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

Int J Neuropsychopharmacol. 2012 Jun;15(5):657-68. doi: 10.1017/S1461145711000848. Epub 2011 Jun 9.


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 mGluR2/3 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / administration & dosage*
  • Amino Acids / pharmacology
  • Animals
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / pharmacology
  • Brain Waves / drug effects*
  • Bridged Bicyclo Compounds, Heterocyclic / administration & dosage*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cerebral Cortex / drug effects*
  • Clozapine / administration & dosage
  • Clozapine / pharmacokinetics
  • Drug Administration Schedule
  • Electrodes, Implanted
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology
  • Haloperidol / administration & dosage
  • Haloperidol / pharmacology*
  • Ketamine / administration & dosage*
  • Ketamine / pharmacology
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*


  • Amino Acids
  • Antipsychotic Agents
  • Bridged Bicyclo Compounds, Heterocyclic
  • Excitatory Amino Acid Antagonists
  • LY 379268
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine
  • Clozapine
  • Haloperidol