Adriani Walter, Macrì Simone, Pacifici Roberta, Laviola Giovanni
Behavioural Pathophysiology Section, Lab F.O.S., Istituto Superiore di Sanità, viale Regina Elena 299, Roma, Italy.
Neuropsychopharmacology. 2002 Aug;27(2):212-24. doi: 10.1016/S0893-133X(02)00295-6.
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 use a number of different 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
早期吸烟被认为具有通向药物滥用的“门户”作用。尼古丁实际上是人类青少年容易获取的一种药物，他们很可能会使用多种不同的精神活性物质。令人惊讶的是，与这个年龄相关的意愿所涉及的心理生物学因素尚未得到充分研究。在实验1中，采用口服自我给药范式，研究了远交群CD - 1小鼠在青春期早期（出生后第24至35天）、中期（出生后第37至48天）或晚期（出生后第50至61天）对尼古丁的消耗情况。在饮水时段（每天2小时），动物可以在自来水和尼古丁溶液（10毫克/升）之间自由选择。6天后，进行了一项递减研究，将尼古丁浓度降至7毫克/升（第7至9天）和5毫克/升（第10至12天），以评估动物是否会通过增加从尼古丁溶液中的摄入量来进行补偿。在实验2中，评估了在1小时饮水时段尼古丁溶液（0、10、30毫克/升）对青春期早期和晚期小鼠运动的精神药理学作用。在实验1中，青春期早期的小鼠对尼古丁溶液表现出明显且稳定的偏好，每日尼古丁摄入量为1.15±0.04毫克/千克。青春期中期的小鼠对任何一瓶溶液都没有表现出偏好，而青春期晚期的小鼠则表现出对尼古丁溶液的回避倾向。在递减研究中，只有青春期早期的小鼠在尼古丁浓度降低时，从尼古丁瓶中的消耗量增加。对可替宁（尼古丁消耗的主要生物标志物）血浆水平的时间进程分析揭示了三个年龄组之间的一些药代动力学差异。在实验2中，饮用尼古丁溶液在青春期早期的小鼠中产生了明显的多动，而在年龄较大的小鼠中则表现出相反的情况。总之，即使不能完全排除味觉因素的作用，但对口服尼古丁消耗的一种特殊自发驱动力以及尼古丁引起的兴奋，在小鼠青春期早期是特定的。目前的动物模型可能有助于研究人类青少年早期吸烟所涉及的心理生物学决定因素。
