Morphine abuse is a global public health problem. Increasing evidence has shown that gut microbiota
dysbiosis plays an important role in several
central nervous system diseases. However, whether there is an association between gut microbiota and
morphine dependence remains unclear. In this study, the effects of
isorhynchophylline on
morphine dependence were evaluated based on the microbiota-gut-brain axis (
MGBA). The results showed that
isorhynchophylline could reverse the changes in alpha and beta diversity, composition, and richness of the intestinal flora occurring in
morphine-dependent zebrafish, as well as the
morphine-induced changes in the expression of
MGBA-related genes in BV2 cells and the brain and intestine of zebrafish. Based on the results, we then used
antibiotics to evaluate whether disrupting the gut microbiota would affect
morphine addiction in zebrafish. The results showed that the
antibiotic-induced intestinal floral imbalance changed the behavior of
morphine-dependent zebrafish, the characteristics of the zebrafish intestinal flora, and the expression of
MGBA-related genes in the zebrafish brain and intestine. Importantly, we also show that, following
antibiotic administration, the ameliorative effects of
isorhynchophylline on
morphine addiction were lost. Together, our results indicate that the gut microbiota interacts with the brain, and
dysbiosis of the intestinal flora may affect the efficacy of
isorhynchophylline in the body. Our findings provide a novel framework for understanding the mechanisms of
morphine addiction through the
MGBA and may provide new therapeutic strategies for the use of Chinese medicines in the prevention of
drug addiction.