谷氨酸的
眶额皮质
神经科学
岛叶皮质
上瘾
心理学
强迫行为
长时程增强
医学
前额叶皮质
谷氨酸受体
精神科
内科学
受体
认知
作者
Yang Chen,Guibin Wang,Wen Zhang,Ying Han,Libo Zhang,Hubo Xu,Shi-Qiu Meng,Lin Lü,Yan-Xue Xue,Jie Shi
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2022-12-23
卷期号:8 (51)
被引量:7
标识
DOI:10.1126/sciadv.abq5745
摘要
Compulsive drug use, a cardinal symptom of drug addiction, is characterized by persistent substance use despite adverse consequences. However, little is known about the neural circuit mechanisms behind this behavior. Using a footshock-punished cocaine self-administration procedure, we found individual variability of rats in the process of drug addiction, and rats with compulsive cocaine use presented increased neural activity of the anterior insular cortex (aIC) compared with noncompulsive rats. Chemogenetic manipulating activity of aIC neurons, especially aIC glutamatergic neurons, bidirectionally regulated compulsive cocaine intake. Furthermore, the aIC received inputs from the orbitofrontal cortex (OFC), and the OFC-aIC circuit was enhanced in rats with compulsive cocaine use. Suppression of the OFC-aIC circuit switched rats from punishment resistance to sensitivity, while potentiation of this circuit increased compulsive cocaine use. In conclusion, our results found that aIC glutamatergic neurons and the OFC-aIC circuit gated the shift from controlled to compulsive cocaine use, which could serve as potential therapeutic targets for drug addiction.
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