Cargando…
Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression
Synthetic cannabinoids have exhibited unpredictable abuse liabilities, especially self-administration (SA) responses in normal rodent models, despite seemingly inducing addiction-like effects in humans. Thus, an efficient pre-clinical model must be developed to determine cannabinoid abuse potential...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060981/ https://www.ncbi.nlm.nih.gov/pubmed/37007015 http://dx.doi.org/10.3389/fphar.2023.1135929 |
_version_ | 1785017200988389376 |
---|---|
author | Sayson, Leandro Val Ortiz, Darlene Mae Lee, Hyun Jun Kim, Mikyung Custodio, Raly James Perez Yun, Jaesuk Lee, Chae Hyeon Lee, Yong Sup Cha, Hye Jin Cheong, Jae Hoon Kim, Hee Jin |
author_facet | Sayson, Leandro Val Ortiz, Darlene Mae Lee, Hyun Jun Kim, Mikyung Custodio, Raly James Perez Yun, Jaesuk Lee, Chae Hyeon Lee, Yong Sup Cha, Hye Jin Cheong, Jae Hoon Kim, Hee Jin |
author_sort | Sayson, Leandro Val |
collection | PubMed |
description | Synthetic cannabinoids have exhibited unpredictable abuse liabilities, especially self-administration (SA) responses in normal rodent models, despite seemingly inducing addiction-like effects in humans. Thus, an efficient pre-clinical model must be developed to determine cannabinoid abuse potential in animals and describe the mechanism that may mediate cannabinoid sensitivity. The Cryab knockout (KO) mice were recently discovered to be potentially sensitive to the addictive effects of psychoactive drugs. Herein, we examined the responses of Cryab KO mice to JWH-018 using SA, conditioned place preference, and electroencephalography. Additionally, the effects of repeated JWH-018 exposure on endocannabinoid- and dopamine-related genes in various addiction-associated brain regions were examined, along with protein expressions involving neuroinflammation and synaptic plasticity. Cryab KO mice exhibited greater cannabinoid-induced SA responses and place preference, along with divergent gamma wave alterations, compared to wild-type (WT) mice, implying their higher sensitivity to cannabinoids. Endocannabinoid- or dopamine-related mRNA expressions and accumbal dopamine concentrations after repeated JWH-018 exposure were not significantly different between the WT and Cryab KO mice. Further analyses revealed that repeated JWH-018 administration led to possibly greater neuroinflammation in Cryab KO mice, which may arise from upregulated NF-κB, accompanied by higher expressions of synaptic plasticity markers, which might have contributed to the development of cannabinoid addiction-related behavior in Cryab KO mice. These findings signify that increased neuroinflammation via NF-κB may mediate the enhanced addiction-like responses of Cryab KO mice to cannabinoids. Altogether, Cryab KO mice may be a potential model for cannabinoid abuse susceptibility. |
format | Online Article Text |
id | pubmed-10060981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100609812023-03-31 Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression Sayson, Leandro Val Ortiz, Darlene Mae Lee, Hyun Jun Kim, Mikyung Custodio, Raly James Perez Yun, Jaesuk Lee, Chae Hyeon Lee, Yong Sup Cha, Hye Jin Cheong, Jae Hoon Kim, Hee Jin Front Pharmacol Pharmacology Synthetic cannabinoids have exhibited unpredictable abuse liabilities, especially self-administration (SA) responses in normal rodent models, despite seemingly inducing addiction-like effects in humans. Thus, an efficient pre-clinical model must be developed to determine cannabinoid abuse potential in animals and describe the mechanism that may mediate cannabinoid sensitivity. The Cryab knockout (KO) mice were recently discovered to be potentially sensitive to the addictive effects of psychoactive drugs. Herein, we examined the responses of Cryab KO mice to JWH-018 using SA, conditioned place preference, and electroencephalography. Additionally, the effects of repeated JWH-018 exposure on endocannabinoid- and dopamine-related genes in various addiction-associated brain regions were examined, along with protein expressions involving neuroinflammation and synaptic plasticity. Cryab KO mice exhibited greater cannabinoid-induced SA responses and place preference, along with divergent gamma wave alterations, compared to wild-type (WT) mice, implying their higher sensitivity to cannabinoids. Endocannabinoid- or dopamine-related mRNA expressions and accumbal dopamine concentrations after repeated JWH-018 exposure were not significantly different between the WT and Cryab KO mice. Further analyses revealed that repeated JWH-018 administration led to possibly greater neuroinflammation in Cryab KO mice, which may arise from upregulated NF-κB, accompanied by higher expressions of synaptic plasticity markers, which might have contributed to the development of cannabinoid addiction-related behavior in Cryab KO mice. These findings signify that increased neuroinflammation via NF-κB may mediate the enhanced addiction-like responses of Cryab KO mice to cannabinoids. Altogether, Cryab KO mice may be a potential model for cannabinoid abuse susceptibility. Frontiers Media S.A. 2023-03-16 /pmc/articles/PMC10060981/ /pubmed/37007015 http://dx.doi.org/10.3389/fphar.2023.1135929 Text en Copyright © 2023 Sayson, Ortiz, Lee, Kim, Custodio, Yun, Lee, Lee, Cha, Cheong and Kim. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Sayson, Leandro Val Ortiz, Darlene Mae Lee, Hyun Jun Kim, Mikyung Custodio, Raly James Perez Yun, Jaesuk Lee, Chae Hyeon Lee, Yong Sup Cha, Hye Jin Cheong, Jae Hoon Kim, Hee Jin Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression |
title | Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression |
title_full | Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression |
title_fullStr | Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression |
title_full_unstemmed | Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression |
title_short | Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression |
title_sort | deletion of cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid jwh-018 via upregulation of striatal nf-κb expression |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060981/ https://www.ncbi.nlm.nih.gov/pubmed/37007015 http://dx.doi.org/10.3389/fphar.2023.1135929 |
work_keys_str_mv | AT saysonleandroval deletionofcryabincreasesthevulnerabilityofmicetotheaddictionlikeeffectsofthecannabinoidjwh018viaupregulationofstriatalnfkbexpression AT ortizdarlenemae deletionofcryabincreasesthevulnerabilityofmicetotheaddictionlikeeffectsofthecannabinoidjwh018viaupregulationofstriatalnfkbexpression AT leehyunjun deletionofcryabincreasesthevulnerabilityofmicetotheaddictionlikeeffectsofthecannabinoidjwh018viaupregulationofstriatalnfkbexpression AT kimmikyung deletionofcryabincreasesthevulnerabilityofmicetotheaddictionlikeeffectsofthecannabinoidjwh018viaupregulationofstriatalnfkbexpression AT custodioralyjamesperez deletionofcryabincreasesthevulnerabilityofmicetotheaddictionlikeeffectsofthecannabinoidjwh018viaupregulationofstriatalnfkbexpression AT yunjaesuk deletionofcryabincreasesthevulnerabilityofmicetotheaddictionlikeeffectsofthecannabinoidjwh018viaupregulationofstriatalnfkbexpression AT leechaehyeon deletionofcryabincreasesthevulnerabilityofmicetotheaddictionlikeeffectsofthecannabinoidjwh018viaupregulationofstriatalnfkbexpression AT leeyongsup deletionofcryabincreasesthevulnerabilityofmicetotheaddictionlikeeffectsofthecannabinoidjwh018viaupregulationofstriatalnfkbexpression AT chahyejin deletionofcryabincreasesthevulnerabilityofmicetotheaddictionlikeeffectsofthecannabinoidjwh018viaupregulationofstriatalnfkbexpression AT cheongjaehoon deletionofcryabincreasesthevulnerabilityofmicetotheaddictionlikeeffectsofthecannabinoidjwh018viaupregulationofstriatalnfkbexpression AT kimheejin deletionofcryabincreasesthevulnerabilityofmicetotheaddictionlikeeffectsofthecannabinoidjwh018viaupregulationofstriatalnfkbexpression |