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.
Nigel C. Jones, Maya Reddy, Paul M Anderson, Michael R Salzberg, Terence J. O'Brien, Didier Pinault
The International Journal of Neuropsychopharmacology June 9, 2011 DOI: 10.1017/s1461145711000848 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Adult male Wistar rats |
| Interventions | Clozapine Haloperidol LY379268 Ketamine |
| Dose | Clozapine 1-5 mg/kg; Haloperidol 0.05-0.25 mg/kg; LY379268 0.3-3 mg/kg; Ketamine 5 mg/kg |
| Measures | EEG gamma power, locomotor activity |
| Topics | Ketamine Esketamine |
| Keywords | Cerebral cortex Animals Rats, wistar Haloperidol Clozapine Amino acids Receptors, n-methyl-d-aspartate Antipsychotic agents Drug administration schedule Electrodes, implanted Male Brain waves |
| Key findings | All three drugs (clozapine, haloperidol, LY379268) reduced baseline EEG gamma power by 30-50% and inhibited ketamine-induced hyperlocomotor activity. However, only the mGluR2/3 agonist LY379268 attenuated ketamine-induced gamma hyperactivity, suggesting typical and atypical antipsychotics reduce cortical gamma oscillations, which may relate to their clinical efficacy. |
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 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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 12
- ( 2R,6R )-hydroxynorketamine exerts mGlu 2 receptor-dependent antidepressant actions Proceedings of the National Academy of Sciences March 13, 2019
- Ketamine alters oscillatory coupling in the hippocampus Scientific Reports August 2, 2013
- The neurophysiology of ketamine: an integrative review Reviews in the Neurosciences May 5, 2020
- Preclinical models of antipsychotic drug action The International Journal of Neuropsychopharmacology June 10, 2013
- Effects of NMDA receptor antagonists on working memory and gamma oscillations, and the mediating role of the GluN2D subunit. Neuropsychopharmacology May 15, 2025
and 7 more in the library
Cites 5
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- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Reversal of Phencyclidine Effects by a Group II Metabotropic Glutamate Receptor Agonist in Rats Science August 28, 1998
- Attenuation of specific PCP-evoked behaviors by the potent mGlu2/3 receptor agonist, LY379268 and comparison with the atypical antipsychotic, clozapine. Psychopharmacology March 1, 2000
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