Tolerance to nicotine in mice lacking α7 nicotinic receptors
Tolerance to nicotine in mice lacking α7 nicotinic receptors
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DOI：
10.1007/s00213-005-2187-5
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发表时间：
2005-07-01
影响因子：
3.4
通讯作者：
Stolerman, IP
中科院分区：
文献类型：
--
作者：
Naylor, C;Quarta, D;Stolerman, IP
基本原理：以前的研究表明，α 7烟碱受体亚单位的基因编码的敲除影响unrugged小鼠的行为，但不影响尼古丁对自发activity.Objectives的急性效应：本研究将这些观察结果扩展到通过时间表控制的行为来评估尼古丁耐受性。训练α 7（-/-）和α 7（+/+）小鼠组在FR 20食物强化时间表下按压杠杆。在两种基因型中测定尼古丁的急性反应率-抑制效应，然后将小鼠再分为每天给予尼古丁（1.2 mg/kg/天）或生理盐水的组。暴露于此方案39天后，剂量-反应曲线进行了redetermined.Results：α 7基因的敲除没有一致的影响unrugged小鼠的按下行为，并没有影响尼古丁（0.2-1.2 mg/kg）的急性，剂量相关，响应率-按下效应。当尼古丁的剂量反应曲线（0.4-2.0 mg/kg）在每日给予药物后重新测定，野生型和敲除小鼠对尼古丁产生了相似的耐受性，如剂量-反应曲线向右移动2.5倍所示。含有α 7亚单位的烟碱受体在调节杠杆中不起重要作用。研究的按压行为或尼古丁的急性行为刺激效应以及对该效应的耐受性的发展。这样的结果与先前的报告表明严重损伤小鼠形成鲜明对比。
Rationale: Previous studies have suggested that a knockout of the gene coding for alpha 7 nicotinic receptor subunits influences the behaviour of undrugged mice but not the acute effect of nicotine on locomotor activity.Objectives: The present studies extend these observations to nicotine tolerance assessed by means of schedule-controlled behaviour.Methods: Groups of alpha 7(-/-) and alpha 7(+/+) mice were trained to press levers under an FR20 schedule of food reinforcement. The acute response rate-depressant effects of nicotine were determined in both genotypes and the mice were then subdivided into groups treated daily with nicotine ( 1.2 mg/kg/day) or saline. After 39 days of exposure to this regimen, the dose-response curves were re-determined.Results: Knockout of the alpha 7 gene had no consistent effect on the lever-pressing behaviour of undrugged mice and did not influence the acute, dose-related, response rate-depressant effect of nicotine ( 0.2-1.2 mg/kg). When dose-response curves for nicotine ( 0.4-2.0 mg/kg) were re-determined after daily dosing with the drug, both wild-type and knockout mice developed similar tolerance to nicotine, as shown by similar to 2.5-fold shifts to the right of the dose-response curves.Conclusions: Nicotinic receptors containing the alpha 7 subunit do not play a significant role in the regulation of the lever-pressing behaviour studied or in the acute behavioural depressant effect of nicotine and the development of tolerance to that effect. Such results contrast with previous reports suggesting profound impairments mice.