Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy: a [(123)I]CNS-1261 SPET study.
Psychopharmacology (Berl)
; 197(3): 401-8, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18176855
ABSTRACT
RATIONALE Ketamine induces effects resembling both positive and negative psychotic symptoms of schizophrenia. These are thought to arise through its action as an uncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. OBJECTIVES:
We used [(123)I]CNS-1261 to study ketamine binding to NMDA receptors in healthy human controls in vivo and its relationship to positive and negative psychotic symptom induction. MATERIALS ANDMETHODS:
Ten healthy controls underwent two single-photon emission tomography scans with [(123)I]CNS-1261. On each occasion, they received a bolus infusion of either ketamine or saline. The Brief Psychiatric Rating Scale (BPRS) was administered at the end of each scan. Predefined regions of interest were used to estimate change in volume of distribution of [(123)I]CNS-1261 following ketamine administration. Two normalised-to-cortex binding indices were also used in order to study effects of ketamine on NMDA receptor availability by region, after correction for global and nonspecific effects.RESULTS:
Ketamine-induced reduction in [(123)I]CNS-1261 volume of distribution in all regions showed the strongest correlation with BPRS negative subscale (p < 0.01). With the normalised-to-cortex measures, NMDA receptor binding in middle inferior frontal cortex showed a significant correlation with BPRS negative subscale (BI1 r = 0.88, BI2 r = 95.9, p < 0.001).CONCLUSIONS:
[(123)I]CNS-1261 binding was modulated by ketamine, a drug known to compete for the same site on the NMDA receptor in vitro. Ketamine may induce negative symptoms through direct inhibition of the NMDA receptor, and positive symptoms may arise through a different neurochemical pathway.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Psicoses Induzidas por Substâncias
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Esquizofrenia
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Tomografia Computadorizada de Emissão de Fóton Único
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Córtex Pré-Frontal
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Receptores de N-Metil-D-Aspartato
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Guanidinas
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Radioisótopos do Iodo
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Ketamina
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article