Serotonergic regulation of cortisol secretion in dogs

The role of serotonin (5-HT) in the control of serum cortisol secretion was studied in 50 conscious beagle dogs. A significant rise in corticosteroids was observed after 1.5 and 3 mg/kg (P less than 0.01) iv fenfluramine, an indirect serotonergic agonist, as well as after 2 (P less than 0.05) and 3 mg/kg (P less than 0.01) iv quipazine, a direct agonist of 5-HT receptors. Both drugs exhibited a dose-related effect. A lower dose of fenfluramine, 0.5 mg/kg, was ineffective when administered iv, but raised serum cortisol (P less than 0.05) after direct injection into a lateral cerebral ventricle, through a chronically implanted brain cannula. The marked increases in corticosteroid concentration produced by the highest fenfluramine and quipazine doses were completely abolished by pretreatment with ketanserin, an antagonist of 5-HT2 receptors, which did not affect cortisol secretion when administered alone. These data suggest that brain serotonergic system plays a role in the control of cortisol secretion in conscious dogs.