Behavioral Neuroscience Division, Department of Psychological Sciences, University of Connecticut, Storrs, CT, 06269-1020, United States; Sage Thereapeutics, Boston, MA, United States.
Behavioral Neuroscience Division, Department of Psychological Sciences, University of Connecticut, Storrs, CT, 06269-1020, United States.
Physiol Behav. 2023 Jan 1;258:114005. doi: 10.1016/j.physbeh.2022.114005. Epub 2022 Oct 22.
Inflammation is linked to motivational deficits seen in depression and other disorders. Lipopolysaccharide (LPS) induces an inflammatory response and impairs motivated behavior in humans and rodents. It has been suggested that inflammation can shift metabolic needs to functions that warrant more response to the perceived threat (e.g., fighting infection), therefore altering aspects of motivation. Animal models have been developed to assess alterations in motivated behavior by giving the animal the option to work (i.e., lever press) for a highly palatable food reward vs. approaching and consuming a freely available, albeit less preferred, food. This model was used to determine if administration of 2-deoxy-D-glucose (2DG), a substance that inhibits glucose uptake and glycolysis, could reverse the motivational deficits induced by LPS in rats. A food preference/intake task was also conducted to see if LPS affected intake of the highly palatable vs. less palatable foods when both are freely available. It was hypothesized that 2-DG would reverse the motivational deficits caused by LPS and there would be no effect on food preference/intake of the highly palatable food. Results showed that 2-DG significantly reversed LPS effects at the lowest dose, while methylphenidate did not. The food intake/preference tests showed that LPS significantly decreased food intake of both foods but did not alter preference for the highly palatable food compared to vehicle. These results suggest that in addition to having effects on exertion of effort during instrumental behavior, LPS also has direct effects on primary food motivation.
炎症与抑郁和其他疾病中观察到的动机缺陷有关。脂多糖(LPS)会引起炎症反应,并损害人类和啮齿动物的动机行为。有人认为,炎症可以将代谢需求转移到需要对感知到的威胁做出更多反应的功能上(例如,对抗感染),从而改变动机的某些方面。已经开发了动物模型来评估动机行为的改变,方法是让动物选择(即按压杠杆)获取高度美味的食物奖励,而不是接近并食用自由可得的、尽管不太受欢迎的食物。该模型用于确定 2-脱氧-D-葡萄糖(2DG)的给药是否可以逆转 LPS 诱导的大鼠的动机缺陷。还进行了食物偏好/摄入任务,以观察 LPS 是否会影响高度美味与不太美味的食物的摄入,而这两种食物都是自由可得的。假设 2-DG 会逆转 LPS 引起的动机缺陷,并且对高度美味食物的食物偏好/摄入没有影响。结果表明,2-DG 在最低剂量下显著逆转了 LPS 的作用,而哌甲酯则没有。食物摄入/偏好测试表明,LPS 显著降低了两种食物的摄入量,但与载体相比,并未改变对高度美味食物的偏好。这些结果表明,除了对工具性行为中的努力发挥有影响外,LPS 还对原发性食物动机有直接影响。
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