Peculiar vulnerability to nicotine oral self-administration in mice during early adolescence
Peculiar vulnerability to nicotine oral self-administration in mice during early adolescence
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DOI：
10.1016/s0893-133x(02)00295-6
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发表时间：
2002-08-01
影响因子：
7.6
通讯作者：
Laviola, G
中科院分区：
文献类型：
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作者：
Adriani, W;Macrì, S;Laviola, G
早期吸烟被认为是药物滥用的“门户”功能。尼古丁实际上是青少年容易获得的药物，他们很可能需要一大堆不同的精神活性剂。令人惊讶的是，这种与年龄相关的意愿所涉及的心理生物学因素却没有得到充分的研究。在实验1中，采用经口自我给药模式，研究了远交CD-1小鼠在青春期早期（出生后第24 - 35天（pnd））、中期（pnd 37 - 48）或晚期（pnd 50 - 61）的尼古丁消耗量。在饮水阶段（2小时/天），动物可以自由选择自来水或尼古丁溶液（10 mg/l）。6天后，进行褪色研究，其中尼古丁浓度降低至7 mg/l（第7-9天）和5 mg/l（第10-12天），以评估动物是否会通过增加尼古丁溶液的摄入量进行补偿。在实验2中，在青春期早期和晚期小鼠中评估了尼古丁溶液（0、10、30 mg/l）在1小时饮酒期间对运动诱导的精神药理学影响。在实验1中，早期青少年对尼古丁溶液表现出明显且稳定的偏好，显示每日尼古丁摄入量为1.15 +/- 0.04 mg/kg。中年青少年没有表现出任何偏好的任何一瓶，而倾向于避免尼古丁溶液被发现为晚期青少年。在褪色研究中。早期青少年是唯一一组显示尼古丁浓度降低的尼古丁瓶消费量增加的人群。可替宁（尼古丁消耗的主要生物标志物）血浆水平的时程分析显示，三个年龄组之间存在一些药代动力学差异。在实验2中，从尼古丁溶液中饮用产生了一个突出的多动症在早期青少年，而一个完全相反的配置文件与老年人。总之，即使不能完全排除味觉因素的作用，但小鼠青春期早期特有的口服尼古丁消耗的自发驱动以及尼古丁诱导的唤醒。目前的动物模型可能是有用的，以调查人类青少年早期吸烟的心理生物学决定因素。
A "gateway" function toward substance abuse has been suggested for early tobacco smoking. Nicotine actually represents an easily available drug for human adolescents, who are very likely to nse a nionber ofdifferent psychoactive agents. Surprisingly, the psychobiological factors involved in this age-related willingness have been poorly investigated. In Experiment 1, nicotine consumption was studied in outbred CD-1 mice during Early (postnatal day (pnd) 24 to 35), Middle (pnd 37 to 48) or Late (pnd 50 to 61) adolescence, in an oral self-administration paradigm. During the drinking session (2 h/day), animals had free choice between either tap water or a nicotine solution (10 mg/l). After a 6-day period, a fading study was carried out, in which nicotine concentration was reduced to 7 mg/l (days 7-9) and 5 mg/l (days 10-12), to assess whether animals would compensate by increasing their intake from the nicotine solution. In Experiment 2, psychopharmacological effects on locomotion induced by the nicotine solution (0, 10, 30 mg/l) during the 1-h drinking session were assessed in Early and Late adolescent mice. In Experiment 1, Early adolescents expressed a marked and stable preference for the nicotine solution, showing a daily nicotine intake of 1.15 +/- 0.04 mg/kg. Middle adolescents did not show any preference for either bottle, whereas a tendency toward avoidance for the nicotine solution was found for Late adolescents. In the fading study. Early adolescents were the only group to show increased consumption from the nicotine bottle as far as nicotine concentration was reduced. A time-course analysis of plasma levels of cotinine (the principal biomarker of nicotine consumption) revealed some pharmacokinetic differences between the three age-groups. In Experiment 2, drinking from a nicotine solution produced a prominent hyperactivity in Early adolescents, whereas a quite opposite profile was associated with older subjects. In summary, even if a role for taste factors cannot be completely ruled out, a peculiar spontaneous drive toward oral nicotine consumption, as well as a nicotine-induced arousal, is specific to Early adolescence in mice. The present animal model might be useful to investigate psychobiological determinants involved in early tobacco smoking in human adolescents.