UGC Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga, Málaga, Spain.
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy.
Int J Eat Disord. 2023 Jun;56(6):1098-1113. doi: 10.1002/eat.23917. Epub 2023 Feb 25.
Consumption of energy-dense palatable "comfort" food can alleviate stress and negative emotions, while abrupt withdrawal from a palatable diet can worsen these symptoms, causing difficulties with adherence to weight-loss diets. Currently, no pharmacological treatment is effective for obesity-related anxiety, so we investigated the endocannabinoid system (ECS), and specifically the fatty acid amide hydrolase (FAAH), as an interesting emerging target in this context because of its key role in the regulation of both energy homeostasis and emotional behavior.
Rats were subjected to exposure and subsequent abstinence from a palatable cafeteria diet. During abstinence period, rats were treated with the selective FAAH inhibitor PF-3845 (10 mg/kg; intraperitoneal administration every other day).
Abstinent rats displayed an anxiogenic-like behavior and changes in the proteins of ECS signaling machinery in brain areas involved both in anxiety and food intake regulation. In particular, withdrawal caused a reduction of the expression of cannabinoid receptors in the nucleus accumbens and of enzymes diacylglycerol lipase alpha and monoacylglycerol lipase (MAGL) in the amygdala. Pharmacological inhibition of FAAH exerted an anxiolytic-like effect in abstinent animals and increased both MAGL expression in amygdala and CB2 expression in prefrontal cortex.
Overall, our results suggest that emotional disturbances associated with dieting are coupled with region-specific alterations in the cerebral expression of the ECS and that the enhancement of the endocannabinoid signaling by FAAH inhibition might represent a novel pharmacological strategy for the treatment of anxiety related to abstinence from palatable food.
The present study focused on evaluating the role of the endocannabinoid system in modulating withdrawal from naturally rewarding activities that have an impact on mood, such as feeding. The variations observed in the emotional behavior of abstinent rats was linked to neuroadaptations of the ECS in specific brain areas.
摄入高热量美味的“舒适”食物可以缓解压力和负面情绪，而突然停止食用美味的食物会使这些症状恶化，导致减肥饮食难以坚持。目前，没有有效的药物治疗与肥胖相关的焦虑症，因此我们研究了内源性大麻素系统（ECS），特别是脂肪酸酰胺水解酶（FAAH），因为它在调节能量平衡和情绪行为方面起着关键作用，所以它是一个有趣的新兴靶点。
使大鼠暴露于美味的自助餐厅饮食中，然后让其戒断。在戒断期间，大鼠接受选择性 FAAH 抑制剂 PF-3845（10mg/kg；每隔一天腹腔注射）治疗。
戒断大鼠表现出焦虑样行为，并改变了参与焦虑和食物摄入调节的脑区的 ECS 信号机制中的蛋白质。特别是，戒断导致伏隔核中大麻素受体的表达减少，杏仁核中二酰基甘油脂肪酶 alpha 和单酰基甘油脂肪酶（MAGL）的表达减少。FAAH 的药理学抑制在戒断动物中表现出抗焦虑样作用，并增加了杏仁核中的 MAGL 表达和前额叶皮层中的 CB2 表达。
总的来说，我们的结果表明，与节食相关的情绪障碍与大脑中 ECS 的特定区域改变有关，而 FAAH 抑制增强内源性大麻素信号可能代表一种治疗与美味食物戒断相关的焦虑的新的药理学策略。
本研究集中评估了内源性大麻素系统在调节从自然奖赏性活动戒断的作用，这些活动会影响情绪，如进食。戒断大鼠情绪行为的变化与特定脑区 ECS 的神经适应有关。
