Predictable chronic stress modulates behavioral and neuroendocrine phenotypes of zebrafish: Influence of two homotypic stressors on stress-mediated responses.

The zebrafish (Danio rerio) has been considered a suitable model organism to assess the evolutionarily conserved bases of behavioral and neuroendocrine responses to stress. Depending on the nature of the stressor, prolonged stress may elicit habituation or evoke long-term changes in the central nervous systems (CNS) often associated with various neuropsychiatric disorders. Conspecific alarm substance (CAS) and net chasing (NC) constitute chemical and physical stressors, respectively, which cause aversive behaviors and physiological changes in fishes. Here, we investigate whether predictable chronic stress (PCS) using two homotypic stressors differently modulates behavioral and physiological responses in zebrafish. PCS-CAS or PCS-NC were performed for 14 days, 2-times daily, while locomotion, exploratory activity, anxiety-like behaviors, and whole-body cortisol levels were measured on day 15. PCS-CAS reduced distance traveled, the number of transitions and time in top area, as well as increased the latency to enter the top in the novel tank test. In the light/dark test, CAS-exposed fish showed decreased time spent in lit area, shorter latency to enter the dark area, and increased risk assessments. PCS-CAS also increased whole-body cortisol levels in zebrafish. Although PCS-NC reduced the latency to enter the dark area, whole-body cortisol levels did not change. Moreover, acute experiments revealed that both CAS and NC promoted anxiogenesis and increased cortisol levels, suggesting habituation to stress following PCS-NC. Overall, our novel findings demonstrate that PCS induces behavioral and physiological changes in zebrafish depending on the nature of the stressor.