Research for the quantitative imaging of serotonergic neuronal transmission in human brain

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Recently, the number of depressive patient is increasing in number according to the change of social environment and the establishment of the solution of etiology and therapeutic strategy is required. It is reported that the serotonin metabolism in human brain is related to the psychiatric disease including depression, but the serotonin synthesis rate and receptor function is still little known. In this research, we performed both basic and clinical investigation for the simplification of the measurement of serotonin synthesis rate and receptor function and the solution of serotonergic neuronal function. As for the simplification of the measurement of serotonin synthesis rate, animal experiment was performed. After the administration of antidepressive drugs in rats, the difference of serotonin synthesis rate of them were compaared with that in normal controls. As a simplified method, standard input function method and one-point calibration method were applied. The error of distribution volume which indicates serotonin synthesis rate was less than 10 % compared with the conventional method, which requires frequent arterial blood sampling. Based on this result, the simplified method was thought to be available. As a dinical, application, this method was used for human study. The regional diferenee of serotonin synthesis rate between depressive subjects and normal controls were observed significantly. We also investigated the effect of serotonergic drugs in human PET study. Cerebral blood flow (CBF) and arterial-capillary blood volume (Vo) were measured before and after oral administration of serotonergic drug in normal volunteer. The reduction of CBF and Vo after administration were observed and the reduction rate was 13 % at maximum. Eighty minutes after administration, CBF and Vo returned to the value at baseline. In this study, it was revealed that serotonergic drug reduce both CBF and Vo by the vasooonstridaon of great cerebral vessels.