Hedonic imbalance in Schizophrenia and prevention with sodium nitroprusside: a behavioral, neurochemical, and neurofunctional characterization

• Grant number: 24/02533-0
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2024
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Vanessa Costhek Abílio
• Grantee: Vanessa Costhek Abílio
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Fabio Cardoso Cruz

Abstract

Schizophrenia is a neuropsychiatric disorder that affects around 0.3% of the world population. Among its symptoms, there are evident alterations in hedonic processes, associated with both social impairments and increased substance consumption, suggesting the presence of a hedonic imbalance. This imbalance has been evaluated by our group in the schizophrenia model of the SHR strain. Simultaneously, we have found that administration of sodium nitroprusside (SNP), a nitric oxide donor, during peri-adolescence, can prevent behavioral alterations in this model. The central objectives of this project are: 1) to characterize in an animal model of schizophrenia (administration of the NMDA antagonist MK-801 during neurodevelopment), behavioral (social behaviors and cocaine consumption), neurochemical (associated with dopaminergic, GABAergic, glutamatergic, and endocannabinoid systems, oxidative stress, and neuroinflammation), and neurofunctional aspects (involvement of the mesolimbic and mesocortical pathways) of a possible hedonic tone imbalance between social stimuli and substance abuse; 2) to evaluate a possible beneficial effect of a preventive treatment with SNP on these alterations; 3) to investigate possible sexual dimorphisms in the hedonic and social alterations found and in the effects of SNP; 4) to characterize the effects of MK-801 exposure in C. elegans through evaluations of survival and development, behavioral, morphological, and parameters of oxidative stress and inflammation. Our project aims to clarify essential aspects that impact the social life of patients with schizophrenia, as well as to evaluate prevention of these social and substance use alterations, which do not adequately respond to currently available therapies. (AU)