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

Abstract

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.