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

Animals Behavior, Animal / drug effects Disease Models, Animal Dronabinol / pharmacology N-Methylaspartate / pharmacology Piperidines / pharmacology Psychotic Disorders / diagnosis Psychotropic Drugs / pharmacology Pyrazoles / pharmacology Receptor, Cannabinoid, CB1 / agonists Stereotyped Behavior / drug effects Zebrafish

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
03 08 2021
Historique:
received: 11 05 2021
accepted: 14 07 2021
entrez: 4 8 2021
pubmed: 5 8 2021
medline: 23 11 2021
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41598-021-95016-4 PMID: 34344922 PMC: PMC8333334
pubmed: 34344922
doi: 10.1038/s41598-021-95016-4
pii: 10.1038/s41598-021-95016-4
pmc: PMC8333334
doi:

Substances chimiques

Piperidines 0
Psychotropic Drugs 0
Pyrazoles 0
Receptor, Cannabinoid, CB1 0
AM 251 3I4FA44MAI
N-Methylaspartate 6384-92-5
Dronabinol 7J8897W37S

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

15693

Subventions

Organisme : NIDA NIH HHS
ID : R01 DA035680
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM132500
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007175
Pays : United States

Informations de copyright

© 2021. The Author(s).

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Auteurs

Amelia Dahlén (A)

Department of Bioengineering and Therapeutic Sciences, and Programs in Biological Sciences and Human Genetics, University of California, San Francisco, CA, 94158, USA. dahlenamelia@gmail.com.
Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, 75124, Uppsala, Sweden. dahlenamelia@gmail.com.

Mahdi Zarei (M)

Department of Bioengineering and Therapeutic Sciences, and Programs in Biological Sciences and Human Genetics, University of California, San Francisco, CA, 94158, USA.

Adam Melgoza (A)

Department of Bioengineering and Therapeutic Sciences, and Programs in Biological Sciences and Human Genetics, University of California, San Francisco, CA, 94158, USA.

Mahendra Wagle (M)

Department of Bioengineering and Therapeutic Sciences, and Programs in Biological Sciences and Human Genetics, University of California, San Francisco, CA, 94158, USA.

Su Guo (S)

Department of Bioengineering and Therapeutic Sciences, and Programs in Biological Sciences and Human Genetics, University of California, San Francisco, CA, 94158, USA. su.guo@ucsf.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › THC-induced behavioral stereotypy in zebrafish...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Comportement › Comportement animal › THC-induced behavioral stereotypy in zebrafish...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › THC-induced behavioral stereotypy in zebrafish...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Terpènes › Cannabinoïdes › Dronabinol › THC-induced behavioral stereotypy in zebrafish...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés dicarboxyliques › N-Méthyl-aspartate › THC-induced behavioral stereotypy in zebrafish...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pipéridines › THC-induced behavioral stereotypy in zebrafish...
questionsmedicales.fr › Troubles mentaux › Schizophrénie et troubles avec traits psychotiques › Troubles psychotiques › THC-induced behavioral stereotypy in zebrafish...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Psychoanaleptiques › THC-induced behavioral stereotypy in zebrafish...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Pyrazoles › THC-induced behavioral stereotypy in zebrafish...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs couplés aux protéines G › Récepteurs de cannabinoïdes › Récepteur cannabinoïde de type CB1 › THC-induced behavioral stereotypy in zebrafish...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Comportement › Comportement stéréotypé › THC-induced behavioral stereotypy in zebrafish...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Poissons › Cypriniformes › Cyprinidae › Danio zébré › THC-induced behavioral stereotypy in zebrafish...