The shallow water test (SWT) as a novel behavioral paradigm to measure anxiety- and despair-like states in zebrafish

Abstract

Affective disorders represent psychiatric conditions characterized by mood and emotional dysregulations, with depression and anxiety being among the most prevalent and frequently co-occurring. Depressive- and anxiety-related disorders can be associated with monoaminergic dysfunction and dysregulation of the GABAergic system. Stress plays a crucial role in the development and progression of these disorders, contributing to neurochemical disbalances. Because despair, a core symptom of depression, lacks well-established paradigms in zebrafish models based on naturalistic conditions, our goal was to report the use of the shallow water test (SWT) as a novel paradigm to assess despair-like behavior in zebrafish when placed in an unescapable shallow water environment. Basically, we exposed zebrafish to two distinct aversive conditions: mild electric shock (ES) as a physical stimulation or the conspecific alarm substance (CAS) as a naturalistic chemical cue (Experiment 1); and tested two pharmacological interventions: fluoxetine and diazepam (Experiment 2). Both stressors significantly reduced distance traveled, absolute turn angle, and average velocity, but only CAS increased the latency to mobility. While diazepam increased distance traveled, maximum speed, and average velocity, fluoxetine had no significant effects. Overall, these findings suggest the SWT as a sensitive and reliable tool for evaluating affective-like states in zebrafish, with implications for translational neurobehavioral research on affective disorders and potential therapeutic interventions.

Keywords: Affective disorders; Aversive stimuli; Despair-related behavior; Pharmacological agents; Zebrafish.