Critical involvement of the orbitofrontal cortex in hyperlocomotion induced by NMDA receptor blockade in mice.
Biochem Biophys Res Commun
; 480(4): 558-563, 2016 Nov 25.
Article
em En
| MEDLINE
| ID: mdl-27793672
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 ArcdVenus 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psicoses Induzidas por Substâncias
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Maleato de Dizocilpina
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Córtex Pré-Frontal
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Receptores de N-Metil-D-Aspartato
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Lobo Frontal
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Hipercinese
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Locomoção
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article