Expression of microRNAs in the serum exosomes of methamphetamine-dependent rats vs. ketamine-dependent rats

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.

Inhibition of Methamphetamine Self-Administration and Reinstatement by Central Blockade of Angiotensin II Receptor in Rats

“…The current study demonstrated the downregulation of NAc miR-219p-5p targeting AT1R after METH SA, compared with yoked-METH and Saline rats. Current findings extend the increasing bodies of research that have demonstrated METHenabled alterations in a number of NAc miRNA expressions associated with various neuronal activities, including metabolism, apoptosis, autophagy, and immune response, potentially via the mitogen-activated protein kinase, CREB, G-protein-coupled receptor, and gonadotropin-releasing hormone signaling pathways (Zhu et al, 2015;Bai et al, 2016;Sim et al, 2017;Li et al, 2018;Zhang et al, 2018). A clinical study has also identified numerous miRNAs as negative regulators in patients with METH use disorder.…”

“…A clinical study has also identified numerous miRNAs as negative regulators in patients with METH use disorder. The majority of studies have used the model of locomotor sensitization and conditioned place preference induced by METH that involves repeated passive administration of METH (Zhu et al, 2015;Li et al, 2018). Two recent studies have investigated the changes in miRNA in rats selfadministering METH.…”

Role of Extracellular Vesicles in Substance Abuse and HIV-Related Neurological Pathologies

“…The vast majority of research into METH abuse and vesicular bodies lies in understanding synaptic vesicles, which are crucial for interneuronal communication, but EVs also contribute to the intercellular communication of the whole nervous system [102]. One paper sequenced the miRNAs found in serum-derived EVs of METH-dependent rats, identifying a total of 301 differentially expressed miRNAs [103]. Four of the differentially regulated miRNA were miR-218b, miR-194-5p, miR-152-3p, and miR-22-3p, which were also noted to be differentially regulated in ketamine dependence [103].…”

“…One paper sequenced the miRNAs found in serum-derived EVs of METH-dependent rats, identifying a total of 301 differentially expressed miRNAs [103]. Four of the differentially regulated miRNA were miR-218b, miR-194-5p, miR-152-3p, and miR-22-3p, which were also noted to be differentially regulated in ketamine dependence [103]. Elevated serum levels of miR-194-5p have been associated with cancers of peripheral organs such as the kidneys and liver [104,105].…”

Long-Term Low-Dose Delta-9-Tetrahydrocannbinol (THC) Administration to Simian Immunodeficiency Virus (SIV) Infected Rhesus Macaques Stimulates the Release of Bioactive Blood Extracellular Vesicles (EVs) that Induce Divergent Structural Adaptations and Signaling Cues

“…As a result, depending on whether the producer cells are healthy or pathologic, EVs will carry markers corresponding to the state of the cells [ 40 , 43 ]. With respect to drug use, EVs have been used to establish signatures linked to methamphetamine, heroin, and alcohol abuse [ 57 , 58 , 59 ]. EVs released by substance-using HIV-infected individuals are known to exhibit pathogenic properties, including increases in cell adhesion, actin reorganization, secretion of metalloproteases, and chemotactic migration toward the HIV secretome [ 42 ].…”