title: Inhibition of cerebral type 1 cannabinoid receptors is associated with impaired auditory mismatch negativity generation in the ketamine model of schizophrenia.
abstract: BACKGROUND
  Preclinical and clinical research suggests that the endogenous cannabinoid system is involved in cognitive impairments related to schizophrenia. In particular, the deficient generation of mismatch negativity (MMN) indicating auditory sensory memory is a characteristic finding in schizophrenic patients. Experimental studies implicate deficient N-methyl-D: -aspartate (NMDA) receptor functioning in such abnormalities.
  
  
  OBJECTIVE
  The primary aim of this study was to investigate the effects of the cannabinoid CB(1) receptor antagonist rimonabant on MMN deficits in the NMDA receptor antagonist model of schizophrenia by using ketamine.
  
  
  METHODS
  Twenty-four healthy male subjects participated in a randomized, double-blind, placebo-controlled cross-over study with subanesthetic doses of intravenous ketamine. The MMNs to frequency and duration deviants were elicited within an auditory oddball paradigm and recorded by a 32-channel EEG. Psychopathology was assessed using the Psychotomimetic States Inventory.
  
  
  RESULTS
  Twenty subjects completed both experimental sessions. Ketamine infusion had no significant effect on MMN amplitudes in both deviance conditions. In contrast to placebo, co-administration of rimonabant produced significant deficits in MMN amplitudes to duration deviants at electrode position Fz.
  
  
  CONCLUSIONS
  The results point to the involvement of the endogenous cannabinoid system in auditory sensory memory as a cognitive key feature in schizophrenia. They particularly suggest that CB(1) receptor antagonism may impair cognitive performance by a disturbed interaction between endocannabinergic activity and glutamatergic neurotransmission implied in schizophrenia.
authors: Department of Psychiatry, LWL University Hospital, Ruhr-University Bochum, Alexandrinenstr. 1, 44791 Bochum, Germany. patrik.roser@rub.de
authors: Patrik
authors: P
authors: Roser
authors: Ida S
authors: IS
authors: Haussleiter
authors: Hee-Jeong
authors: HJ
authors: Chong
authors: Christoph
authors: C
authors: Maier
authors: Wolfram
authors: W
authors: Kawohl
authors: Christine
authors: C
authors: Norra
authors: Georg
authors: G
authors: Juckel
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