Nucleus accumbens CREB activity is necessary for nicotine conditioned place preference.
Nucleus accumbens CREB activity is necessary for nicotine conditioned place preference.
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伏隔核Creb活性对于尼古丁条件的位置偏好是必需的。
DOI：
10.1038/npp.2009.11
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发表时间：
2009-07
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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尼古丁改变多巴胺神经元放电的能力是导致尼古丁奖励的第一步，但激活尼古丁乙酰胆碱受体下游的细胞内信号通路可能对尼古丁暴露的长期后果至关重要，包括条件奖励。转录因子环amp调节结合蛋白（CREB）对新基因转录很重要，其磷酸化形式（pCREB）促进突触强度的长期变化。先前的研究表明伏隔核（NAc） CREB活动与可卡因和吗啡奖励的调节有关，并表明尼古丁条件位置偏好（CPP）与NAc CREB激活有关。目前尚不清楚CPP是否引起CREB的磷酸化，或者pCREB的升高是否支持尼古丁CPP。在当前的研究中，我们研究了在没有室选择的新环境下，在尼古丁的巴甫洛夫条件反射中CREB和pCREB的水平。在没有尼古丁的情况下，尼古丁环境调节导致小鼠NAc外壳的pCREB水平升高，但NAc核心的pCREB水平没有升高。为了测试CREB在NAc壳中的活性是否有助于线索诱导的反应，从而可能沉淀尼古丁寻求，我们在C57BL/6J小鼠的NAc壳中使用病毒介导的基因转移显性负CREB结构，发现在训练前破坏CREB激活会在一定剂量范围内阻止尼古丁的位置偏好。综上所述，这些研究确定了NAc外壳是CREB活动对尼古丁CPP至关重要的大脑区域。
The ability of nicotine to alter firing of dopamine neurons is the first step leading to nicotine reward, but activation of intracellular signaling pathways downstream of nicotinic acetylcholine receptors is likely to be critical for longer-term consequences of nicotine exposure, including conditioned reward. The transcription factor cyclic AMP-regulated binding protein (CREB) is important for new gene transcription and in its phosphorylated form (pCREB) promotes long-term changes in synaptic strength. Previous studies have implicated nucleus accumbens (NAc) CREB activity in the modulation of cocaine and morphine reward, and have shown that nicotine conditioned place preference (CPP) is associated with NAc CREB activation. It is not clear whether CPP elicits phosphorylation of CREB or if elevations in pCREB support nicotine CPP. In the current study, we investigated levels of CREB and pCREB during Pavlovian conditioning with nicotine in a novel context in the absence of chamber choice. Nicotine context conditioning resulted in elevated pCREB levels in the NAc shell but not the NAc core of mice following placement in the nicotine-paired chamber in the absence of nicotine. To test if CREB activity in the NAc shell contributes to cue-induced responses that may precipitate nicotine seeking, we used viral-mediated gene transfer of a dominant negative CREB construct in the NAc shell of C57BL/6J mice and found that disruption of CREB activation prior to training blocked nicotine place preference across a range of doses. Taken together, these studies identify the NAc shell as a brain region where CREB activity is essential for nicotine CPP.
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影响因子：
4.7
作者：
Pandey, SC;Roy, A;Mittal, N
通讯作者：
Mittal, N
影响因子：
16.2
作者：
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作者：
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影响因子：
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作者：
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通讯作者：
Childress, Anna Rose
DOI：
10.1073/pnas.172091899
发表时间：
2002-08-20
影响因子：
11.1
作者：
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通讯作者：
Nestler, EJ