A Novel Behavioral Test Battery to Assess Global Drug Effects Using the Zebrafish

Abstract

The zebrafish (Danio rerio) has been at the forefront of neurobiological research and is steadily gaining favor as a model for behavioral applications. The ease of handling, high yield of progeny, and efficient mode of drug delivery make this species a particularly useful model for behavior. Here, we append to the growing body of literature on zebrafish behavior by introducing a novel behavioral battery of tests aimed at identifying drug induced alterations in social and motoric behaviors. In a series of experiments, zebrafish were exposed to MK-801 (0, 2 μM, 20 μM), SFK 38393 (0, 10 μM, 100 μM), and ethanol (0, 0.5%, 1.0%) for one hour and overt locomotor behaviors were scored. Following a one-hour treatment exposure, circling behavior (a thigmotaxic display typical of dysregulated glutamate function) was scored from videotape at specific time points over a 37-minute session. In a separate experiment the zebrafish’s natural tendency to shoal (social display) was analyzed using a novel open-field paradigm that examined fish distribution over quadrants. Most notably, MK-801 (20 μM) significantly increased circling behavior compared to controls. However, shoaling displays were disrupted when zebrafish were exposed to both MK-801 and SKF 38393 (20 μM and 100 μM respectively). Our results, in part, complement existing knowledge about zebrafish behavior following acute drug exposure. Additionally, our novel approach to assessing shoaling behavior, reported here, introduces an alternative view of social/group behavior in the zebrafish that is sensitive to both NMDA and dopaminergic manipulation.