Environmental enrichment protects against stress-induced anxiety: Role of glucocorticoid receptor, ERK, and CREB signaling in the basolateral amygdala.
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.
Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, 05508-000, Brazil.
Leonardo S
LS
Novaes
Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, 05508-000, Brazil.
Nilton Barreto
NB
Dos Santos
Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, 05508-000, Brazil.
Rafaela F P
RFP
Batalhote
Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, 05508-000, Brazil.
Marília Brinati
MB
Malta
Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, 05508-000, Brazil.
Rosana
R
Camarini
Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, 05508-000, Brazil.
Cristoforo
C
Scavone
Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, 05508-000, Brazil. Electronic address: cdmunhoz@usp.br.
Carolina Demarchi
CD
Munhoz
D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D066272:Basolateral Nuclear Complex / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics; D004777:Environment; D017781:Genes, Immediate-Early / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D011965:Receptors, Glucocorticoid
Anxiety; Basolateral amygdala; CREB; ERK; Environment enrichment; Glucocorticoids; Stress