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Recapitulation of Neuropsychiatric Behavioral Features in Mice Using Acute Low-dose MK-801 Administration

Experimental Neurobiology 2019년 28권 6호 p.697 ~ 708
 ( Mabunga Darine Froy N. ) - Konkuk University School of Medicine Department of Neuroscience

박동현 ( Park Dong-Hyun ) - Konkuk University School of Medicine Department of Neuroscience
 ( Ryu On-Jeon ) - Konkuk University School of Medicine Department of Neuroscience
 ( Valencia Schley T. ) - Konkuk University School of Medicine Department of Neuroscience
 ( Adil Keremkleroo Jym L. ) - Konkuk University School of Medicine Department of Neuroscience
김선민 ( Kim Seon-Min ) - Konkuk University School of Medicine Department of Neuroscience
권경자 ( Kwon Kyoung-Ja ) - Konkuk University School of Medicine Department of Neuroscience
신찬영 ( Shin Chan-Young ) - Konkuk University School of Medicine Department of Neuroscience
전세진 ( Jeon Se-Jin ) - Konkuk University School of Medicine Department of Neuroscience

Abstract


Despite some innate limitations, animal models are a potent investigative tool when used to model specific symptoms of a disorder. For example, MK-801, an N-methyl-D-aspartate receptor antagonist, is used as a pharmacological tool to induce symptoms found in some neuropsychiatric disorders. However, a close examination of literature suggests that the application window of MK-801 doses is relatively narrow between individual behavioral paradigms, necessitating careful characterization of the evoked behavioral aberrations and the doses used to induce them. Moreover, variation in behaviors depending on the animal strain, gender of the subject, and the timing of administration is observed, making it difficult to compare the behavioral characteristics reported in different studies. We aim to characterize the behavioral aberrations induced by different doses of MK-801 in CD-1 mice and create a ready reference for future studies. We used CD-1 mice to recapitulate behavioral impairments resulting from acute administration of MK-801. In 0.1 mg kg?1, we observed diminished spontaneous alteration during the Y-maze test, while 0.12 mg kg?1 resulted in hyperlocomotion and social deficit. Mice treated with 0.2 and 0.3 mg kg?1 of MK-801 demonstrated a decreased self-grooming. Finally, all doses significantly impaired cliff avoidance behaviors suggesting increased impulsivity. These results affirm that MK-801 can effectively model various symptoms of different neuropsychiatric disorders in a dose-dependent manner. The observed sensitivity against spatial-memory impairment and impulsive behaviors at low concentration of MK-801 suggest that MK801 may modulate cognitive function and impulsivity in even lower concentration before it can modulate other behavioral domains.

키워드

MK-801; Behavioral domains; Neuropsychiatric disorders; Animal model
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