β2 subunit-containing nicotinic receptors mediate the enhancing effect of nicotine on trace cued fear conditioning in C57BL/6 mice
β2 subunit-containing nicotinic receptors mediate the enhancing effect of nicotine on trace cued fear conditioning in C57BL/6 mice
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DOI：
10.1007/s00213-006-0624-8
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发表时间：
2007-02-01
影响因子：
3.4
通讯作者：
Gould, Thomas J.
中科院分区：
文献类型：
--
作者：
Davis, Jennifer A.;Gould, Thomas J.
理论基础：先前的研究表明，急性尼古丁给药可以增强情境恐惧条件反射和痕量线索恐惧条件反射的习得。α 4 β 2尼古丁乙酰胆碱受体（nAChRs）的药理抑制可阻断尼古丁对情境恐惧条件反射的增强作用，而α 7 nAChRs则不能。同样，基因缺失β 2 nAChR亚基而非α 7 nAChR亚基阻断了尼古丁对情境恐惧条件反射的增强作用。目的：本研究采用nAChR亚基敲除小鼠，比较含β 2亚基的nAChR和含α 7亚基的nAChR参与尼古丁对海马依赖性痕量线索恐惧条件反射和情境恐惧条件反射的影响。方法：β 2 nAChR亚基敲除小鼠、α 7 nAChR亚基敲除小鼠及其野生型仔鼠在训练和测试前5分钟分别给予尼古丁或生理盐水。采用5种条件刺激（CS; 30 s， 85 dB白噪声）-痕迹刺激(30 s)-非条件刺激（US； 2 s足震）对小鼠进行训练。24小时后对环境冻结和CS冻结进行评估。结果：在野生型鼠窝和α 7 nAChR亚基敲除小鼠中，尼古丁给药增强了情境恐惧和痕量线索恐惧条件反射。相比之下，尼古丁没有增强β 2 nAChR亚基敲除小鼠的情境恐惧条件反射和痕量线索恐惧条件反射。结论：这些结果表明，含有β 2亚基的nAChR而不是含有α 7 nAChR亚基的nAChR在尼古丁对情境和痕量线索恐惧条件反射的增强作用中起关键作用。
Rationale: Previous research indicates that acute nicotine administration enhances the acquisition of contextual fear conditioning and trace cued fear conditioning. Pharmacological inhibition of alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs), but not alpha 7 nAChRs, blocked the enhancing effect of nicotine on contextual fear conditioning. Similarly, genetic deletion of the beta 2 nAChR subunit but not the alpha 7 nAChR subunit blocked the enhancing effect of nicotine on contextual fear conditioning.Objectives: In the present study, nAChR subunit knockout mice were used to compare the involvement of beta 2 subunit-containing nAChRs and alpha 7 subunit-containing nAChRs in the effects of nicotine on hippocampus-dependent trace cued fear conditioning and contextual fear conditioning.Methods: beta 2 nAChR subunit knockout mice, alpha 7 nAChR subunit knockout mice, and their wild-type littermates received either nicotine or saline 5 minutes before training and testing. Mice were trained using five conditioned stimulus (CS; 30 s, 85 dB white noise)-trace (30 s)-unconditioned stimulus (US; 2 s footshock) pairings. Freezing to the context and freezing to the CS were assessed 24 h later.Results: Both contextual and trace cued fear conditioning were enhanced by nicotine administration in wild-type littermates and in alpha 7 nAChR subunit knockout mice. In contrast, neither contextual fear conditioning nor trace cued fear conditioning was enhanced by nicotine administration in beta 2 nAChR subunit knockout mice.Conclusions: These results suggest that beta 2 subunit-containing nAChRs but not alpha 7 nAChR subunit-containing nAChRs are critically involved in the enhancing effect of nicotine on contextual and trace cued fear conditioning.