title: Effects of MK-801 treatment across several pre-clinical analyses including a novel assessment of brain metabolic function utilizing PET and CT fused imaging in live rats.
abstract: BACKGROUND
  Functional imaging studies in schizophrenic patients have demonstrated metabolic brain abnormalities during cognitive tasks. This study aimed to 1) introduce a novel analysis of brain metabolic function in live animals to characterize the hypo- and hyperfrontality phenomena observed in schizophrenia and following NMDA antagonist exposure, and 2) identify a robust and representative MK-801 treatment regimen that effectively models brain metabolic abnormalities as well as a range of established behavioural abnormalities representative of schizophrenia.
  
  
  METHODS
  The validity of the MK-801 animal model was examined across several established pre-clinical tests, and a novel assessment of brain metabolic function using PET/CT fused imaging. In the present study, MK-801 was administered acutely at 0.1 mg/kg and 0.5 mg/kg, and sub-chronically at 0.5 mg/kg daily for 7 days.
  
  
  RESULTS
  Acute treatment at 0.5 mg/kg-disrupted facets of memory measured through performance in the 8-arm radial maze task and generated abnormalities in sensorimotor gating, social interaction and locomotor activity. Furthermore, this treatment regimen induced hyperfrontality (increased brain metabolic function in the prefrontal area) observed via PET/CT fused imaging in the live rat.
  
  
  CONCLUSIONS
  While PET and CT fused imaging in the live rat offers a functional representation of metabolic function, more advanced PET/CT integration is required to analyze more discrete brain regions.
  
  
  CONCLUSIONS
  These findings provide insight on the effectiveness of the MK-801 pre-clinical model of schizophrenia and provide an optimal regimen to model schizophrenia. PET/CT fused imaging offers a highly translatable tool to assess hypo- and hyperfrontality in live animals.
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: R P
authors.initials: RP
authors.lastname: Daya
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: J K
authors.initials: JK
authors.lastname: Bhandari
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: P A
authors.initials: PA
authors.lastname: Hui
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Radiology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Farncombe
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada. Electronic address: mishrar@mcmaster.ca.
authors.forename: R K
authors.initials: RK
authors.lastname: Mishra
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011859:Radiography; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012559:Schizophrenia / Q000378:metabolism*; D055139:Sensory Gating / Q000187:drug effects
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
keywords: Animal model; MK-801; PET and CT fused imaging; Schizophrenia