Cigarette smoking and resultant nicotine dependence remain major public health problems. Most smokers begin before the age of 18, yet preclinical models have insufficiently characterized the development of nicotine dependence in adolescence. To categorize the short-term effects of chronic nicotine administration throughout adolescence and adulthood, we exposed male Sprague Dawley rats to 14 days of continuously delivered nicotine (0, 1.2 or 4.8 mg/kg/d) using a subcutaneous osmotic minipump, starting between postnatal day 33 (p33) and p96. Next, to explore the effects of extended exposure to chronic nicotine, we exposed male Sprague Dawley rats to 42 days of continuous nicotine starting in adolescence (p33) or early adulthood (p68). Somatic and affective signs of precipitated withdrawal (PW) were observed after a mecamylamine (1.5 mg/kg, i.p.) challenge as compared to a saline injection. Short term nicotine exposure starting at p96, well within the adult period, elicited a significant increase in somatic PW as measured by a composite behavioral score. In contrast, adolescent exposure to nicotine elicited a unique behavioral profile, dependent on the starting age of exposure. Late adolescence exposure was characterized by scratching while adult exposure was characterized by facial tremors and yawns. Extended exposure to nicotine resulted in age specific characteristic nicotine withdrawal behaviors, including scratches, ptosis and locomotion, distinct from the short-term exposure. Thus, nicotine dependence severity, based on the expression of total somatic PW behaviors, is not observed until the adult period, and differences between adolescents and adults are observed using a more nuanced behavioral scoring approach. We conclude that age of nicotine initiation affects somatic withdrawal signs and their magnitude. These data serve as a foundation for understanding the underlying brain mechanisms of nicotine dependence and their development over adolescence and early adulthood.

吸烟和由此产生的尼古丁依赖性仍然是主要的公共卫生问题。大多数吸烟者在18岁之前就开始吸烟，但临床前模型不足以表征青春期对尼古丁的依赖性。为了对整个青春期和成年期长期服用尼古丁的短期影响进行分类，我们使用皮下渗透微型泵将雄性Sprague Dawley大鼠暴露于连续14天的尼古丁（0、1.2或4.8 mg / kg / d），从出生后开始第33天（p33）和p96。接下来，为了探讨长期暴露于慢性尼古丁的影响，我们从雄性Sprague Dawley大鼠暴露于青春期（p33）或成年初期（p68）开始连续42天服用尼古丁。美卡明胺（1.5 mg / kg，ip ）相比，盐水注射挑战。从p96开始的短期尼古丁暴露，正好在成人时期内，通过综合行为评分来衡量，导致人体PW显着增加。相反，青少年接触烟碱会引起独特的行为特征，这取决于接触的起始年龄。青春期晚期暴露特征为抓挠，成人暴露特征为面部震颤和打哈欠。长期接触尼古丁会导致特定年龄的尼古丁戒断行为，包括划痕，上睑下垂和运动，这与短期接触不同。因此，直到成年期才观察到基于总体细胞PW行为表达的尼古丁依赖性严重程度，并且使用更细微的行为评分方法来观察青少年与成年人之间的差异。我们得出结论，尼古丁起始年龄影响躯体戒断症状及其严重程度。这些数据为了解尼古丁依赖性的基本脑机制及其在青春期和成年早期的发育奠定了基础。