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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.

Original publication

DOI

10.1097/00004647-199605000-00008

Type

Journal article

Journal

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Publication Date

05/1996

Volume

16

Pages

418 - 426

Addresses

Department of Neuroscience, New York Psychiatric Institute, New York, USA.

Keywords

Brain, Prefrontal Cortex, Humans, Fluorine Radioisotopes, Serotonin, Fenfluramine, Deoxyglucose, Fluorodeoxyglucose F18, Glucose, Serotonin Uptake Inhibitors, Tomography, Emission-Computed, Tissue Distribution, Reference Values, Adult, Female, Male