Unraveling the Mechanisms of Propofol-Induced Psychological Dependence: A Multi-Omics Approach Linked to Gut Microbiota in Hippocampal Function. Mus musculus

Introduction: Drug abuse is becoming a global public health crisis. According to the United Nations, the number of drug users worldwide has increased dramatically over the past decade, with a surge in the number of drug abusers. The problem was exacerbated by the expanding market for illicit drugs and the increasing availability of synthetic drugs such as fentanyl. Clinical drug abuse is a problem that requires particular attention, and the potential addictive properties of some drugs and their mechanisms of action are currently unknown, which limits the development and implementation of drug addiction intervention strategies.Methods: Eight-week-old C57BL/6J mice were used as study subjects. A mental dependence model was established using the conditional position preference experiment (CPP), and the hippocampal tissues of the model mice were subjected to RNA-seq transcriptome sequencing, LC-MS non-targeted metabolome sequencing, and intestinal macro-genome sequencing in order to discover propofol mental dependence signature genes. Correlation analyses of transcriptomics and metabolomics were performed using the Spearman method, and gene-metabolite networks were mapped using Cytoscape software. Real-time fluorescence quantitative PCR and immunoprotein blotting (Western blotting) methods were used to validate the characterized genes.