Abstract
Drug abuse is a public health and social problem. A number of studies have reported that drug addiction is associated with microRNAs (miRNAs). By comparing the expression of miRNAs in the serum exosomes of methamphetamine-dependent and ketamine-dependent rats, the aim of the present study was to provide insights into the miRNA-mediated associations between the two groups. Published results on conditioned place preference (CPP) in rats conditioned by methamphetamine and ketamine were replicated. The expression of miRNAs in serum exosomes were determined by gene-chip sequencing. The potential target genes of differentially expressed (DE) co-miRNAs were predicted in the methamphetamine and ketamine rats, then functional analysis of their target genes was performed. Methamphetamine and ketamine reward greatly increased the activity time and distance in the intrinsically non-preferred side of the behavioral apparatus when compared with controlled rats (P<0.01). In addition, methamphetamine upregulated the expression of 276 miRNAs and downregulated 25 miRNAs, while ketamine only downregulated the expression of 267 miRNAs. Ten DE co-miRNAs in the two model groups were identified. Functional analysis revealed that DE co-miRNAs are involved in the development of addiction at different stages, and their target genes were enriched in 'vesicular transport', 'amphetamine addiction', 'dopaminergic synapse' and 'GABAergic synapse'. Therefore, it was suggested that these co-miRNAs may have a strong association with drug addiction, and they may be involved in the different addiction processes, which partly explains methamphetamine and ketamine addiction.