Despite years of research, our understanding of the mechanisms by which inflammation induces depression is still limited. As clinical data points to a strong association between depression and motivational alterations, we sought to (1) characterize the motivational changes that are associated with inflammation in mice, and (2) determine if they depend on inflammation-induced activation of indoleamine 2,3 dioxygenase-1 (IDO1). Lipopolysaccharide (LPS)-treated or spared nerve injured (SNI) wild type (WT) and Ido1-/- mice underwent behavioral tests of antidepressant activity (e.g., forced swim test) and motivated behavior, including assessment of (1) reward expectancy using a food-related anticipatory activity task, (2) willingness to work for reward using a progressive ratio schedule of food reinforcement, (3) effort allocation using a concurrent choice task, and (4) ability to associate environmental cues with reward using conditioned place preference. LPS- and SNI-induced deficits in behavioral tests of antidepressant activity in WT but not Ido1-/- mice. Further, LPS decreased food related-anticipatory activity, reduced performance in the progressive ratio task, and shifted effort toward the preferred reward in the concurrent choice task. These effects were observed in both WT and Ido1-/- mice. Finally, SNI mice developed a conditioned place preference based on relief from pain in an IDO1-independent manner. These findings demonstrate that the motivational effects of inflammation do not require IDO1. Further, they indicate that the motivational component of inflammation-induced depression is mechanistically distinct from that measured by behavioral tests of antidepressant activity.

中文翻译：

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在炎症诱导的抑郁症小鼠模型中发生的动机变化与吲哚胺 2,3 双加氧酶无关。

尽管进行了多年的研究，但我们对炎症诱发抑郁的机制的理解仍然有限。由于临床数据表明抑郁症和动机改变之间存在很强的关联，我们试图 (1) 描述与小鼠炎症相关的动机变化，以及 (2) 确定它们是否依赖于炎症诱导的吲哚胺 2,3 活化双加氧酶-1 (IDO1)。脂多糖 (LPS) 治疗或神经损伤 (SNI) 野生型 (WT) 和 Ido1-/- 小鼠接受了抗抑郁活性的行为测试（例如强迫游泳测试）和动机行为，包括评估 (1) 奖励期望使用与食物相关的预期活动任务，（2）使用渐进式食物强化比例计划来获得奖励的意愿，(3) 使用并发选择任务分配努力，以及 (4) 使用条件位置偏好将环境线索与奖励联系起来的能力。LPS 和 SNI 诱导的 WT 抗抑郁活性行为测试中的缺陷，而不是 Ido1-/- 小鼠。此外，LPS 减少了与食物相关的预期活动，降低了渐进比例任务的表现，并将努力转向并发选择任务中的首选奖励。在 WT 和 Ido1-/- 小鼠中都观察到了这些影响。最后，SNI 小鼠以独立于 IDO1 的方式产生了一种基于缓解疼痛的条件性位置偏好。这些发现表明炎症的激励作用不需要 IDO1。更远，