Activation of protein kinase A in the amygdala modulates anxiety-like behaviors in social defeat exposed mice. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Yang, Liu; Shi, Li-Jun; Yu, Jin; Zhang, Yu-Qiu
• Is Part Of: Molecular brain. Volume 9:Issue 1(2016)
• Page Start: 1
• Page End: 13
• Publication Date: 2016-12
• Subjects: Social defeat -- Anxiety -- PKA -- CREB -- Amygdala; Brain -- Periodicals; Molecular biology -- Periodicals; 573.86
• DOI: 10.1186/s13041-015-0181-3
• Languages: English
• ISSNs: 1756-6606

Abstract

Abstract Background Social defeat (SD) stress induces social avoidance and anxiety-like phenotypes. Amygdala is recognized as an emotion-related brain region such as fear, aversion and anxiety. It is conceivable to hypothesize that activation of amygdala is involved in SD-dependent behavioral defects. Results SD model was established using C57BL/6J mice that were physically defeated by different CD-1 mice for 10 days. Stressed mice exhibited decreased social interaction level in social interaction test and significant anxiety-like behaviors in elevated plus maze and open field tests. Meanwhile, a higher phosphorylation of PKA and CREB with a mutually linear correlation, and increased Fos labeled cells in the basolateral amygdala (BLA) were observed. Activation of PKA in the BLA by 8-Br-cAMP, a PKA activitor, significantly upregulated pCREB and Fos expression. To address the role of PKA activation on SD stress-induced social avoidance and anxiety-like behaviors, 8-Br-cAMP or H-89, a PKA inhibitor, was continuously administered into the bilateral BLA by a micro-osmotic pump system during the 10-day SD period. Neither H-89 nor 8-Br-cAMP affected the social behavior. Differently, 8-Br-cAMP significantly relieved anxiety-like behaviors in both general and moderate SD protocols. H-89 per se did not have anxiogenic effect in naïve mice, but aggravated moderate SD stress-induced anxiety-like behaviors. The antidepressant clomipramine reduced SD-induced anxiety and up-regulated pPKA level in the BLA. Conclusions These results suggest that SD-driven PKA activation in the basolateral amygdala is actually a compensatory rather than pathogenic response in the homeostasis, and modulating amygdaloid PKA may exhibit potency in the therapy of social derived disorders.