Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET)

被引:313
作者
Vollenweider, FX
Leenders, KL
Oye, I
Hell, D
Angst, J
机构
[1] PAUL SCHERRER INST,PET DEPT,CH-5232 VILLIGEN,SWITZERLAND
[2] UNIV OSLO,SCH MED,DEPT PHARMACOL,N-0316 OSLO,NORWAY
关键词
model psychosis; schizophrenia; glutamate; (S)- and (R)-ketamine enantiomeres; N-methyl-D-aspartate (NMDA) receptor; sigma receptor; cerebral glucose metabolism; frontal cortex; PET (positron emission tomography); F-18]fluorodeoxyglucose (FDG);
D O I
10.1016/S0924-977X(96)00042-9
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Until recently, racemic ketamine (S-ketamine/R-ketamine=50:50) has been used to study NMDA receptor hypofunction in relation to pathophysiological models of schizophrenia. Ketamine given to normal humans in subanesthetic doses produces a model psychosis including both positive and negative symptoms of schizophrenia. More recently it has been shown that at subanesthetic doses the pure (S)- and (R)-ketamine enantiomeres interact differently with the NMDA and sigma receptor sites in human brain. It was found that (S)-ketamine binds with a 3-4 time higher affinity to the PCP binding site of the NMDA receptor than (R)-ketamine, and that at these concentrations (R)-ketamine interacts also weakly with the sigma receptor sites, where (S)-ketamine binds only negligibly. To further investigate the role of NMDA-receptor mediated neurotransmission in schizophrenic psychosis, the effects of pure (S)- and (R)-ketamine enantiomeres on brain energy metabolism in normal humans using positron emission tomography and [F-18]fluorodeoxyglucose (FDG) are reported here. Psychotomimetic doses of (S)-ketamine increased cerebral metabolic rates of glucose (CMRglu) markedly in the frontal cortex including the anterior cingulate, parietal and left sensorimotor cortex, and in the thalamus. The metabolic changes in the frontal and left temporal cortex correlated with ego-disintegration and hallucinatory phenomena. Equimolar doses of (R)-ketamine tended to decrease CMRglu across brain regions and significantly suppressed CMRglu in the temporomedial cortex and left insula. (R)-ketamine did not produce psychotic symptoms, but a state of relaxation. The (S)-ketamine-induced metabolic hyperfrontality appears to parallel similar metabolic findings in acute psychotic schizophrenic patients and encourages further investigations of glutamatergic disturbances in schizophrenia. (C) 1997 Elsevier Science B.V.
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页码:25 / 38
页数:14
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