Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects.
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).


METHODS
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.
Smith
G S
GS
Department of Psychiatry, New York University, School of Medicine, New York, USA.
Dewey
S L
SL
Brodie
J D
JD
Logan
J
J
Vitkun
S A
SA
Simkowitz
P
P
Schloesser
R
R
Alexoff
D A
DA
Hurley
A
A
Cooper
T
T
Volkow
N D
ND
D000368:Aged; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D005277:Fenfluramine / Q000097:blood / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy; D011388:Prolactin / Q000097:blood; D020891:Raclopride; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012457:Salicylamides; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D004298:Dopamine; D018492:Dopamine Antagonists; D005277:Fenfluramine; D006719:Homovanillic Acid; D011388:Prolactin; D020891:Raclopride; D011954:Receptors, Dopamine; D012457:Salicylamides; D017367:Selective Serotonin Reuptake Inhibitors