Evidence for negative feedback control of the release of [3H]serotonin from superfused mouse cerebellum slices induced by electrical field stimulation.

Slices of mouse cerebellum preloaded with [3H]serotonin were superfused with a solution of Krebs-Ringer phosphate. The effects of exogenous serotonin, serotonin antagonists, fluoxetine, Ca2+ absence, Ca2+ chelation and frequency of stimulation on basal and electrically induced tritium overflow were investigated. Exogenous unlabeled serotonin decreased the stimulus-evoked tritium overflow in a concentration-related manner. This effect was blocked by simultaneous administration of methiothepin, but not by methysergide. When given alone, methiothepin did not alter the electrically induced tritium overflow at 50 Hz, but did potentiate the increased tritium overflow produced at 100 Hz. The basal tritium efflux was increased by exogenous serotonin, but this effect was reversed by the simultaneous administration of fluoxetine. Under this condition exogenous serotonin reduced the basal tritium efflux in a concentration-related manner. Superfusion of the slices with a Ca2+-free solution alone or in the presence of EGTA, reduced the basal tritium efflux and the stimulated tritium overflow. These results support the existence of serotoninergic presynaptic inhibitory autoreceptors in the cerebellum of the mouse.