Role of corticosterone in conditioned and unconditioned fear: involvement of the dopaminergic pathway ventral tegmental area-basolateral amygdala

• Grant number: 24/22530-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2025
• End date: February 29, 2028
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Amanda Ribeiro de Oliveira
• Grantee: Joyce Nonato Chiossi
• 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

Abstract

Metyrapone, an inhibitor of adrenal corticosteroid synthesis, has been shown to reduce both conditioned and unconditioned defensive responses in male rats. In conditioned fear, corticosterone appears to modulate dopamine release in the basolateral amygdala (BLA) through activation of mineralocorticoid receptors (MR) in the ventral tegmental area (VTA). However, the relationship between corticosterone and dopamine in the expression of unconditioned fear remains poorly explored. Furthermore, females, due to their cyclical hormonal fluctuations, may manifest alterations in their responses to stressful situations depending on the phase of the estrous cycle. Thus, the aim of the present study is to investigate the interaction between corticosterone and dopaminergic neurotransmission in the VTA-BLA pathway during the expression of conditioned and unconditioned fear in male and female rats at different phases of the estrous cycle. For this, adult male and female Wistar rats will be used, which will undergo surgery to implant cannulae directed bilaterally to the VTA or BLA. After recovery from surgery, vaginal smears will be performed daily to monitor the estrous cycle for approximately 14 days in females and equivalent handling will be conducted in males. After this period, the animals will undergo the elevated plus maze test and, starting the following day, the contextual conditioned fear protocol will begin. Before the elevated plus maze test and before the contextual conditioned fear test, metyrapone (intraperitoneally) and quinpirole (intra-BLA) or sulpiride (intra-VTA) will be administered. Metyrapone is expected to reduce the expression of unconditioned and conditioned fear responses, in addition to causing impairment in the extinction of conditioned fear. It is also expected that the increase in dopamine concentrations in the BLA will reverse these effects of metyrapone. (AU)