Early adolescent subchronic low-dose nicotine exposure increases subsequent cocaine and fentanyl self-administration in Sprague-Dawley rats.
Early adolescent subchronic low-dose nicotine exposure increases subsequent cocaine and fentanyl self-administration in Sprague-Dawley rats.
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DOI：
10.1097/fbp.0000000000000593
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发表时间：
2021-02-01
影响因子：
1.6
通讯作者：
Lotfipour S
中科院分区：
文献类型：
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作者：
Cardenas A;Martinez M;Saenz Mejia A;Lotfipour S
在青春期，含有尼古丁的电子烟的使用量呈指数级上升。临床前研究表明，在青春期早期接触尼古丁，而不是成年后，会增加随后的药物摄取和奖励。尽管越来越多的临床趋势强调兴奋剂使用障碍与阿片类药物流行有关，但很少有研究评估青少年尼古丁暴露对阿片类药物摄入量的影响。我们目前的研究目的是建立一种新的动物模型来评估青少年尼古丁暴露与随后的阿片类药物摄入量之间的因果关系。在这项工作中，我们首先使用一个公认的4天尼古丁范例来复制先前的研究。大鼠给予小剂量尼古丁(2x，30μg/kg/0.1mL，静脉注射)。青春期早期(PN28-31)或成年期(PN86-89)。在PN32或PN90尼古丁预处理后，动物接受手术静脉注射精神刺激剂可卡因(500μg/kg/Inf)或阿片类药物芬太尼(2.5μg/kg/Inf)。我们成功地证明了青少年，但不是成年人，尼古丁暴露增加了雄性大鼠的可卡因自我给药。此外，我们说明了青少年早期(而不是成人)尼古丁暴露可增强芬太尼的自我给药，这种作用与性别无关。总体而言，我们的发现强调了青春期是一个独特的发育期，容易受到尼古丁诱导的可卡因和芬太尼自我给药增强的影响。
An exponential rise in nicotine-containing electronic-cigarette use has been observed during the period of adolescence. Preclinical studies have shown that nicotine exposure during early adolescence, but not adulthood, increases subsequent drug intake and reward. Although growing clinical trends highlight that stimulant use disorders are associated with the opioid epidemic, very few studies have assessed the effects of adolescent nicotine exposure on opioid intake. The objective of our current study is to develop a new animal model to assess the causal relationship of adolescent nicotine exposure on subsequent opioid intake. In this effort, we first replicate previous studies using a well-established 4-day nicotine paradigm. Rats are pretreated with a low dose of nicotine (2x, 30 μg/kg/0.1 mL, i.v.) or saline during early adolescence (PN 28–31) or adulthood (PN 86–89). Following nicotine pretreatment on PN 32 or PN 90, animals underwent operant intravenous self-administration for the psychostimulant, cocaine (500 μg/kg/infusion (inf)) or the opioid, fentanyl (2.5 μg/kg/inf). We successfully show that adolescent, but not adult, nicotine exposure enhances cocaine self-administration in male rats. Furthermore, we illustrate early adolescent, but not adult nicotine exposure enhances fentanyl self-administration, independent of sex. Overall, our findings highlight that adolescence is a unique period of development that is vulnerable to nicotine-induced enhancement for cocaine and fentanyl self-administration in rats.