A new method to measure brain serotonin synthesis in vivo. I. 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 alpha-methyl-L-tryptophan (alpha-MTrp), which is converted in vivo into alpha-methylserotonin (alpha-M5HT). Since alpha-M5HT is not a substrate for monoamine oxidase, it is accumulated in the brain tissue. Data are presented to confirm time-dependent conversion of alpha-MTrp into alpha-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 less than 3% incorporation of alpha-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 approximately 20 min. The rate of serotonin synthesis is highest in the pineal body.