Gouty Shawn, Silveira Julia Tomoyasu, Cote Thomas E, Cox Brian M
Department of Pharmacology & Molecular Therapeutics, Uniformed Services University, Bethesda, MD, 20814, USA.
Cell Mol Neurobiol. 2021 Jul;41(5):1119-1129. doi: 10.1007/s10571-020-01026-7. Epub 2021 Jan 5.
The amygdala plays an important role in the integration of responses to noxious and fearful stimuli. Sensory information from many systems is integrated in the lateral and basolateral amygdala and transmitted to the central amygdala, the major output nucleus of the amygdala regulating both motor and emotional responses. The network of intercalated cells (ITC) which surrounds the lateral and basolateral amygdala and serves to modulate information flow from the lateral amygdala to the central nucleus, express a very high local concentration of mu-type opioid receptors. Loss of the ITC neurons impairs fear extinction. We demonstrate here that exposure of rats to a severe stress experience resulted in a marked downregulation of the level of expression of mu opioid receptors in the ITC nuclei over a period of at least 24 h after the end of the stress exposure. The endogenous opioid dynorphin is also expressed in the central and ITC nuclei of the amygdala. Following stress exposure, we also observed an increase in the expression in the more lateral regions of the central amygdala of pro-dynorphin mRNA and a peptide product of pro-dynorphin with known affinity for mu opioid receptors. It is possible that the downregulation of mu receptors in ITC neurons after stress may result from sustained activation and internalization of mu receptors following a stress-induced increase in the release of endogenous opioid peptides.
杏仁核在对有害和恐惧刺激的反应整合中起重要作用。来自许多系统的感觉信息在杏仁核的外侧和基底外侧核整合,并传递到杏仁核的主要输出核——中央杏仁核,后者调节运动和情绪反应。围绕外侧和基底外侧杏仁核并调节从外侧杏仁核到中央核信息流的插入细胞(ITC)网络,表达非常高的局部浓度的μ型阿片受体。ITC神经元的缺失会损害恐惧消退。我们在此证明,大鼠经历严重应激后,在应激暴露结束后的至少24小时内,ITC核中μ阿片受体的表达水平显著下调。内源性阿片肽强啡肽也在杏仁核的中央核和ITC核中表达。应激暴露后,我们还观察到中央杏仁核外侧区域中前强啡肽mRNA以及对μ阿片受体具有已知亲和力的前强啡肽肽产物的表达增加。应激后ITC神经元中μ受体的下调可能是由于应激诱导内源性阿片肽释放增加后μ受体的持续激活和内化所致。