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Am J Psychiatry 1997; 154:490-496
Copyright © 1997 by American Psychiatric Association
Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects
GS Smith, SL Dewey, JD Brodie, J Logan, SA Vitkun, P Simkowitz, R Schloesser, DA Alexoff, A Hurley, T Cooper and ND Volkow
Department of Psychiatry, New York University, School of Medicine, New York, USA.
OBJECTIVE: This 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).
METHOD: Two 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 p.o.) 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. RESULTS: Levels 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. CONCLUSIONS: The 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.
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