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

• Grant number: 21/10014-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): October 01, 2022
• Effective date (End): September 30, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fernando Morgan de Aguiar Correa
• Grantee: Ivaldo de Jesus Almeida Belém Filho
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

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 cope, in submissive animals. Repeated or excessive exposure to social stress promotes behavioral (depressive and anhedonic-like behaviors), cardiovascular (increased heart rate) and dysautonomia (decreased cardiac variability, increased sympathetic and reduced parasympathetic activity) changes in preclinical models that correspond to findings in humans. Stressful situations, induced by the social stress model, are modulated by several central structures; for example, the participation of oxytocin from the hypothalamic paraventricular nucleus (PVN) in passive defensive behavioral responses as well as in cardiovascular responses has been demonstrated. Oxytocin appears as a possible neuromodulator during the process of social stress and/or may be a potential therapeutic agent to reverse 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, oxytocin treatment 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; variability of blood pressure and heart rate, and spontaneous baroreflex), as well as the expression of oxytocin and its receptor in central areas, by qPCR. Additionally, to evaluate the participation of oxytocin in the 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 the stress consolidation. (AU)