Injury and Recovery Laboratory, Department of Neuroscience, Ohio State University, Columbus, OH, USA.
Injury and Recovery Laboratory, Department of Neuroscience, Ohio State University, Columbus, OH, USA.
Physiol Behav. 2022 Dec 1;257:113998. doi: 10.1016/j.physbeh.2022.113998. Epub 2022 Oct 17.
Increased neuroinflammation relative to controls is observed in major depression. Moreover, depressive disorders are significantly elevated in conditions which increase neuroinflammation (e.g., brain injury, Parkinson's disease, Alzheimer's disease). To better understand the relationship between neuroinflammation and depression, additional research is needed. The current set of studies made use of the progressive ratio (PR) task in male rats, a stable measure of motivation which can be evaluated daily and thus is ideally suited for examining a potential role for chronic neuroinflammation in depressive-like behavior. Lipopolysaccharide (LPS) was used to induce an inflammatory response. Experiment 1 confirmed prior acute LPS administration experiments for sensitivity of the PR task, with a large effect at 2 mg/kg, a partial effect at 1 mg/kg, and no effect at 0.5 mg/kg. Experiment 2 evaluated a dose-response of continuous s.c. LPS infusion but found no significant elevation in brain cytokines after 14 days at any doses of 0.1, 0.5, 1, or 2 mg/kg/week. Experiment 3 assessed motivation during continuous s.c. infusion of a large 5 mg/kg/week LPS dose and found no significant impairments in motivation, but transient decreases in rates of lever pressing (i.e., only motoric deficits). Experiment 4 measured motivation during continuous ICV infusion of 10.5 μg/kg/week LPS and found significantly decreased motivation without changes to rates of lever pressing (i.e., only motivational deficits). Together these results suggest that the PR task is efficient for evaluating models of chronic inflammation, and that the adaptive response to chronic LPS exposure, even when delivered centrally, may necessitate alternative strategies for generating long-term neuroinflammation.
与对照组相比,重度抑郁症患者的神经炎症明显增加。此外,在增加神经炎症的情况下,抑郁障碍的发病率显著升高(例如,脑损伤、帕金森病、阿尔茨海默病)。为了更好地理解神经炎症与抑郁之间的关系,需要进一步的研究。本研究系列利用雄性大鼠的渐进比率(PR)任务,这是一种稳定的动机测量方法,可以每天进行评估,因此非常适合研究慢性神经炎症在抑郁样行为中的潜在作用。脂多糖(LPS)用于诱导炎症反应。实验 1 证实了先前急性 LPS 给药实验中 PR 任务的敏感性,2mg/kg 时效果显著,1mg/kg 时部分有效,0.5mg/kg 时无效。实验 2 评估了连续皮下 LPS 输注的剂量反应,但在任何剂量(0.1、0.5、1 或 2mg/kg/周)下连续 14 天都未发现脑细胞因子显著升高。实验 3 评估了连续皮下输注大剂量 5mg/kg/周 LPS 时的动机,发现动机没有明显受损,但杠杆按压率短暂下降(即仅运动缺陷)。实验 4 测量了连续脑室内输注 10.5μg/kg/周 LPS 时的动机,发现动机明显降低,而杠杆按压率没有变化(即仅动机缺陷)。这些结果表明,PR 任务对于评估慢性炎症模型是有效的,即使中枢给予 LPS,对慢性 LPS 暴露的适应性反应也可能需要采用其他策略来产生长期的神经炎症。
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