The effects of antidepressants on serotonin turnover in discrete regions of rat brain.

Serotonin (5-HT) turnover was measured in hypothalamus, hippocampus, cortex, septum and nucleus caudatus of rats after acute or chronic treatment with antidepressants. Acute chlorimipramine (1.8 -- 16.2 mg/kg i.p.) decreased 5-HT turnover in all the areas tested as measured by the rate of accumulation of 5-hydroxyindoleacetic acid after probenecid, or the rate of accumulation of 5-hydroxytryptophan after decarboxylase inhibition. However, chlorimipramine failed to reduce the rate of 5-HT accumulation after monoamine oxidase inhibition. Chronic chlorimipramine treatment (3 times daily for 2 weeks) did not change the 5-HT turnover. Fluoxetine, which like chlorimipramine specifically blocks 5-HT uptake also decreased 5-HT synthesis. In contrast, no change in 5-HT turnover was observed after desmethylimipramine, amitriptyline, iprindole or amphetamine which affect the catecholaminergic, but not serotoninergic systems.