Acute administration of typical and atypical antipsychotics reduces EEG gamma power, but only the preclinical compound LY379268 reduces the ketamine-induced rise in gamma power

Nigel C. Jones, Maya Reddy, Paul Anderson, Michael R. Salzberg, Terence J. O'Brien, Didier Pinault

Research output: Contribution to journalArticleResearchpeer-review

66 Citations (Scopus)

Abstract

A single non-anaesthetic dose of ketamine, a non-competitive NMDA receptor (NMDAR) antagonist with hallucinogenic properties, induces cognitive impairment and psychosis, and aggravates schizophrenia symptoms in patients. In conscious rats an equivalent dose of ketamine induces key features of animal models of acute psychosis, including hyperlocomotor activity, deficits in prepulse inhibition and gating of auditory evoked potentials, and concomitantly increases the power of ongoing spontaneously occurring gamma (30-80 Hz) oscillations in the neocortex. This study investigated whether NMDAR antagonist-induced aberrant gamma oscillations could be modulated by acute treatment with typical and atypical antipsychotic drugs. Extradural electrodes were surgically implanted into the skull of adult male Wistar rats. After recovery, rats were subcutaneously administered either clozapine (1-5 mg/kg, n=7), haloperidol (0.05-0.25 mg/kg; n=8), LY379268 (a preclinical agonist at mGluR 2/3 receptors: 0.3-3 mg/kg; n=5) or the appropriate vehicles, and 30 min later received ketamine (5 mg/kg s.c.). Quantitative measures of EEG gamma power and locomotor activity were assessed throughout the experiment. All three drugs significantly reduced the power of baseline EEG gamma oscillations by 30-50%, an effect most prominent after LY379268, and all inhibited ketamine-induced hyperlocomotor activity. However, only pretreatment with LY379268 attenuated trough-to-peak ketamine-induced gamma hyperactivity. These results demonstrate that typical and atypical antipsychotic drugs acutely reduce cortical gamma oscillations, an effect that may be related to their clinical efficacy.

Original languageEnglish
Pages (from-to)657-668
Number of pages12
JournalInternational Journal of Neuropsychopharmacology
Volume15
Issue number5
DOIs
Publication statusPublished - Jun 2012
Externally publishedYes

Keywords

  • Antipsychotic
  • EEG
  • gamma power
  • ketamine
  • schizophrenia

Cite this