Brain Monoamine Changes Modulate the Corticotropin-releasing Hormone Receptor 1-mediated Behavioural Response to Acute Thermal Stress in Zebrafish Larvae

While central monoamines play a role in regulating stress-related locomotory activity, the modulation of monoamines by the corticosteroid stress axis in shaping acute behavioural responses are unclear. We investigated whether the corticotropin-releasing hormone receptor 1 (Crhr1) modulation of stress-related behavioral response involves monoamine regulation by subjecting Crhr1 knockout (crhr1) zebrafish (Danio rerio) to an acute thermal stressor (TS: +5 °C above ambient for 60 min). The TS-induced cortisol response and hyper locomotory activity in the WT larvae was abolished in fish lacking Crhr1. However, both genotypes induced a heat shock protein response to the TS. The crhr1 larvae showed a region-specific difference in the distribution of serotonin (5-HT)- and tyrosine hydroxylase-positive cells in the brain. This corresponded with increases in whole-body transcript abundance of dopamine beta-hydroxylase, tryptophan hydroxylase 2, and solute carrier family 6-member 4a. Cotreatment with either epinephrine or 5-HT, but not cortisol, was able to rescue the TS-mediated hypo locomotory activity and thigmotaxis seen in the crhr1 larvae. Together, these results indicate that Crhr1 is essential not only for mediating the TS-induced hyperactivity but also for maintaining the basal locomotory activity and anxiogenic response during stress. The latter response depends on the central monoamine regulation by Crhr1 in zebrafish larvae.