Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signaling
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 analys...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.997701/full |
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| author | Sang-Hoon Song Won-Jun Jang Eun Young Jang Oc-Hee Kim Haesoo Kim Taekwon Son Dong-Young Choi Sooyeun Lee Chul-Ho Jeong |
| author_facet | Sang-Hoon Song Won-Jun Jang Eun Young Jang Oc-Hee Kim Haesoo Kim Taekwon Son Dong-Young Choi Sooyeun Lee Chul-Ho Jeong |
| author_sort | Sang-Hoon Song |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:22:32Z |
| format | Article |
| id | doaj.art-5faed25a30e445d4b2714d7a4d4544c5 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-14T07:22:32Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-5faed25a30e445d4b2714d7a4d4544c52022-12-22T02:06:06ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.997701997701Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signalingSang-Hoon Song0Won-Jun Jang1Eun Young Jang2Oc-Hee Kim3Haesoo Kim4Taekwon Son5Dong-Young Choi6Sooyeun Lee7Chul-Ho Jeong8College of Pharmacy, Keimyung University, Daegu, South KoreaCollege of Pharmacy, Keimyung University, Daegu, South KoreaPharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon, South KoreaPharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon, South KoreaCollege of Pharmacy, Keimyung University, Daegu, South KoreaKorea Brain Bank, Korea Brain Research Institute, Daegu, South KoreaCollege of Pharmacy, Yeungnam University, Gyeongsan, South KoreaCollege of Pharmacy, Keimyung University, Daegu, South KoreaCollege of Pharmacy, Keimyung University, Daegu, South KoreaMicroRNA (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.https://www.frontiersin.org/articles/10.3389/fphar.2022.997701/fullmethamphetamineRNA sequencingmicroRNAself-administrationlocomotor activityglucocorticoid receptor |
| spellingShingle | Sang-Hoon Song Won-Jun Jang Eun Young Jang Oc-Hee Kim Haesoo Kim Taekwon Son Dong-Young Choi Sooyeun Lee Chul-Ho Jeong Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signaling Frontiers in Pharmacology methamphetamine RNA sequencing microRNA self-administration locomotor activity glucocorticoid receptor |
| title | Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signaling |
| title_full | Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signaling |
| title_fullStr | Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signaling |
| title_full_unstemmed | Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signaling |
| title_short | Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signaling |
| title_sort | striatal mir 183 5p inhibits methamphetamine induced locomotion by regulating glucocorticoid receptor signaling |
| topic | methamphetamine RNA sequencing microRNA self-administration locomotor activity glucocorticoid receptor |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.997701/full |
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