Yohn Samantha E, Arif Yumna, Haley Allison, Tripodi Guiseppe, Baqi Younis, Müller Christa E, Miguel Noemi San, Correa Mercè, Salamone John D
Department of Psychological Sciences, University of Connecticut, Storrs, CT, 06269-1020, USA.
Universität Bonn, Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie, Bonn, Germany.
Psychopharmacology (Berl). 2016 Oct;233(19-20):3575-86. doi: 10.1007/s00213-016-4392-9. Epub 2016 Aug 6.
Motivational dysfunctions such as anergia, fatigue, and reduced effort expenditure are common in patients with depression and other disorders. Pro-inflammatory cytokines are implicated in depression, and cytokine administration induces motivational deficits in humans.
These studies focused on the effects of the cytokine interleukin-6 (IL-6) on effort-related decision-making.
Rats were assessed using the concurrent fixed ratio 5-lever pressing/chow feeding choice procedure, which measures the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (lab chow).
IL-6 (2.0-8.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing chow intake. Further experiments showed that the adenosine A2A antagonist MSX-3 and the stimulant methylphenidate attenuated the effort-related impairments produced by IL-6, increasing lever pressing and decreasing chow intake in IL-6 treated rats. The same doses of IL-6 did not alter food intake or preference in parallel free-feeding choice studies, demonstrating that these low doses were not altering preference for the high carbohydrate pellets or generally suppressing appetite. Also, IL-6 did not affect body temperature. Microdialysis studies showed that 8.0 μg/kg IL-6 significantly decreased extracellular dopamine in nucleus accumbens core.
In summary, IL-6 reduces the tendency to work for food, even at low doses that do not produce fever or loss of appetite. Dopaminergic mechanisms may be involved in these effort-related effects. This research has implications for the involvement of cytokines in motivational dysfunctions such as anergia and fatigue.
动力功能障碍，如无活力、疲劳和努力支出减少，在抑郁症和其他疾病患者中很常见。促炎细胞因子与抑郁症有关，并且细胞因子给药会在人类中诱发动力缺陷。
这些研究聚焦于细胞因子白细胞介素-6（IL-6）对与努力相关的决策的影响。
使用同时进行的固定比率5杠杆按压/食物摄取选择程序对大鼠进行评估，该程序测量大鼠在同时存在但不太喜欢的替代食物（实验室饲料）的情况下为偏好食物（高碳水化合物颗粒）工作的倾向。
IL-6（2.0 - 8.0μg/kg腹腔注射）改变了选择行为，显著减少杠杆按压并增加食物摄取量。进一步的实验表明，腺苷A2A拮抗剂MSX-3和兴奋剂哌甲酯减弱了IL-6产生的与努力相关的损伤，增加了IL-6处理的大鼠的杠杆按压并减少了食物摄取量。相同剂量的IL-6在平行的自由进食选择研究中未改变食物摄取或偏好，表明这些低剂量并未改变对高碳水化合物颗粒的偏好或普遍抑制食欲。此外，IL-6不影响体温。微透析研究表明，8.0μg/kg IL-6显著降低伏隔核核心的细胞外多巴胺。
总之，即使在不引起发热或食欲不振的低剂量下，IL-6也会降低为食物工作的倾向。多巴胺能机制可能参与这些与努力相关的效应。这项研究对于细胞因子在诸如无活力和疲劳等动力功能障碍中的作用具有启示意义。
