Environmental enrichment protection on acute stress-induced late anxiety-like behavior and fear extinction impairment in rats: role of glucocorticoid receptor signaling in the basolateral nucleus of amygdala.

Author(s)

Leonardo Santana Novaes

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2018-06-21

Examining board members

Carolina Demarchi Munhoz; Rosana Camarini; Newton Sabino Canteras; Raquel Vecchio Fornari; Deborah Suchecki

• Advisor: Carolina Demarchi Munhoz

Abstract

The consequences of stressful events on human health, especially related to psychiatric disorders, have gained attention in recent years due the increasing number of comorbidities associated to stress in large cities. Anxiety-related disorders are common among the psychiatric patients and are widely present in studies devoted to stress, which use different approaches to investigate the neurobiological mechanisms underlying the persistence of anxiety symptoms caused by a stressful event. Either acute restraint stress or systemic injection of corticosterone (CORT, a rodent glucocorticoid) in rats leads to enhanced anxiety-like behavior and dendritic branch remodeling in the basolateral amygdala complex (BLA) 10 days later. Also, some studies showed that exposure to environmental enrichment (EE) reverted the long- lasting anxiety-like behavior and the repeated stress-induced BLA dendritic hypertrophy in rats. In a recent study, we found that EE prevented anxiety-related behavior in adult rats observed immediately after acute restraint stress. This protective role of EE appears to be due to the prevention of the stress-induced increase in neuronal activity and in glucocorticoid receptor (GR) nuclear activity in the BLA. In this study, we showed that EE prevented the restraint stress-induced long-lasting anxiety and contextual fear extinction impairment in adult rats. However, it is not yet clear if this protective role of EE is related to changes in the dendritic branch and/or in the GR signaling in the BLA. The present study sought to determine whether the preventive effect of EE on persistent stress-related changes in behavior as well as in the BLA morphology and activity are attributed to CORT signaling. We found that the EE- induced protection on anxiety-like behavior and fear extinction impairment 10 days after acute restraint stress was not related to prevention of the increase in spine density in BLA. Moreover, systemic injection of GC synthesis inhibitor (metyrapone) prevented the anxiety-like behavior 10 days after stress, showing that GC signaling during stress is crucial to late stress-related behavior. Finally, by antagonizing the genomic signaling of the endogenous GR in the BLA, through the use of recombinant DNA technology, we prevented the emergence of anxiety-related behavior 10 days after acute stress. (AU)

• FAPESP's process: 12/24002-0 - Effects of environmental enrichment in long-lasting anxiety symptoms triggered by acute stress: implications in the emotional memory acquisition
• Grantee: Leonardo Santana Novaes
• Support Opportunities: Scholarships in Brazil - Doctorate