Morphine is one of the most severely abused drugs in the world. Previous research on
morphine addiction has focused on the central nervous system (CNS). Studies have shown that a two-way regulation of the brain and gut microbiota (GM), suggesting a link between GM and
CNS disease. However, the functional mechanism underlying the relationship between intestinal flora and
morphine dependence is unclear. In this study, the effect of
sinomenine on
morphine addiction was evaluated based on the microbiota-gut-brain axis (
MGBA). The results show that the GM plays an important role in
morphine dependence.
Morphine treatment induced zebrafish conditional position preference (
CPP), and significantly changed zebrafish GM characteristics and the expression of
MGBA-related genes in the zebrafish brain and intestine. Importantly,
sinomenine, an
alkaloid with a similar structure to
morphine, can reverse these
morphine-induced changes. Subsequently,
morphine-dependent
CPP training was performed after
antibiotic administration. After
antibiotic treatment, zebrafish
CPP behavior, the composition and proportions of the zebrafish GM, and the expression of
MGBA-related genes in zebrafish were changed. More interestingly,
sinomenine was no longer effective in treating
morphine dependence, indicating that
antibiotic-driven intestinal flora imbalance alters the efficacy of
sinomenine on
morphine-dependent zebrafish. This study confirms that the
MGBA is bidirectionally regulated, highlighting the key role of the GM in the formation and treatment of
morphine dependence, and may provide new treatment strategies for using
traditional Chinese medicine to treat
drug addiction.