Effects of continuous oral nicotine administration on brain nicotinic receptors and responsiveness to nicotine in C57Bl/6 mice.
Effects of continuous oral nicotine administration on brain nicotinic receptors and responsiveness to nicotine in C57Bl/6 mice.
复制标题
连续口服尼古丁对 C57Bl/6 小鼠大脑烟碱受体和尼古丁反应的影响。
DOI：
10.1007/s002130050818
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发表时间：
1999
影响因子：
3.4
通讯作者：
Pauly,JR
中科院分区：
文献类型：
--
作者：
Sparks,JA;Pauly,JR
在评估长期药物给药反应中发生的长期生物行为适应的研究中，药物递送途径是一个重要的考虑因素。在这些研究中，持续输注（静脉或皮下）或间歇腹腔注射（或皮下）是最常用的慢性给药途径。本研究的目的是确定慢性口服尼古丁暴露对雌性C57Bl/6小鼠尼古丁敏感性和脑尼古丁胆碱能受体的影响。小鼠随机分为不同治疗组，给予2%糖精，含0 ~ 200 μg/ml烟碱（游离碱）。在初步实验中，在小鼠体内植入无线电遥测装置；饮用含尼古丁的饮料溶液会导致夜间（但不是白天）活动显著增加，并改变体温的昼夜变化。口服尼古丁暴露导致血浆可替宁水平的剂量相关升高，可替宁是尼古丁的主要代谢物。连续暴露（30 d）于口服尼古丁（200 μg/ml）导致小鼠对急性尼古丁刺激的运动抑制和降体温作用具有显著的耐受性。使用[3H]-胞氨酸（α4 nAChr）和[125I]-α-bungarotoxin （α7 nAChr）作为放射配体，定量放射自显影术评估了脑烟碱受体数量的显著增加。这些结果表明，慢性口服尼古丁给雌性C57Bl/6小鼠引起的行为和生化变化类似于其他慢性尼古丁给药途径所发生的变化。
The route of drug delivery is an important consideration in studies that evaluate the long-term biobehavioral adaptations that occur in response to chronic drug administration. Continuous infusions (intravenous or subcutaneous) or intermittent intraperitoneal (or subcutaneous) injections are the most commonly utilized routes of chronic drug delivery in these studies. The purpose of the present study was to determine the effects of chronic oral nicotine exposure on sensitivity to nicotine and brain nicotinic cholinergic receptors in female C57Bl/6 mice. Mice were randomized to different treatment groups that received 2% saccharin, containing 0–200 μg/ml nicotine (free base). In preliminary experiments, radiotelemetry devices were implanted in the mice; consumption of the nicotine-containing drinking solution caused a significant increase in home-cage nocturnal (but not diurnal) activity and also altered circadian alterations in body temperature. Oral nicotine exposure resulted in dose-related elevations in plasma levels of cotinine, a primary nicotine metabolite. Continuous exposure (30 days) to oral nicotine (200 μg/ml) resulted in the expression of significant tolerance to the locomotor depressant and hypothermic actions of acute nicotine challenge. This tolerance was accompanied by a significant increase in brain nicotinic receptor number assessed by quantitative autoradiography using [3H]-cytisine (α4 nAChr) and [125I]-α-bungarotoxin (α7 nAChr) as radioligands. These results suggest that chronic oral nicotine delivery to female C57Bl/6 mice results in behavioral and biochemical changes that resemble changes that occur following other routes of chronic nicotine delivery.