Nicotine Dependence and Reward Differ between Adolescent and Adult Male Mice

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Abstract
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.