title: Alterations of hippocampal and prefrontal GABAergic interneurons in an animal model of psychosis induced by NMDA receptor antagonism.
abstract: Some behavioral symptoms and neuropathological features of schizophrenia, like alterations of local GABAergic interneurons, could be emulated in an animal model of psychosis based on prolonged low-dose exposure to N-methyl-D-aspartate (NMDA) receptor antagonists, e.g. MK-801. Employing this model, we examined distinct subpopulations of GABAergic interneurons within the hippocampus and prefrontal cortex. Compared to saline control, animals receiving MK-801 exhibited a decreased density of hippocampal parvalbumin-positive interneurons. A co-administration of the antipsychotic drug haloperidol ameliorated this effect of MK-801 on PV(+) interneurons in the hippocampus, but led to a marked reduction of PV immunoreactivity in the prefrontal cortex, when comparing with saline, MK-801 or haloperidol treatment alone. Neither calretinin immunoreactivity nor nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining, representing neuronal nitric oxide synthase activity mostly detectable in interneurons, was altered by either treatment. With special reference to the hippocampus, these data show that a prolonged application of low-dose NMDA receptor antagonist could, in part, mimic some neuropathologic findings in human schizophrenia, thus strengthening the idea that (sub-) chronic NMDA receptor antagonism in animals is a viable approach in mimicking aspects of schizophrenia. Moreover, this study provides further evidence for regional differences in the response of GABAergic interneurons to NMDA receptor antagonism and antipsychotic treatment.
authors.affiliation: Department of Psychiatry, Division of Molecular and Clinical Neurobiology, Ludwig-Maximilians University of Munich, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Braun
authors.forename: Just
authors.initials: J
authors.lastname: Genius
authors.forename: Heinz
authors.initials: H
authors.lastname: Grunze
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007395:Interneurons / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000473:pathology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology*; D011618:Psychotic Disorders / Q000473:pathology*; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012559:Schizophrenia / Q000139:chemically induced / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D006220:Haloperidol