Labelled alpha-methyl-L-tryptophan as a tracer for the study of the brain serotonergic system

The alpha-methyl-L-trypotophan (alpha-MTrp) method for the study of the brain serotonergic system is based on the fact that labelled alpha-MTrp is taken up by and, in part, retained in the brain, and this retention (trapping) is proportional to brain serotonin (5-HT) synthesis. A 3-compartment model is proposed in which the plasma, the precursor and irreversible pools are mathematically distinct compartments. The irreversible compartment is assumed to be the one in which the tracer is trapped. By definition, the tracer from the irreversible compartment does not exchange directly with the plasma compartment. The rate at which labelled alpha-MTrp is trapped is converted to the rate of 5-HT synthesis by dividing it by a conversion factor, called the lumped constant, and multiplying it by the plasma-free tryptophan concentration. Our results revealed that brain 5-HT synthesis can be influenced by the extraneuronal concentration of 5-HT and that, generally, the influence is not uniform throughout the brain. They also suggest that brain trapping of labelled alpha-MTrp relates to 5-HT synthesis. The proposed procedure for converting the rate at which labelled alpha-MTrp is trapped to brain 5-HT synthesis rates is based on measurements that suggest that plasma-free Trp relates to brain 5-HT synthesis. However, as with all biological models, there is likely room for improvement in our approach.