POSITRON EMISSION TOMOGRAPHIC IMAGING OF SEROTONIN ACTIVATION EFFECTSON PREFRONTAL CORTEX IN HEALTHY-VOLUNTEERS

Serotonergic system abnormalities have been implicated in major depres sion, suicide, violence, alcoholism, and other psychopathologies. The prolactin response to fenfluramine has been widely used as a neuroendo crine probe to study brain serotonin responsivity. We have extended th is methodology by using the positron emission tomography (PET) F-18-fl uorodeoxyglucose ((18)FDG) method to examine the fenfluramine-induced changes in regional cerebral glucose metabolism (rCMR(glu)), an indica tor 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 f enfluramine on day 2. The second group, of 10 subjects, was tested on two consecutive occasions without drug or placebo. Data were analyzed for significant rCMR(glu) changes on day 2 vs day 1 using the statisti cal parametric mapping method (p < 0.01). Subjects who did not receive drugs showed no statistically significant areas of rCMR(glu) increase or decrease on day 2 versus day 1. In contrast, the group that receiv ed fenfluramine showed significant fenfluramine-induced responses. Are as of rCMR(glu) increases involved mainly the left prefrontal and left temperoparietal cortex. Within the prefrontal cortex, two major areas of rCMR(glu) increase included, first, an area centered on the anteri or cingulate and, second, an area in the lateral prefrontal cortex inv olving principally the inferior, middle, and superior frontal gyri. So me decreases in rCMR(glu) were observed, principally in the right hemi sphere. This PET-fenfluramine paradigm is a potentially useful method for studying abnormalities of serotonin function in the prefrontal cor tex.