Continuous nicotine infusion reduces nicotine self-administration in rats with 23-h/day access to nicotine
Continuous nicotine infusion reduces nicotine self-administration in rats with 23-h/day access to nicotine
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DOI：
10.1016/s0091-3057(01)00775-4
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发表时间：
2002-05-01
影响因子：
3.6
通讯作者：
Pentel, PR
中科院分区：
文献类型：
--
作者：
LeSage, MG;Keyler, DE;Pentel, PR
以大鼠为研究对象，研究了持续尼古丁输注对尼古丁自我给药（NSA）的影响，并将其作为人体尼古丁替代疗法（NRT）的模型。在NSA模型中，大鼠每天获得23小时的尼古丁，以近似吸烟者的尼古丁获取条件。为了估计与NSA相关的血清尼古丁浓度，在模拟NSA期间测量了动脉和静脉血清尼古丁浓度。尼古丁以0.03 mg/kg/inf / 30剂量/12小时的方式非偶然给药，或在中午给药后测量60剂量/12小时的浓度。测量的平均浓度范围与吸烟者报告的相似（静脉浓度6 - 59 ng/ml，动脉浓度42 - 96 ng/ml）。通过渗透泵非偶然给药不同剂量的尼古丁，研究了连续尼古丁输注对小鼠NSA的影响，这些小鼠每天给药23小时，分别给药0.01或0.03 mg/kg/inf。在所有输注速率下，持续尼古丁输注均可显著抑制NSA，但仅在0.01 mg/kg/inf NSA单位剂量下，抑制与速率相关。尼古丁输注率产生的静脉血清尼古丁浓度等于或超过与模拟NSA相关的静脉峰值水平，仅在较低的NSA单位剂量下比较低的输注率更有效。最高尼古丁输注率对食物维持反应没有持续影响，表明其抑制NSA的特异性。这些数据为研究大鼠NRT提供了一个模型。(C) 2002爱思唯尔科学有限公司版权所有。
The effects of continuous nicotine infusion on nicotine self-administration (NSA) were studied in rats as a model of nicotine replacement therapy (NRT) in humans. A NSA model in which rats had 23-h/day access to nicotine was used to approximate nicotine access conditions in cigarette smokers. In order to estimate serum nicotine concentrations associated with NSA, arterial and venous serum nicotine concentrations were measured during a simulation of NSA. Nicotine was noncontingently administered as 30 doses/12 h of 0.03 mg/kg/inf or 60 doses/12 h concentrations were measured after doses in the middle of the day. The range of mean concentrations measured was similar to those reported in cigarette smokers (venous concentrations 6 - 59 ng/ml, arterial concentrations 42 - 96 ng/ml). The effects of continuous nicotine infusion on NSA were studied by noncontingently administering nicotine at various rates via osmotic pump to animals self-administering nicotine (0.01 or 0.03 mg/kg/inf) during 23-h/day sessions. Continuous nicotine infusion at all infusion rates substantially suppressed NSA, but suppression was rate-related only for the 0.01-mg/kg/inf NSA unit dose. Nicotine infusion rates producing venous serum nicotine concentrations equaling or exceeding the peak venous levels associated with simulated NSA were more effective than lower infusion rates only at the lower NSA unit dose. The highest nicotine infusion rate had no sustained effect on food-maintained responding, demonstrating its specificity for suppression of NSA. These data provide a model for studying NRT in the rat. (C) 2002 Elsevier Science Inc. All rights reserved.