title: Medial-frontal cortex hypometabolism in chronic phencyclidine exposed rats assessed by high resolution magic angle spin 11.7 T proton magnetic resonance spectroscopy.
abstract: BACKGROUND
  Proton magnetic resonance spectroscopy ((1)H-MRS) clinical studies of patients with schizophrenia document prefrontal N-acetylaspartate (NAA) reductions, suggesting an effect of the disease or of antipsychotic medications. We studied in the rat the effect of prolonged exposure to a low-dose of the NMDA glutamate receptor antagonist phencyclidine (PCP) on levels of NAA, glutamate and glutamine in several brain regions where metabolite reductions have been reported in chronically medicated patients with schizophrenia.
  
  
  METHODS
  Two groups of ten rats each were treated with PCP (2.58 mg/kg/day) or vehicle and were sacrificed after 1 month treatment. Concentrations of neurochemicals were determined with high resolution magic angle (HR-MAS) (1)H-MRS at 11.7 T in ex vivo punch biopsies from the medial frontal and cingulate cortex, striatum, nucleus accumbens, amygdala and ventral hippocampus.
  
  
  RESULTS
  PCP treatment reduced NAA, glutamate, glycine, aspartate, creatine, lactate and GABA in medial frontal cortex. In the nucleus accumbens, PCP reduced levels of NAA, aspartate and glycine; similarly aspartate and glycine were reduced in the striatum. Finally the amygdala and hippocampus had elevations in glutamine and choline, respectively.
  
  
  CONCLUSIONS
  Low-dose PCP in rats models prefrontal NAA and glutamate reductions documented in chronically-ill schizophrenia patients. Chronic glutamate NMDA receptor blockade in rats replicates an endophenotype in schizophrenia and may contribute to the prefrontal hypometabolic state in schizophrenia.
authors.affiliation: Department of Psychiatry, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. jbustillo@salud.unm.edu
authors.forename: Juan
authors.initials: J
authors.lastname: Bustillo
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Galloway
authors.forename: Farhad
authors.initials: F
authors.lastname: Ghoddoussi
authors.forename: Federico
authors.initials: F
authors.lastname: Bolognani
authors.forename: Nora
authors.initials: N
authors.lastname: Perrone-Bizzozero
mesh_terms: D000818:Animals; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats
chemical_list: D010622:Phencyclidine