Effects of nitric oxide-related compounds in the acute ketamine animal model of schizophrenia
Ludmyla Kandratavicius, Priscila Alves Balista, Daniele C. Wolf, João Abrão, Paulo Roberto Barbosa Évora, Alfredo José Rodrigues, Cristiano Chaves, João Paulo Maia‐de‐oliveira, João Pereira Leite, Serdar Dursun, Glen B. Baker, Francisco Silveira Guimarães, Jaime E. C. Hallak
BMC Neuroscience March 5, 2015 DOI: 10.1186/s12868-015-0149-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Sodium nitroprusside Glyceryl trinitrate Methylene blue |
| Topics | Ketamine Esketamine |
| Keywords | Schizophrenia object-oriented programming Sodium nitroprusside Therapeutic effect Nitric oxide Pharmacology Snp Open field Nmda receptor Anesthesia |
| Citations | 40 |
| Key points | Sodium nitroprusside treatment consistently reduced ketamine-induced hyperlocomotion in rats, and therapeutic administration of glyceryl trinitrate and sodium nitroprusside improved long-term memory. |
Abstract
Background: Better treatments for schizophrenia are urgently needed. The therapeutic use of the nitric oxide (NO)-donor sodium nitroprusside (SNP) in patients with schizophrenia has shown promising results. The role of NO in schizophrenia is still unclear, and NO modulation is unexplored in ketamine (KET) animal models to date. In the present study, we compared the behavioral effects of pre- and post-treatment with SNP, glyceryl trinitrate (GTN), and methylene blue (MB) in the acute KET animal model of schizophrenia. The present study was designed to test whether acute SNP, GTN, and MB treatment taken after (therapeutic effect) or before (preventive effect) a single KET injection would influence the behavior of rats in the sucrose preference test, object recognition task and open field.
Results: The results showed that KET induced cognitive deficits and hyperlocomotion. Long- term memory improvement was seen with the therapeutic GTN and SNP treatment, but not with the preventive one. MB pretreatment resulted in long-term memory recovery. GTN pre-, but not post-treatment, tended to increase vertical and horizontal activity in the KET model. Therapeutic and preventive SNP treatment consistently decreased KET-induced hyperlocomotion.
Conclusion: NO donors - especially SNP - are promising new pharmacological candidates in the treatment of schizophrenia. In addition, we showed that the potential impact of NO-related compounds on KET-induced behavioral changes may depend on the temporal window of drug administration.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 5
- Role of the NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways in the anti-psychotic effects of aripiprazole and sertindole in ketamine-induced schizophrenia-like behaviors in rats InflammoPharmacology July 25, 2022
- BPC 157, L-NAME, L-Arginine, NO-Relation, in the Suited Rat Ketamine Models Resembling “Negative-Like” Symptoms of Schizophrenia Biomedicines June 21, 2022
- Neuroprotective effects of curcumin-loaded nanophytosome on ketamine-induced schizophrenia-like behaviors and oxidative damage in male mice. Neuroscience Letters September 15, 2021
- Combined Low Dose of Ketamine and Social Isolation: A Possible Model of Induced Chronic Schizophrenia-Like Symptoms in Male Albino Rats Brain Science July 1, 2021
- Effects of sodium nitroprusside in the prevention of schizophrenia-like symptoms induced by ketamine – A translational double-blind study December 1, 2017
Cites 4
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Effect of Baseline Anxious Depression on Initial and Sustained Antidepressant Response to Ketamine The Journal of Clinical Psychiatry September 25, 2014
- The interplay of cannabinoid and NMDA glutamate receptor systems in humans: preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 15, 2011
- Blockade of phencyclidine-induced effects by a nitric oxide donor. British Journal of Pharmacology July 1, 2000