Abstract
Although numerous studies have confirmed that the mechanisms of opiate addiction include genetic and epigenetic aspects, the results of such studies are inconsistent. Here, we downloaded gene expression profiling information, GSE87823, from the Gene Expression Omnibus database. Samples from males between ages 19 and 35 were selected for analysis of differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were used to analyze the pathways associated with the DEGs. We further constructed protein-protein interaction (PPI) networks using the STRING database and used 10 different calculation methods to validate the hub genes. Finally, we utilized the Basic Local Alignment Search Tool (BLAST) to identify the DEG with the highest sequence similarity in mouse and detected the change in expression of the hub genes in this animal model using RT-qPCR. We identified three key genes, ADCY9, PECAM1, and IL4. ADCY9 expression decreased in the nucleus accumbens of opioid-addicted mice compared with control mice, which was consistent with the change seen in humans. The importance and originality of this study are provided by two aspects. Firstly, we used a variety of calculation methods to obtain hub genes; secondly, we exploited homology analysis to solve the difficult challenge that addiction-related experiments cannot be carried out in patients or healthy individuals. In short, this study not only explores potential biomarkers and therapeutic targets of opioid addiction but also provides new ideas for subsequent research on opioid addiction.
Highlights
Opioid abuse is currently a severe global epidemic problem for public health (Rudd et al, 2016; Roxburgh et al, 2017)
We identified 289 differentially expressed genes (DEGs) in the nucleus accumbens (NAc) of heroin addicts compared with normal control NAc, including 166 downregulated and 123 upregulated DEGs (Figure 2)
In the CC group, the upregulated DEGs were enriched in the terms vacuolar proton-transporting V-type ATPase complex, and cytoplasm, and the downregulated DEGs were enriched in the terms phagocytic cup and intracellular organelle (Figure 3C)
Summary
Opioid abuse is currently a severe global epidemic problem for public health (Rudd et al, 2016; Roxburgh et al, 2017). In 2015, data from the WHO database revealed 450,000 deaths due to drug misuse globally. Among these deaths, 168,000 were due to opioid overdose. From 2000 to 2015, the mortality rates related to opioid overdose increased by 500%. Opioid overdose-related deaths increased by 11% between 2014 and 2015 alone It is urgent to explore the mechanism of opioid addiction
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