Mouse experiment reveals a new mechanism for opioid tolerance

  The reporter learned from the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences that the Zheng Hui research team of the hospital has cooperated with other research teams at home and abroad to reveal the regulatory effect of the key transcription factor NeuroD1 on the spatial learning and memory ability of mice and the tolerance of opioids. The new mechanism of resistance to opioids was discovered, and the research results were recently published online in the international academic journal Biological Psychiatry.

  According to the introduction, the specific mechanism of drug tolerance and how to effectively reduce the generation of drug tolerance has always been an important research topic in the field of neuropharmacology. Since the 1960s and 1970s, researchers have always believed that drug tolerance is closely related to the body's learning and memory capabilities, but it has been difficult to provide clear evidence in experimental data.

  Zheng Hui's research team started from NeuroD1 and the spatial learning and memory abilities of mice, and found that long-term use of opioids (8 days in the experiment) would lead to a rapid decrease in NeuroD1 activity. On the one hand, the decrease in NeuroD1 activity will cause a decrease in the analgesic effect of opioids in a short period of time (a few days), leading to rapid drug tolerance; on the other hand, the decrease in NeuroD1 activity will occur after a relatively long time. (A few weeks) Reduce the spatial learning and memory ability of mice, thereby hindering the development of drug tolerance. Since the effects of the two parts are at different time stages, the mode of opioid use will greatly affect the judgment of the relationship between drug tolerance and learning and memory.

  The research results reveal the regulatory effect of learning and memory on drug tolerance, suggesting that if opioids are used while avoiding the reduction of NeuroD1 activity in time, the development of drug tolerance can be reduced.