Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects.
Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects.
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在正常人受试者中用[11C]雷氯必利和 PET 测量多巴胺的血清素能调节。
DOI：
10.1176/ajp.154.4.490
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Volkow,ND
中科院分区：
文献类型：
--
作者：
Smith,GS;Dewey,SL;Brodie,JD;Logan,J;Vitkun,SA;Simkowitz,P;Schloesser,R;Alexoff,DA;Hurley,A;Cooper,T;Volkow,ND
这项研究是通过使用正电子发射断层扫描（PET）（纹状体多巴胺D2受体的放射性示踪剂）来测量体内多巴胺能调节。（[11 C]雷氯必利），以及血清素系统的药理学挑战（丁、l-芬氟拉明）。方法在给予5-羟色胺之前，对11名正常男性受试者进行了两项使用[11 C]雷氯必利的PET研究-释放剂和再摄取抑制剂芬氟拉明（60 mg po），3小时后。使用[11 C]雷氯必利数据的图形分析方法推导D2受体的分布体积。芬氟拉明，norfenfluramine，高香草酸（HVA），皮质醇，和催乳素的血浆水平进行了determined.ResultsLevels芬氟拉明和催乳素芬氟拉明管理后2小时升高，并保持显着升高，在第二次扫描，而HVA和皮质醇的水平在扫描的时间没有显着改变。观察到[11 C]雷氯必利的特异性结合（纹状体）和从特异性结合（纹状体减去小脑）中减去的非特异性结合显着减少。[11 C]雷氯必利和非特异性结合（小脑）的代谢率没有显着改变的芬氟拉明intervention.ConclusionsThe观察到的减少[11 C]雷氯必利结合是一致的增加多巴胺浓度和血清素的能力，刺激多巴胺的活性。在体内测量多巴胺能调节的能力可能对精神分裂症、重度抑郁症、强迫症和物质滥用的病因和治疗机制的研究有影响。
ObjectiveThis study was undertaken to measure serotonergic modulation of dopamine in vivo by using positron emission tomography (PET), a radiotracer for the striatal dopamine D2 receptor ([11C] raclopride), and a pharmacologic challenge of the serotonin system (d, l-fenfluramine).MethodTwo PET studies using [11C] raclopride were performed in 11 normal male subjects before administration of the serotonin-releasing agent and reuptake inhibitor fenfluramine (60 mg po) and 3 hours afterward. A graphical analysis method was used with the [11C] raclopride data to derive the distribution volume of D2 receptors. Plasma levels of fenfluramine, norfenfluramine, homovanillic acid (HVA), cortisol, and prolactin were determined.ResultsLevels of fenfluramine and prolactin were elevated 2 hours after fenfluramine administration and remained significantly elevated during the second scan, while levels of HVA and cortisol were not altered significantly during the time of scanning. A significant decrease in the specific binding (striatum) and the nonspecific binding subtracted from the specific binding (striatum minus cerebellum) of [11C] raclopride was observed. The rate of metabolism of [11C] raclopride and the nonspecific binding (cerebellum) were not significantly altered by the fenfluramine intervention.ConclusionsThe observed decrease in [11C] raclopride binding is consistent with an increase in dopamine concentrations and with the ability of serotonin to stimulate dopamine activity. The ability to measure serotonergic modulation of dopamine in vivo may have implications for the study of etiologic and therapeutic mechanisms in schizophrenia, major depressive disorder, obsessive-compulsive disorder, and substance abuse.