THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior.
Scientific reports August 3, 2021 Amelia Dahlén, Mahdi Zarei, Adam Melgoza et al.
High doses of THC, a Cannabis constituent, increase psychosis risk in humans. Using adult zebrafish, which share a conserved endocannabinoid system with mammals, THC caused a concentration-dependent behavioral stereotypy, including distinctive circular swimming measured by a novel Repetition Index (RI). This RI was reduced by co-administration of the NMDA receptor agonist NMDA, suggesting THC's effects involve NMDA receptor antagonism. The GABA receptor antagonist pentylenetetrazol also reduced the RI. The cannabinoid receptor 1 inverse agonist AM251 did not reduce the behavior, while the cannabinoid receptor 2 inverse agonist AM630 significantly reduced it, pointing to cannabinoid receptor 2 as a possible mediator. The antipsychotic sulpiride also reduced the THC-induced RI. The model may help elucidate mechanisms linking Cannabis to psychosis.