Adamec Robert, Blundell Jacqueline, Burton Paul
Department of Psychology, Memorial University, St. John's, NF, Canada.
Physiol Behav. 2005 Sep 15;86(1-2):75-91. doi: 10.1016/j.physbeh.2005.06.026.
The present study investigated the role of NMDA receptors in behavioral and neuroplastic changes in amygdala efferent (central amygdala to periaqueductal gray-ACE-PAG) and amygdala afferent (ventral angular bundle to basolateral amygdala-VAB-BLA) pathways in response to predator stress. Effects on brain and behavioral response to predator stress of competitive block of NMDA receptors with a dose of 10 mg/kg of CPP (3-(2-carboxypiperazin4-yl)propyl-l-phosphonic acid) were studied. Behavioral response to stress was tested with hole board, elevated plus maze, light/dark box, social interaction and acoustic startle tests. CPP was administered i.p. 30 min prior to predator stress and blocked the effects of predator on some but not all behaviors measured 8-9 days later. Effects of predator stress and CPP on potentials evoked in the PAG by single pulse stimulation of the ACE and in the BLA by single pulse stimulation of VAB were assessed 10-11 days after predator stress. Predator stress potentiated ACE-PAG evoked potentials in the right but not the left hemisphere, replicating previous work. Predator stress potentiated VAB-BLA transmission in both hemispheres 10-11 days after predator stress. Right hemisphere VAB-BLA potentiation replicated and extended past studies showing right hemisphere potentiation at 1 and 9 days after stress. Left VAB-BLA potentiation effects differed from the long term depression seen in VAB-BLA at 1 and 9 days after stress in previous studies. CPP blocked predator stress-induced potentiation of ACE-PAG and VAB-BLA evoked potentials in the right hemisphere. CPP did not block left VAB-BLA potentiation, rather CPP amplified it. Left hemisphere effects of CPP were interpreted as reflecting block of NMDA dependent long term depression, which unmasked a non-NMDA dependent potentiation. Taken together, the findings add to a body of evidence suggesting that a syndrome of behavioral changes follows predator stress. Components of this syndrome likely depend on changes in separable neural substrates. Potentiation of ACE-PAG and VAB-BLA evoked potentials in the right hemisphere likely mediates a subset of changes in behavior. Moreover, a medial ACE-PAG pathway is implicated in mediating stress-induced changes in startle amplitude. In contrast, a lateral ACE-PAG pathway is implicated in mediating changes in startle habituation. Finally, consistent with cat and human studies, the right hemisphere appears particularly important in long term response to stress.
本研究调查了N-甲基-D-天冬氨酸（NMDA）受体在杏仁核传出（从中央杏仁核到导水管周围灰质-ACE-PAG）和杏仁核传入（从腹侧角束到基底外侧杏仁核-VAB-BLA）通路的行为和神经可塑性变化中对捕食者应激的反应所起的作用。研究了用10mg/kg的3-(2-羧基哌嗪-4-基)丙基-1-膦酸（CPP）竞争性阻断NMDA受体对捕食者应激的脑和行为反应的影响。用洞板试验、高架十字迷宫试验、明暗箱试验、社交互动试验和听觉惊吓试验测试对应激的行为反应。在捕食者应激前30分钟腹腔注射CPP，并在8-9天后阻断了捕食者对部分而非全部所测行为的影响。在捕食者应激后10-11天评估捕食者应激和CPP对通过ACE单脉冲刺激在PAG中诱发的电位以及通过VAB单脉冲刺激在BLA中诱发的电位的影响。捕食者应激增强了右侧而非左侧半球的ACE-PAG诱发电位，重复了先前的研究结果。捕食者应激在应激后10-11天增强了两侧半球的VAB-BLA传递。右侧半球VAB-BLA的增强重复并扩展了过去的研究，这些研究显示在应激后1天和9天右侧半球有增强。左侧VAB-BLA的增强效应与先前研究中应激后1天和9天在VAB-BLA中所见的长期抑制不同。CPP阻断了捕食者应激诱导的右侧半球ACE-PAG和VAB-BLA诱发电位的增强。CPP没有阻断左侧VAB-BLA的增强，反而增强了它。CPP对左侧半球的影响被解释为反映了NMDA依赖性长期抑制的阻断，从而揭示了一种非NMDA依赖性的增强。综上所述，这些发现增加了一系列证据，表明行为变化综合征是捕食者应激后的结果。该综合征的组成部分可能取决于可分离神经基质的变化。右侧半球ACE-PAG和VAB-BLA诱发电位的增强可能介导了行为变化的一个子集。此外，内侧ACE-PAG通路与介导应激诱导的惊吓幅度变化有关。相反，外侧ACE-PAG通路与介导惊吓习惯化的变化有关。最后，与猫和人类研究一致，右侧半球在对应激的长期反应中似乎特别重要。
