title: 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.
abstract: 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.
authors.affiliation: Prague Psychiatric Center, Ústavní 91, 18103, Prague 8, Czech Republic; 3rd Faculty of Medicine, Charles University in Prague, Ruská 87, 100 00 Prague 10, Czech Republic. Electronic address: fujakova@pcp.lf3.cuni.cz.
authors.forename: Michaela
authors.initials: M
authors.lastname: Fujáková
authors.affiliation: Prague Psychiatric Center, Ústavní 91, 18103, Prague 8, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Páleníček
authors.affiliation: Prague Psychiatric Center, Ústavní 91, 18103, Prague 8, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Brunovský
authors.affiliation: Prague Psychiatric Center, Ústavní 91, 18103, Prague 8, Czech Republic.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Gorman
authors.affiliation: Prague Psychiatric Center, Ústavní 91, 18103, Prague 8, Czech Republic; 3rd Faculty of Medicine, Charles University in Prague, Ruská 87, 100 00 Prague 10, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Tylš
authors.affiliation: Prague Psychiatric Center, Ústavní 91, 18103, Prague 8, Czech Republic; 3rd Faculty of Medicine, Charles University in Prague, Ruská 87, 100 00 Prague 10, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Kubešová
authors.affiliation: Prague Psychiatric Center, Ústavní 91, 18103, Prague 8, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Řípová
authors.affiliation: Czech Technical University in Prague, Faculty of Biomedical Engineering, Nám. Sítná 3105, 272 01 Kladno, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Krajča
authors.affiliation: Prague Psychiatric Center, Ústavní 91, 18103, Prague 8, Czech Republic; 3rd Faculty of Medicine, Charles University in Prague, Ruská 87, 100 00 Prague 10, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Horáček
mesh_terms: D000596:Amino Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects* / Q000379:methods; D007649:Ketamine / Q000633:toxicity; D008297:Male; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D016896:Treatment Outcome
chemical_list: D000596:Amino Acids; D014150:Antipsychotic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D007649:Ketamine
keywords: Electroencephalography (EEG); Functional connectivity; Ketamine; Open field; Prepulse inhibition; mGlu2/3 agonist LY379268