Psychopharmacology

, Volume 218, Issue 4, pp 611–620

Inhibition of cerebral type 1 cannabinoid receptors is associated with impaired auditory mismatch negativity generation in the ketamine model of schizophrenia

  • Patrik Roser
  • Ida S. Haussleiter
  • Hee-Jeong Chong
  • Christoph Maier
  • Wolfram Kawohl
  • Christine Norra
  • Georg Juckel
Original Investigation

DOI: 10.1007/s00213-011-2352-y

Cite this article as:
Roser, P., Haussleiter, I.S., Chong, HJ. et al. Psychopharmacology (2011) 218: 611. doi:10.1007/s00213-011-2352-y

Abstract

Rationale

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.

Objectives

The primary aim of this study was to investigate the effects of the cannabinoid CB1 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 CB1 receptor antagonism may impair cognitive performance by a disturbed interaction between endocannabinergic activity and glutamatergic neurotransmission implied in schizophrenia.

Keywords

Mismatch negativityKetamineNMDARimonabantCB1 receptorSchizophrenia

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Patrik Roser
    • 1
  • Ida S. Haussleiter
    • 1
  • Hee-Jeong Chong
    • 1
  • Christoph Maier
    • 2
  • Wolfram Kawohl
    • 3
  • Christine Norra
    • 1
  • Georg Juckel
    • 1
  1. 1.Department of Psychiatry, LWL University HospitalRuhr-University BochumBochumGermany
  2. 2.Department of Anesthesiology, University Hospital BergmannsheilRuhr-University BochumBochumGermany
  3. 3.Department of Social and General Psychiatry ZH WestPsychiatric University Hospital ZurichZurichSwitzerland