The stress response is a coping mechanism of animals for adverse events threatening their homeostasis, which involves neural, endocrine, and autonomic reactions. Glucocorticoids are among the primary hormones secreted following stressful stimuli, responsible for preparing glucose for animals' fight-or-flight response. Cortisol is the primary glucocorticoid hormone in teleosts and humans, able to cross the blood-brain barrier and to influence neurons and their activity. Although extensive studies report that early life chronic stress can predispose to long-lasting changes in neural circuits and behaviors, little is known about the role played by elevated cortisol in early life. Therefore, we employed the zebrafish (Danio rerio) to investigate the short-term and long-term effects of acute and chronic cortisol elevation early in life. In our study, this was done by using behavioral assays and whole-brain imaging techniques detecting phosphorylated extracellular signal-regulated kinase 1/2 (pERK) and total ERK.
Acute exposure to waterborne cortisol (0.85 µg/ml for 2 hours) did not modify locomotion and anxiety-like behaviors in 5 day-old zebrafish larvae. Acute cortisol exposure inhibited brain activity, especially in the ventral diencephalon, whereas a broad increase in brain activity was observed 2 hours post-exposure. Repeated cortisol exposure (0.85 µg/ml) for 2 hours per day from the 3rd to 5th day of life did not affect survival. Behaviorally, the fish exposed to early life chronic cortisol exhibited higher anxiety-like behavior compared to control at 1 week, showing higher locomotor activity and thigmotaxis. At 2 weeks, no difference in anxiety-like behavior was seen between the two groups. 1-month old fish exposed to early life chronic cortisol showed a bolder early reaction in the novel tank test, which shows that chronic cortisol could affect the behavior of fish in the long term. Brain activity was broadly increased in chronically treated fish at 1 week, with only sparse, local differences remained in 2 week-old fish.
In conclusion, cortisol exposure during early life affected zebrafish behavior and basal neuronal activity at later life stages.