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

• Published in: Psychopharmacology Vol. 234; no. 2; pp. 211 - 222
• Main Authors: Hurtubise, Jessica L., Marks, Wendie N., Davies, Don A., Catton, Jillian K., Baker, Glen B., Howland, John G.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2017; Springer; Springer Nature B.V
• Subjects: Animals; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Antipsychotic Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Dizocilpine Maleate - pharmacology; Dizocilpine Maleate - toxicity; Dosage and administration; Dose-Response Relationship, Drug; Drug interactions; Excitatory Amino Acid Antagonists - pharmacology; Male; Memory; Memory Disorders - chemically induced; Memory Disorders - prevention & control; Memory, Short-Term - drug effects; Memory, Short-Term - physiology; Neurosciences; Nitric oxide; Nitroprusside; Nitroprusside - pharmacology; Nootropic Agents - pharmacology; Observations; Original Investigation; Pharmacology/Toxicology; Pilot Projects; Psychiatry; Psychomotor Performance - drug effects; Psychomotor Performance - physiology; Psychopharmacology; Rats; Rats, Long-Evans; Schizophrenia; Schizophrenia - drug therapy; Vasodilator Agents - pharmacology; Vasodilator Agents - therapeutic use; Schizophrenia; Nitric oxide donor; Working memory; NMDA receptor; Pattern separation
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-016-4451-2

Rationale 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. Objective 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. Methods 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. Results 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. Conclusion 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.