Mann J J, Malone K M, Diehl D J, Perel J, Nichols T E, Mintun M A
Department of Neuroscience, New York Psychiatric Institute, New York, USA.
J Cereb Blood Flow Metab. 1996 May;16(3):418-26. doi: 10.1097/00004647-199605000-00008.
Serotonergic system abnormalities have been implicated in major depression, suicide, violence, alcoholism, and other psychopathologies. The prolactin response to fenfluramine has been widely used as a neuroendocrine probe to study brain serotonin responsivity. We have extended this methodology by using the positron emission tomography (PET) 18F-fluorodeoxyglucose (18FDG) method to examine the fenfluramine-induced changes in regional cerebral glucose metabolism (rCMRglu), an indicator of changes in regional neuronal activity. We report results on 16 healthy controls, each of whom underwent two PET studies. One group of six subjects had a placebo on day 1 and a single 60 mg oral dose of fenfluramine on day 2. The second group, of 10 subjects, was tested on two consecutive occasions without drug or placebo. Data were analyzed for significant rCMRglu changes on day 2 vs day 1 using the statistical parametric mapping method (p < 0.01). Subjects who did not receive drugs showed no statistically significant areas of rCMRglu increase or decrease on day 2 versus day 1. In contrast, the group that received fenfluramine showed significant fenfluramine-induced responses. Areas of rCMRglu increases involved mainly the left prefrontal and left temperoparietal cortex. Within the prefrontal cortex, two major areas of rCMRglu increase included, first, an area centered on the anterior cingulate and, second, an area in the lateral prefrontal cortex involving principally the inferior, middle, and superior frontal gyri. Some decreases in rCMRglu were observed, principally in the right hemisphere. This PET-fenfluramine paradigm is a potentially useful method for studying abnormalities of serotonin function in the prefrontal cortex.
血清素能系统异常与重度抑郁症、自杀、暴力行为、酒精中毒及其他精神病理学问题有关。对芬氟拉明的催乳素反应已被广泛用作一种神经内分泌探针来研究大脑血清素反应性。我们通过使用正电子发射断层扫描（PET）18F-氟脱氧葡萄糖（18FDG）方法扩展了这一方法，以检查芬氟拉明诱导的局部脑葡萄糖代谢（rCMRglu）变化，rCMRglu是局部神经元活动变化的一个指标。我们报告了16名健康对照者的结果，他们每人都接受了两项PET研究。一组6名受试者在第1天服用安慰剂，在第2天口服单次60毫克芬氟拉明。第二组10名受试者在连续两次测试中未服用药物或安慰剂。使用统计参数映射方法分析第2天与第1天rCMRglu的显著变化数据（p < 0.01）。未接受药物治疗的受试者在第2天与第1天相比，rCMRglu增加或减少的区域无统计学显著差异。相比之下，接受芬氟拉明治疗的组显示出芬氟拉明诱导的显著反应。rCMRglu增加的区域主要包括左前额叶和左颞顶叶皮质。在前额叶皮质内，rCMRglu增加的两个主要区域，首先是以扣带回前部为中心的区域，其次是外侧前额叶皮质中主要涉及额下回、额中回和额上回的区域。观察到一些rCMRglu降低，主要在右半球。这种PET-芬氟拉明范式是研究前额叶皮质血清素功能异常的一种潜在有用方法。
