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
| Autor: | Terence J. O'Brien, Didier Pinault, Maya Reddy, Paul Anderson, Michael R. Salzberg, Nigel C. Jones |
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| Přispěvatelé: | Pinault, Didier, Department of Medicine, University of Melbourne-Royal Melbourne Hospital, Department of Psychiatry [Melbourne], Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne-Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, Department of Neurology, Physiopathologie clinique et expérimentale de la schizophrénie, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by a University of Melbourne Joint Projects grant (NJ and DP). NJ is supported by an NHMRC Career Development Award. |
| Rok vydání: | 2011 |
| Předmět: |
Male
MESH: Amino Acids medicine.medical_treatment Pharmacology MESH: Bicyclo Compounds Heterocyclic Antipsychotic Haloperidol MESH: Animals Pharmacology (medical) EEG Amino Acids Clozapine Prepulse inhibition Cerebral Cortex gamma power MESH: Excitatory Amino Acid Antagonists Electrodes Implanted Psychiatry and Mental health NMDA receptor [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Antipsychotic Agents medicine.drug Psychosis ketamine MESH: Rats medicine.drug_class Atypical antipsychotic MESH: Drug Administration Schedule Receptors N-Methyl-D-Aspartate Article Drug Administration Schedule medicine Animals Ketamine [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Rats Wistar MESH: Clozapine MESH: Brain Waves MESH: Receptors N-Methyl-D-Aspartate business.industry MESH: Ketamine MESH: Rats Wistar Bridged Bicyclo Compounds Heterocyclic medicine.disease Brain Waves MESH: Male MESH: Cerebral Cortex Rats MESH: Haloperidol schizophrenia MESH: Antipsychotic Agents MESH: Electrodes Implanted business Excitatory Amino Acid Antagonists |
| Zdroj: | International Journal of Neuropsychopharmacology International Journal of Neuropsychopharmacology, Oxford University Press (OUP), 2012, 15 (5), pp.657-68. ⟨10.1017/S1461145711000848⟩ |
| ISSN: | 1469-5111 1461-1457 |
| DOI: | 10.1017/s1461145711000848 |
| Popis: | 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 abnormal behaviour, hyperlocomotion, deficits in prepulse inhibition to an acoustic startle response and gating of auditory evoked potentials, and concomitantly increases the power of spontaneously occurring gamma 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. Adult male Wistar rats that has been implanted with extradural electrodes were placed in an arena for 30 minutes (baseline) and then subcutaneously administered either clozapine (1–5mg/kg, n=7), haloperidol (0.05 – 0.25mg/kg; n=8), LY379268 (a preclinical agonist at mGluR2/3 receptors: 0.3 – 3mg/kg; n=5) or their vehicles alone, and 30 minutes later received ketamine (5mg/kg sc). 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. |
| Databáze: | OpenAIRE |
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