Discovery Of MicroRNA With Differential Expressions In Central Nervous System And Plasma Of Methamphetamine-addicted Rats

Objective Drug addiction is a chronic, relapsed brain disease. As a novel addictive drug, the trend of amphetamine-type stimulant (ATS) addiction appears to be more serious. Discovery of new molecules associated with ATS addiction has important scientific significance and potential application value. The purpose of this study is finding differential expressed miRNAs in methamphetamine addiction and their potential regulatory functions in different addicted stages, exploring the possibility as candidate biomarkers, which provides clues for elucidation of drug addiction neurobiological mechanism and diagnosis and treatment of drug addiction.Methods1. We estabilish methamphetamine-induced rat self-administration model through the right jugular vein intubation operation. Then we start acquisition drug training and escalation drug training.2. Using miRNA microarray and SYBR Green real-time quantitative PCR, we select and verify differential expressed miRNAs in addictive region. Combined with bioinformatics analysis, we understand potential function of miRNAs and their predicted targets and identify candidate miRNAs.3. Detecting the level of circulating miRNA in plasma through RT-qPCR.Result1. We establish methamphetamine-induced rat self-administration model, which lays the foundation for exploring the neurobiological mechanism of methamphetamine addiction.2.12and8possible differential expressed miRNAs were found in dorsal striatum and prefrontal cortex of methamphetamine-addicted rats with regular drug use or compulsive drug use. Bioinformatics analysis show the function of11differential expressed miRNAs including miR-x6 and their targets may be associated with methamphetamine addiction and its neurotoxicity, which is worthy of further study.3. Circulating miR-xl8has a downward trend in methamphetamine-addicted rats characterized with compulsive drug use behavior and circulating miR-xl9is up-regulated in methamphetamine-addicted rats characterized with regulatory and compulsive drug use behavior.ConclusionIn summary, our study establish methamphetamine-induced rat self-administration model, which can well simulate human addiction behavior.19possible differential expressed miRNAs were found in dorsal striatum and prefrontal cortex of addicted rats.2possible differential expressed circulating miRNAs were detected in plasma. These results will provide important clues for study of miRNA in methamphetamine addcition and exploring the role of circulating miRNA as candidate biomarker in addiction diagnosis.