Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2
Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2
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DOI：
10.1523/jneurosci.19-12-05016.1999
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发表时间：
1999-06
期刊：
影响因子：
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通讯作者：
J. Radulovic;A. Rühmann;T. Liepold;J. Spiess
中科院分区：
文献类型：
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作者：
J. Radulovic;A. Rühmann;T. Liepold;J. Spiess
促肾上腺皮质激素释放因子（CRF）通过CRF受体亚型1（CRFR 1）和2（CRFR 2）对学习和焦虑的差异调节被证明。作为学习范式，使用了小鼠的情境和音调依赖性恐惧条件反射。在训练前将CRF注射到背侧海马中增强了通过CRFR 1的学习，这一发现证明了这种作用可以通过局部注射非选择性CRFR拮抗剂astressin而不是CRFR 2特异性拮抗剂antisauvagine-30（抗Svg-30）来预防。与此相反，注射CRF到外侧中间隔损害学习通过CRFR 2，证明了抗sauvagine-30阻断这种效果的能力。当antisauvagine-30单独注射到外侧中间隔，学习增强。当将astressin或antisauvagine-30注入背侧海马时，未观察到这种学习的紧张性控制。在训练后将CRF注射到背侧海马和外侧中间隔也分别增强和损害学习。提示CRF对记忆巩固有一定作用。得出的结论是，所观察到的效果反映了联想学习的变化，而不是唤醒，注意力或动机。虽然20 pmol人/大鼠CRF的剂量足以显著影响学习，但需要5倍以上的剂量才能通过注射到隔膜中来诱导焦虑。固定1小时产生的应激反应，其中包括通过隔CRFR 2诱导焦虑和随后通过海马CRFR 1增强学习。通过区域特异性注射astressin和antisauvagine-30证明了任一受体亚型的参与。
The differential modulation of learning and anxiety by corticotropin-releasing factor (CRF) through CRF receptor subtypes 1 (CRFR1) and 2 (CRFR2) is demonstrated. As learning paradigm, context- and tone-dependent fear conditioning of the mouse was used. Injection of CRF into the dorsal hippocampus before training enhanced learning through CRFR1 as demonstrated by the finding that this effect was prevented by the local injection of the unselective CRFR antagonist astressin, but not by the CRFR2-specific antagonist antisauvagine-30 (anti-Svg-30). In contrast, injection of CRF into the lateral intermediate septum impaired learning through CRFR2, as demonstrated by the ability of antisauvagine-30 to block this effect. When antisauvagine-30 was injected alone into the lateral intermediate septum, learning was enhanced. Such tonic control of learning was not observed when astressin or antisauvagine-30 was injected into the dorsal hippocampus. Injection of CRF after the training into the dorsal hippocampus and the lateral intermediate septum also enhanced and impaired learning, respectively. Thus, it was indicated that CRF acted on memory consolidation. It was concluded that the observed effects reflected changes of associative learning and not arousal, attention, or motivation. Although a dose of 20 pmol human/rat CRF was sufficient to affect learning significantly, a fivefold higher dose was required to induce anxiety by injection into the septum. Immobilization for 1 hr generated a stress response that included the induction of anxiety through septal CRFR2 and the subsequent enhancement of learning through hippocampal CRFR1. The involvement of either receptor subtype was demonstrated by region-specific injections of astressin and antisauvagine-30.