The present study focused on investigating the effect of toll-like receptor 4 (TLR4) antagonist Lipopolysaccharide-Rhodobacter sphaeroides(LPS-RS) on acute, stress-induced voluntary ethanol preference and drinking behaviour, neuronal components activation, and gene expression associated with stress and addictive behaviour. This study involved the exposure of restraint stress and social isolation using Swiss Albino mice. Two-bottle choice ethanol preference analysis was used in the evaluation of voluntary ethanol seeking and drinking behaviour. Several behavioural assessments were carried out to assess fear and anxiety-like behaviour, neuromuscular ability, motor coordination and locomotion. Morphological and immunoreactivity analysis and gene expression analysis were done after the completion of behavioural assessments. TLR4 antagonist LPS-RS treated stressed-mice showed a significant decrease in ethanol drinking compared with stressed mice. Behavioural results showed that stress exposure induced fear and anxiety-like behaviour; however; no significant deficit was found on motor coordination, neuromuscular ability, locomotion and exploratory behaviour among groups. Morphological analysis showed no significant change in the prefrontal cortex and hippocampus among all groups, while immunoreactivity analysis showed higher expression of c-Fos in prefrontal cortex and hippocampus, higher TLR4 expression in the prefrontal cortex and glial fibrillary acidic protein (GFAP) in hippocampus among stressed-animals. Stressed-mice also showed significant increase in TLR4, Nuclear Factor-Kappa B (NF-kB), inducible nitric oxide synthase (iNOS), dopamine receptor D2 (DRD2), cyclic adenosine monophosphate (cAMP) response element binding protein-1 (CREB-1) and opioid receptor MU-1 (OPRM-1) genes expression compared with control and LPS-RS treated stressed-mice. As a conclusion, the antagonism of TLR4 could provide therapeutic value in the treatment of stress-induced addiction.

中文翻译：

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Toll 样受体 4 拮抗剂脂多糖-球形红杆菌对急性应激诱导的自愿乙醇偏好和饮酒行为的作用：体内瑞士白化小鼠模型

本研究的重点是研究 Toll 样受体 4 (TLR4) 拮抗剂脂多糖-球形红杆菌 (LPS-RS) 对急性应激诱导的自愿乙醇偏好和饮酒行为、神经元成分激活以及与应激相关的基因表达的影响和成瘾行为。这项研究涉及使用瑞士白化小鼠暴露束缚压力和社会孤立。两瓶选择乙醇偏好分析用于评估自愿乙醇寻求和饮酒行为。进行了若干行为评估以评估恐惧和焦虑样行为、神经肌肉能力、运动协调和运动。行为评估完成后进行形态学和免疫反应性分析以及基因表达分析。与应激小鼠相比，TLR4 拮抗剂 LPS-RS 治疗应激小鼠的乙醇摄入量显着减少。行为结果表明，压力暴露会诱发恐惧和类似焦虑的行为；然而; 组间运动协调性、神经肌肉能力、运动和探索行为未见明显缺陷。形态学分析显示各组前额叶皮层和海马体无明显变化，而免疫反应性分析显示前额叶皮层和海马中c-Fos表达较高，前额叶皮层中TLR4表达较高，海马中胶质纤维酸性蛋白（GFAP）较高。压力大的动物。应激小鼠还表现出 TLR4、核因子-κB (NF-kB)、诱导型一氧化氮合酶 (iNOS)、多巴胺受体 D2 (DRD2)、与对照和 LPS-RS 处理的应激小鼠相比，环磷酸腺苷 (cAMP) 反应元件结合蛋白-1 (CREB-1) 和阿片受体 MU-1 (OPRM-1) 基因表达。总而言之，TLR4 的拮抗作用可以在治疗压力诱发的成瘾中提供治疗价值。