HIPPOCAMPAL CRF, NE, AND NMDA SYSTEM INTERACTIONS IN MEMORY PROCESSING IN THE RAT
HIPPOCAMPAL CRF, NE, AND NMDA SYSTEM INTERACTIONS IN MEMORY PROCESSING IN THE RAT
复制标题
DOI：
10.1002/syn.890140207
复制
发表时间：
1993-06-01
期刊：
影响因子：
2.3
通讯作者：
LIN, WR
中科院分区：
文献类型：
--
作者：
LEE, EHY;LEE, CP;LIN, WR
本研究探讨了海马齿状回促肾上腺皮质激素释放因子（corticotropin-releasing factor，CRF）及其与去甲肾上腺素（norepinephrine，NE）和N-甲基-D-天冬氨酸（N-methyl-D-aspartate，NMDA）系统在调节大鼠记忆过程中的相互作用及其神经机制。采用单向被动回避任务。结果表明，CRF（80 ng），当直接注射到DG，一致和显着提高大鼠的记忆保持。去甲肾上腺素能神经毒素DSP-4，在高剂量（4微克），损害记忆。DSP-4在中等剂量（2 μ g），这并不影响保留单独，拮抗CRF的记忆增强作用。同样，β-肾上腺素能拮抗剂普萘洛尔，在高剂量（8微克），减少保留。在低剂量（80 ng），这本身并没有显着影响保留，普萘洛尔也阻止了CRF的记忆改善效果。此外，直接NE输注DG显着改善保留性能的剂量敏感的方式。CRF和NE的联合给药没有进一步增强保留。这些结果共同表明，CRF和NE促进记忆可能通过相同的机制，而不是独立的。相比之下，选择性NMDA受体拮抗剂2-氨基-5-膦酰基戊酸酯（AP 5）和MK 801在高剂量下显著损害记忆保持（AP 5为0.8和3.2 μ g，MK 801为2和10 μ g）。当MK 801的剂量（80 ng）不能显著改变记忆力时，它完全阻断了CRF的记忆促进作用。这些结果表明，CRF也通过NMDA受体介导间接增强记忆。最后，MK 801在80 ng也成功地拮抗NE在DG中的记忆促进作用。我们已经证明，MK 801，在相互作用研究中选择的剂量，没有显着改变自发活动。这些结果共同表明，CRF，通过突触前易化机制，可能有利于NE释放的DG;增加NE释放和β-肾上腺素能受体在DG的刺激导致NMDA受体激活在同一地区。这一系列事件增强了海马的记忆巩固过程，并解释了CRF促进大鼠保持能力的神经机制。相同的神经肽/神经递质相互作用可能具有其他生理和神经病理学意义。
In the present study, we investigated the neural mechanisms of corticotropin-releasing factor (CRF) and the interactions among CRF, norepinephrine (NE), and N-methyl-D-aspartate (NMDA) systems in the dentate gyrus (DG) of hippocampus in modulating the memory process of rats. One-way passive avoidance task was adopted. Results indicated that CRF (80 ng), when directly injected into the-DG, consistently and significantly enhanced memory retention in rats. The noradrenergic neurotoxin DSP-4, at a high dose (4 mug), impaired memory. DSP-4 at a moderate dose (2 mug), which did not affect retention alone, antagonized the memory-enhancing effect of CRF. Similarly, the beta-adrenergic antagonist propranolol, at a high dose (8 mug), reduced retention. At a low dose (80 ng), which did not markedly affect retention by itself, propranolol also prevented the memory-improving effect of CRF. Moreover, direct NE infusions to the DG significantly improved retention performance in a dose-sensitive manner. Coadministration of CRF and NE did not further enhance retention. These results together suggest that CRF and NE facilitated memory probably through the same instead of independent mechanisms. In contrast, the selective NMDA receptor antagonists 2-amino-5-phosphonopentanoate (AP5) and MK801, at high doses markedly impaired memory retention (0.8 and 3.2 mug for AP5, 2 and 10 mug for MK801). At a dose of MK801 that did not significantly alter retention alone (80 ng), it completely blocked the memory-facilitating effect of CRF. These results indicate that CRF enhanced memory indirectly through NMDA receptor mediation also. Finally, MK801 at 80 ng also successfully antagonized the memory-facilitating effect of NE in the DG. We have demonstrated that MK801, at the dose chosen for interaction studies, did not markedly alter locomotor activity. These results together suggest that CRF, through a presynaptic facilitation mechanism, possibly facilitates NE release in the DG; increased NE release and stimulation of beta-adrenergic receptors in the DG result in NMDA receptor activations in the same area. This sequence of events enhance the memory consolidation process in the hippocampus and explained the neural mechanism of CRF in facilitating retention performance in rats. The same neuropeptide/neurotransmitter interactions may have other physiological and neuropathological implications.