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A novel microRNA, novel-m009C, regulates methamphetamine rewarding effects

Methamphetamine (METH) is a widely abused psychostimulant, whose hyper-rewarding property is believed to underlie its addictive effect, but the molecular mechanism regulating this effect remains unclear. We previously reported that decreased expression of a novel microRNA (miRNA), novel-m009C, is im...

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Autores principales: Zhu, Li, Wu, Feifei, Yan, Zhilan, He, Lijun, Wang, Shufei, Hu, Haohao, Goh, Eyleen L. K., Zhu, Yingjie, Guan, Fanglin, Chen, Teng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708597/
https://www.ncbi.nlm.nih.gov/pubmed/35715487
http://dx.doi.org/10.1038/s41380-022-01651-2
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author Zhu, Li
Wu, Feifei
Yan, Zhilan
He, Lijun
Wang, Shufei
Hu, Haohao
Goh, Eyleen L. K.
Zhu, Yingjie
Guan, Fanglin
Chen, Teng
author_facet Zhu, Li
Wu, Feifei
Yan, Zhilan
He, Lijun
Wang, Shufei
Hu, Haohao
Goh, Eyleen L. K.
Zhu, Yingjie
Guan, Fanglin
Chen, Teng
author_sort Zhu, Li
collection PubMed
description Methamphetamine (METH) is a widely abused psychostimulant, whose hyper-rewarding property is believed to underlie its addictive effect, but the molecular mechanism regulating this effect remains unclear. We previously reported that decreased expression of a novel microRNA (miRNA), novel-m009C, is implicated in the regulation of METH hyperlocomotion. Here, we found that novel-m009C may be homologous to hsa-miR-604. Its expression is consistently downregulated in the nucleus accumbens (NAc) of mice when exposed to METH and cocaine, whereas significant alterations in novel-m009C expression were not observed in the NAc of mice subjected to other rewarding and psychiatric stimuli, such as sucrose, morphine and MK-801. We further found the substantial reduction in novel-m009C expression may be regulated by both dopamine receptor D1 (D1R) and D2 (D2R). Increasing novel-m009C levels in the NAc attenuated METH-induced conditioned place preference (CPP) and hyperlocomotion, whereas inhibiting novel-m009C expression in the NAc enhanced these effects but did not change the preference of mice for a natural reward, i.e., sucrose. These effects may involve targeting of genes important for the synaptic transmission, such as Grin1 (NMDAR subunit 1). Our findings demonstrate an important role for NAc novel-m009C in regulating METH reward, reveal a novel molecular regulator of the actions of METH on brain reward circuitries and provide a new strategy for treating METH addiction based on the modulation of small non-coding RNAs.
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spelling pubmed-97085972022-12-01 A novel microRNA, novel-m009C, regulates methamphetamine rewarding effects Zhu, Li Wu, Feifei Yan, Zhilan He, Lijun Wang, Shufei Hu, Haohao Goh, Eyleen L. K. Zhu, Yingjie Guan, Fanglin Chen, Teng Mol Psychiatry Article Methamphetamine (METH) is a widely abused psychostimulant, whose hyper-rewarding property is believed to underlie its addictive effect, but the molecular mechanism regulating this effect remains unclear. We previously reported that decreased expression of a novel microRNA (miRNA), novel-m009C, is implicated in the regulation of METH hyperlocomotion. Here, we found that novel-m009C may be homologous to hsa-miR-604. Its expression is consistently downregulated in the nucleus accumbens (NAc) of mice when exposed to METH and cocaine, whereas significant alterations in novel-m009C expression were not observed in the NAc of mice subjected to other rewarding and psychiatric stimuli, such as sucrose, morphine and MK-801. We further found the substantial reduction in novel-m009C expression may be regulated by both dopamine receptor D1 (D1R) and D2 (D2R). Increasing novel-m009C levels in the NAc attenuated METH-induced conditioned place preference (CPP) and hyperlocomotion, whereas inhibiting novel-m009C expression in the NAc enhanced these effects but did not change the preference of mice for a natural reward, i.e., sucrose. These effects may involve targeting of genes important for the synaptic transmission, such as Grin1 (NMDAR subunit 1). Our findings demonstrate an important role for NAc novel-m009C in regulating METH reward, reveal a novel molecular regulator of the actions of METH on brain reward circuitries and provide a new strategy for treating METH addiction based on the modulation of small non-coding RNAs. Nature Publishing Group UK 2022-06-17 2022 /pmc/articles/PMC9708597/ /pubmed/35715487 http://dx.doi.org/10.1038/s41380-022-01651-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhu, Li
Wu, Feifei
Yan, Zhilan
He, Lijun
Wang, Shufei
Hu, Haohao
Goh, Eyleen L. K.
Zhu, Yingjie
Guan, Fanglin
Chen, Teng
A novel microRNA, novel-m009C, regulates methamphetamine rewarding effects
title A novel microRNA, novel-m009C, regulates methamphetamine rewarding effects
title_full A novel microRNA, novel-m009C, regulates methamphetamine rewarding effects
title_fullStr A novel microRNA, novel-m009C, regulates methamphetamine rewarding effects
title_full_unstemmed A novel microRNA, novel-m009C, regulates methamphetamine rewarding effects
title_short A novel microRNA, novel-m009C, regulates methamphetamine rewarding effects
title_sort novel microrna, novel-m009c, regulates methamphetamine rewarding effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708597/
https://www.ncbi.nlm.nih.gov/pubmed/35715487
http://dx.doi.org/10.1038/s41380-022-01651-2
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