 (GLT-1) 负责清除大部分细胞外谷氨酸。星形细胞胱氨酸/谷氨酸逆向转运蛋白 (xCT) 还调节谷氨酸稳态。在这项研究中，我们研究了可卡因暴露和氨苄西林/舒巴坦 (AMP/SUL)（一种已知可上调 GLT-1 和 xCT 的 β-内酰胺类抗生素）对复发样乙醇摄入量和中皮质边缘星形细胞谷氨酸转运蛋白表达的影响。大脑区域。方法 雄性嗜酒 (P) 大鼠可自由获取乙醇 5 周。第 6 周，大鼠连续 12 天暴露于可卡因（20 mg/kg，腹腔注射）或盐水。然后移除乙醇瓶7天；在最后 5 天内，对 P 大鼠施用 AMP/SUL（100 或 200 mg/kg，腹腔注射）或盐水。重新引入乙醇瓶，并测量 4 天的乙醇摄入量。结果 可卡因暴露诱导了酒精剥夺效应 (ADE)，该效应部分与伏隔核 (NAc) 核心中 GLT-1 和 xCT 表达的减少有关。 AMP/SUL（100 mg/kg，腹腔注射）减弱了 ADE，而 AMP/SUL（200 mg/kg，腹腔注射）在 4 天的乙醇再暴露期间减少了乙醇摄入，并上调了 NAc 核心中的 GLT-1 和 xCT 表达、NAc 壳和背内侧前额皮质 (dmPFC)。结论 这项研究表明，这些星形胶质细胞谷氨酸转运蛋白可能被视为治疗多物质滥用的潜在目标。