MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside
- 348 Downloads
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.
KeywordsSchizophrenia 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.
- Kandratavicius L, Balista P, Wolf D et al (2015) Effects of nitric oxide-related compounds in the acute ketamine animal model of schizophrenia. BMC Neurosci 16. doi: 10.1186/s12868-015-0149-3
- Lins BR, Howland JG (2016) Effects of the metabotropic glutamate receptor 5 positive allosteric modulator CDPPB on rats tested with the paired associates learning task in touchscreen-equipped operant conditioning chambers. Behav Brain Res 301:152–160. doi: 10.1016/j.bbr.2015.12.029 CrossRefPubMedGoogle Scholar
- Talpos JC, McTighe SM, Dias R et al (2010) Trial-unique, delayed nonmatching-to-location (TUNL): a novel, highly hippocampus-dependent automated touchscreen test of location memory and pattern separation. Neurobiol Learn Mem 94:341–352. doi: 10.1016/j.nlm.2010.07.006 CrossRefPubMedPubMedCentralGoogle Scholar
- Trevlopoulou A, Touzlatzi N, Pitsikas N (2016) The nitric oxide donor sodium nitroprusside attenuates recognition memory deficits and social withdrawal produced by the NMDA receptor antagonist ketamine and induces anxiolytic-like behaviour in rats. Psychopharmacology 233:1045–1054. doi: 10.1007/s00213-015-4181-x CrossRefPubMedGoogle Scholar