Shram Megan J, Siu Eric C K, Li Zhaoxia, Tyndale Rachel F, Lê Anh D
Department of Neuroscience, Centre for Addiction and Mental Health, 33 Russell Street, T700, Toronto, ON, Canada M5S 2S1.
Psychopharmacology (Berl). 2008 Jun;198(2):181-90. doi: 10.1007/s00213-008-1115-x. Epub 2008 Apr 3.
Adolescent onset of smoking is associated with a rapid progression to dependence. Although adolescents may exhibit a greater susceptibility to nicotine addiction, relatively little is known about the influence of the aversive effects of nicotine withdrawal in maintaining smoking behavior.
The present study investigated age differences in the motivational effects of mecamylamine-precipitated and spontaneous nicotine withdrawal in adolescent and adult rats using the conditioned place aversion procedure (CPA).
In experiment 1, adolescent (postnatal day (PD) 28) and adult (PD60) male Wistar rats chronically treated with nicotine (3 or 6 mg/kg/day, s.c.) received mecamylamine (1 mg/kg, s.c.), a nicotinic receptor antagonist, or vehicle prior to place conditioning; physical withdrawal signs were also measured. Experiment 2 was conducted to increase nicotine levels in which adolescents were treated with 4.5 or 9 mg/kg/day nicotine. In experiment 3, age differences in spontaneous nicotine withdrawal were evaluated.
Nicotine-treated adults developed a CPA to the mecamylamine-associated compartment and expressed significant physical withdrawal signs, whereas similarly treated adolescents did not. Increasing nicotine exposure levels did not modify the adolescent response to mecamylamine-precipitated withdrawal. Spontaneous nicotine withdrawal produced similar physical withdrawal signs in adolescents and adults, but did not elicit CPA.
The current study indicates that adolescent rats are less responsive to the aversive effects of mecamylamine-precipitated, but not spontaneous, nicotine withdrawal compared to adult rats. These findings suggest that adolescents and adults may exhibit similar sensitivity to the affective and physical effects of withdrawal following smoking cessation.
青少年开始吸烟与迅速发展为烟瘾有关。尽管青少年可能对尼古丁成瘾表现出更高的易感性，但关于尼古丁戒断的厌恶效应在维持吸烟行为中的影响，我们所知相对较少。
本研究使用条件性位置厌恶程序（CPA），调查了青少年和成年大鼠中，美加明诱发的和自发的尼古丁戒断在动机效应上的年龄差异。
在实验1中，长期接受尼古丁（3或6毫克/千克/天，皮下注射）治疗的青少年（出生后第28天）和成年（出生后第60天）雄性Wistar大鼠，在位置条件化之前接受烟碱受体拮抗剂美加明（1毫克/千克，皮下注射）或赋形剂；同时测量身体戒断症状。进行实验2以提高尼古丁水平，其中青少年接受4.5或9毫克/千克/天的尼古丁治疗。在实验3中，评估了自发尼古丁戒断的年龄差异。
接受尼古丁治疗的成年大鼠对与美加明相关的隔室产生了条件性位置厌恶，并表现出明显的身体戒断症状，而接受类似治疗的青少年则没有。增加尼古丁暴露水平并未改变青少年对美加明诱发的戒断反应。自发的尼古丁戒断在青少年和成年大鼠中产生了类似的身体戒断症状，但未引发条件性位置厌恶。
当前研究表明，与成年大鼠相比，青少年大鼠对美加明诱发的而非自发的尼古丁戒断的厌恶效应反应较小。这些发现表明，青少年和成年人在戒烟后对戒断的情感和身体影响可能表现出相似的敏感性。
