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Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents
Mepirapim is a synthetic cannabinoid that has recently been abused for recreational purposes. Although serious side effects have been reported from users, the dangerous pharmacological effects of Mepirapim have not been scientifically demonstrated. In this study, we investigated the addictive potent...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229951/ https://www.ncbi.nlm.nih.gov/pubmed/35745629 http://dx.doi.org/10.3390/ph15060710 |
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author | Hur, Kwang-Hyun Lee, YouYoung Donio, Audrey Lynn Ma, Shi-Xun Lee, Bo-Ram Kim, Seon-Kyung Lee, Jae-Gyeong Kim, Young-Jung Kim, MinJeong Yoon, SeolMin Lee, SooYeun Lee, Yong-Sup Lee, Seok-Yong Jang, Choon-Gon |
author_facet | Hur, Kwang-Hyun Lee, YouYoung Donio, Audrey Lynn Ma, Shi-Xun Lee, Bo-Ram Kim, Seon-Kyung Lee, Jae-Gyeong Kim, Young-Jung Kim, MinJeong Yoon, SeolMin Lee, SooYeun Lee, Yong-Sup Lee, Seok-Yong Jang, Choon-Gon |
author_sort | Hur, Kwang-Hyun |
collection | PubMed |
description | Mepirapim is a synthetic cannabinoid that has recently been abused for recreational purposes. Although serious side effects have been reported from users, the dangerous pharmacological effects of Mepirapim have not been scientifically demonstrated. In this study, we investigated the addictive potential of Mepirapim through an intravenous self-administration test and a conditioned place preference test in rodents. Moreover, to determine whether the pharmacological effects of Mepirapim are mediated by cannabinoid receptors, we investigated whether Mepirapim treatment induces cannabinoid tetrad symptoms in mice. Lastly, to identify Mepirapim induced neurochemical maladaptation in the brains of mice, we performed microdialysis, western blots and neurotransmitter enzyme-linked immunosorbent assays. In the results, Mepirapim supported the maintenance of intravenous self-administration and the development of conditioned place preference. As a molecular mechanism of Mepirapim addiction, we identified a decrease in GABAeric signalling and an increase in dopaminergic signalling in the brain reward circuit. Finally, by confirming the Mepirapim-induced expression of cannabinoid tetrad symptoms, we confirmed that Mepirapim acts pharmacologically through cannabinoid receptor one. Taken together, we found that Mepirapim induces addiction-related behaviours through neurochemical maladaptation in the brain. On the basis of these findings, we propose the strict regulation of recreational abuse of Mepirapim. |
format | Online Article Text |
id | pubmed-9229951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92299512022-06-25 Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents Hur, Kwang-Hyun Lee, YouYoung Donio, Audrey Lynn Ma, Shi-Xun Lee, Bo-Ram Kim, Seon-Kyung Lee, Jae-Gyeong Kim, Young-Jung Kim, MinJeong Yoon, SeolMin Lee, SooYeun Lee, Yong-Sup Lee, Seok-Yong Jang, Choon-Gon Pharmaceuticals (Basel) Article Mepirapim is a synthetic cannabinoid that has recently been abused for recreational purposes. Although serious side effects have been reported from users, the dangerous pharmacological effects of Mepirapim have not been scientifically demonstrated. In this study, we investigated the addictive potential of Mepirapim through an intravenous self-administration test and a conditioned place preference test in rodents. Moreover, to determine whether the pharmacological effects of Mepirapim are mediated by cannabinoid receptors, we investigated whether Mepirapim treatment induces cannabinoid tetrad symptoms in mice. Lastly, to identify Mepirapim induced neurochemical maladaptation in the brains of mice, we performed microdialysis, western blots and neurotransmitter enzyme-linked immunosorbent assays. In the results, Mepirapim supported the maintenance of intravenous self-administration and the development of conditioned place preference. As a molecular mechanism of Mepirapim addiction, we identified a decrease in GABAeric signalling and an increase in dopaminergic signalling in the brain reward circuit. Finally, by confirming the Mepirapim-induced expression of cannabinoid tetrad symptoms, we confirmed that Mepirapim acts pharmacologically through cannabinoid receptor one. Taken together, we found that Mepirapim induces addiction-related behaviours through neurochemical maladaptation in the brain. On the basis of these findings, we propose the strict regulation of recreational abuse of Mepirapim. MDPI 2022-06-03 /pmc/articles/PMC9229951/ /pubmed/35745629 http://dx.doi.org/10.3390/ph15060710 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hur, Kwang-Hyun Lee, YouYoung Donio, Audrey Lynn Ma, Shi-Xun Lee, Bo-Ram Kim, Seon-Kyung Lee, Jae-Gyeong Kim, Young-Jung Kim, MinJeong Yoon, SeolMin Lee, SooYeun Lee, Yong-Sup Lee, Seok-Yong Jang, Choon-Gon Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents |
title | Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents |
title_full | Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents |
title_fullStr | Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents |
title_full_unstemmed | Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents |
title_short | Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents |
title_sort | mepirapim, a novel synthetic cannabinoid, induces addiction-related behaviors through neurochemical maladaptation in the brain of rodents |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229951/ https://www.ncbi.nlm.nih.gov/pubmed/35745629 http://dx.doi.org/10.3390/ph15060710 |
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