The lumped constant of α-methyl-l-tryptophan is not influenced by drugs acting through serotonergic system

Lumped constant (LC) is a constant used to convert brain trapping constant of α-methyl-l-tryptophan (using α-(14)C-methyl-l-tryptophan) into the constant for conversion of tryptophan into serotonin (5-hydroxytryptamine, 5-HT), which can be then used with certain assumptions in the calculation of the brain regional 5-HT synthesis rate. The aim of the present study was to investigate the acute effects of two drugs on the regional stability of the LC and possible effect on its value. Drugs used were a selective 5-HT reuptake inhibitor, fluoxetine, and a drug that releases 5-HT and inhibits 5-HT uptake, d,l-fenfluramine. The values of the LC from those experiments were compared with the value of LC obtained in the saline treated rats. KT is the constant for tryptophan conversion into 5-HT, which was measured by an autoradiographic method in more than twenty brain regions, using labelled tryptophan ((14)C-Trp) as tracer, after the fraction incorporated into proteins was removed. The trapping constant K(α) for α-methyl-l-tryptophan was also measured autoradiographically in a separate group of rats. All measurements were done in drug and saline (control) treated rats. The regional LC constants were calculated as the ratios between KT and K(α). Statistical evaluation showed that the regional values in each of these three sets were normally distributed, and that the three sets of LC values calculated as the mean of logarithmic differences (saline 0.450 ± 0.055; fluoxetine 0.429 ± 0.091; d,l-fenfluramine 0.48 ± 0.09) did not differ significantly. The overall weighted mean value of the LC from all three sets of measurements was 0.452 ± 0.041, and this value was not significantly different from the LC value of 0.42 ± 0.07, i.e. value obtained in our previous studies. These results showed the unaltered LC value in discrete rat brain regions after treatment with fluoxetine or d,l-fenfluramine, and confirmed that the numerical value of the LC used in our previous studies was not altered by treatment with drugs affecting 5-HT transmission and 5-HT synthesis rate.