Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784734909695262720
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
work_keys_str_mv AT hurkwanghyun mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT leeyouyoung mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT donioaudreylynn mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT mashixun mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT leeboram mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT kimseonkyung mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT leejaegyeong mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT kimyoungjung mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT kimminjeong mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT yoonseolmin mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT leesooyeun mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT leeyongsup mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT leeseokyong mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents
AT jangchoongon mepirapimanovelsyntheticcannabinoidinducesaddictionrelatedbehaviorsthroughneurochemicalmaladaptationinthebrainofrodents