, Volume 234, Issue 2, pp 211–222 | Cite as

MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside

  • Jessica L. Hurtubise
  • Wendie N. Marks
  • Don A. Davies
  • Jillian K. Catton
  • Glen B. Baker
  • John G. HowlandEmail author
Original Investigation



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.


Schizophrenia NMDA receptor Nitric oxide donor Working memory Pattern separation 



This research was supported by an operating grant from the Canadian Institutes for Health Research (CIHR; #125984) and a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC). JGH is a CIHR New Investigator. JLH and WNM received salary support from the College of Medicine at the University of Saskatchewan. GBB received salary support and grant funding from the University of Alberta.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Jessica L. Hurtubise
    • 1
  • Wendie N. Marks
    • 1
  • Don A. Davies
    • 1
  • Jillian K. Catton
    • 1
  • Glen B. Baker
    • 2
  • John G. Howland
    • 1
    Email author
  1. 1.Department of PhysiologyUniversity of SaskatchewanSaskatoonCanada
  2. 2.Department of Psychiatry (NRU)University of AlbertaEdmontonCanada

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