Effort but not Reward Sensitivity is Altered by Acute Sickness Induced by Experimental Endotoxemia in Humans.
Effort but not Reward Sensitivity is Altered by Acute Sickness Induced by Experimental Endotoxemia in Humans.
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DOI：
10.1038/npp.2017.231
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
van der Schaaf ME
中科院分区：
文献类型：
--
作者：
Draper A;Koch RM;van der Meer JW;Aj Apps M;Pickkers P;Husain M;van der Schaaf ME
人类的疾病行为的特点是情绪低落和疲劳，这被认为反映了涉及优先事项重组的动机变化。然而，尚不清楚动机背后的哪些具体过程发生了改变。我们测试了细菌内毒素大肠杆菌脂多糖（LPS）是否影响动机行为的两个可分离的结构，即努力和奖励敏感性。在熟悉了 5 个努力水平后，参与者就所提供的股份（1、4、8、12 或 15 个苹果）是否“值得付出努力”（手持测力计中最大自愿收缩的 10%、27.5%、45%、62.5% 和 80%）做出了一系列接受/拒绝决定。努力和奖励水平被参数化地调节，以消除它们对选择的影响。总体而言，29 名健康年轻男性接受了 LPS（2ng/kg；n=14）或安慰剂（0.9% 盐水；n=15）。在注射 LPS/安慰剂之前、注射后 2 小时和 5 小时评估努力投入任务以及自我报告的抑郁和疲劳。 LPS 注射后 8 小时内每小时评估一次细胞因子和疾病症状。与基线和安慰剂相比，LPS 暂时增加了白细胞介素 6 和肿瘤坏死因子 α、疾病症状、体温和自我报告的疲劳以及注射后抑郁症。这些变化伴随着 LPS 引起的高努力选项接受率的下降，但没有显着影响注射后 2 小时的奖励敏感性，注射后 5 小时部分恢复。我们认为 LPS 引起的动机变化可能是由于中脑边缘多巴胺的改变所致。我们的行为范式可用于进一步研究炎症对精神疾病和慢性疾病动机行为的影响。
Sickness behavior in humans is characterized by low mood and fatigue, which have been suggested to reflect changes in motivation involving reorganization of priorities. However, it is unclear which specific processes underlying motivation are altered. We tested whether bacterial endotoxin E. coli lipopolysaccharide (LPS) affected two dissociable constructs of motivational behavior, ie, effort and reward sensitivity. After familiarization with 5 effort levels, participants made a series of accept/reject decisions on whether the stake offered (1, 4, 8, 12, or 15 apples) was ‘worth the effort’ (10%, 27.5%, 45%, 62.5%, and 80% of maximal voluntary contraction in a hand-held dynamometer). Effort and reward levels were parametrically modulated to dissociate their influence on choice. Overall, 29 healthy young males were administered LPS (2 ng/kg; n=14) or placebo (0.9% saline; n=15). The effort-stake task, and self-reported depression and fatigue were assessed prior to LPS/placebo injection, 2 and 5 h post injection. Cytokines and sickness symptoms were assessed hourly till 8 h after LPS injection. LPS transiently increased interleukin-6 and tumor necrosis factor-α, sickness symptoms, body temperature and self-reported fatigue, and depression post injection relative to baseline and placebo. These changes were accompanied by LPS-induced decreases in acceptance rates of high-effort options, without significantly affecting reward sensitivity 2 h post injection, which were partially recovered 5 h post injection. We suggest that LPS-induced changes in motivation may be due to alterations to mesolimbic dopamine. Our behavioral paradigm could be used to further investigate effects of inflammation on motivational behavior in psychiatric and chronic illnesses.
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