Ketamine modulates aggressive behavior in adult zebrafish

Abstract Ketamine is a non-competitive glutamatergic antagonist that induces analgesia and anesthesia. Although ketamine displays anxiolytic and antidepressant properties, it may induce pro-psychosis and hallucinogen effects, as well as stereotypic behaviors following acute administration at sub-anesthetic doses. Since heightened aggression is maladaptive and may comorbid with various neuropsychiatric disorders, we aimed to investigate whether ketamine modulates aggressive behavior in adult zebrafish. Fish were acutely exposed to 2, 20, and 40 mg/L ketamine for 20 min and their locomotion, exploratory activity, and aggression towards mirror were further assessed. Ketamine (2 mg/L) increased aggression-related phenotypes, while 20 and 40 mg/L reduced aggression and elicited stereotypic behaviors by causing hyperlocomotion, altering motor patterns, and increasing circling behavior at the higher concentration tested. Collectively, our data expand the utility of zebrafish models to investigate the influence of sub-anesthetic concentrations of ketamine on aggression behavior domain in translational neuropsychiatric research field.