5-HT(2A/2C) receptor agonist-induced increase in urinary isatin excretion in rats: reversal by both diazepam and...

Isatin, a stress-related biological substance, increases in rat urine in association with elevated catecholamine biosynthesis during stress. The goal of this study was to unravel how the biosynthetic pathway of isatin is related to stress response. The importance of the serotonergic compounds in anxiety, which is the major emotional process of stress response, has emerged. m-Chlorophenylpiperazine (m-CPP), a 5-HT(1A/1B/2A/2C) receptor agonist, and (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride [(+/-)-DOI], a 5-HT(2A/2C) agonist, both of which have anxiogenic properties, induced a marked increase in 24-hr urinary isatin excretion, whereas neither 1-(m-chlorophenyl)-biguanide (m-CPBG), a 5-HT3 agonist, nor 2-methyl-5-HT, a 5-HT(3,4) agonist, affected urinary isatin excretion. 5-HT(2A/2C) receptor antagonists such as ketanserin and ritanserin prevented the increase in urinary isatin excretion induced by the 5-HT(2A/2C) receptor agonist m-CPP. These findings are the first to provide evidence that pharmacological substances cause increases in urinary isatin excretion via specific 5-HT receptors, probably 5-HT(2A/2C) receptors. In addition, both the synthetic glucocorticoid dexamethasone and diazepam prevented the m-CPP-induced increase in urinary isatin excretion. These observations suggest that the mechanism by which m-CPP elicits enhancing effects on urinary isatin excretion has something in common with stress response involving activation of hypothalamic CRF cells and the sympathetic nervous system.