title: Differential effects of NMDA antagonists on high frequency and gamma EEG oscillations in a neurodevelopmental model of schizophrenia.
abstract: Neuroanatomical, electrophysiological and behavioural abnormalities following timed prenatal methylazoxymethanol acetate (MAM) treatment in rats model changes observed in schizophrenia. In particular, MAM treatment on gestational day 17 (E17) preferentially disrupts limbic-cortical circuits, and is a promising animal model of schizophrenia. The hypersensitivity of this model to the NMDA receptor antagonist-induced hyperactivity has been proposed to mimic the increase in sensitivity observed in schizophrenia patients following PCP and Ketamine administration. However, how this increase in sensitivity in both patients and animals translates to differences in EEG oscillatory activity is unknown. In this study we have shown that MAM-E17 treated animals have an increased response to the hyperlocomotor and wake promoting effects of Ketamine, PCP, and MK801 but not to the competitive antagonist SDZ 220,581. These behavioural changes were accompanied by altered EEG responses to the NMDAR antagonists, most evident in the gamma and high frequency (HFO) ranges; altered sensitivity of these neuronal network oscillations in MAM-exposed rats is regionally selective, and reflects altered interneuronal function in this neurodevelopmental model.
authors.affiliation: Lilly Centre for Cognitive Neuroscience, Eli Lilly and Company, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK. keith.phillips@bristol.ac.uk
authors.forename: K G
authors.initials: KG
authors.lastname: Phillips
authors.forename: M C
authors.initials: MC
authors.lastname: Cotel
authors.forename: A P
authors.initials: AP
authors.lastname: McCarthy
authors.forename: D M
authors.initials: DM
authors.lastname: Edgar
authors.forename: M
authors.initials: M
authors.lastname: Tricklebank
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Neill
authors.forename: M W
authors.initials: MW
authors.lastname: Jones
authors.forename: K A
authors.initials: KA
authors.lastname: Wafford
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D058256:Brain Waves / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology*; D018592:Cross-Over Studies; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000633:toxicity; D011247:Pregnancy; D011422:Propionates / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012559:Schizophrenia / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D001713:Biphenyl Compounds; D018691:Excitatory Amino Acid Antagonists; D011422:Propionates; D016194:Receptors, N-Methyl-D-Aspartate; C104918:alpha-amino-2'-chloro-5-(phosphonomethyl)(1,1'-biphenyl)-3-propanoic acid; D008746:Methylazoxymethanol Acetate