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成年大鼠与青春期大鼠尼古丁暴露后恐惧条件反射和焦虑样行为的长期变化

Long-term changes in fear conditioning and anxiety-like behavior following nicotine exposure in adult versus adolescent rats.

作者信息

Smith Laura N, McDonald Craig G, Bergstrom Hadley C, Brielmaier Jennifer M, Eppolito Amy K, Wheeler Tracey L, Falco Adriana M, Smith Robert F

机构信息

Department of Psychology, George Mason University, MS 3F5, Fairfax, VA 22030, USA.

出版信息

Pharmacol Biochem Behav. 2006 Sep;85(1):91-7. doi: 10.1016/j.pbb.2006.07.014. Epub 2006 Aug 17.

DOI:10.1016/j.pbb.2006.07.014
PMID:16919320
Abstract

Adolescent nicotine exposure is associated with long-term use, and it has been suggested that this vulnerability to addiction may relate to lasting anxiogenic effects of the drug. However, few studies have addressed long-term effects of adolescent nicotine, and fewer yet have compared adolescent to adult exposure. Male and female Long-Evans rats continuously received nicotine bitartrate or sodium tartrate via osmotic mini-pumps over 15 days either during adolescence (p28-42) or adulthood (p85-99). Initial nicotine dose (free base) was either low (1 mg/kg/day) or high (2 mg/kg/day). Open field behavior and fear conditioning were assessed in adulthood, 1 month post-dosing. Animals pretreated with nicotine during adolescence showed less center time in a novel open field than sham controls. Conversely, the two nicotine doses differentially affected fear conditioning. Animals pretreated with low nicotine during adolescence demonstrated superior acquisition of the task compared to sham control animals; however, unlike either high nicotine-pretreated or sham control animals, they failed to extinguish the learned behavior. In contrast, animals pretreated during adulthood did not behave significantly different from sham controls on either task. Overall, nicotine-pretreatment during adolescence induced effects on behaviors related to fear and anxiety in adulthood, while comparable pretreatment during adulthood failed to produce significant residual effects.

摘要

青少年接触尼古丁与长期使用有关,有人认为这种对成瘾的易感性可能与该药物持久的致焦虑作用有关。然而,很少有研究探讨青少年尼古丁的长期影响,更少有人将青少年接触与成人接触进行比较。雄性和雌性Long-Evans大鼠在青春期(第28 - 42天)或成年期(第85 - 99天)通过渗透微型泵持续15天接受酒石酸尼古丁或酒石酸钠。初始尼古丁剂量(游离碱)要么低(1毫克/千克/天)要么高(2毫克/千克/天)。在给药后1个月的成年期评估旷场行为和恐惧条件反射。青春期用尼古丁预处理的动物在新的旷场中表现出比假手术对照组更少的中央时间。相反,两种尼古丁剂量对恐惧条件反射有不同影响。青春期用低剂量尼古丁预处理的动物与假手术对照组相比,在任务习得方面表现更优;然而,与高剂量尼古丁预处理组或假手术对照组动物不同的是,它们未能消除习得行为。相比之下,成年期预处理的动物在这两项任务上的行为与假手术对照组没有显著差异。总体而言,青春期尼古丁预处理对成年期与恐惧和焦虑相关的行为产生了影响,而成年期类似的预处理未能产生显著的残留影响。

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