THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior.
Amelia Dahlén, Mahdi Zarei, Adam Melgoza, Mahendra Wagle, Su Guo
Scientific Reports August 3, 2021 DOI: 10.1038/s41598-021-95016-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Adult zebrafish |
| Interventions | THC NMDA pentylenetetrazol AM251 AM630 sulpiride |
| Topics | Cannabis |
| Key findings | THC induces a concentration-dependent behavioral stereotypy in adult zebrafish, which is reduced by NMDA, pentylenetetrazol, AM630, and sulpiride, but not by AM251. |
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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 3
- Psychotic-Like Experiences in Young Recreational Users of Ketamine: A Case Study. Journal of Psychoactive Drugs January 8, 2025
- A circuit dissection of perception-action decoupling in S-ketamine-induced hallucination-like states. Molecular Psychiatry September 19, 2026
- THE INFLUENCE OF CANNABIS ON THE DEVELOPMENT OF SCHIZOPHRENIA - A REVIEW International Journal of Innovative Technologies in Social Science March 27, 2026
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and 8 more in the library