The long-lasting effects of acute stress on the contextual extinction memory: Participation of glucocorticoid receptors in the prefrontal cortex

Author(s)

Jessica Rosa

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2019-03-07

Examining board members

Leonardo Resstel Barbosa Moraes; Leandro José Bertoglio; Norberto Garcia Cairasco; Antonio de Pádua Carobrez; Francisco Silveira Guimarães

• Advisor: Leonardo Resstel Barbosa Moraes

Abstract

It has been proposed that a brief exposure to stress leads to deficits in fear memory extinction. Interestingly, extinction learning can be used as treatment for phobia or posttraumatic stress disorder (PTSD). However, further evidence is still necessary to completely understand the memory extinction process. One brain region highly involved in memory formation and extinction is the prefrontal cortex (PFC). Its ventromedial portion (vmPFC) is widely associated with neuroendocrine and behavior responses during stressful situations. Additionally, there is a high expression of glucocorticoid receptors in this area. Thus, the current study investigated the effects of acute stress, along with the role of glucocorticoid receptors present in the vmPFC in the memory extinction learning. To this aim male Wistar rats with infusion cannulae stereotaxically implanted in the prelimbic (PL) or infralimbic (IL) regions of the vmPFC were divided in two independent groups: 1) Stressed group (1h restraint stress); 2) Control group (no stress). On the seventy day, both groups were exposed to extinction of contextual fear conditioning protocol. Our results demonstrated that the both groups were able to extinct fear responses over the time during extinction session, but only the stressed group showed an increase of contextual fear conditioning expression. Interestingly, on the next day, the stressed group demonstrated significantly less extinction retrieval than not-stressed group. This suggests that acute stress do not impaired acquisition but promotes a deficit in extinction fear memory consolidation. Moreover, the glucocorticoid receptor antagonist (RU 486; 10ng/side) microinjected into the PL or IL, immediately after the extinction session, attenuated such deficit in stressed animals. On the other hand, the MRs antagonist (RU 28318) at a dose of 150ng/100nl/side microinject to the IL immediately after the extinction session didn\'t attenuate such deficit in stressed animals. Our results unveiled that a brief and single stress episode prior to contextual fear conditioning leads to extinction deficit. Furthermore, our data suggests that glucocorticoid receptors in vmPFC are necessary for the impairing extinction memory promoted by acute stress. This study is important to characterizing how stress affects memory extinction and could offer new insights about the extinction-based exposure therapy. (AU)

• FAPESP's process: 15/11800-3 - The role of acute stress and mineralocorticoid and glucocorticoid receptors present in the prefrontal cortex in the memory extinction learning
• Grantee: Jessica Rosa
• Support Opportunities: Scholarships in Brazil - Doctorate