PUBLICATION
THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior
- Authors
- Dahlén, A., Zarei, M., Melgoza, A., Wagle, M., Guo, S.
- ID
- ZDB-PUB-210805-1
- Date
- 2021
- Source
- Scientific Reports 11: 15693 (Journal)
- Registered Authors
- Guo, Su, Wagle, Mahendra
- Keywords
- none
- MeSH Terms
-
- Animals
- Behavior, Animal/drug effects*
- Disease Models, Animal
- Dronabinol/pharmacology*
- N-Methylaspartate/pharmacology
- Piperidines/pharmacology
- Psychotic Disorders/diagnosis
- Psychotic Disorders/drug therapy
- Psychotic Disorders/etiology*
- Psychotic Disorders/metabolism
- Psychotropic Drugs/pharmacology*
- Pyrazoles/pharmacology
- Receptor, Cannabinoid, CB1/agonists
- Stereotyped Behavior/drug effects*
- Zebrafish
- PubMed
- 34344922 Full text @ Sci. Rep.
Citation
Dahlén, A., Zarei, M., Melgoza, A., Wagle, M., Guo, S. (2021) THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior. Scientific Reports. 11:15693.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping