title: Impaired limbic cortico-striatal structure and sustained visual attention in a rodent model of schizophrenia.
abstract: BACKGROUND
  N-methyl-d-aspartate receptor (NMDAR) dysfunction is thought to contribute to the pathophysiology of schizophrenia. Accordingly, NMDAR antagonists such as phencyclidine (PCP) are used widely in experimental animals to model cognitive impairment associated with this disorder. However, it is unclear whether PCP disrupts the structural integrity of brain areas relevant to the profile of cognitive impairment in schizophrenia.
  
  
  METHODS
  Here we used high-resolution magnetic resonance imaging and voxel-based morphometry to investigate structural alterations associated with sub-chronic PCP treatment in rats.
  
  
  RESULTS
  Sub-chronic exposure of rats to PCP (5mg/kg twice daily for 7 days) impaired sustained visual attention on a 5-choice serial reaction time task, notably when the attentional load was increased. In contrast, sub-chronic PCP had no significant effect on the attentional filtering of a pre-pulse auditory stimulus in an acoustic startle paradigm. Voxel-based morphometry revealed significantly reduced grey matter density bilaterally in the hippocampus, anterior cingulate cortex, ventral striatum, and amygdala. PCP-treated rats also exhibited reduced cortical thickness in the insular cortex.
  
  
  CONCLUSIONS
  These findings demonstrate that sub-chronic NMDA receptor antagonism is sufficient to produce highly-localized morphological abnormalities in brain areas implicated in the pathogenesis of schizophrenia. Furthermore, PCP exposure resulted in dissociable impairments in attentional function.
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill).
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Barnes
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill).
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sawiak
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill).
authors.forename: Daniele
authors.initials: D
authors.lastname: Caprioli
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill).
authors.forename: Bianca
authors.initials: B
authors.lastname: Jupp
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill).
authors.forename: Guido
authors.initials: G
authors.lastname: Buonincontri
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill).
authors.forename: Adam C
authors.initials: AC
authors.lastname: Mar
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill).
authors.forename: Michael K
authors.initials: MK
authors.lastname: Harte
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill).
authors.forename: Paul C
authors.initials: PC
authors.lastname: Fletcher
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill).
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill).
authors.forename: Jo C
authors.initials: JC
authors.lastname: Neill
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill). jwd20@cam.ac.uk.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Dalley
mesh_terms: D000818:Animals; D001288:Attention; D001307:Auditory Perception; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D066128:Gray Matter / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D010622:Phencyclidine; D065808:Prepulse Inhibition; D051381:Rats; D013216:Reflex, Startle; D012559:Schizophrenia / Q000473:pathology*; D012565:Schizophrenic Psychology; D014796:Visual Perception
chemical_list: D010622:Phencyclidine
keywords: 5-CSRTT; PCP; VBM; anterior cingulate cortex; hippocampus