de Ceglia Marialuisa, Romano Adele, Di Bonaventura Maria Vittoria Micioni, Gavito Ana, Botticelli Luca, Di Bonaventura Emanuela Micioni, Friuli Marzia, Cifani Carlo, de Fonseca Fernando Rodríguez, Gaetani Silvana
UGC de Salud Mental y Unidad Clínica de Neurología, Grupo de Neuropsicofarmacología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga, 29010 Málaga, Spain.
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy.
Curr Neuropharmacol. 2025;23(4):458-474. doi: 10.2174/1570159X23666241107160840.
Alterations of dopamine (DA) transmission in the brain reward system can be associated with an addictive-like state defined as food addiction (FA), common in obese individuals. Subjects affected by FA experience negative feelings when abstinent from their preferred diet and may develop mood disorders, including depression, sustained by alterations in brain DA pathways.
This study aims to investigate the impact of long-term abstinence from a palatable diet on depressive-like behavior in rats, exploring neurochemical alterations in monoamine and endocannabinoid signaling in DA-enriched brain regions, including ventral tegmental area, dorsolateral striatum, substantia nigra and medial prefrontal cortex.
Rats underwent exposure and subsequent abstinence from a palatable cafeteria diet. During abstinence, animals were treated with fatty acid amide hydrolase (FAAH) inhibitor PF-3845 (10 mg/kg, intraperitoneal administration every other day). Lastly, animals were subjected to a forced swimming test, and their brains were dissected and processed for high-performance liquid chromatography measurement of monoamines and western blot analyses of markers of the endocannabinoid machinery.
After the withdrawal from the palatable diet, animals showed depressive-like behavior, coupled with significant variations in the concentration of brain monoamines and in the expression of endocannabinoid signalling machinery proteins in cited brain areas. Treatment with PF-3845 exerted an antidepressant- like effect and restored part of the alterations in monoaminergic and endocannabinoid systems.
Overall, our results suggest that abstinence from a cafeteria diet provokes emotional disturbances linked to neuroadaptive changes in monoamines and endocannabinoid signalling in brain areas partaking to DA transmission that could partially be restored by the enhancement of endocannabinoid signalling through FAAH inhibition.
大脑奖赏系统中多巴胺（DA）传递的改变可能与一种成瘾样状态有关，这种状态被定义为食物成瘾（FA），在肥胖个体中很常见。受FA影响的个体在戒除他们偏爱的饮食时会经历负面情绪，并且可能会因大脑DA通路的改变而患上包括抑郁症在内的情绪障碍。
本研究旨在调查长期戒除美味饮食对大鼠抑郁样行为的影响，探索富含DA的脑区（包括腹侧被盖区、背外侧纹状体、黑质和内侧前额叶皮质）中单胺和内源性大麻素信号传导的神经化学改变。
大鼠接受美味自助餐饮食的暴露及随后的戒除。在戒除期间，动物接受脂肪酸酰胺水解酶（FAAH）抑制剂PF - 3845（10 mg/kg，隔天腹腔注射）治疗。最后，对动物进行强迫游泳试验，并解剖其大脑，用于单胺的高效液相色谱测量和内源性大麻素机制标志物的蛋白质印迹分析。
从美味饮食中戒除后，动物表现出抑郁样行为，同时所提及脑区的脑单胺浓度和内源性大麻素信号传导机制蛋白的表达有显著变化。PF - 3845治疗产生了类似抗抑郁的作用，并恢复了单胺能和内源性大麻素系统的部分改变。
总体而言，我们的结果表明，戒除自助餐饮食会引发与参与DA传递的脑区中，单胺和内源性大麻素信号传导的神经适应性变化相关的情绪障碍，通过抑制FAAH增强内源性大麻素信号传导可部分恢复这些障碍。
