André Jessica M, Gulick Danielle, Portugal George S, Gould Thomas J
Department of Psychology, Neuroscience Program, Temple University, Philadelphia, PA 19122, United States.
Behav Brain Res. 2008 Jul 19;190(2):174-81. doi: 10.1016/j.bbr.2008.02.018. Epub 2008 Feb 20.
Nicotine withdrawal is associated with multiple symptoms such as anxiety, increased appetite, and disrupted cognition in humans. Although animal models have provided insights into the somatic and affective symptoms of nicotine withdrawal, less research has focused on the effects of nicotine withdrawal on cognition. Therefore, in this study, C57BL/6J mice were used to test the effects of withdrawal from chronic nicotine on foreground and background contextual fear conditioning, which present the context as a primary or secondary stimulus, respectively. Mice withdrawn from 12 days of chronic nicotine (6.3mg/kg/day) or saline were trained and tested in either foreground or background contextual fear conditioning; nicotine withdrawal-associated deficits in contextual fear conditioning were observed in both conditions. Mice were also tested for the effects of withdrawal on pre-pulse inhibition of the acoustic startle reflex (PPI), a measure of sensory gating, and on the acoustic startle reflex. Mice withdrawn from 12 days of chronic nicotine (6.3 or 12.6 mg/kg/day) or saline underwent one 30-min PPI and startle session; no effect of withdrawal from chronic nicotine on PPI or startle was observed for either dose at 24h after nicotine removal. Therefore, mice were tested at different time points following withdrawal from 12.6 mg/kg/day chronic nicotine (8, 24, and 48 h after nicotine removal). No effect of withdrawal from chronic nicotine was observed at any time point for PPI. Overall, these results demonstrate that nicotine withdrawal disrupts two methods of contextual learning but not sensory gating in C57BL/6J mice.
尼古丁戒断与多种症状相关，如焦虑、食欲增加以及人类认知紊乱。尽管动物模型已为尼古丁戒断的躯体和情感症状提供了深入见解，但较少有研究关注尼古丁戒断对认知的影响。因此，在本研究中，使用C57BL/6J小鼠来测试慢性尼古丁戒断对前景和背景情境恐惧条件反射的影响，前景和背景情境恐惧条件反射分别将情境呈现为主要或次要刺激。从12天的慢性尼古丁（6.3毫克/千克/天）或生理盐水戒断的小鼠，在前景或背景情境恐惧条件反射中接受训练和测试；在两种条件下均观察到与尼古丁戒断相关的情境恐惧条件反射缺陷。还测试了小鼠戒断对听觉惊吓反射的前脉冲抑制（PPI，一种感觉门控测量指标）以及对听觉惊吓反射的影响。从12天的慢性尼古丁（6.3或12.6毫克/千克/天）或生理盐水戒断的小鼠进行一次30分钟的PPI和惊吓实验；在去除尼古丁后24小时，两种剂量的慢性尼古丁戒断对PPI或惊吓均未观察到影响。因此，对从12.6毫克/千克/天慢性尼古丁戒断后的不同时间点（去除尼古丁后8、24和48小时）的小鼠进行测试。在任何时间点，慢性尼古丁戒断对PPI均未观察到影响。总体而言，这些结果表明，尼古丁戒断会破坏C57BL/6J小鼠的两种情境学习方法，但不会破坏感觉门控。
