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

Summary 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.