Study of the brain serotonergic system with labeled alpha-methyl-L-tryptophan

alpha -Methyl-L-tryptophan (alpha -MTrp) is an artificial amino acid and an analog of tryptophan (Trp), the precursor of the neurotransmitter serotoni n (5-HT). In this article we have summarized available data, which suggest that the measurement of the unidirectional uptake of alpha -MTrp and its co nversion to 5-HT synthesis rates is a valid approach for the determination of brain 5-HT synthesis rates. The main feature on which the model is based is the trapping of labeled alpha -MTrp in brain tissue. An overview of opp osing opinions, which suggest that there is a need for a metabolic conversi on of tracer, is also presented and discussed critically. As with all biolo gical modeling there is likely to be room for improvements of the proposed biological model. In addition, there are a limited number of clearly define d circumstances in which the method is confounded by the metabolism of labe led alpha -MTrp via the kynurenine pathway. Nonetheless, a significant body of evidence suggests that labeled alpha -MTrp is a useful tracer to study brain 5-HT synthesis in most circumstances. Calculation of 5-HT synthesis r ates depends on the plasma-free tryptophan concentration, which, according to the balance of arguments in the literature, is a more appropriate parame ter than the total-plasma tryptophan. The method, as proposed by us, can be used in conjunction with autoradiographic measurements in laboratory anima ls, and with positron emission tomography in large animals and humans. We r eview studies in animals looking at the normal control of 5-HT synthesis an d the way in which it is altered by drugs, as well as initial studies inves tigating healthy humans and patients with neuropsychiatric disorders.