【文献分享】在持续疼痛下抑制进食的神经回路

  在人类中，持续的疼痛往往会导致食欲下降。然而，这种行为背后的神经回路仍不清楚。在这里，我们发现，在持续疼痛的小鼠模型中，前扣带皮层（GluACC）的谷氨酸能神经元产生的回路投射到下丘脑外侧区（GluLHA）的谷氨酸神经元，以减少食物摄入。反过来，这些GluLHA神经元投射到下丘脑弓状核（POMCArc）中的前阿片胰岛素皮质素神经元，这是一个众所周知的参与减少食物摄入的神经元群体。体内钙成像和多四极管电生理记录显示GluACC → GluLHA → 在持续疼痛的小鼠模型中，电弧回路被激活，雄性和雌性的进食行为都会减少。使用化学遗传学抑制这种回路可以减轻进食抑制症状。我们的研究表明，GluACC → GluLHA → 电弧电路通过POMC神经元活动参与驱动持续疼痛下进食的抑制。这种以前未被识别的途径可以作为疼痛相关疾病的潜在靶点进行探索。

#Sucrose operant responding#

Procedures were based on published methods2-4. Mice operant-conditioning chambers (Zhongshi, Beijing, China) were equipped with nose poke port and liquid dipper port delivering sucrose liquid rewards. Light-emitting diode (LED) light on the top of nose poke port cued the mice for nose pokes but turned off during time-out periods. Before operant task training, mice were single housed and food restricted to attain 85% to 90% of the free feeding weight. Foodrestricted mice were first trained on an FR1 schedule for 2 days, in which each nose poke triggered the delivery of 0.01 ml of sucrose liquid reward with a time-out period of 30 s. This was followed by at least 4 days of the FR4 schedule (four nose pokes trigger the delivery of one reward with a time-out period of 20 s) until mice obtained a maximum of 20 rewards. Once they completed the FR4 training, the motivation for sucrose self-administration was tested using a Progressive Ratio (PR) schedule. In the PR session, the number of responses on the nose poke port to obtain the rewards increased with the dose. The increase in the number of correct responses followed the equation response ratio = (5 × e(0.2 × infusion number) – 5) rounded to the nearest integer, that resulting in the following PR steps: 1, 2, 6, 9, 12, 15, 20, 25, 32, 40, 50, 62, 77, 955. PR schedule was run daily until the differences between rewards earned on two 

consecutive days was less than or equal to 2. Mice that do not meet this criterion or earned less than five rewards during the PR schedule were excluded.

For the study on the effects of pain on the motivated behavior, successfully trained mice were subsequently tested for PR and FR1 operation tasks at the tenth day and the eleventh day after saline or CFA injection, respectively (C57BL/6J male mice aged 9 weeks). Rewards searches used Labmaze V3.0 (Zhongshi, China) for further analysis.

#Sucrose operant responding#

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