Dose-response relationships between systemically administered l-tryptophan or l-5-hydroxytryptophan and raphe unit activity in the rat

In contrast to previous reports that l-5-hydroxytryptophan (l-5-HTP) is without effect on raphe unit activity, systemic administration of l-tryptophan or l-5-HTP produced similar dose-dependent decreases in raphe unit activity, ranging from 0-15% at 10 mg/kg to 60-90% at 100 mg/kg doses. The dose-response curve forms a plateau for doses above 100 mg/kg of l-5-HTP or l-tryptophan. Neurochemical studies revealed that administration of varying doses of l-tryptophan or l-5-HTP (10-100 mg/kg, i.p.) under conditions simulating those of the unit recording procedure, produced dosedependent increases in forebrain serotonin of up to 42% and 353% for a 100 mg/kg dose of l-tryptophan or l-5-HTP, respectively. These data suggest that exogeneously administered l-5-HTP serves as an effective serotonin precursor in central serotonergic neurones. Furthermore, increases in forebrain serotonin levels within the range of normal diurnal variations dramatically depress raphe unit activity, indicating that diurnal changes in brain serotonin metabolism may significantly affect the activity of serotonin-containing neurones.