Ketamine modulates the exploratory dynamics and homebase-related behaviors of adult zebrafish

Abstract

Anxiety is a protective behavior when animals face aversive conditions, but commonly associated with various neuropsychiatric disorders when exacerbated. Drug repurposing has emerged as a valuable strategy to use existing pharmaceuticals for new therapeutic purposes. Ketamine, traditionally used as an anesthetic, acts as a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, and evidence has shown potential anxiolytic and antidepressant effects at subanesthetic doses. However, the influence of ketamine on multiple behavioral domains in vertebrates is not completely understood. Here, we evaluated the potential modulatory effect of ketamine on the spatio-temporal exploratory dynamics and homebase-related behaviors in adult zebrafish using the open field test (OFT). Animals were exposed to subanesthetic concentrations of ketamine (0, 2, 20, and 40 mg/L) for 20 min and locomotion- exploration- and homebase-related behaviors were assessed in a single 30-min trial. Our data revealed that ketamine (20 and 40 mg/L) induced hyperlocomotion, as verified by the increased total distance traveled. All concentrations tested elicited circling behavior, a stereotyped-like response which gradually reduced across the periods of test. We also observed modulatory effects of ketamine on the spatio-temporal exploratory pattern, in which the reduced thigmotaxis and homebase activity, associated with the increased average length of trips were suggestive of anxiolytic-like effects. Collectively, our novel findings support the modulatory effects of ketamine on the spatio-temporal exploratory activity, as well as the utility of homebase-related measurements to evaluate the behavioral dynamics of zebrafish.