Effect of serotonin-releasing drugs on serum corticosterone concentration in rats

(+/-)p-Chloroamphetamine hydrochloride, at doses of 1-8 mg/kg i.p. in rats, caused a dose-related increase in serum corticosterone concentration. The increase occurred rapidly, within 30 min, and was over within 4 h. Evidence that the increase was mediated by serotonin release consisted of the following findings: (1) a similar increase did not occur with (+/-)o-chloroamphetamine or (+/-)p-chloro-alpha-methylbenzylamine, analogs of p-chloroamphetamine lacking its ability to deplete serotonin; (2) the increase was prevented by prior treatment with p-chlorophenylalanine, which reduced the brain stores of serotonin available for release by p-chloroamphetamine; (3) the increase was prevented by prior treatment with fluoxetine, an inhibitor of the uptake pump on serotonin neurons, which blocks serotonin release by p-chloroamphetamine, and (4) the increase was mimicked by fenfluramine and norfenfluramine, agents known to release brain serotonin in a manner similar to the action of p-chloroamphetamine. These findings strengthen earlier evidence that brain serotonin neurons have a stimulatory influence on pituitary-adrenocortical function in rats.