title: MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside.
abstract: The cognitive symptoms observed in schizophrenia are not consistently alleviated by conventional antipsychotics. Following a recent pilot study, sodium nitroprusside (SNP) has been identified as a promising adjunct treatment to reduce the working memory impairments experienced by schizophrenia patients.
  
  
  
  The present experiments were designed to explore the effects of SNP on the highly translatable trial-unique, delayed nonmatching-to-location (TUNL) task in rats with and without acute MK-801 treatment.
  
  
  
  SNP (0.5, 1.0, 2.0, 4.0, and 5.0 mg/kg) and MK-801 (0.05, 0.075, and 0.1 mg/kg) were acutely administered to rats trained on the TUNL task.
  
  
  
  Acute MK-801 treatment impaired TUNL task accuracy. Administration of SNP (2.0 mg/kg) with MK-801 (0.1 mg/kg) failed to rescue performance on TUNL. SNP (5.0 mg/kg) administration nearly 4 h prior to MK-801 (0.05 mg/kg) treatment had no preventative effect on performance impairments. SNP (2.0 mg/kg) improved performance on a subset of trials.
  
  
  
  These results suggest that SNP may possess intrinsic cognitive-enhancing properties but is unable to block the effects of acute MK-801 treatment on the TUNL task. These results are inconsistent with the effectiveness of SNP as an adjunct therapy for working memory impairments in schizophrenia patients. Future studies in rodents that assess SNP as an adjunct therapy will be valuable in understanding the mechanisms underlying the effectiveness of SNP as a treatment for schizophrenia.
authors.affiliation: Department of Physiology, University of Saskatchewan, GB33, Health Sciences Building, 107 Wiggins Rd, Saskatoon, SK, S7N 5E5, Canada.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Hurtubise
authors.affiliation: Department of Physiology, University of Saskatchewan, GB33, Health Sciences Building, 107 Wiggins Rd, Saskatoon, SK, S7N 5E5, Canada.
authors.forename: Wendie N
authors.initials: WN
authors.lastname: Marks
authors.affiliation: Department of Physiology, University of Saskatchewan, GB33, Health Sciences Building, 107 Wiggins Rd, Saskatoon, SK, S7N 5E5, Canada.
authors.forename: Don A
authors.initials: DA
authors.lastname: Davies
authors.affiliation: Department of Physiology, University of Saskatchewan, GB33, Health Sciences Building, 107 Wiggins Rd, Saskatoon, SK, S7N 5E5, Canada.
authors.forename: Jillian K
authors.initials: JK
authors.lastname: Catton
authors.affiliation: Department of Psychiatry (NRU), University of Alberta, Edmonton, AB, T6G 2B7, Canada.
authors.forename: Glen B
authors.initials: GB
authors.lastname: Baker
authors.affiliation: Department of Physiology, University of Saskatchewan, GB33, Health Sciences Building, 107 Wiggins Rd, Saskatoon, SK, S7N 5E5, Canada. john.howland@usask.ca.
authors.forename: John G
authors.initials: JG
authors.lastname: Howland
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology; D010865:Pilot Projects; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D012559:Schizophrenia / Q000188:drug therapy; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D018697:Nootropic Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D016291:Dizocilpine Maleate
keywords: NMDA receptor; Nitric oxide donor; Pattern separation; Schizophrenia; Working memory