Ketamine, an NMDA receptor antagonist, produced concentration-dependent behavioral changes in adult zebrafish. Acute exposure reduced social interaction and increased swimming activity and rotational behavior. These effects did not intensify with repeated daily dosing over five days and were not present 48 hours after the final treatment, indicating no behavioral sensitization or lasting disruption. The findings support zebrafish as a model for acute schizophrenia-like behavioral phenotypes induced by NMDA receptor blockade, but the lack of sustained effects differs from rodent studies.
NMDAR antagonists like MK-801 and ketamine induce behavioral changes in zebrafish that model schizophrenia symptoms, including social interaction and memory deficits, but results for locomotor and exploratory behaviors are mixed. A review of 44 studies found that zebrafish are a suitable alternative to rodents for studying these drug-induced phenotypes, though more research is needed to understand species differences.