Authors: James M Stone Kjell Erlandsson Erik Arstad Lisa Squassante Vincenzo Teneggi Rodrigo A Bressan John H Krystal Peter J Ell Lyn S Pilowsky
Publish Date: 2008/01/05
Volume: 197, Issue: 3, Pages: 401-408
Abstract
Ten healthy controls underwent two singlephoton emission tomography scans with 123ICNS1261 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 123ICNS1261 following ketamine administration Two normalisedtocortex binding indices were also used in order to study effects of ketamine on NMDA receptor availability by region after correction for global and nonspecific effectsKetamineinduced reduction in 123ICNS1261 volume of distribution in all regions showed the strongest correlation with BPRS negative subscale p 001 With the normalisedtocortex measures NMDA receptor binding in middle inferior frontal cortex showed a significant correlation with BPRS negative subscale BI1 r = 088 BI2 r = 959 p 0001123ICNS1261 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 pathwayLSP EA KE were supported by a UK Medical Research Council Senior Clinical Research Fellowship to LSP JS and RAB were supported by a research grant from GlaxoSmithKline JS is currently a Medical Research Council Clinical Research Training Fellow JHK was funded by US National Institute on Alcohol Abuse and Alcoholism KO5 AA 14906–01 US Department of Veterans Affairs Schizophrenia Biological Research Center and Alcohol Research Center All experiments were performed with full ethical approval in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki
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