Involvement of mineralocorticoid and glucocorticoid receptors in the ventral tegmental area in the expression of conditioned and unconditioned fear in male and female rats

• Grant number: 23/02122-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2023
• End date: August 31, 2026
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Amanda Ribeiro de Oliveira
• Grantee: Leticia Mitsuko Taguchi
• Host Institution: Centro de Educação e Ciências Humanas (CECH). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 22/02986-0 - Involvement of dopaminergic mechanisms in conditioned and unconditioned fear: modulation by hormonal factors, AP.PNGP.PI
• Associated scholarship(s): 25/06416-1 - The Role of Sex in Vagus Nerve Stimulation-Induced Modulation of Contextual Fear, BE.EP.DR

Abstract

In association with other mediators, corticosterone orchestrates the various elements of the stress response. Corticosteroids act by binding to receptors of two types: mineralocorticoids (MR) and glucocorticoids (GR). MR antagonism in the ventral tegmental area (VTA), but not GR antagonism, appears to reduce conditioned fear responses in male rats. Considering the fact that the female brain acts in a context of chemical alterations caused by the cyclic synthesis of sexual hormones, female rats can manifest alterations in the response to stressful situations depending on the phase of the estrous cycle. Therefore, the present study aims to evaluate the effects of VTA MR and GR blockade on the expression of conditioned and unconditioned fear in male and female rats at different stages of the estrous cycle. For this, male and female Wistar rats separated into proestrus/estrus and metestrus/diestrus will be used. Spironolactone (experiment 1) and mifepristone (experiment 2) will be administered in the VTA and the animals will be submitted to the elevated plus maze (EPM) and context-conditioned fear tests. The behaviors evaluated in the EPM will be: the number of entries into the open and closed arms, time spent in the open arms, rearing, stretching, head-dipping, grooming, exploration of the end of the open arm, and immobility; freezing will be the behavior evaluated in context-conditioned fear. Blockade of MR, but not GR, is expected to reduce the expression of the conditioned freezing response in both males and females, without affecting unconditioned fear.