Presynaptic serotonin receptors regulate the release of 3H-serotonin in hypothalamic slices of the rabbit

Hypothalamic slices of the rabbit brain were incubated with 10(-7) M of 3H-serotonin (3H-5HT). After the incubation and an initial washout period, a nearly constant basal efflux of tritium was detected. This basal efflux was not significantly altered by Ca2+-free solution or by the 5HT-antagonist metitepin (10(-5) M), but was augmented by chlorimipramine (10(-5) M) and by unlabelled 5HT (10(-6) M); the acceleration caused by unlabelled 5HT was absent in presence of chlorimipramine (10(-5) M). Both electrical stimulation (4 Hz, 50 mA, 2 min) and high K+ (50 mM) induced an overflow of 3H. This overflow was nearly abolished in Ca2+-free solution. In presence of chlorimipramine (10(-5) M) both the tritium overflow evoked by electrical stimulation and that evoked by high K+ were augmented by metitepin (10(-5) M) and decreased in a concentration dependent manner by unlabelled serotonin (10(-8) - 10(-6) M); the latter effect was antagonized by metitepin (10(-6) M and 10(-5) M). These experiments suggest that in rabbit hypothalamic slices, the release of 3H-5HT is controlled by a negative feedback mechanism acting via presynaptic serotonin receptors.