Professor Shi Jie's team revealed the neural circuit mechanism of compulsive drug-seeking behavior in drug addiction

Drug addiction is a serious brain disease, and about 284 million people around the world currently use drugs, which not only harms personal health, but also leads to the widespread spread of infectious diseases such as AIDS, which is a major public health problem
facing the international community.
One of the core clinical features of drug addiction is compulsive drug use, in which the addict is desperate to seek and use drugs
even though he knows that drug use will bring endless harm to his health and family.
At present, the biological basis of compulsive drug-seeking behavior is not clear, and revealing the neural circuit mechanism of compulsive drug-seeking behavior for targeted intervention may be a key breakthrough point
to solve the problem of drug addiction.

The anteriorinsularcortex (aIC) acts as an integrated center for information in the brain and is involved in a variety of important brain functions
such as sensation, cognition, learning, and memory.
Previous animal studies have shown that aIC is involved in drug addiction and mediates the reward effect of addictive drugs, and clinical studies have found that smokers have reduced craving for tobacco and increased intention to quit after insula stroke, suggesting that aIC may be a key brain region
mediating compulsive drug-seeking behavior, a core feature of drug addiction.
However, due to the limitations of previous animal models and technical methods, the circuit mechanism of insula in compulsive foraging behavior has not been systematically studied
.

Recently, Professor Shi Jie's team from the China Institute of Drug Dependence of Peking University published an online report entitled "An orbitofrontal cortex-anterior insular cortex" in the international important journal Science Advances circuit gates compulsive cocaine use", which first reported the role of the OFC-aIC neural circuit in compulsive drug-seeking behavior plays an important regulatory role
.
The researchers first clustered behavioral indicators in different dimensions of cocaine-addicted rats and found that about 30% of addicted rats exhibited compulsive drug-seeking behavior
.
Subsequently, the researchers used techniques such as immunofluorescence, fiber optic recording, and whole-cell patch-clamp recording to find that aIC and O FC-aIC were present in rats with obsessive-compulsive drug-seeking behavior phenotypes Abnormal activation
of neural circuits.
The use of chemogenetics to inhibit aIC and O FC-aIC neural circuits can significantly reduce the compulsive drug-seeking behavior of rats and activate aIC and O The FC-aIC neural circuit can induce obsessive-compulsive drug-seeking behavior
.
In addition, the researchers also found that glutamatergic neurons are the main types
of neurons that regulate compulsive drug-seeking behavior in both aIC and O FC-aIC neural circuits.
This study reveals for the first time that aIC and OFC-aIC neural circuits play an important regulatory role in compulsive drug-seeking behavior, and provide a new intervention target for the prevention and treatment of drug addiction.

Dr.
Chen Yang of the Chinese Institute of Drug Dependence, Peking University, Associate Professor Wang Guibin of the Institute of Materia Medica, Chinese Academy of Medical Sciences are co-first authors of this paper, Professor Shi Jie, Associate Researcher Xue Yanxue and Academician Lu Lin of the China Institute of Drug Dependence, Peking University He is the co-corresponding author
of this article.

Citations: Chen, Y.
, Wang, G.
, Zhang, W.
, Han, Y.
, Zhang, L.
, Xu, H.
, Meng, S.
, Lu, L.
, Xue, Y.
, & Shi, J.
(2022).
An orbitofrontal cortex-anterior insular cortex circuit gates compulsive cocaine use.
ScienceAdvances, 8(51), eabq5745.

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(China Institute of Drug Dependence, Peking University)