Blockade of CRF1 receptors in the central nucleus of the amygdala attenuates the dysphoria associated with nicotine withdrawal in rats.
Blockade of CRF1 receptors in the central nucleus of the amygdala attenuates the dysphoria associated with nicotine withdrawal in rats.
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DOI：
10.1016/j.pbb.2011.12.001
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发表时间：
2012-03
影响因子：
3.6
通讯作者：
Alexander, Jon C.
中科院分区：
文献类型：
--
作者：
Bruijnzeel, Adrie W.;Ford, Jenna;Rogers, Jessica A.;Scheick, Stacey;Ji, Yue;Bishnoi, Mahendra;Alexander, Jon C.
大多数吸烟者在急性戒断期复发，此时戒断症状最严重。本研究的目的是探讨促肾上腺皮质激素释放因子（CRF）和杏仁核中央核（CeA）的去甲肾上腺素能传递在戒烟相关焦虑中的作用。研究了CRF 1受体阻断剂、α1-肾上腺素能受体阻断剂或α2-肾上腺素能受体刺激剂是否可减少大鼠中与尼古丁戒断相关的脑奖赏功能缺陷。尼古丁依赖是通过植入递送尼古丁溶液的微型泵来诱导的。烟碱乙酰胆碱受体拮抗剂美加明可促使戒断。一个离散试验颅内自我刺激程序被用来评估尼古丁戒断的负面情感方面。大脑奖励阈值的升高指示大脑奖励功能的缺陷。在所有的实验中，美加明提高了长期接受尼古丁治疗的大鼠的大脑奖励阈值，而对盐水治疗的对照大鼠的大脑奖励阈值没有影响。CRF 1受体拮抗剂R278995/CRA 0450的CeA内给药完全防止了尼古丁处理大鼠中的美加明胺诱导的脑奖励阈值升高，并且不影响盐水处理对照大鼠的脑奖励阈值。R278995/CRA 0450也被证明可以阻断sigma-1受体，但没有证据表明这会影响负面情绪状态。CeA内给予α1-肾上腺素能受体拮抗剂哌唑嗪或α2-肾上腺素能受体激动剂可乐定不影响尼古丁或生理盐水处理大鼠的脑奖励阈值。这些研究表明，CRF 1受体拮抗剂可以通过阻断CeA中的CRF 1受体来减少与戒烟相关的烦躁不安。
The majority of smokers relapse during the acute withdrawal phase when withdrawal symptoms are most severe. The goal of the present studies was to investigate the role of corticotropin-releasing factor (CRF) and noradrenergic transmission in the central nucleus of the amygdala (CeA) in the dysphoria associated with smoking cessation. It was investigated if blockade of CRF1 receptors, blockade of α1-adrenergic receptors, or stimulation of α2-adrenergic receptors in the CeA diminishes the deficit in brain reward function associated with nicotine withdrawal in rats. Nicotine dependence was induced by implanting minipumps that delivered a nicotine solution. Withdrawal was precipitated with the nicotinic acetylcholine receptor antagonist mecamylamine. A discrete-trial intracranial self-stimulation procedure was used to assess the negative affective aspects of nicotine withdrawal. Elevations in brain reward thresholds are indicative of a deficit in brain reward function. In all the experiments, mecamylamine elevated the brain reward thresholds of the rats chronically treated with nicotine and did not affect the brain reward thresholds of the saline-treated control rats. Intra-CeA administration of the CRF1 receptor antagonist R278995/CRA0450 completely prevented the mecamylamine-induced elevations in brain reward thresholds in the nicotine-treated rats and did not affect the brain reward thresholds of the saline-treated control rats. R278995/CRA0450 has also been shown to block sigma-1 receptors but there is no evidence that this could affect negative mood states. Intra-CeA administration of the α1-adrenergic receptor antagonist prazosin or the α2-adrenergic receptor agonist clonidine did not affect the brain reward thresholds of the nicotine or saline-treated rats. These studies suggest that CRF1 receptor antagonists may diminish the dysphoria associated with smoking cessation by blocking CRF1 receptors in the CeA.
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影响因子：
3.6
作者：
Greenwell, Thomas N.;Walker, Brendan M.;Cottone, Pietro;Zorrilla, Eric P.;Koob, George F.
通讯作者：
Koob, George F.
DOI：
10.1073/pnas.0707585104
发表时间：
2007-10-23
影响因子：
11.1
作者：
George, Olivier;Ghozland, Sandy;Koob, George F.
通讯作者：
Koob, George F.
影响因子：
5
作者：
Kamei, H;Kameyama, T;Nabeshima, T
通讯作者：
Nabeshima, T
影响因子：
7.6
作者：
Bruijnzeel, Adrie W.;Zislis, George;Gold, Mark S.
通讯作者：
Gold, Mark S.
影响因子：
3.4
作者：
DOHERTY, K;KINNUNEN, T;GARVEY, AJ
通讯作者：
GARVEY, AJ