Abstract
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.
Highlights
IntroductionMorphine is often used for surgery, trauma, severe pain accompanying burns, or three-step analgesia in patients with advanced cancer
Morphine is an opioid receptor agonist with excellent analgesic effects
Distance matrices among samples were generated based on Bray–Curtis similarity algorithms at the Operational taxonomic units (OTUs) level, and are reported according to principal coordinate analysis (PCoA) and nonmetric multidimensional scaling (NMDS) (Figure 3C)
Summary
Morphine is often used for surgery, trauma, severe pain accompanying burns, or three-step analgesia in patients with advanced cancer. Morphine addiction harms the central nervous system (CNS) of Sinomenine Effects on Morphine-Dependent Zebrafish the body and affects the peripheral system. Numerous studies have shown that CNS disease is closely related to the intestinal microbiota. Studies in germ free (GF) animals and in animals exposed to pathogenic bacterial infections, probiotics, or antibiotic drugs have shown that gut microbes play a role in regulating anxiety, mood, cognition, and pain (Cryan and Dinan, 2012). The emerging concept of the MGBA shows that mutual regulation of the gut microbiota (GM) and the brain may be a new approach to treating complex CNS diseases
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