Erk activation in the amygdala and hippocampus induced by fear conditioning in ethanol withdrawn rats: Modulation by mk-801
Erk activation in the amygdala and hippocampus induced by fear conditioning in ethanol withdrawn rats: Modulation by mk-801
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DOI：
10.1016/j.euroneuro.2011.01.001
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发表时间：
2011-12-01
影响因子：
5.6
通讯作者：
Delia Martijena, Irene
中科院分区：
文献类型：
--
作者：
Eugenia Bertotto, Maria;Martina Maldonado, Noelia;Delia Martijena, Irene
细胞外信号调节激酶（ERK）通路可被NMDA受体激活，参与恐惧条件反射和药物成瘾。我们以前已经表明，退出慢性乙醇管理促进了上下文恐惧记忆的形成。为了探索这种效应涉及的神经底物和潜在机制，我们检查了：1）杏仁核的中央（CeA）和基底外侧（BLA）核以及背侧海马（dHip）中的ERK 1/2激活，2）NMDA受体拮抗剂MK-801对恐惧条件反射和ERK激活的影响，以及3）输注U 0126的影响，一种MEK抑制剂，进入BLA对乙醇戒断大鼠恐惧记忆形成的影响。通过含乙醇的液体饮食依赖的大鼠在乙醇戒断的第3天进行情境恐惧条件反射。高基础水平的p-ERK被发现在CeA和dHip从乙醇撤出大鼠。在对照组（60 min）和乙醇戒断组（30 min和60 min），恐惧条件化后BLA中ERK的激活均显著增加。在训练前给予MK-801（剂量对对照组大鼠无影响），可防止BLA中ERK磷酸化的增加，并在24 h后减弱乙醇戒断大鼠的冻结反应。此外，在恐惧条件反射之前，将U 0126注入BLA而不是CeA会破坏恐惧记忆的形成。这些结果表明，增加的恐惧记忆可以连接到ERK磷酸化的变化，可能是由于NMDA受体激活BLA在乙醇戒断大鼠。(C)2011 Elsevier B.V.和ECNP。All rights reserved.
The extracellular signal-regulated kinase (ERK) pathway, which can be activated by NMDA receptor stimulation, is involved in fear conditioning and drug addiction. We have previously shown that withdrawal from chronic ethanol administration facilitated the formation of contextual fear memory. In order to explore the neural substrates and the potential mechanism involved in this effect, we examined: 1) the ERK1/2 activation in the central (CeA) and basolateral (BLA) nuclei of the amygdala and in the dorsal hippocampus (dHip), 2) the effect of the NMDA receptor antagonist MK-801 on fear conditioning and ERK activation and 3) the effect of the infusion of U0126, a MEK inhibitor, into the BLA on fear memory formation in ethanol withdrawn rats. Rats made dependent via an ethanol-containing liquid diet were subjected to contextual fear conditioning on day 3 of ethanol withdrawal. High basal levels of p-ERK were found in CeA and dHip from ethanol withdrawn rats. ERK activation was significantly increased both in control (60 min) and ethanol withdrawn rats (30 and 60 min) in BLA after fear conditioning. Pre-training administration of MK-801, at a dose that had no effect on control rats, prevented the increase in ERK phosphorylation in BLA and attenuated the freezing response 24 h later in ethanol withdrawn rats. Furthermore, the infusion of U0126 into the BLA, but not the CeA, before fear conditioning disrupted fear memory formation. These results suggest that the increased fear memory can be linked to changes in ERK phosphorylation, probably due to NMDA receptor activation in BLA in ethanol withdrawn rats. (C) 2011 Elsevier B.V. and ECNP. All rights reserved.