D1/D5 receptors and histone deacetylation mediate the Gateway Effect of LTP in hippocampal dentate gyrus.
D1/D5 receptors and histone deacetylation mediate the Gateway Effect of LTP in hippocampal dentate gyrus.
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DOI：
10.1101/lm.032292.113
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发表时间：
2014-02-18
期刊：
影响因子：
--
通讯作者：
Kandel ER
中科院分区：
文献类型：
--
作者：
Huang YY;Levine A;Kandel DB;Yin D;Colnaghi L;Drisaldi B;Kandel ER
海马齿状回（DG）对于空间记忆至关重要，也被认为参与药物相关联想记忆的形成。在这里，我们尝试通过研究连续暴露于尼古丁和可卡因对 DG 中的长期突触增强 (LTP) 的影响来测试网关假说的一个方面。我们发现单次注射可卡因不会改变 LTP。然而，先用尼古丁进行预处理，然后再注射一次可卡因，会导致 LTP 显着增强。尼古丁的这种启动效应是单向的：如果在尼古丁之前服用可卡因，则 LTP 不会增强。尼古丁和可卡因诱导的促进作用可以通过口服多巴胺 D1/D5 受体拮抗剂 (SKF 83566) 来阻断，并通过 D1/D5 激动剂 (SKF 38393) 来增强。组蛋白脱乙酰化抑制剂辛二酰苯胺异羟肟酸（SAHA）的应用模拟了尼古丁对可卡因的启动作用。相比之下，在 CREB 结合蛋白 (CBP) 单倍体不足且仅具有一个功能性 CBP 等位基因的转基因小鼠中，尼古丁对可卡因的启动作用被阻断，因此表现出组蛋白乙酰化减少。这些结果表明，海马体的 DG 是一个重要的大脑区域，有助于尼古丁对可卡因的启动作用。此外，多巴胺-D1受体/PKA信号通路的激活和组蛋白脱乙酰化/CBP介导的转录都是DG中尼古丁启动效应所必需的。
The dentate gyrus (DG) of the hippocampus is critical for spatial memory and is also thought to be involved in the formation of drug-related associative memory. Here, we attempt to test an aspect of the Gateway Hypothesis, by studying the effect of consecutive exposure to nicotine and cocaine on long-term synaptic potentiation (LTP) in the DG. We find that a single injection of cocaine does not alter LTP. However, pretreatment with nicotine followed by a single injection of cocaine causes a substantial enhancement of LTP. This priming effect of nicotine is unidirectional: There is no enhancement of LTP if cocaine is administrated prior to nicotine. The facilitation induced by nicotine and cocaine can be blocked by oral administration of the dopamine D1/D5 receptor antagonist (SKF 83566) and enhanced by the D1/D5 agonist (SKF 38393). Application of the histone deacetylation inhibitor suberoylanilide hydroxamic acid (SAHA) simulates the priming effect of nicotine on cocaine. By contrast, the priming effect of nicotine on cocaine is blocked in genetically modified mice that are haploinsufficient for the CREB-binding protein (CBP) and possess only one functional CBP allele and therefore exhibit a reduction in histone acetylation. These results demonstrate that the DG of the hippocampus is an important brain region contributing to the priming effect of nicotine on cocaine. Moreover, both activation of dopamine-D1 receptor/PKA signaling pathway and histone deacetylation/CBP mediated transcription are required for the nicotine priming effect in the DG.
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影响因子：
3.3
作者：
BRAUN, A;FABBRINI, G;CHASE, TN
通讯作者：
CHASE, TN
影响因子：
2.3
作者：
Gozen, Oguz;Balkan, Burcu;Pogun, Sakire
通讯作者：
Pogun, Sakire
影响因子：
3.5
作者：
Iniguez, Sergio D.;Charntikov, Sergios;Baella, Shelley A.;Herbert, Matthew S.;Bolanos-Guzman, Carlos A.;Crawford, Cynthia A.
通讯作者：
Crawford, Cynthia A.
影响因子：
56.9
作者：
KANDEL, D
通讯作者：
KANDEL, D
DOI：
10.1016/j.devbrainres.2004.08.004
发表时间：
2004-11-25
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Collins, SL;Montano, R;Izenwasser, S
通讯作者：
Izenwasser, S