1. The concentrations of 5-hydroxytryptamine in the rat brain have been shown to vary with clock hour. Highest concentrations were observed at 13.00 h. and lowest concentrations at 01.00 h. 2. The twenty-four hour variation in brain tryptophan concentrations, tryptophan uptake, 5-hydroxytryptophan concentrations and uptake, 5-hydroxyindole-3-acetic acid concentrations and the activities of tryptophan-5-hydroxylase, 5-hydroxytryptophan decarboxylase and monoamine oxidase have been determined. The effects of inhibitors of catecholamine synthesis on the twenty-four hour rhythm of 5-hydroxy-tryptamine concentrations, and the effects of drugs which alter brain. 5-hydroxytryptamine concentrations on locomotor activity were determined. 3. Brain and serum (free and bound) tryptophan concentrations vary with clock hour, but the rhythm is 180 degrees out of phase with that of 5-hydroxytryptamine. The uptake of 14 C-tryptophan into, synaptosomes also varies with clock hour. 4. The rate of conversion of 5-hydroxytryptophan to 5-hydroxytryptamine was greater during the hours of light than during the hours of darkness, although the activity of the enzyme did not vary and substrate and pyridoxal phosphate availability were not limiting factors. 5. 5-hydroxyindole-3-acetic acid concentrations exhibit a twenty-four hour rhythm which follows the rhythm of 5-hydroxytryptamine concentrations. 6. Monoamine oxidase inhibitors, a-methyl-p-tyrosine and 6-hydroxydopamine abolish the twenty-four hour rhythm of 5-hydroxytryptamine concentrations and elevate brain levels of the amine. 7. It is proposed that the twenty-four hour variation of 5-hydroxytryptamine concentrations in the rat brain are controlled, at least in part, by the twenty-four hour variation of 5-hydroxytryptophan decarboxylase activity, which in turn is significantly influenced by the concentration of catecholamines in the brain.
|Date of Award||1974|