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Evaluation of acute treatment with cannabidiol and sodium nitroprusside in male and female rats in a model of ketamine S+-induced psychosis: behavioral and molecular characterization

Grant number: 19/05391-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2019
Effective date (End): January 31, 2022
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal researcher:Jaime Eduardo Cecilio Hallak
Grantee:Isabella Caroline da Silva Dias
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Schizophrenia (SZ) is one of the most debilitating mental disorders. The cause of the disorder is unknown, but the main hypothesis points to anomalies occurring during neurodevelopment that may culminate in the onset of symptoms during adolescence. Symptoms are generally classified into five broad categories: positive, negative, disorganized, affective, and cognitive deficits. A significant factor to be considered in this disorder is sex, since it presents differences in epidemiology, pathophysiology, response to treatment and prognosis between men and women. But little research has been aimed at investigating this issue. The current treatment for SZ is considered unsatisfactory, as in addition to the various adverse effects, antipsychotics are insufficient to fully act on all SZ symptoms. In this sense, other drugs with different mechanisms of action have been studied and demonstrated complementary antipsychotic effects, and sometimes even more effective, such as cannabidiol (CBD) and sodium nitroprusside (NPS). Due to ethical issues, animal research becomes a valuable tool to deepen the understanding of the mechanisms of action involved in this differentiated performance. Therefore, in this work we propose to investigate the effect of acute treatment of CBD and NPS, alone and in combination, in adolescent male and female rats in the S+ ketamine psychosis model. Furthermore, we propose to investigate in the behavioral and neurochemical sphere the mechanism of action of these drugs. To this end, the present project was divided into 3 major stages: pilot experiment, 1 and 2. The pilot experiment will be carried out with the objective of standardizing the doses of the drugs used, since the combination of CBD + NPS is unprecedented in the literature. Experiment 1 concerns the behavioral part evaluated in the open field test and tissue collection. Experiment 2, on the other hand, is the application of neurochemical techniques on tissues collected in experiment 1. At the moment, the pilot experiment is finished and we are halfway through experiment 1. (AU)

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