Kota D, Martin B R, Robinson S E, Damaj M I
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Box 980613, Richmond, VA 23298-0613, USA.
J Pharmacol Exp Ther. 2007 Jul;322(1):399-407. doi: 10.1124/jpet.107.121616. Epub 2007 Apr 19.
The present study defined age differences in several aspects of nicotine dependence using male mice of two age groups [postnatal day (PND) 28 and PND 70]. Adolescent and adult mice displayed differences in acute sensitivity to nicotine, rewarding and withdrawal effects, development of tolerance to nicotine, and nicotinic receptor function. In the condition place preference model, adolescent mice displayed a higher sensitivity to nicotine than adults. In addition, in spontaneous and mecamylamine-precipitated withdrawal models, adolescent mice displayed fewer withdrawal signs than adults. In response to acute nicotine, it was found that adolescent mice displayed greater nicotine-induced antinociception compared with adult counterparts in the tail-flick test. Furthermore, differences in tolerance to nicotine were also noted in that adolescents developed a significantly higher degree of tolerance to nicotine in the hot-plate test compared with adults. Finally, using rubidium efflux assays, it was found that adolescent nicotinic receptors in different brain areas displayed significantly increased functionality compared with adult receptors. These data indicate that the underlying receptor mechanisms of nicotine dependence differ for adults and adolescents, suggesting that the effectiveness of smoking cessation therapies will differ for various age groups.
本研究使用两个年龄组（出生后第28天和第70天）的雄性小鼠，从几个方面定义了尼古丁依赖的年龄差异。青春期和成年小鼠在对尼古丁的急性敏感性、奖赏和戒断效应、对尼古丁耐受性的发展以及烟碱型受体功能方面存在差异。在条件性位置偏爱模型中，青春期小鼠对尼古丁的敏感性高于成年小鼠。此外，在自发和美加明诱发的戒断模型中，青春期小鼠表现出的戒断症状比成年小鼠少。在急性尼古丁反应方面，发现在甩尾试验中，与成年小鼠相比，青春期小鼠表现出更强的尼古丁诱导的抗伤害感受。此外，在对尼古丁的耐受性方面也存在差异，即在热板试验中，青春期小鼠对尼古丁产生的耐受性程度明显高于成年小鼠。最后，通过铷外流试验发现，与成年受体相比，不同脑区的青春期烟碱型受体功能显著增强。这些数据表明，成年人和青少年尼古丁依赖的潜在受体机制不同，这表明戒烟疗法对不同年龄组的有效性也会有所不同。
