Involvement of the dorsal hippocampal renin-angiotensin system (RAS) in cardiovascular, behavioral, and neuroendocrine responses evoked by restraint stress in rats.

• Grant number: 25/00522-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fernando Morgan de Aguiar Correa
• Grantee: Bruna Reato Brandão
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

This project explores the effects of acute restraint stress (RS) on cardiovascular, autonomic, and behavioral responses, emphasizing the role of the renin-angiotensin system (RAS) in the dorsal hippocampus. Stress activates the RAS, resulting in changes in blood pressure and heart rate, primarily mediated by AT-1, AT-2, and Mas receptors. The study aims to investigate how the selective inhibition of these receptors in the dorsal hippocampus can modulate physiological and behavioral responses to stress, hypothesizing that AT-1 receptor inhibition has a protective effect, attenuating RS-induced alterations. The research suggests that RAS modulation, particularly in central regions such as the hippocampus, could offer a therapeutic target for mitigating the adverse effects of acute stress.The study will use male Sprague-Dawley rats weighing between 250 and 280g, housed under controlled temperature and light conditions. The animals will undergo stereotaxic surgery for the implantation of guide cannulas in the dorsal hippocampus (DH) and, after eight days, a second surgery for femoral artery cannulation to record blood pressure (BP) and heart rate (HR). Stress will be induced by restraint, and BP, HR, and tail temperature will be monitored during the exposure. Bilateral microinjections in the DH will be performed to evaluate the effects of drugs on physiological and behavioral responses. Animal behavior will be analyzed using the elevated plus maze (EPM) and open field test (OF), while plasma corticosterone levels will be measured using an ELISA assay post-stress. At the end of the experiments, animals will be euthanized, and their brains collected for histological analysis. Data analysis will be conducted using statistical software.