title: Activation of protein kinase A in the amygdala modulates anxiety-like behaviors in social defeat exposed mice.
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.
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, 1202 Mingdao Building, 131 Dong An Road, Shanghai, 200032, China. ribaike@163.com.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, 1202 Mingdao Building, 131 Dong An Road, Shanghai, 200032, China. benben231016@163.com.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Shi
authors.affiliation: Department of Integrative Medicine and Neurobiology, Shanghai Medical School, Fudan University, Shanghai, 200032, China. yujin@shmu.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, 1202 Mingdao Building, 131 Dong An Road, Shanghai, 200032, China. yuqiuzhang@fudan.edu.cn.
authors.forename: Yu-Qiu
authors.initials: YQ
authors.lastname: Zhang
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D001007:Anxiety / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D001362:Avoidance Learning / Q000187:drug effects; D002997:Clomipramine / Q000494:pharmacology / Q000627:therapeutic use; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012919:Social Behavior; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy / Q000201:enzymology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D047428:Protein Kinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D017868:Cyclic AMP-Dependent Protein Kinases; D002997:Clomipramine