[Animal Experiment]-Reveal a new mechanism of opioid tolerance in mouse experiments

  Journalists from Zheng Zheng's research team at the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences cooperated with research teams at home and abroad to regulate NeuroD1 and NeuroD1, which are the main transcription factors for mouse spatial learning and memory and opioid resistance. A new mechanism of anti-opioid drugs was discovered, and the research results were recently published online in the international academic journal "Biological Psychiatry". Initially, the specific mechanisms of drug resistance and the methods to effectively reduce the development of drug resistance have always been important research topics in the field of neuropharmacology. Since the 1960s and 1970s, researchers have always believed that drug resistance is closely related to human learning and memory capabilities, but it is difficult to provide clear evidence in experimental data.

  Zheng Hui’s team started with the spatial learning and memory abilities of NeuroD1 and mice, and found that long-term use of opioids (8 days in the experiment) led to a rapid decline in NeuroD1 activity. On the one hand, the decrease in NeuroD1 activity will reduce the analgesic effect of opioids in a short period of time (a few days) and rapidly increase drug resistance. On the other hand, after a relatively long period of time, NeuroD1 activity decreases.

  (several weeks) It impairs the development of drug resistance by reducing the spatial learning and memory abilities of mice. Since the effects of these two parts are at different stages, the way opioids are used will greatly affect drug resistance and the determination of the relationship between learning and memory. The results of the study show that learning and memory have a regulatory effect on drug resistance, and that opioids can be used to inhibit the development of drug resistance while avoiding the decrease in NeuroD1 activity.