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首页> 外文期刊>Behavioural pharmacology >ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice
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ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice

机译：ABT-089而非ABT-107改善了C57BL6 / J小鼠的尼古丁戒断所致的认知功能障碍

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Nicotine withdrawal produces cognitive deficits that can predict relapse. Amelioration of these cognitive deficits emerges as a target in current smoking cessation therapies. In rodents, withdrawal from chronic nicotine disrupts contextual fear conditioning (CFC), whereas acute nicotine enhances this hippocampus-specific learning and memory. These modifications are mediated by beta(2)-subunit-containing (beta(2)*) nicotinic acetylcholine receptors in the hippocampus. We aimed to test ABT-089, a partial agonist of alpha(4)beta(2)*, and ABT-107, an alpha(7) nicotinic acetylcholine receptor agonist, for amelioration of cognitive deficits induced by withdrawal from chronic nicotine in mice. Mice underwent chronic nicotine administration (12.6 mg/kg/day or saline for 12 days), followed by 24 h of withdrawal. At the end of withdrawal, mice received 0.3 or 0.6 mg/kg ABT-089 or 0.3 mg/kg ABT-107 (doses were determined through initial dose-response experiments and prior studies) and were trained and tested for CFC. Nicotine withdrawal produced deficits in CFC that were reversed by acute ABT-089, but not ABT-107. Cued conditioning was not affected. Taken together, our results suggest that modulation of hippocampal learning and memory using ABT-089 may be an effective component of novel therapeutic strategies for nicotine addiction. Behavioural Pharmacology 26:241-248 Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
机译：尼古丁戒断会产生认知缺陷，可以预测复发。这些认知缺陷的改善已成为当前戒烟治疗的目标。在啮齿动物中，从慢性尼古丁中退出会破坏情境恐惧调节（CFC），而急性尼古丁会增强这种海马特定的学习和记忆。这些修饰是由海马中包含β（2）-亚基的（β（2）*）烟碱乙酰胆碱受体介导的。我们旨在测试ABT-089（α（4）beta（2）*的部分激动剂）和ABT-107（α（7）烟碱型乙酰胆碱受体激动剂）对小鼠慢性尼古丁戒断所致认知功能障碍的缓解作用。小鼠接受慢性尼古丁给药（12.6 mg / kg /天或生理盐水治疗12天），然后停药24小时。撤药结束时，小鼠接受0.3或0.6 mg / kg ABT-089或0.3 mg / kg ABT-107（剂量是通过初始剂量反应实验和先前研究确定的），并接受了CFC的训练和测试。尼古丁戒断所产生的CFC缺乏症可以通过急性ABT-089来克服，但不能通过ABT-107来克服。提示条件不受影响。两者合计，我们的研究结果表明，使用ABT-089调节海马学习和记忆可能是尼古丁成瘾新治疗策略的有效组成部分。行为药理学26：241-248版权所有（C）2015 Wolters Kluwer Health，Inc.保留所有权利。

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