A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction
A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction
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DOI：
10.1038/s41467-020-14458-y
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发表时间：
2020-02-07
影响因子：
16.6
通讯作者：
Maldonado, Rafael
中科院分区：
文献类型：
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作者：
Domingo-Rodriguez, Laura;Ruiz de Azua, Inigo;Maldonado, Rafael
食物成瘾与肥胖和饮食失调有关，其特点是行为失控和强迫性食物摄入。在这里，我们使用食物成瘾小鼠模型报告，背侧端脑谷氨酸能神经元中大麻素1型受体的缺乏阻止了食物成瘾样行为的发展，这与内侧前额叶皮层（mPFC）和伏隔核（NAc）突触兴奋性传递的增强有关。相比之下，mPFC-NAc 通路中神经元活动的化学遗传学抑制会诱发强迫性的食物寻找。转录组分析和基因操作发现，mPFC-NAc 通路中多巴胺 D2 受体表达的增加会促进成瘾样表型。我们的研究揭示了一种新的神经生物学机制，它是食物成瘾发展的弹性和脆弱性的基础，这可能为针对这种疾病的新颖有效的干预措施铺平道路。
Food addiction is linked to obesity and eating disorders and is characterized by a loss of behavioral control and compulsive food intake. Here, using a food addiction mouse model, we report that the lack of cannabinoid type-1 receptor in dorsal telencephalic glutamatergic neurons prevents the development of food addiction-like behavior, which is associated with enhanced synaptic excitatory transmission in the medial prefrontal cortex (mPFC) and in the nucleus accumbens (NAc). In contrast, chemogenetic inhibition of neuronal activity in the mPFC-NAc pathway induces compulsive food seeking. Transcriptomic analysis and genetic manipulation identified that increased dopamine D2 receptor expression in the mPFC-NAc pathway promotes the addiction-like phenotype. Our study unravels a new neurobiological mechanism underlying resilience and vulnerability to the development of food addiction, which could pave the way towards novel and efficient interventions for this disorder.