Levin Edward D, Rezvani Amir H, Montoya Daniel, Rose Jed E, Swartzwelder H Scott
Neurobehavioral Research Laboratory, Department of Psychiatry, Duke University Medical Center, 341 Bell Building, Box #3412, Durham, NC 27710, USA.
Psychopharmacology (Berl). 2003 Sep;169(2):141-9. doi: 10.1007/s00213-003-1486-y. Epub 2003 May 23.
Although the great majority of tobacco addiction begins during adolescence, little is known about differential nicotine effects in adolescents versus adults.
A rat model was used to determine the impact of the age of onset on nicotine self-administration.
In expt 1, nicotine self-administration of female Sprague-Dawley rats over a range of acute doses (0.01-0.08 mg/kg per infusion) was determined in adolescent (beginning at 54-62 days) versus adult (beginning at 84-90 days). In expt 2, chronic nicotine self-administration over 4 weeks from adolescence into adulthood was compared with the chronic self-administration beginning in adulthood. In expt 3, adolescent-adult differences in nicotine effects on body temperature and locomotor responses were determined.
Adolescent-onset rats showed a significant main effect of increased nicotine intake compared with adult-onset rats in an eight-fold range of acute unit doses/infusion. Significant age differences were also seen in the chronic level of nicotine self-administration. Over 4 weeks, the adolescent-onset group had nearly double the rate of nicotine self-administration of the benchmark nicotine dose (0.03 mg/kg per infusion) compared to the adult-onset group. This increased nicotine intake persisted into adulthood. Adolescent rats had significantly greater response than adults to the hypothermic effects of nicotine, but had significantly less response than adults to the reduction in locomotor activity seen after nicotine.
Adolescent-onset nicotine self-administration in female rats was associated with significantly higher levels of nicotine self-administration versus rats, which began nicotine self-administration in adulthood. This greater self-administration persists into adulthood and may underlie greater propensity of adolescents to nicotine addiction.
尽管绝大多数烟草成瘾始于青春期,但对于青少年与成年人在尼古丁效应差异方面知之甚少。
使用大鼠模型来确定开始使用尼古丁的年龄对尼古丁自我给药的影响。
在实验1中,测定了青春期(54 - 62日龄开始)和成年期(84 - 90日龄开始)雌性斯普拉格 - 道利大鼠在一系列急性剂量(每次输注0.01 - 0.08毫克/千克)下的尼古丁自我给药情况。在实验2中,比较了从青春期到成年期持续4周的慢性尼古丁自我给药与成年期开始的慢性自我给药情况。在实验3中,确定了尼古丁对体温和运动反应影响方面的青少年 - 成年人差异。
在急性单位剂量/输注范围达八倍的情况下,与成年期开始使用尼古丁的大鼠相比,青春期开始使用尼古丁的大鼠显示出尼古丁摄入量增加的显著主效应。在尼古丁自我给药的慢性水平上也观察到显著的年龄差异。在4周时间里,与成年期开始使用尼古丁的组相比,青春期开始使用尼古丁的组对基准尼古丁剂量(每次输注0.03毫克/千克)的尼古丁自我给药率几乎高出一倍。这种增加的尼古丁摄入量持续到成年期。与成年大鼠相比,青春期大鼠对尼古丁的降温效应反应显著更大,但对尼古丁后出现的运动活动减少反应显著更小。
与成年期开始尼古丁自我给药的大鼠相比,雌性大鼠青春期开始尼古丁自我给药与显著更高水平的尼古丁自我给药相关。这种更强的自我给药持续到成年期,可能是青少年对尼古丁成瘾倾向更大的基础。