Dynorphin/kappa Opioid Receptor Activation In The Amygdala Mediate Depressive-like Behaviors Induced By Chronic Social Defeat Stress

The purpose of this paper is to detect the mechanisms of depressive-like behaviors in mice induced by chronic social defeat stress.We utilized biochemical methods such as,western blot,immunofluorescence to detect the change of dynorphin/κ opioid receptor system and downstream signaling molecules(p38 MAPK,ERK)in several brain regions(amygdala,hippocampus,hypothalamus,nucleus accumbens,prefrontal cortex)which are mainly related to depression.By use of microinjection and behavioral methods,we figured out that κ opioid receptor antagonist nor BNI mediated the depressive-like behaviors.The experimental results are as follows:1.The mice were exposed to chronic social defeat stress,and the time during which they were active in the social area in the social interaction test was significantly reduced after two weeks of stress.This phenomenon indicated that two weeks of stress induced the depressive-like behaviors in experimental animals.2.Systemic administration of κ opioid receptor antagonist nor BNI 24 hours before the first day of chronic social defeat stress significantly blocked the social avoidance behavior of mice.It could not be achieved if nor BNI was administered after two weeks of stress.3.The social avoidance caused by chronic social defeat stress was significantly blocked on those mice where κ opioid receptors have been completely knocked out.4.After two weeks of chronic social defeat stress,the result of immunofluorescence told us the c-fos signals were activated in amygdala,while not in hippocampus,hypothalamus or other regions.This reminded us an increased activity in amygdala after stress.5.After two weeks of stress,the result of western blot showed an elevation in expression of dynorphin A protein compared with blank group.This change also occurred in basolateral amygdala,but not in other brain regions such as the dorsal amygdala and hippocampus.6.24 hours before first day of chronic social defeat stress,the microinjection of nor BNI into amygdala or basolateral amygdala rescued stress induced social avoidance.7.The biochemical experiment pointed out that the levels of p38 MAPK in the amygdala were obviously increased after stress,and the elevation could be blocked by administration of nor BNI into amygdala.8.Intra amygdala injection of p38 interfering virus obstruct social avoidance induced by chronic social defeat stress.In summary,our study demonstrated that expression of p38 MAPK caused by activation of amygdala κ opioid receptor may be one of the mechanisms of depressivelike behavior in experimental animals after chronic social defeat stress.