The corticotropin-releasing factor receptor 1 antagonist CP-154,526 reverses stress-induced learning deficits in mice
The corticotropin-releasing factor receptor 1 antagonist CP-154,526 reverses stress-induced learning deficits in mice
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DOI：
10.1016/s0166-4328(02)00244-9
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发表时间：
2003-01-22
影响因子：
2.7
通讯作者：
Spiess, J
中科院分区：
文献类型：
--
作者：
Blank, T;Nijholt, I;Spiess, J
神经肽促肾上腺皮质激素释放因子（CRF）作为下丘脑-垂体-肾上腺轴的主要生理调节剂，协调内分泌对应激的反应。我们评估了非肽能性CRF受体1拮抗剂CP-154,526对应激诱导的情境依赖性恐惧条件反射和海马突触可塑性变化的影响。固定化前预注射CP-154,526可以克服固定化后立即训练小鼠的学习障碍。暴露于急性应激降低了海马CA1区自磷酸化Ca2+/钙调素依赖性蛋白激酶II （CaNIKII）的数量。当动物在固定前用CP-154,526预处理时，海马自磷酸化CaNIKII的量升高。应激动物海马CA1区的电生理研究显示，CP-154,526预处理对长期增强无显著影响，但对脉冲配对促进（PPF）有显著提高。选择性CaNIKII抑制剂KN-62可以阻止cp -154,526诱导的恐惧调节和PPF增强。结果表明，CP-154,526预处理可拮抗急性应激后的学习障碍。(C) 2002 Elsevier Science B.V.版权所有
The neuropeptide corticotropin-releasing factor (CRF) coordinates the endocrine responses to stress as a major physiological regulator of the hypothalamic-pituitary-adrenal axis. We assessed the effect of the non-peptidergic CRF receptor 1 antagonist CP-154,526 on stress-induced changes in context-dependent fear conditioning and hippocampal synaptic plasticity. The learning impairment of mice trained immediately after I It immobilization could be overcome by preinjection of CP-154,526 before exposure to immobilization. Exposure to acute stress reduced the amount of autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaNIKII) in the hippocampal CA1 area. When animals were pretreated with CP-154,526 before immobilization, the amount of hippocampal autophosphorylated CaNIKII was elevated. Electrophysiological studies in the hippocampal CA1 region of stressed animals revealed no significant effects of the CP-154,526 pretreatment on long-term potentiation but a significant elevation of paired-pulse facilitation (PPF) was observed. The CP-154,526-induced enhancements in fear conditioning and PPF could be prevented by the selective CaNIKII inhibitor KN-62. Our results demonstrated that learning impairment after acute stress was antagonized by CP-154,526 pretreatment. (C) 2002 Elsevier Science B.V. All rights reserved.