1. Academic Validation
  2. Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signaling

Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signaling

  • Front Pharmacol. 2022 Sep 26;13:997701. doi: 10.3389/fphar.2022.997701.
Sang-Hoon Song 1 Won-Jun Jang 1 Eun Young Jang 2 Oc-Hee Kim 2 Haesoo Kim 1 Taekwon Son 3 Dong-Young Choi 4 Sooyeun Lee 1 Chul-Ho Jeong 1
Affiliations

Affiliations

  • 1 College of Pharmacy, Keimyung University, Daegu, South Korea.
  • 2 Pharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon, South Korea.
  • 3 Korea Brain Bank, Korea Brain Research Institute, Daegu, South Korea.
  • 4 College of Pharmacy, Yeungnam University, Gyeongsan, 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.

Keywords

RNA sequencing; glucocorticoid receptor; locomotor activity; methamphetamine; microRNA; self-administration.

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