The Mechanism Of ? Opioid Receptor Agonist U50,488H-induced Conditioned Place Aversion

Background: Kappa opioid receptor agonists cause negative mood in rodents,but the underlying mechanisms remain unclear.Activation of p38 mitogen activated protein kinase(MAPK)was involved in the regulation of emotional behavior.Purpose: The purpose of our work was to study whether p38 MAPK activation to participate in the regulation of aversion behavior.Method: Here we use C57 BL / 6 mice as a research object,with kappa opioid receptor agonists U50,488 H producing aversion behavior,by SDS-PAGE and immunofluorescence to detect the kappa opioid receptor downstream signaling pathway p38 mitogen activated protein kinase(MAPK)activation in emotion-related brain areas-amygdala,hippocampus and nucleus accumbens,while using the conditioned place aversion behavior test and microinjecting p38 MAPK inhibitor SB203580 in amygdala.Furthermore,U50,488 H mediated conditioned place aversion behavior were detected.Result: 1.The kappa opioid receptor agonist U50,488 H causes significant conditioned place aversion behaviour in C57BL/6 mice.2.U50,488 H induced significant conditioned place aversion,which accompanied distinct p38 MAPK activation in theamygdala,but not in the nucleus accumbens and hippocampus.3.Microinjection of p38 inhibitor SB203580 in amygdala significantly inhibited p38 MAPK activation,and completely blocked the conditioned place aversion behaviour.Conclusion: Overall,the above results indicate that p38 MAPK mediates kappa opioid receptor agonists induced aversion behaviour.