THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior

Abstract High doses of the Cannabis constituent Δ9-tetrahydrocannabinol (THC) increase the risk of psychosis in humans. Highly accessible animal models are needed to address underlying mechanisms. Using zebrafish with a conserved endocannabinoid system, this study investigates the acute effects of T...

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Autores principales:	Amelia Dahlén, Mahdi Zarei, Adam Melgoza, Mahendra Wagle, Su Guo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f903a028aa4c46adbdb82681be89fea7
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spelling	oai:doaj.org-article:f903a028aa4c46adbdb82681be89fea72021-12-02T14:53:35ZTHC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior10.1038/s41598-021-95016-42045-2322https://doaj.org/article/f903a028aa4c46adbdb82681be89fea72021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95016-4https://doaj.org/toc/2045-2322Abstract High doses of the Cannabis constituent Δ9-tetrahydrocannabinol (THC) increase the risk of psychosis in humans. Highly accessible animal models are needed to address underlying mechanisms. Using zebrafish with a conserved endocannabinoid system, this study investigates the acute effects of THC on adult zebrafish behavior and the mechanisms involved. A concentration-dependent THC-induced behavioral stereotypy akin to THC’s effect in rats and the psychotropics phencyclidine and ketamine in zebrafish was established. Distinctive circular swimming during THC-exposure was measured using a novel analytical method that we developed, which detected an elevated Repetition Index (RI) compared to vehicle controls. This was reduced upon co-administration of N-methyl-D-aspartate (NMDA) receptor agonist NMDA, suggesting that THC exerts its effects via biochemical or neurobiological mechanisms associated with NMDA receptor antagonism. Co-treatment of γ‐aminobutyric acid receptor antagonist pentylenetetrazol also showed signs of reducing the RI. Since THC-induced repetitive behavior remained in co-administrations with cannabinoid receptor 1 inverse agonist AM251, the phenotype may be cannabinoid receptor 1-independent. Conversely, the inverse cannabinoid receptor 2 agonist AM630 significantly reduced THC-induced behavioral stereotypy, indicating cannabinoid receptor 2 as a possible mediator. A significant reduction of the THC-RI was also observed by the antipsychotic sulpiride. Together, these findings highlight this model’s potential for elucidating the mechanistic relationship between Cannabis and psychosis.Amelia DahlénMahdi ZareiAdam MelgozaMahendra WagleSu GuoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amelia Dahlén Mahdi Zarei Adam Melgoza Mahendra Wagle Su Guo THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior
description	Abstract High doses of the Cannabis constituent Δ9-tetrahydrocannabinol (THC) increase the risk of psychosis in humans. Highly accessible animal models are needed to address underlying mechanisms. Using zebrafish with a conserved endocannabinoid system, this study investigates the acute effects of THC on adult zebrafish behavior and the mechanisms involved. A concentration-dependent THC-induced behavioral stereotypy akin to THC’s effect in rats and the psychotropics phencyclidine and ketamine in zebrafish was established. Distinctive circular swimming during THC-exposure was measured using a novel analytical method that we developed, which detected an elevated Repetition Index (RI) compared to vehicle controls. This was reduced upon co-administration of N-methyl-D-aspartate (NMDA) receptor agonist NMDA, suggesting that THC exerts its effects via biochemical or neurobiological mechanisms associated with NMDA receptor antagonism. Co-treatment of γ‐aminobutyric acid receptor antagonist pentylenetetrazol also showed signs of reducing the RI. Since THC-induced repetitive behavior remained in co-administrations with cannabinoid receptor 1 inverse agonist AM251, the phenotype may be cannabinoid receptor 1-independent. Conversely, the inverse cannabinoid receptor 2 agonist AM630 significantly reduced THC-induced behavioral stereotypy, indicating cannabinoid receptor 2 as a possible mediator. A significant reduction of the THC-RI was also observed by the antipsychotic sulpiride. Together, these findings highlight this model’s potential for elucidating the mechanistic relationship between Cannabis and psychosis.
format	article
author	Amelia Dahlén Mahdi Zarei Adam Melgoza Mahendra Wagle Su Guo
author_facet	Amelia Dahlén Mahdi Zarei Adam Melgoza Mahendra Wagle Su Guo
author_sort	Amelia Dahlén
title	THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior
title_short	THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior
title_full	THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior
title_fullStr	THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior
title_full_unstemmed	THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior
title_sort	thc-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f903a028aa4c46adbdb82681be89fea7
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THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior

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