Varenicline Ameliorates Nicotine Withdrawal-Induced Learning Deficits in C57BL/6 Mice
Varenicline Ameliorates Nicotine Withdrawal-Induced Learning Deficits in C57BL/6 Mice
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DOI：
10.1037/a0012601
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发表时间：
2008-10-01
影响因子：
1.9
通讯作者：
Gould, Thomas J.
中科院分区：
文献类型：
--
作者：
Raybuck, Jonathan D.;Portugal, George S.;Gould, Thomas J.
Varenicline是α4β2烟碱型乙酰胆碱受体(NAChRs)的部分激动剂和α7 nAChRs的完全激动剂，已被批准用于戒烟治疗。尽管最近的临床试验支持varenicline在控制全球尼古丁戒断症状和戒烟方面的有效性，但它对特定戒断相关行为的动物模型的影响尚未得到测试。本研究评估了varenicline对情景恐惧条件反射的影响及其对尼古丁(6.3 mg/kg/d)戒断诱导的情景恐惧条件反射缺陷的影响。当单独给药时，varenicline(0.01，0.1，1.0 mg/kg)对情景恐惧条件反射没有影响，但(0.1 mg/kg)防止了与尼古丁戒断相关的情景恐惧条件反射缺陷。这些数据首次证明，在动物模型中，varenicline逆转了尼古丁戒断诱导的缺陷，并表明varenicline可能在治疗尼古丁戒断相关的学习和记忆缺陷方面有效。
Varenicline, a partial agonist for alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs) and full agonist for alpha 7 nAChRs, has been approved for the treatment of smoking cessation. Although recent clinical trials support the efficacy of varenicline for managing global nicotine withdrawal symptoms and for smoking cessation, its effects on animal models of specific withdrawal-associated behaviors have not been tested. The present study evaluated the effects of varenicline on contextual fear conditioning and its effects on nicotine (6.3 mg/kg/day) withdrawal-induced deficits in contextual fear conditioning. Varenicline (0.01, 0.1, 1.0 mg/kg) had no effect on contextual fear conditioning when administered alone, but (0.1 mg/kg) prevented nicotine withdrawal-associated deficits in contextual fear conditioning. These data demonstrate, for the first time, that varenicline reverses nicotine withdrawal-induced deficits in an animal model and suggest that varenicline may be effective at treating nicotine withdrawal-associated deficits in learning and memory.