Chinese scholars have made progress in the research of addiction memory mechanism

Figure Addiction cues regulate the dynamic reshaping mechanism of synaptic memory in addiction

With the support of the National Natural Science Foundation of China (grant number: 81822017, 82101565), the team of Professor Yuan Yifei of the Shanghai Mental Health Center (National Center for Mental Illness) made progress in the study of the mechanism of addictive memory, and the research results were based on "Retrieval-extinction of drug memory requires AMPA receptor.
" trafficking", published online in the journal Science Advances on December 23
, 2022.
Link to the paper: _istranslated="1">.

The core symptom of addiction is relapse behavior due to intense psychological cravings, and the clinical risk factor is exposure to drugs or drug-related cues
.
But how addiction cues extract addictive memories ultimately leads to intense cravings and impulsive drug use behavior, is unclear
.
Based on the early discovery that medial prefrontal cortex (mPFC) is the core region of drug-related cue processing in addicts, this study uses animal models to further reveal the dynamic mechanism
of glutamate receptor transport induced by addiction cues in the mPFC region 。 The study found that the glutamate synaptic transmission of pyramidal neurons in the mPFC region of normal animals was dominated by calcium-impermeable AMPA receptors (CI-AMPARs), and the glutamate transmission was enhanced after addiction.
After 10 minutes of exposure to the addiction cue, glutamate synaptic transmission on pyramidal neurons in the mPFC region of addicted animals decreases rapidly, accompanied by a decrease in synaptic components of calcium-permeable AMPA receptors (CP-AMPARs) and a rapid downmembrane
.
This phenomenon can last up to 6 hours, after which synaptic transmission intensity returns to the pre-cue state
.
The researchers used targeted peptide tools to interfere with the lower membrane of CP-AMPA receptors, and found that the phenomenon of cue extraction to promote regression training would be blocked.
Further intervention in the memory re-enactment process of CP-AMPA receptor re-epimembrane can effectively block the relapse behavior
.
The dynamic transport process of CP-AMPA receptors is mediated by activation of dopamine type 1 (D1) receptors (figure).

This study revealed the synaptic dynamic remodeling mechanism of the interaction between addiction cues and addiction memory, elucidated the important role of glutamate receptor transport in mPFC region involved in the regulation of addictive behavior, and provided new ideas
for addiction intervention strategies.