Smith Gwenn S, Ma Yilong, Dhawan Vijay, Chaly Thomas, Eidelberg David
Department of Psychiatry Research, the Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, New York 11004, USA.
Synapse. 2009 Jan;63(1):1-6. doi: 10.1002/syn.20574.
The effect of a pharmacologic increase in serotonin concentrations on striatal dopamine (D2) receptor availability has been measured in several studies using positron emission tomography (PET) and the radiotracer [11C]-raclopride as a method for the in vivo imaging of serotonin modulation of striatal dopamine in human subjects. These studies have shown that an acute increase in serotonin concentrations produced a decrease in striatal D2 receptor availability. The current study was undertaken to measure the effects of a more pharmacologically selective serotonergic agent compared to previous studies, the serotonin reuptake inhibitor, citalopram, on striatal D2 receptor availability. Twelve healthy control subjects underwent two PET scans performed on the same day following i.v. administration of saline (Scan 1) and citalopram (Scan 2, 40 mg, i.v.). The [11C]-raclopride data were analyzed with a graphical analysis method using the cerebellum as the input function. Plasma levels of citalopram, cortisol, and prolactin were measured. The citalopram concentrations peaked at the end of infusion (EOI) and remained relatively consistent from 30 min to 3 h postinfusion. An increase in cortisol and prolactin concentrations was observed from the EOI until 60 min after the EOI. A significant decrease in striatal D2 receptor availability was observed after citalopram infusion (-5%), presumably due to an increase in endogenous dopamine concentrations. In summary, i.v. administration of the selective serotonin reuptake inhibitor, citalopram, produced modest reductions in striatal D2 receptor availability, consistent with other human [11C]-raclopride studies using less pharmacologically selective serotonergic agents.
在多项研究中，使用正电子发射断层扫描（PET）和放射性示踪剂[11C] - 雷氯必利作为体内成像方法，测量了血清素浓度的药理学增加对纹状体多巴胺（D2）受体可用性的影响，以此研究人类受试者中血清素对纹状体多巴胺的调节作用。这些研究表明，血清素浓度的急性增加会导致纹状体D2受体可用性降低。本研究旨在测量与先前研究相比，药理学上更具选择性的血清素能药物——血清素再摄取抑制剂西酞普兰对纹状体D2受体可用性的影响。12名健康对照受试者在同一天接受了两次PET扫描，分别在静脉注射生理盐水（扫描1）和西酞普兰（扫描2，40毫克，静脉注射）后进行。使用小脑作为输入函数，通过图形分析方法分析[11C] - 雷氯必利数据。测量了西酞普兰、皮质醇和催乳素的血浆水平。西酞普兰浓度在输注结束时达到峰值，并在输注后30分钟至3小时内保持相对稳定。从输注结束到输注结束后60分钟，观察到皮质醇和催乳素浓度增加。西酞普兰输注后，纹状体D2受体可用性显著降低（-5%），这可能是由于内源性多巴胺浓度增加所致。总之，静脉注射选择性血清素再摄取抑制剂西酞普兰会使纹状体D2受体可用性适度降低，这与其他使用药理学选择性较低的血清素能药物的人类[11C] - 雷氯必利研究结果一致。
