title: Establishment of a schizophrenic animal model through chronic administration of MK-801 in infancy and social isolation in childhood.
abstract: Although an increasing amount of evidence supports a "two-hit" hypothesis for the neurodevelopmental model of schizophrenia, there has been no development in animal models to test this hypothesis.
  
  
  
  An animal model was established by chronic administration of 0.1, 0.3, and 0.5mg/kg MK-801 in P7-P21 rats followed by four weeks of social isolation in childhood and then five days of social housing. Animal behaviors were measured by the open field (OF) test, the novel object recognition (NOR) test, the prepulse inhibition (PPI) test, and the elevated plus maze (EPM) test.
  
  
  
  We found a significant decrease in the NOR index in adolescent rats compared to saline control rats when administering 0.5mg/kg of MK-801 (P=0.02). We found that social isolation had no significant effect on NOR index, though social isolation significantly increased the total distance traveled and significantly decreased the resting time in adolescent rats in the OF test (P<0.001 and P=0.003, respectively). In contrast, we observed that MK-801 administration showed no significant effects on either total distance traveled or resting time. Both MK-801 administration and social isolation had no significant effect on the percent of PPI and startle amplitudes in adolescent rats. Social isolation significantly reduced the open arm entries in adolescent rats in the EPM test (P=0.023), but it did not reduce the ratio to enter the open arms and the stay time in open arm. Administration of MK-801 showed no significant effect on the indexes of entering the open arms in the EPM test on adolescent rats.
  
  
  
  MK-801 intervention in infancy is associated with the damage of long-term visual memory, whereas social isolation in childhood is associated with the increased spontaneous activity and anxiety levels. Administration of MK-801 in infancy and social isolation in childhood are two independent factors on the neurodevelopmental defects.
authors.affiliation: Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, PR China; Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, PR China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Hong
authors.affiliation: Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China. Electronic address: chenxghn@gmail.com.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D065808:Prepulse Inhibition / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000139:chemically induced* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D016037:Single-Blind Method; D012934:Social Isolation / Q000523:psychology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate
keywords: Akt phosphorylation; Animal model; Dose; MK-801; Psychotomimetic effects