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

Trevlopoulou, Aikaterini; Touzlatzi, Ntilara; Pitsikas, Nikolaos

doi:10.1007/s00213-015-4181-x

Cited by 43 publications

(38 citation statements)

References 70 publications

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“…In the present study, SNP neither prevented (Fig 4; 5.0 mg/kg; 3 h and 35 min prior to MK-801) nor rescued (Fig 3; 2.0 mg/kg; 5 min prior to MK-801) MK-801-induced impairments in the TUNL task. Our findings fail to replicate previous reports of reduced cognitive impairments in patients (Maia-de-Oliveira et al 2015a) and ketamine-treated rats (Trevlopoulou et al 2016) following SNP, suggesting that acute MK-801 administration in the TUNL task may not be an appropriate paradigm to study the effects SNP in schizophrenia.…”

Section: Snp Did Not Block Mk-801-induced Impairments But Improved Pacontrasting

confidence: 99%

“…This experiment did not replicate previous rodent or human studies that demonstrated SNP ability to reduce psychomimetic or symptom presentation respectively (Hallak et al 2013;Maia-de-Oliveira et al 2015a;Maia-deOliveira et al 2015b;Trevlopoulou et al 2016). There are several explanations for the differences between previous studies and the present one.…”

Section: Nitric Oxide Sodium Nitroprusside and Schizophreniacontrasting

confidence: 57%

“…However, when SNP was administered as an adjunct treatment to patients with schizophrenia, it reduced working memory impairments on the n-back task (Maia-de-Oliveira et al 2015a). Previous rodent studies have mirrored these findings as SNP reduces ketamine-induced cognitive deficits (Trevlopoulou et al 2016). In the present study, SNP neither prevented (Fig 4; 5.0 mg/kg; 3 h and 35 min prior to MK-801) nor rescued (Fig 3; 2.0 mg/kg; 5 min prior to MK-801) MK-801-induced impairments in the TUNL task.…”

Section: Snp Did Not Block Mk-801-induced Impairments But Improved Pamentioning

confidence: 82%

“…Secondly, this was the first study using the TUNL task as a measure of working memory. Previous studies have observed SNP restores novelty preference and recognition memory in rodents (Trevlopoulou et al 2016). …”

Section: Nitric Oxide Sodium Nitroprusside and Schizophreniamentioning

confidence: 86%

“…In these studies, the administration of SNP in conjunction with an NMDA receptor antagonist attenuated locomotor behavior, social behavior, and novel object recognition abnormalities. These measurements are believed to be rodent analogues to aspects of the positive, negative and cognitive symptoms of schizophrenia (Maiade-Oliveira et al 2015b;Trevlopoulou et al 2016). Rodent effects were observed up to one week after administration, further supporting the long-term efficacy of SNP (Maia-de-Oliveira et al 2015b).…”

Section: Introductionmentioning

confidence: 92%

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

et al. 2016

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The cognitive symptoms observed in schizophrenia are highly prevalent and predictive of patient functional outcome but are not usually alleviated by conventional antipsychotics. In a recent pilot study, sodium nitroprusside (SNP), a nitric oxide donor, was identified as a promising adjunct treatment to reduce the working memory impairments experienced by schizophrenia patients.Adjunctive SNP has also been reported to decrease the positive and negative symptoms experienced by patients for weeks following a single administration. The mechanisms underlying these changes and the areas of cognition affected remain largely unknown.Therefore, it is of interest to examine the effects of SNP using a rodent model of schizophrenia that has demonstrated predictive validity. The aim of the present experiment was to explore the effects of SNP on the acute MK-801 rodent model of schizophrenia using a highly translatable task in order to establish its validity. Working memory and pattern separation were measured using the trial-unique, delayed nonmatching-to-location (TUNL) task in touchscreen-equipped operant conditioning chambers. Acute MK-801 administration 25 minutes prior to task initiation impaired both areas of cognition. When SNP and MK-801 were administered within 5 minutes of each other, no interaction was observed. Interestingly, SNP improved performance on trials with difficult to discriminate patterns (p=0.058). Previous rodent studies using the ketamine model of schizophrenia and the novel object preference task observed a preventative effect of SNP administration. When we administered SNP nearly 4 hours prior to MK-801, no cognitive improvements were observed. Our results suggest that SNP may have intrinsic cognitive enhancing properties but is not capable of reducing MK-801-induced working memory and pattern separation impairments in the TUNL task. This study failed to mirror the results of the human pilot study that observed improved working memory following SNP administration.iii Further, it did not replicate previous animal studies using ketamine. Ultimately, the findings suggest that the effects of MK-801 in the TUNL task may not hold the predictive validity needed for its use in the study of SNP. In order to advance the understanding of SNP, future studies should investigate other translatable paradigms to establish validity. iv ACKNOWLDGEMENTSFirst and foremost, I would like to thank my supervisor Dr. John Howland, for his guidance and encouragement over the past three years. He believed in my abilities before I had proven them to myself and pushed me to be the best scientist and student I could be. John has provided me with countless opportunities to grow as a researcher and selflessly helped me make decisions about my future. I would not be where I am today without him and will always be grateful to have had such an incredible mentor in my life.I would like to thank my committee members, Dr.

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Section: Snp Did Not Block Mk-801-induced Impairments But Improved Pacontrasting

confidence: 99%

Section: Nitric Oxide Sodium Nitroprusside and Schizophreniacontrasting

confidence: 57%

Section: Snp Did Not Block Mk-801-induced Impairments But Improved Pamentioning

confidence: 82%

Section: Nitric Oxide Sodium Nitroprusside and Schizophreniamentioning

confidence: 86%

Section: Introductionmentioning

confidence: 92%

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

et al. 2016

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Effects of Anesthetic Ketamine on Anxiety-Like Behaviour in Rats

et al. 2019

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Antidyskinetic Effect of 7-Nitroindazole and Sodium Nitroprusside Associated with Amantadine in a Rat Model of Parkinson’s Disease

Bortolanza

Bariotto-dos-Santos²,

Pereira³

et al. 2016

Neurotox Res

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Amantadine is the noncompetitive antagonist of N-methyl-D-aspartate, receptor activated by the excitatory neurotransmitter glutamate. It is the only effective medication used to alleviate dyskinesia induced by L-3,4-dihydroxyphenylalanine (L-DOPA) in Parkinson's disease patients. Unfortunately, adverse effects as abnormal involuntary movements (AIMs) known as L-DOPA-induced dyskinesia limit its clinical utility. Combined effective symptomatic treatment modalities may lessen the liability to undesirable events. Likewise drugs known to interfere with nitrergic system reduce AIMs in animal models of Parkinson's disease. We aimed to analyze an interaction between amantadine, neuronal nitric oxide synthase inhibitor (7-nitroindazole, 7NI), and nitric oxide donor (sodium nitroprusside, SNP) in 6-hydroxydopamine-(6-OHDA)-lesioned rats (microinjection in the medial forebrain bundle) presenting L-DOPA-induced dyskinesia (20 mg/kg, gavage, during 21 days). We confirm that 7NI-30 mg/kg, SNP-2/4 mg/kg and amantadine-40 mg/kg, individually reduced AIMs. Our results revealed that co-administration of sub-effective dose of amantadine (10 mg/kg) plus sub-effective dose of 7NI (20 mg/kg) potentiates the effect of reducing AIMs scores when compared to the effect of the drugs individually. No superior benefit on L-DOPA-induced AIMs was observed with the combination of amantadine and SNP. The results revealed that combination of ineffective doses of amantadine and 7NI represents a new strategy to increase antidyskinetic effect in L-DOPA-induced AIMs. It may provide additional therapeutic benefits to Parkinson's disease patients from these disabling complications at lower and thus safer and more tolerable doses than required when either drug is used alone. To close, we discuss the paradox of both nitric oxide synthase inhibitor and/or donor produced AIMs reduction by targeting nitric oxide synthase.

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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

Abstract: Our findings illustrate a functional interaction between the nitrergic and glutamatergic system that may be of relevance for schizophrenia-like behavioural deficits. The data also suggest a role of NO in anxiety.

Cited by 43 publications

References 70 publications

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

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

Effects of Anesthetic Ketamine on Anxiety-Like Behaviour in Rats

Antidyskinetic Effect of 7-Nitroindazole and Sodium Nitroprusside Associated with Amantadine in a Rat Model of Parkinson’s Disease

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