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Postnatal Administration of Dizocilpine Inhibits Neuronal Excitability in PFC and Induces Social Deficits Detected by MiceProfiler

Authors :
Qian Wang
Qingqing Shi
Ling Xu
Wenbo Zhao
Kunkun Pang
Jing Zhang
Dexiao Zhu
Yue Zhao
Hui Wang
Jinhao Sun
Jintao Wu
Source :
Molecular Neurobiology. 54:8152-8161
Publication Year :
2016
Publisher :
Springer Science and Business Media LLC, 2016.

Abstract

Schizophrenia is a devastating mental disease with social deficit as its core component of negative symptoms, which could be induced in rodents by dizocilpine (MK-801), a noncompetitive NMDA receptor antagonist. NMDA receptors are highly expressed during the postnatal period. However, less attention has been paid to the effects of postnatal MK-801 administration on social interaction. In this study, we evaluated the effects of postnatal administration of MK-801 on social interaction and explored the possible mechanisms. Postnatal day-7 mice were intraperitoneally injected with MK-801 twice daily for 5 days, and their social interaction repertoire was monitored by a computerized video in the 10th week. The contact event, relative position event, stop-state, and dynamic event were analyzed with MiceProfiler automatic idTracker system. The results showed that MK-801 reduced the number of the contact events, relative position events, and stop-states, while increased the number and duration of dynamic events. These changes implied that MK-801-injected mice had indifference and lower motivation in social interaction and could be a useful model for studies on the social deficit of schizophrenia. The prefrontal cortex is the key region for social interaction behaviors. Slice patch clamp was performed to analyze the cellular excitability of prefrontal cortical neurons after postnatal treatment with MK-801 in mice. The results demonstrated that MK-801 injection reduced the frequency and amplitude of action potentials, but increased the frequency of miniature inhibitory postsynaptic currents. These data illustrated that the excitability of neurons in the prefrontal cortex was inhibited. Finally, immunoblotting data demonstrated that MK-801 significantly decreased the levels of sirtuin 1 (SIRT1) and phosphorylated protein kinase B (p-PKB) in the prefrontal cortex (both P

Details

ISSN :
15591182 and 08937648
Volume :
54
Database :
OpenAIRE
Journal :
Molecular Neurobiology
Accession number :
edsair.doi.dedup.....e8c8323e2ac00578a7e411d5cf178863