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1.
CNS Neurosci Ther ; 24(7): 624-632, 2018 07.
Article in English | MEDLINE | ID: mdl-29656549

ABSTRACT

AIMS: The treatment of schizophrenia with antipsychotics is still unsatisfactory. Therefore, the search for new treatments and prevention is crucial, and animal models are fundamental tools for this objective. Preclinical and clinical data evidence the antipsychotic profile of sodium nitroprusside (SNP), a nitric oxide (NO) donor. We aimed to investigate SNP in treating and/or preventing the schizophrenia-related behaviors presented by the spontaneously hypertensive rats (SHR) strain. METHODS: Wistar rats (WR) and SHRs were submitted to two schemes of treatment: (i) a single injection of SNP or vehicle in adulthood; (ii) a long-term early treatment from 30 to 60 postnatal day with SNP or vehicle. The following behaviors were evaluated 24 hours after the acute treatment or 30 days after the long-term treatment: locomotion, social interaction, and contextual fear conditioning. RESULTS: Spontaneously hypertensive rats presented hyperlocomotion, decreased social interaction, and impaired contextual fear conditioning. Single injection of SNP decreased social interaction in both strains and induced a deficit in contextual fear conditioning in WR. Oppositely, early treatment with SNP prevented the behavioral abnormalities in adult SHRs without promoting any effects in WR. CONCLUSION: Our preclinical data point to SNP as a preventive and safe strategy with a broad range of effectiveness to the positive, negative, and cognitive symptoms of schizophrenia.


Subject(s)
Mental Disorders/etiology , Mental Disorders/prevention & control , Nitric Oxide Donors/therapeutic use , Nitroprusside/therapeutic use , Schizophrenia/complications , Schizophrenic Psychology , Age Factors , Animals , Body Weight/drug effects , Conditioning, Psychological/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Fear/drug effects , Interpersonal Relations , Locomotion/drug effects , Male , Rats , Rats, Inbred SHR , Rats, Wistar
2.
Schizophr Res ; 176(2-3): 552-559, 2016 10.
Article in English | MEDLINE | ID: mdl-27338757

ABSTRACT

Schizophrenia is a highly disabling mental disorder, in which genetics and environmental factors interact culminating in the disease. The treatment of negative symptoms and cognitive deficits with antipsychotics is currently inefficient and is an important field of research. Environmental enrichment (EE) has been suggested to improve some cognitive deficits in animal models of various psychiatric disorders. In this study, we aimed to evaluate a possible beneficial effect of early and long-term exposure to EE on an animal model of schizophrenia, the SHR strain. Young male Wistar rats (control strain) and SHRs (21 post-natal days) were housed for 6weeks in two different conditions: in large cages (10 animals per cage) containing objects of different textures, forms, colors and materials that were changed 3 times/week (EE condition) or in standard cages (5 animals per cage - Control condition). Behavioral evaluations - social interaction (SI), locomotion, prepulse inhibition of startle (PPI) and spontaneous alternation (SA) - were performed 6weeks after the end of EE. SHRs presented deficits in PPI (a sensorimotor impairment), SI (mimicking the negative symptoms) and SA (a working memory deficit), and also hyperlocomotion (modeling the positive symptoms). EE was able to reduce locomotion and increase PPI in both strains, and to prevent the working memory deficit in SHRs. EE also increased the number of neurons in the CA1 and CA3 of the hippocampus. In conclusion, EE can be a potential nonpharmacological strategy to prevent some behavioral deficits associated with schizophrenia.


Subject(s)
Environment , Housing, Animal , Schizophrenia/prevention & control , Animals , Cerebrum/pathology , Disease Models, Animal , Male , Motor Activity , Neurons/pathology , Prepulse Inhibition , Random Allocation , Rats, Inbred SHR , Rats, Wistar , Reflex, Startle , Schizophrenia/pathology , Schizophrenia/physiopathology , Social Behavior
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