title: Postnatal Administration of Dizocilpine Inhibits Neuronal Excitability in PFC and Induces Social Deficits Detected by MiceProfiler.
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 < 0.05). Taken together, our results indicated that administration of MK-801 to postnatal mice induces social interaction deficits possibly due to inhibiting the neuronal excitability and decreasing the levels of SIRT1 and p-PKB in the prefrontal cortex.
authors.affiliation: Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Dexiao
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Rehabilitation, Qilu Children's Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Kunkun
authors.initials: K
authors.lastname: Pang
authors.affiliation: Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China. sunjinhao1106@163.com.
authors.forename: Jinhao
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016291:Dizocilpine Maleate / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate
keywords: Dizocilpine; MiceProfiler; Neuronal excitability; Schizophrenia; Social interaction deficits