Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Pharmacology and Experimental Therapeutics, University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA.
Biomolecules. 2020 Jul 10;10(7):1030. doi: 10.3390/biom10071030.
Exposure to ethanol commonly manifests neuroinflammation. Beta (β)-lactam antibiotics attenuate ethanol drinking through upregulation of astroglial glutamate transporters, especially glutamate transporter-1 (GLT-1), in the mesocorticolimbic brain regions, including the nucleus accumbens (Acb). However, the effect of β-lactam antibiotics on neuroinflammation in animals chronically exposed to ethanol has not been fully investigated. In this study, we evaluated the effects of ampicillin/sulbactam (AMP/SUL, 100 and 200 mg/kg, i.p.) on ethanol consumption in high alcohol drinking (HAD1) rats. Additionally, we investigated the effects of AMP/SUL on GLT-1 and -methyl-d-aspartate (NMDA) receptor subtypes (NR2A and NR2B) in the Acb core (AcbCo) and Acb shell (AcbSh). We found that AMP/SUL at both doses attenuated ethanol consumption and restored ethanol-decreased GLT-1 and NR2B expression in the AcbSh and AcbCo, respectively. Moreover, AMP/SUL (200 mg/kg, i.p.) reduced ethanol-increased high mobility group box 1 (HMGB1) and receptor for advanced glycation end-products (RAGE) expression in the AcbSh. Moreover, both doses of AMP/SUL attenuated ethanol-elevated tumor necrosis factor-alpha (TNF-α) in the AcbSh. Our results suggest that AMP/SUL attenuates ethanol drinking and modulates NMDA receptor NR2B subunits and HMGB1-associated pathways.
暴露于乙醇通常会表现出神经炎症。β-内酰胺类抗生素通过上调中皮层边缘脑区（包括伏隔核）的星形胶质细胞谷氨酸转运体，特别是谷氨酸转运体-1（GLT-1），来减少乙醇的摄入。然而，β-内酰胺类抗生素对长期暴露于乙醇的动物的神经炎症的影响尚未得到充分研究。在这项研究中，我们评估了氨苄西林/舒巴坦（AMP/SUL，100 和 200mg/kg，腹腔注射）对高酒精摄入（HAD1）大鼠乙醇摄入的影响。此外，我们还研究了 AMP/SUL 对伏隔核核心（AcbCo）和伏隔核壳（AcbSh）中 GLT-1 和 -甲基-d-天冬氨酸（NMDA）受体亚基（NR2A 和 NR2B）的影响。我们发现，两种剂量的 AMP/SUL 均可减少乙醇的摄入，并分别恢复乙醇降低的 AcbSh 和 AcbCo 中的 GLT-1 和 NR2B 表达。此外，AMP/SUL（200mg/kg，腹腔注射）可降低 AcbSh 中乙醇增加的高迁移率族蛋白 B1（HMGB1）和晚期糖基化终产物受体（RAGE）的表达。此外，两种剂量的 AMP/SUL 均可减轻 AcbSh 中乙醇升高的肿瘤坏死因子-α（TNF-α）。我们的结果表明，AMP/SUL 可减少乙醇的摄入，并调节 NMDA 受体 NR2B 亚基和 HMGB1 相关通路。
