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EVALUATION OF NEUROBIOLOGICAL AND BEHAVIORAL EFFECTS OF INTRANASAL ADMINISTRATION OF OXYTOCIN IN RATS

Grant number: 22/10001-3
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2022
Effective date (End): October 31, 2023
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Carlos Eduardo Neves Girardi
Grantee:Giuliana Mayumi Iyda
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Oxytocin is a hormone synthesized in the hypothalamus that acts peripherally, inducing uterine contraction and the milk ejection reflex, and centrally, modulating social and reproductive behaviors. Beneficial effects of intranasal oxytocin have indicated its potential clinical use for numerous mental disorders that exhibit social deficits. However, there are controversies in the literature about the mechanisms of action of intranasal administration of oxytocin. Spontaneously hypertensive rats (SHR) show significant behavioral changes, especially in sociability, in addition to reduced production and release of central oxytocin, being an important model to test the effect of exogenous oxytocin with therapeutic potential in mental disorders. Therefore, the aim of this project is to explore the potential of intranasal administration of oxytocin to reverse social deficits in SHR and its possible neurobiological substrates. For this, an acute intranasal administration of synthetic oxytocin will be performed, followed by a behavioral test to evaluate the effects of this administration on the sociability of Wistar and SHR rats, followed by euthanasia and brain extraction to evaluate the expression of the fos protein through immunohistochemistry and oxytocin gene by qRT-PCR, both in the hypothalamus, in addition to ELISA assay to detect peripheral concentrations of oxytocin. Considering that some mental disorders are characterized by impairment in social functioning, in addition to deficits in the oxytocinergic system, similar to what is observed in SHR rats, the findings obtained here may provide possible insights into the related physiological bases of the action of oxytocin on behavior and its possible therapeutic application in disorders involving social deficits.

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