The effect of ((-)-2-oxa-4-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY379268), an mGlu2/3 receptor agonist, on EEG power spectra and coherence in ketamine model of psychosis
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24631484
DOI
10.1016/j.pbb.2014.03.001
PII: S0091-3057(14)00071-9
Knihovny.cz E-resources
- Keywords
- Electroencephalography (EEG), Functional connectivity, Ketamine, Open field, Prepulse inhibition, mGlu2/3 agonist LY379268,
- MeSH
- Amino Acids pharmacology therapeutic use MeSH
- Antipsychotic Agents pharmacology therapeutic use MeSH
- Bridged Bicyclo Compounds, Heterocyclic pharmacology therapeutic use MeSH
- Electroencephalography drug effects methods MeSH
- Ketamine toxicity MeSH
- Rats MeSH
- Disease Models, Animal * MeSH
- Rats, Wistar MeSH
- Psychotic Disorders drug therapy physiopathology MeSH
- Receptors, Metabotropic Glutamate agonists MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Amino Acids MeSH
- Antipsychotic Agents MeSH
- Bridged Bicyclo Compounds, Heterocyclic MeSH
- Ketamine MeSH
- LY 379268 MeSH Browser
- metabotropic glutamate receptor 2 MeSH Browser
- metabotropic glutamate receptor 3 MeSH Browser
- Receptors, Metabotropic Glutamate MeSH
In the present study we investigated the potential antipsychotic effects of the mGlu2/3 agonist LY379268 on changes in EEG power spectra and coherence in the ketamine model of psychosis. In order to use behaviorally active drug doses, experiments detecting changes in locomotor activity and sensorimotor gating were also conducted. In EEG experiments, adult male Wistar rats were injected with ketamine 30 mg/kg i.p. and LY379268 3 mg/kg i.p. Cortical EEG was recorded from twelve (2 × 6) electrodes placed homolaterally on each hemisphere. To avoid interference with the behavioral hyperactivity of ketamine challenge, the behavioral activity of animals was simultaneously registered at the time of recording. Subsequent power spectral and coherence analyses were assessed in epochs corresponding to behavioral inactivity. Analysis of segments with behavioral activity compared to inactivity was also performed. The effects of LY379268 3 mg/kg i.p. on the deficits in sensorimotor processing and on hyperlocomotion induced by ketamine were evaluated in the test of prepulse inhibition of acoustic startle reaction (PPI ASR) and in the open field. LY379268 reversed the ketamine-induced hyperlocomotion but had no effect on ketamine-induced PPI deficits. In EEG epochs corresponding to behavioral inactivity ketamine decreased the power in the delta band, induced a power increase in the high frequency bands and globally decreased EEG coherence. Pretreatment with the LY379268 completely reversed the ketamine-induced power increase in high frequency bands and had a partial effect on EEG coherence. LY379268 alone induced a decrease of beta, high beta and low-gamma power, and an increase in coherence in high frequency bands. Additional analysis revealed that behavioral activity increases power as well as coherence in most frequency bands. In conclusion, agonism of mGlu2/3 receptors was effective in reversing most of the changes induced by ketamine, however due to the lack of effectiveness on PPI deficits its potential antipsychotic properties remain disputable.
References provided by Crossref.org
