A NEW METHOD TO MEASURE BRAIN-SEROTONIN SYNTHESIS INVIVO .1. THEORY AND BASIC DATA FOR A BIOLOGICAL MODEL

We describe here an autoradiographic method to measure the in vivo rate of serotonin synthesis in rat brain. The method is based on the use of the L-tryptophan analogue α-methyl-L-tryptophan (α-MTrp), which is converted in vivo into α-methylserotonin (α-M5HT). Since α-M5HT is not a substrate for monoamine oxidase, it is accumulated in the brain tissue. Data are presented to confirm time-dependent conversion of α-MTrp into α-M5HT in the dorsal raphe nucleus and also in the pineal body, an organ outside the blood-brain barrier. It has also been shown that washing brain slices in 10% trichloroacetic acid results in <3% incorporation of α-MTrp into brain proteins. The rates of synthesis are calculated in several grossly dissected brain structures by using tracer kinetics and a three-compartment biological model. The half-life of the precursor pool is estimated to be ~20 min. The rate of serotonin synthesis is highest in the pineal body.