Neonatal treatment with a competitive NMDA antagonist results in response-specific disruption of conditioned fear in preweanling rats.
Neonatal treatment with a competitive NMDA antagonist results in response-specific disruption of conditioned fear in preweanling rats.
复制标题
使用竞争性 NMDA 拮抗剂进行新生儿治疗会导致断奶前大鼠条件性恐惧的反应特异性破坏。
DOI：
10.1007/s00213-005-0291-1
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发表时间：
2006
影响因子：
3.4
通讯作者：
Hunt,PamelaS
中科院分区：
文献类型：
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作者：
Hunt,PamelaS
N-甲基-d-天冬氨酸(NMDA)受体参与神经发育过程，包括细胞增殖、突触形成和细胞凋亡。一些研究报告称，在发育早期使用NMDA拮抗剂可以导致行为的长期变化。例如，古尔德和卡梅伦[Behav Neurosci111：49-56(1997a)]已经证明，出生后第5天单次注射竞争性N-甲基-D-天冬氨酸拮抗剂CGp 43487会影响暴露于天敌气味中的幼鼠的行为不动。记录刺激诱发的行为不动(冰冻)和心率变化以检查反应的损害。方法动物在PD 5单次注射CGP 43487 0、2.5和5.0 mg/kg。在PD 2 0个受试者给予嗅觉或听觉条件刺激(CS)的配对或不配对的呈现，以及110dB白噪声的非条件刺激。结果给予CGP处理的幼鼠在条件冷冻条件下表现出损伤，但对嗅觉和听觉刺激的心率条件性变化的表达没有影响。结论NMDA拮抗剂治疗新生儿以一种反应特异性的方式影响恐惧表达。这些数据表明，参与冷冻表达的神经系统中由拮抗剂诱导的改变在生命早期受到NMDA受体阻断的影响。
RationaleTheN-methyl-d-aspartate (NMDA) receptor has been implicated in processes of neurodevelopment, including cell proliferation, synaptogenesis, and apoptosis. Several studies have reported that administration of NMDA antagonists early in development can cause long-lasting changes in behavior. For example, Gould and Cameron [Behav Neurosci 111:49–56 (1997a)] have shown that a single injection of the competitive NMDA antagonist CGP 43487 on postnatal day (PD) 5 affected behavioral immobility in young rats exposed to the odor of a natural predator.ObjectivesThis experiment was undertaken to determine whether the behavioral effects previously reported would also be seen with conditioned cues. Both stimulus-elicited behavioral immobility (freezing) and changes in heart rate were recorded to examine impairments in responding across multiple measures.MethodsAnimals were given a single injection of 0, 2.5, or 5.0 mg/kg CGP 43487 on PD 5. On PD 20 subjects were given paired or unpaired presentations of either an olfactory or auditory conditioned stimulus (CS) with a 110-dB-white-noise unconditioned stimulus. CS-elicited freezing and changes in heart rate were measured.ResultsPups treated with CGP exhibited impairments in conditioned freezing, but were unaffected in their expression of conditioned changes in heart rate, to both olfactory and auditory stimuli.ConclusionsThese results indicate that neonatal treatment with an NMDA antagonist affects the expression of fear in a response-specific manner. The data suggest that antagonist-induced alterations in neural systems involved in the expression of freezing are affected by NMDA receptor blockade early in life.