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| Author(s): |
Isabella Caroline da Silva Dias
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2024-03-22 |
| Examining board members: |
Jaime Eduardo Cecilio Hallak;
Rodrigo Campos Cardoso;
Lívea Dornéla Godoy
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| Advisor: | Jaime Eduardo Cecilio Hallak |
| Abstract | |
Schizophrenia (SZ) is one of the most debilitating mental disorders that exists. Symptoms are generally classified into three broad categories; positive and negative symptoms and cognitive deficits. Current treatments for the disorder remain unsatisfactory in covering all types of symptoms. Furthermore, available antipsychotics produce significant adverse effects related to sensorimotor and endocrine control, among others. ln this sense, cannabidiol (CBD) and sodium nitroprusside (SNP) have demonstrated interesting effects in pre-and clinicai research, as they have more abrangent and relatively safer effects. lhe cause of SZ is unknown, but the main hypothesis points to anomalies occurring during neurodevelopment that may culminate in the appearance of the first symptoms during adolescence. The knowledge of the pathophysiology of the disorder is the main ally in the search for more effective treatments, therefore, research on animais becomes a valuable tool. ln this sense, the ketamine (KET) model is one of the most used, as it can mi mie the three types of symptoms in rodents. KET has two optical isomers, R(-) and S(+) (KET S). The S isomer has more affinity for NMDA receptors, so it is believed that it may produce more SZ-like symptoms than the other types of KET. When mixed, the most popular form of KET is produced, racemic (KET R). One of the main characteristics of the disorder is the difference between the sexes. Research indicates that SZ manifests differently in men and women in terms of pathophysiology, epidemiology, response to treatment, and prognosis. However, little work has been carried out to systematically investigate this issue. Considering the above, in this thesis we pro pose to investigate new therapeutic approaches during the neurodevelopment phase, with the pre-treatment of CBD and SNP, isolated and in combination (manuscript 1); investigate whether there is a difference between ketamines (racemic mixture and S+ isomer) in producing SZ-like symptoms in adolescent rats (manuscript 2); and finally, investigate the therapeutic efficacy of treatment with CBD and SNP (alone and in combination) in a acute treatment in adolescent rats (short communication, manuscript 3). lt is important to highlight that the 3 studies were carried out on female and male rats. (AU) | |
| FAPESP's process: | 19/05391-4 - 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 |
| Grantee: | Isabella Caroline da Silva Dias |
| Support Opportunities: | Scholarships in Brazil - Doctorate |