Prolonged exposure to stressors suppresses exploratory behavior in zebrafish larvae

Environmental stressors induce rapid physiological and behavioral shifts in vertebrate animals. However, the neurobiological mechanisms responsible for stress-induced changes in behavior are complex and not well understood. Similar to mammalian vertebrates, zebrafish adults display a preference for dark environments that is associated with predator avoidance, enhanced by stressors, and broadly used in assays for anxiety-like behavior. Although the larvae of zebrafish are a prominent model organism for understanding neural circuits, few studies have examined the effects of stressors on their behavior. This study examines the effects of noxious chemical and electric shock stressors on locomotion and light preference in zebrafish larvae. We found that both stressors elicited similar changes in behavior. Acute exposure induced increased swimming activity. while prolonged exposure depressed activity. Neither stressor produced a consistent shift in light-dark preference, but prolonged exposure to these stressors resulted in a pronounced decrease in exploration of different visual environments. We also examined the effects of exposure to a noxious chemical cue using whole-brain calcium imaging, and identified neural correlates in the area postrema, an area of the hindbrain containing noradrenergic and dopaminergic neurons. Pharmaceutical blockade experiments showed that a-adrenergic receptors contribute to the behavioral response to an acute stressor but are not necessary for the response to a prolonged stressor. These results indicate that zebrafish larvae have complex behavioral responses to stressors comparable to those of adult animals, and also suggest that these responses are mediated by similar neural pathways.