Oxytocin involvement in central and peripheral effects evoked by restrain stress in rats

Author(s)

Ivaldo de Jesus Almeida Belém Filho

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2022-08-04

Examining board members

Fernando Morgan de Aguiar Correa; Felipe Villela Gomes; Daniel Breseghello Zoccal

• Advisor: Fernando Morgan de Aguiar Correa

Abstract

Studies have shown stress as an important factor that predisposes to the development of cardiovascular diseases and psychiatric disorders. Several models used to study stress-related disorders that produces functional and behavioral responses, involving endogenous substances as modulators or stress markers, and interestingly, the restraint stress (RS) induces the release of oxytocin (OT) into the circulation. OT is a neuropeptide hormone produced in the hypothalamus, and secreted on demand into the bloodstream via the posterior pituitary. In this sense, there may be a physiological effect against the ER. Thus, we aimed to evaluate the involvement of OT in central and peripheral effects evoked by RS. RS increased blood pressure, heart rate, and plasma OT content, but not vasopressin. Treatment with atosiban (a Gi agonist) inhibited restraint-evoked tachycardia without affecting blood pressure. However, this effect was no longer observed after sinoaortic denervation, treatment with homatropine (M2 muscarinic antagonist) or hypophysectomy, indicating that oxytocin-mediated parasympathetic activation when secreted into the periphery is responsible for blocking the increase in tachycardic responses observed in the group treated with atosiban. Corroborating this, the treatment with L-368,899 (oxytocin antagonist) showed an opposite effect to that of atosiban, increasing tachycardic responses to restraint. The analysis of HR variability revealed an effect of the treatments in increasing the low frequency bands (LF) at the high dose of the antagonist and increasing the sympathovagal balance (LF/HF) at the low dose. In addition, somatic analysis revealed that RS failed to promote a deleterious morphofunctional effect. As for the behavioral effects, the stressed animals showed anxiogenic-like behavior, 24h after the RS session, seen in the time and entries in the open arms of the EPM (%) and in the reduction of time in the central quadrants of the open field. Animals treated with L-368,899 displayed potentiated anxiogenic-like behaviors. Hormonal dosage performed after RS showed an increase in corticosterone release in all stressed groups; as for OT, ER+vehicle animals showed a high increase compared to the Naïve group, but the treatments affected this response, in a dose-response inhibition curve, where the lower dose (0.3µg) potentiated this peripheral OT secretion , whereas the dose of 1µg presented values similar to the ER+vehicle group, and the dose of 3 blocked secretion, leading to levels similar to Naïve, demonstrating a change in the system at the central level. There was no increase in vasopressin in either group. When evaluating the participation of OT in central structures, CeA and PVN, we found similar effects in both structures regarding cardiovascular control, reduction of tachycardia after the use of the antagonist; however, CeA presents this control independent of the autonomic, while PVN is mediated by cardiac sympathetic activation. In the behavioral evaluation, we observed two responses: in CeA it seems to have an anti-stress effect of the antagonist, where the highest dose seems to reduce anxiogeniclike behaviors; as for the PVN, the antagonist promoted anxiogenic-like effect in all tests performed. Corticosterone release was not altered by treatments in CeA and PVN, only at the highest dose in CeA. Thus, the ER model proved to be an effective model inducing autonomic, neuroendocrine, somatic and behavioral activation. OT, acting on its receptor, seems to promote central and peripheral protective effects to several systems. (AU)

• FAPESP's process: 16/25502-7 - Cardiovascular, behavioral, neuroendocrine and morphofunctional effects evoked by acute restraint in rats: involvement of the oxytocinergic pathway
• Grantee: Ivaldo de Jesus Almeida Belém Filho
• Support Opportunities: Scholarships in Brazil - Doctorate