Serotonin release in human cerebral cortex and its modulation via serotonin receptors

Human cerebral cortex slices were prepared from brain tissue which had to be removed in order to gain access to deep-seated tumours. Subsequent to incubation with [3H]serotonin, the slices were superfused with physiological salt solution containing paroxetine, and 3H overflow was evoked by electrical field stimulation. The evoked tritium overflow (86% of which was accounted for by unmetabolized [3H]serotonin) was abolished by tetrodotoxin or omission of calcium from the superfusion fluid. Unlabelled serotonin decreased, and the serotonin receptor antagonist metitepin increased, the evoked overflow. The inhibition produced by serotonin was antagonized by metitepin. It is concluded that serotonin release in human cerebral cortex is modulated by inhibitory serotonin receptors, which may be localized presynaptically on the serotoninergic nerve fibers themselves. There are marked similarities between human and rat brain cortex with respect to action potential-induced, Ca2+-dependent serotonin release and its modulation via serotonin receptors.