Glutamate modulation of dopamine measured in vivo with positron emission tomography (PET) and 11C-raclopride in normal human subjects.
Subanesthetic doses of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine exacerbate psychosis in schizophrenic patients, and ketamine has significant abuse liability. These observations indicate that a secondary effect of ketamine may be to increase dopamine concentrations. The present study was undertaken using positron emission tomography (PET) and the dopamine (D2) radiotracer 11C-raclopride to determine whether ketamine would decrease D2 receptor availability, indicative of an increase in dopamine concentrations. Two scans were performed in seven male control subjects before and after administration of ketamine (0.5 mg/kg, i.v. infused over 20 min). Ketamine significantly increased cortisol levels and decreased dopamine receptor availability in the striatum (specific binding), but not in the cerebellum (nonspecific binding). In addition, the cerebellar binding subtracted from the striatal binding (to account for changes in nonspecific binding) was significantly decreased after ketamine administration. These results provide in vivo evidence for the ability of ketamine to increase striatal dopamine concentrations, consistent with the role of the NMDA receptor in modulating dopamine function.
Smith
G S
GS
Department of Psychiatry, New York University School of Medicine, New York, USA.
Schloesser
R
R
Brodie
J D
JD
Dewey
S L
SL
Logan
J
J
Vitkun
S A
SA
Simkowitz
P
P
Hurley
A
A
Cooper
T
T
Volkow
N D
ND
Cancro
R
R
D000328:Adult; D002250:Carbon Radioisotopes; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D007649:Ketamine / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D017072:Neostriatum / Q000033:anatomy & histology / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D020891:Raclopride; D012016:Reference Values; D012457:Salicylamides; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D012457:Salicylamides; D018698:Glutamic Acid; D020891:Raclopride; D007649:Ketamine; D011388:Prolactin; D004298:Dopamine; D006719:Homovanillic Acid