The effects of lipopolysaccharide exposure on social interaction, cytokine expression, and alcohol consumption in male and female mice.
The effects of lipopolysaccharide exposure on social interaction, cytokine expression, and alcohol consumption in male and female mice.
复制标题
脂多糖暴露对雄性和雌性小鼠社交互动、细胞因子表达和饮酒的影响。
DOI：
10.1016/j.physbeh.2023.114159
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发表时间：
2023
影响因子：
2.9
通讯作者：
Schank,JR
中科院分区：
文献类型：
--
作者：
DeckerRamirez,EB;Arnold,ME;McConnell,KT;Solomon,MG;Amico,KN;Schank,JR
最近的许多研究表明，炎症途径在抑郁样行为和过量饮酒中起到了作用。脂多糖(LPS)是革兰氏阴性菌的细胞壁成分，可用于在临床前研究环境中触发啮齿动物的强烈炎症反应，以研究这种关系背后的机制。在我们的研究中，我们将雄性和雌性小鼠暴露于脂多糖中，并使用社交互动(SI)测试来评估抑郁样行为，在两瓶选择程序中的饮酒情况，以及使用定量PCR来评估炎症介质的表达。我们发现，注射后24小时，注射内毒素可降低雌性小鼠的SI，但对雄性小鼠无明显影响。脂多糖导致雄性和雌性小鼠的促炎细胞因子表达增加；然而，观察到的细胞因子上调的某些方面在雌性小鼠中比雄性小鼠更大。一组单独的雄性和雌性小鼠在接受生理盐水或脂多糖注射之前喝了12天酒，我们发现这会增加雄性和雌性小鼠的酒精摄入量。我们之前已经观察到神经激肽-1受体(NK1R)在酒精摄入量增加以及对内毒素的炎症和行为反应中的作用。NK1R是神经肽SP的内源性靶点，该系统在抑郁、焦虑、药物/酒精寻求、疼痛和炎症中发挥着广泛的作用。因此，我们在饮酒前使用了NK1R拮抗剂。这种治疗减少了用脂多糖处理的雌性小鼠不断增加的酒精消耗量，但不影响雄性小鼠的饮酒。综上所述，这些结果表明，女性对内毒素的某些生理和行为影响更敏感，但内毒素会增加两性的饮酒量。此外，NK1R拮抗剂可以减少因内毒素治疗而增加的酒精消耗量，这与我们之前的发现一致。
Much recent research has demonstrated a role of inflammatory pathways in depressive-like behavior and excess alcohol consumption. Lipopolysaccharide (LPS) is a cell wall component of gram-negative bacteria that can be used to trigger a strong inflammatory response in rodents in a preclinical research setting to study the mechanisms behind this relationship. In our study, we exposed male and female mice to LPS and assessed depressive-like behavior using the social interaction (SI) test, alcohol consumption in the two-bottle choice procedure, and expression of inflammatory mediators using quantitative PCR. We found that LPS administration decreased SI in female mice but had no significant impact on male mice when assessed 24 h after injection. LPS resulted in increased proinflammatory cytokine expression in both male and female mice; however, some aspects of the cytokine upregulation observed was greater in female mice as compared to males. A separate cohort of male and female mice underwent drinking for 12 days before receiving a saline or LPS injection, which we found to increase alcohol intake in both males and females. We have previously observed a role of the neurokinin-1 receptor (NK1R) in escalated alcohol intake, and in the inflammatory and behavioral response to LPS. The NK1R is the endogenous target of the neuropeptide SP, and this system has wide ranging roles in depression, anxiety, drug/alcohol seeking, pain, and inflammation. Thus, we administered a NK1R antagonist prior to alcohol access. This treatment reduced escalated alcohol consumption in female mice treated with LPS but did not affect drinking in males. Taken together, these results indicate that females are more sensitive to some physiological and behavioral effects of LPS administration, but that LPS escalates alcohol consumption in both sexes. Furthermore, NK1R antagonism can reduce alcohol consumption that is escalated by LPS treatment, in line with our previous findings.