Comparison of the behavioral effects of cigarette smoke and pure nicotine in rats
Comparison of the behavioral effects of cigarette smoke and pure nicotine in rats
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DOI：
10.1016/j.pbb.2010.05.008
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发表时间：
2010-08-01
影响因子：
3.6
通讯作者：
Pentel, Paul R.
中科院分区：
文献类型：
--
作者：
Harris, Andrew C.;Mattson, Christina;Pentel, Paul R.
烟草依赖的动物模型通常依赖于非肠道注射纯尼古丁。使用香烟烟雾吸入的模型可能会更准确地模拟吸烟者的尼古丁暴露。这项研究的主要目标是验证使用暴露条件给大鼠吸烟的方法，这些暴露条件与临床相关，并产生与行为活跃剂量的纯尼古丁产生的大脑尼古丁水平相似的水平。第二个目标是开始检查吸烟对行为的影响。单纯鼻部暴露(NOE)10-45分钟或全身暴露(WBE)14小时，血清尼古丁浓度与吸烟者相近(14-55 ng/ml)，无过量一氧化碳暴露。每日尼古丁(0.1毫克/公斤，S.C.)诱发了运动敏化，而45分钟的NOE在相同范围内产生的脑尼古丁水平没有。尼古丁0.125 mg/kg S.C.通过颅内自我刺激阈值的升高来衡量慢性尼古丁注射后的逆转戒断，而4小时的WBE产生类似的脑尼古丁水平则不是。这些数据证明了以临床相关剂量将香烟烟雾传递给大鼠的可行性，并提供了初步证据，表明在烟雾中传递的尼古丁的行为影响可能不同于纯尼古丁。(C)2010 Elsevier Inc.保留所有权利。
Animal models of tobacco dependence typically rely on parenteral administration of pure nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. The primary goal of this study was to validate methods for administering cigarette smoke to rats using exposure conditions that were clinically relevant and also produced brain nicotine levels similar to those produced by behaviorally active doses of pure nicotine. A secondary goal was to begin examining the behavioral effects of smoke. Nose-only exposure (NOE) to smoke for 10-45 min or whole-body exposure (WBE) to smoke for 14 h produced serum nicotine concentrations similar to those in smokers (14-55 ng/ml), without excessive carbon monoxide exposure. Daily nicotine (0.1 mg/kg, s.c.) induced locomotor sensitization whereas 45-min NOE producing brain nicotine levels within the same range did not. Nicotine 0.125 mg/kg s.c. reversed withdrawal from a chronic nicotine infusion as measured by elevations in intracranial self-stimulation thresholds whereas 4-h WBE producing similar brain nicotine levels did not. These data demonstrate the feasibility of delivering cigarette smoke to rats at clinically relevant doses, and provide preliminary evidence that the behavioral effects of nicotine delivered in smoke may differ from those of pure nicotine. (C) 2010 Elsevier Inc. All rights reserved.