Characterization of the effects of an ACE inhibitor and a beta blocker on behaviors associated with schizophrenia in an animal model: the SHR strain

• Grant number: 14/16454-3
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2015
• Effective date (End): May 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Vanessa Costhek Abílio
• Grantee: Veronica Vilela de Oliveira Justi
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Schizophrenia is one of the most serious and often disabling psychiatric disorders, affecting 1% of world population. It is characterized by positive symptoms such as delusions and hallucinations; negative symptoms such as affective flattening and alogia; and cognitive deficits. Meanwhile, an association between schizophrenia and hypertension is reported, suggesting a possible role of the renin-angiotensin system in the disease, since this is one of the most important regulators of blood pressure. However, the possible link between hypertension and schizophrenia is not well established, but data in the literature show cognitive improvement from the administration of ACE inhibitors, and beta blockers, in addition, on antipsychotic treatment patients refractory to the use of the latter has been increasing, since this class of drugs seems to act in the improvement of symptoms of anxiety. In this context, the lineage of animals spontaneously hypertensive SHR (spontaneously hypertensive rats) is suggested as a good model for the study of schizophrenia, based on behavioral and neurochemical changes made by this strain and the specific beneficial effects of antipsychotics. Therefore, the aim of this study is to evaluate the effects of treatment with an angiotensin converting enzyme inhibitor and a beta blocker on an animal model of schizophrenia - the SHR (hypertensive rats spontaneously) lineage. The first objective, the study will assess the effects of acute treatment on the behavioral changes observed in adulthood that model symptoms of schizophrenia in this lineage. As a second objective will be assessed a possible preventive effect of early treatment (during adolescence) on these behavioral changes assessed in adulthood. Finally, we evaluate the changes of blood pressure in animals of each group after administration of drugs. The results of this study may in the future provide a better understanding of the pathophysiology of schizophrenia, as well as new drugs and therapeutic strategies to treat this disease, leading to a better quality of life for patients and reduce the suffering of the family. (AU)