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先前的慢性暴露消除了尼古丁对大鼠的条件作用。

Previous chronic exposure eliminates the conditioning effect of nicotine in rats.

机构信息

Ege University, Center for Brain Research, Bornova, 35100 Izmir, Turkey.

出版信息

Brain Res Bull. 2011 Jul 15;85(6):339-45. doi: 10.1016/j.brainresbull.2011.05.011. Epub 2011 May 26.

DOI:10.1016/j.brainresbull.2011.05.011
PMID:21640169
Abstract

Smoking continues to be a major health problem and unfortunately smoking cessation interventions have limited success; the conditioning effects of nicotine and individual differences in tobacco addiction are important factors that underlie this setback. The aim of the current study was to investigate nicotine-induced conditioned place preference (CPP) in male and female rats which were previously exposed to a free choice of oral nicotine or water and showed different preferences for nicotine; subsequently nicotine intake also varied between subjects. Exposure patterns were varied in three experiments to allow for assessing the effect of adult v.s. adolescent exposure. The design of CPP testing enabled testing for the possible confounding effects of withdrawal or tolerance. A total of 150 male and female rats were used in three experiments. The oral nicotine choice was provided for at least six weeks in all experiments. Our results replicate our previous findings that nicotine induces CPP in male, but not female rats not pre-exposed to nicotine. Previous nicotine exposure, irrespective of the amount of nicotine consumed, eliminated the conditioning effects of nicotine in a new context. The diminished CPP response was more pronounced in rats exposed to nicotine as adolescents than those exposed as adults. This reduced responsiveness cannot be explained by tolerance. The neuroplastic changes caused by chronic nicotine administration or the strong conditioning to receiving nicotine in the home cage before CPP testing may underlie the weakened responsiveness. These findings support the well known clinical notion that smoking cessation attempts are more successful in a novel environment, not previously connected with smoking.

摘要

吸烟仍是一个主要的健康问题,不幸的是,戒烟干预措施的成功率有限;尼古丁的条件作用效应和烟草成瘾的个体差异是导致这一挫折的重要因素。本研究的目的是调查先前暴露于口服尼古丁或水的自由选择并表现出对尼古丁不同偏好的雄性和雌性大鼠中的尼古丁诱导的条件位置偏好(CPP);随后,受试者之间的尼古丁摄入量也有所不同。在三个实验中改变暴露模式,以评估成年和青少年暴露的影响。CPP 测试的设计允许测试戒断或耐受的可能混杂效应。总共使用了 150 只雄性和雌性大鼠进行了三个实验。在所有实验中,至少提供了六周的口服尼古丁选择。我们的结果复制了我们之前的发现,即未暴露于尼古丁的雄性,但不是雌性大鼠,尼古丁诱导 CPP。以前的尼古丁暴露,无论消耗的尼古丁量如何,都会消除新环境中尼古丁的条件作用效应。与成年期暴露相比,青春期暴露于尼古丁的大鼠的 CPP 反应减弱更为明显。这种反应性降低不能用耐受来解释。慢性尼古丁给药引起的神经可塑性变化或在 CPP 测试之前在家笼中接受尼古丁的强烈条件作用可能是反应性减弱的基础。这些发现支持了一个众所周知的临床观点,即戒烟尝试在一个新的环境中更成功,而不是以前与吸烟有关的环境。

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