title: Critical involvement of the orbitofrontal cortex in hyperlocomotion induced by NMDA receptor blockade in mice.
abstract: Glutamatergic N-methyl-d-aspartate (NMDA) receptors play critical roles in several neurological and psychiatric diseases. Blockade by noncompetitive NMDA receptor antagonist leads to psychotomimetic effects; however, the brain regions responsible for the effects are not well understood. Here, we determined the specific brain regions responsive to MK-801, a noncompetitive NMDA receptor antagonist, by mapping Arc expression as an indicator of neuronal activity using Arc::dVenus reporter mice. MK-801 increased dVenus expression predominantly in the orbitofrontal cortex (OFC) and, as expected, induced a marked hyperlocomotion. Local OFC lesions selectively attenuated the early phase (0-30 min) of MK-801-induced hyperlocomotion. Further, clozapine, an atypical antipsychotic, effectively attenuated both the MK-801-induced dVenus expression in the OFC and hyperlocomotion. These results suggest that the OFC may be critically involved in NMDA receptor-mediated psychotic-like behavioral abnormalities.
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Kaoru
authors: K
authors: Seiriki
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Atsushi
authors: A
authors: Kasai
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Takahiro
authors: T
authors: Kuwaki
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Pharmacology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Takanobu
authors: T
authors: Nakazawa
authors: Division of Morphological Neuroscience, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors: Shun
authors: S
authors: Yamaguchi
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Division of Bioscience, Institute for Datability Science, Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: hasimoto@phs.osaka-u.ac.jp.
authors: Hitoshi
authors: H
authors: Hashimoto
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology*; D006948:Hyperkinesis / Q000139:chemically induced / Q000503:physiopathology*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D011605:Psychoses, Substance-Induced / Q000503:physiopathology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
keywords: Antipsychotic; Arc; Clozapine; Hyperlocomotion; NMDA receptor antagonist; Orbitofrontal cortex