Corticotropin-releasing hormone receptor 1 mediates the enhanced locomotor activity and metabolic demands to an acute thermal stress in adult zebrafish.

Abstract

We recently showed that Crh-Crhr1 signalling is essential for acute stress-related locomotor activity in zebrafish larvae. However, the possibility that Crhr1 activation may also initiate the acute metabolic demands for stress coping was unexplored. Here, we tested the hypothesis that Crhr1 signalling is essential for the thermal stressor-induced increases in the acute metabolic rate, a key response for coping with the enhanced energy demands during stress. We tested this by using a wildtype (WT) and a ubiquitous Crhr1 knockout (crhr1^-/-) zebrafish and subjecting them to an acute thermal stressor (TS: +5°C above ambient for 60 min). The TS induced the heat shock proteins response in both genotypes, but the elevated cortisol response observed in the WT was absent in the crhr1^-/- mutant. The TS also increased the locomotor activity and the metabolic rate in the WT fish, but this response was inhibited in the crhr1^-/- mutants. To test if this was due to a lack of TS-induced cortisol elevation in the crhr1^-/- mutant, we mimicked the response in the WT fish by treating them with metyrapone, an 11β-hydroxylase inhibitor. While metyrapone inhibited the TS-induced cortisol elevation in the WT, it did not affect the metabolic rate. The lack of Crhr1 also reduced the swimming performance, and the lower U_crit in the mutants corresponded with alterations in muscle energy metabolism. Together, our results indicate that Crh-Crhr1 signalling, independent of downstream cortisol action, is essential for the TS-induced acute hyperlocomotor activity and the associated increases in the metabolic demand for stress coping.