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 via OpenAlex
Summary
Nitric oxide donors, especially sodium nitroprusside (SNP), show promise for treating schizophrenia. In a rat model using ketamine to induce schizophrenia-like behaviors, SNP given either before or after ketamine consistently reduced hyperlocomotion. Glyceryl trinitrate and SNP given after ketamine improved long-term memory, while methylene blue given before ketamine also improved long-term memory. The effects depended on whether the drug was administered before or after ketamine, suggesting the timing of treatment matters. These findings indicate that nitric oxide modulation could be a new pharmacological approach for schizophrenia.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Sodium nitroprusside Glyceryl trinitrate Methylene blue |
| Topics | Ketamine |
| Keywords | Schizophrenia object-oriented programming Sodium nitroprusside Therapeutic effect Nitric oxide Pharmacology |
| Citations | 40 |
| Key finding | 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.