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

近年来，随着社会环境的变化，抑郁症患者的数量不断增加，需要建立病因的解决和治疗策略。据报道，人脑中5 -羟色胺代谢与抑郁症等精神疾病有关，但5 -羟色胺的合成速率和受体功能仍知之甚少。在本研究中，我们为简化血清素合成速率和受体功能的测量以及血清素能神经元功能的解决方案进行了基础和临床研究。为简化血清素合成速率的测定，采用动物实验。给药后，比较各组大鼠血清素合成率与正常对照的差异。作为一种简化方法，采用标准输入函数法和一点定标法。与常规方法相比，血清素合成率的分布体积误差小于10%，而常规方法需要频繁的动脉采血。在此基础上，认为简化方法是可行的。作为临床应用，该方法已用于人体研究。血清素合成率在抑郁组和正常组之间存在显著的区域差异。我们还研究了血清素能药物在人体PET研究中的作用。测定正常志愿者口服5 -羟色胺类药物前后脑血流量（CBF）和动脉毛细血管血容量（Vo）。观察给药后CBF和Vo的降低，最大降低率为13%。给药80分钟后，CBF和Vo恢复到基线值。本研究发现，血清素能药物通过扩张大脑血管而降低CBF和Vo。

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.