The zebrafish (Danio rerio) is emerging as a promising model organism for experimental
studies of stress and anxiety. Here we further validate zebrafish models of stress
by analyzing how environmental and pharmacological manipulations affect their behavioral
and physiological phenotypes. Experimental manipulations included exposure to alarm
pheromone, chronic exposure to fluoxetine, acute exposure to caffeine, as well as
acute and chronic exposure to ethanol. Acute (but not chronic) alarm pheromone and
acute caffeine produced robust anxiogenic effects, including reduced exploration,
increased erratic movements and freezing behavior in zebrafish tested in the novel
tank diving test. In contrast, ethanol and fluoxetine had robust anxiolytic effects,
including increased exploration and reduced erratic movements. The behavior of several
zebrafish strains was also quantified to ascertain differences in their behavioral
profiles, revealing high-anxiety (leopard, albino) and low-anxiety (wild type) strains.
We also used LocoScan (CleverSys Inc.) video-tracking tool to quantify anxiety-related
behaviors in zebrafish, and dissect anxiety-related phenotypes from locomotor activity.
Finally, we developed a simple and effective method of measuring zebrafish physiological
stress responses (based on a human salivary cortisol assay), and showed that alterations
in whole-body cortisol levels in zebrafish parallel behavioral indices of anxiety.
Collectively, our results confirm zebrafish as a valid, reliable, and high-throughput
model of stress and affective disorders.