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A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signaling
Sang-Hoon Song1, Won-Jun Jang1, Eun Young Jang2
1College of Pharmacy, Keimyung University, Daegu, South Korea.
Abstract:
MicroRNA (miRNA)-mediated striatal gene regulation may play an important role in methamphetamine (METH) addiction. This study aimed to identify changes in novel miRNAs and their target genes during METH self-administration and investigate their roles in METH-induced locomotion. RNA sequencing analysis revealed that mir-183-5p was upregulated in the striatum of METH self-administered rats, and target gene prediction revealed that the glucocorticoid receptor (GR) gene, Nr3c1, was a potential target gene for mir-183-5p. We confirmed that single and repeated METH administrations increased METH-induced locomotion and plasma corticosterone levels in rats. Additionally, increased miR-185-5p expression and decreased GR gene expression were observed only in the repeated-METH-injection group but not in the single-injection group. We then investigated the effects of miR-183-5p on METH-induced locomotion using a miR-183-5p mimic and inhibitor. Injection of a mir-183-5p mimic in the striatum of rats attenuated METH-induced locomotion, whereas injection of a miR-183-5p inhibitor enhanced the locomotor activity in METH-administered rats. Furthermore, the miR-183-5p mimic reduced the phosphorylation of tyrosine hydroxylase (TH) whereas the inhibitor increased it. Taken together, these results indicate that repeated METH injections increase striatal miR-183-5p expression and regulate METH-induced locomotion by regulating GR expression in rats, thereby suggesting a potential role of miR-183-5p as a novel regulator of METH-induced locomotion.
Insights
Methamphetamine (METH) addiction involves striatal gene regulation by microRNA (miRNA). Repeated METH use increases striatal miR-183-5p, which regulates METH-induced locomotion by affecting glucocorticoid receptor (GR) expression in rats.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- MicroRNA (miRNA)-mediated gene regulation in the striatum is implicated in methamphetamine (METH) addiction.
- Understanding novel miRNAs and their targets in METH addiction is crucial for developing therapeutic strategies.
Purpose of the Study:
- To identify changes in novel miRNAs and their target genes during METH self-administration.
- To investigate the role of these miRNAs in METH-induced locomotion.
Main Methods:
- RNA sequencing was used to identify differentially expressed miRNAs in the striatum of METH self-administered rats.
- Target gene prediction and validation were performed to identify potential miRNA targets.
- In vivo experiments involved administering METH, miRNA mimics, and inhibitors to assess effects on locomotion and gene expression.
Main Results:
- miR-183-5p was upregulated in the striatum following METH self-administration.
- Glucocorticoid receptor (GR) gene (Nr3c1) was identified as a potential target of miR-183-5p.
- miR-183-5p mimic attenuated METH-induced locomotion, while an inhibitor enhanced it, suggesting a regulatory role in METH-induced locomotor activity.
Conclusions:
- Repeated METH injections increase striatal miR-183-5p expression.
- miR-183-5p regulates METH-induced locomotion in rats, potentially by modulating GR expression.
- miR-183-5p represents a novel regulatory target for METH-induced locomotion.
