Serotonin release varies with brain tryptophan levels

摘要

The effects on serotonin release of varying brain tryptophan levels within the physiologic range are directly examined. Interactions between tryptophan availability and frequency of membrane depolarization in controlling serotonin release are also addressed. Reducing tryptophan levels in rat hypothalamic slices (by superfusing them with medium supplemented with 100 microns leucine) decreases tissue serotonin levels as well as both spontaneous and electrically evoked serotonin release. Conversely, elevating tissue tryptophan levels (by superfusing slices with medium supplemented with 2 microns tryptophan) increases both tissue serotonin levels and serotonin release. Serotonin release was found to be affected independently by tryptophan availability and frequency of electrical field-stimulation (1-5 Hz), since increasing both variables produced nearly additive increases in release. These observations demonstrate for the first time that both precursor-dependent elevations and reductions in brain serotonin levels produce proportionate changes in serotonin release, and that the magnitude of the tryptophan effect is unrelated to neuronal firing frequency. The data support the hypothesis that serotonin release is proportionate to intracellular serotonin levels.