Environmental enrichment protects against stress-induced anxiety: Role of glucocorticoid receptor, ERK, and CREB signaling in the basolateral amygdala

Author(s)

Novaes, Leonardo S. ; dos Santos, Nilton Barreto ; Batalhote, Rafaela F. P. ; Malta, Marilia Brinati ; Camarini, Rosana ; Scavone, Cristoforo ; Munhoz, Carolina Demarchi

• Document type: Journal article
• Source: Neuropharmacology; v. 113, p. 10-pg., 2017-02-01.

Abstract

Environmental enrichment (EE) is an experimental animal model that enhances an animal's opportunity to interact with sensory, motor, and social stimuli, compared to standard laboratory conditions. A prominent benefit of EE is the reduction of stress-induced anxiety. The relationship between stress and the onset of anxiety-like behavior has been widely investigated in experimental research, showing a clear correlation with structural changes in the hippocampus and basolateral amygdala (BLA). However, the mechanisms by which EE exerts its protective roles in stress and anxiety remain unclear, and it is not known whether EE reduces the effects of acute stress on animal behavior shortly following the cessation of stress. We found that EE can prevent the emergence of anxiety-like symptoms in rats measured immediately after acute restraint stress (1 h) and this effect is not due to changes in systemic release of corticosterone. Rather, we found that stress promotes a rapid increase in the nuclear translocation of glucocorticoid receptor (GR) in the BLA, an effect prevented by previous EE exposure. Furthermore, we observed a reduction of ERK (a MAPK protein) and CREB activity in the BLA promoted by both EE and acute stress. Finally, we found that EE decreases the expression of the immediate-early gene EGR-1 in the BLA, indicating a possible reduction of neuronal activity in this region. Hyperactivity of BLA neurons has been reported to accompany anxiety-like behavior and changes in this process may be one of the mechanism by which EE exerts its protective effects against stress-induced anxiety. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 16/03572-3 - The relationship between glucocorticoid receptor activation and the neuronal hyperexcitability in the basolateral amygdala in the restraint stress-induced long-lasting anxiety and their implications in the impaired contextual fear extinction
• Grantee: Carolina Demarchi Munhoz
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/13843-8 - Protection conferred by environmental enrichment on stress-induced anxiety: the importance of GR, ERK, and CREB pathways in the rat basolateral amygdala
• Grantee: Leonardo Santana Novaes
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/24727-4 - Comparison of the therapeutical effects of dexamethasone (a synthetic glucocorticoid analogue), and G1 (a G-coupled estrogen receptor, GPER agonist) on the EAE-induced neuroinflammation
• Grantee: Carolina Demarchi Munhoz
• Support Opportunities: Regular Research Grants