Cortisol production by interrenal cells in rainbow trout (Oncorhynchus mykiss) is stimulated by 5-HT4 receptor activation

• Serotonin stimulates the fish stress axis but the receptors involved remain unclear. • All levels of the stress axis expressed 5htr1a , 5htr2 and 5htr4. • Serotonin injection in vivo raised circulating cortisol levels but not crf or ACTH. • Cortisol production by interrenal cells was mediated by the 5-HT 4 receptor. Although serotonin (5-HT) can stimulate the hypothalamic-pituitary-interrenal (HPI) axis in fishes, the sites of 5-HT action and the receptor subtypes involved remain unclear. Therefore, the present study identified potential sites of 5-HT action within the HPI axis of rainbow trout, Oncorhynchus mykiss , and examined which of three 5-HT receptor subtypes mediated effects of 5-HT on cortisol production. Expression of the receptors 5htr1a , 5htr2 and 5htr4 was detected at all three levels of the HPI axis, with significantly higher transcript abundance in the preoptic area (POA) of the brain than in the pituitary or head kidney. Administration of 300nmol kg −1 5-HT, but not 30nmol kg −1 , to cannulated rainbow trout significantly increased circulating cortisol. Despite this cortisol response, no specific effects of 5-HT administration on POA transcript abundance of corticotropin-releasing factor ( crf ) or circulating adrenocorticotropic hormone (ACTH) concentrations were detected. To assess the direct actions of 5-HT on cortisol production, head kidney tissue was incubated in vitro with 5-HT or selective 5-HT receptor agonists. Neither the 5-HT 1A receptor agonist 8-hydroxy-2-(di- n -propylamino)-tetralin (8-OH-DPAT) nor the 5-HT 2 receptor agonist α-methyl-5-hydroxytryptamine maleate (α −methyl 5-HT) stimulated cortisol production. However, head kidney cortisol production was significantly increased by the 5-HT 4 receptor agonist cisapride, an effect that was eliminated when tissue was incubated with a combination of cisapride and the 5-HT 4 receptor antagonist GR125487. Collectively, these data support a role for 5-HT in HPI axis activation in rainbow trout, and suggest that effects of 5-HT in the head kidney are mediated by the 5-HT 4 receptor.