Involvement of oxytocinergic neurotransmission from the hypothalamic paraventricular nucleus on defensive responses, behavioral and cardiovascular alterations in rats submitted to the intermittent social stress model.

• Grant number: 23/03044-0
• Support Opportunities: Regular Research Grants
• Duration: December 01, 2023 - November 30, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fernando Morgan de Aguiar Correa
• Grantee: Fernando Morgan de Aguiar Correa
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Cristiane Busnardo Santiago

Abstract

Studies using models of social stressors are increasingly important, as they are related to pathological processes. The social defeat model promotes defensive behaviors in rats, especially passive coping in submissive animals. Repeated or excessive exposure to social stress promotes behavioral alterations (depressive and anhedonic-like behaviors), cardiovascular (increase in heart rate) and dysautonomia (reduction in cardiac variability, increase in sympathetic activity and reduction in parasympathetic activity) in preclinical models that correspond to findings in humans. Stressful situations, induced by the social stress model, are modulated by several core structures; for example, the participation of oxytocin in the hypothalamic paraventricular nucleus (PVN) has been demonstrated in passive behavioral responses of defense, as well as in cardiovascular responses. Oxytocin appears as a possible neuromodulator during the process of social stress and/or may be a potential therapeutic agent to reverse long-lasting changes when stress has ceased. Therefore, this project hypothesizes that animals submitted to the intermittent social stress model show increased oxytocinergic neurotransmission in the PVN, and in areas related to behavioral responses and cardiovascular control. Furthermore, after the changes induced by the social stress model have been established treatment with oxytocin can reverse these effects. Thus, rats subjected to social defeat through the resident-intruder model will be used, repeated for a period of 7 consecutive days, and behavioral (anhedonia), cardiovascular (blood pressure; heart rate; ECG, variability in blood pressure and heart rate) will be evaluated. and the spontaneous baroreflex), as well as the expression of oxytocin and its receptor in central areas, by qPCR. Additionally, to assess the role of oxytocin in changes associated with stress, a group of animals will be treated systemically with an oxytocin receptor antagonist, L-368,899, during the entire period of stress). In another experimental group, the ability of oxytocin to reverse changes in social stress will be evaluated; for that, the animals will receive oxytocin or L368,899 intra-PVN after stress consolidation. (AU)