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在整个孕期持续暴露于尼古丁和乙醇会导致年轻成年大鼠后代对尼古丁自我给药的习得增强。

Combined exposure to nicotine and ethanol throughout full gestation results in enhanced acquisition of nicotine self-administration in young adult rat offspring.

作者信息

Matta Shannon G, Elberger Andrea J

机构信息

Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, 874 Union Ave., Crowe 115, Memphis, TN 38163, USA.

出版信息

Psychopharmacology (Berl). 2007 Aug;193(2):199-213. doi: 10.1007/s00213-007-0767-2. Epub 2007 Apr 3.

Abstract

RATIONALE

Epidemiological evidence shows positive correlation between either maternal cigarette smoking or alcohol consumption on subsequent drug-taking behavior in offspring. However, the consequences of full gestational exposure to both drugs have not been studied experimentally despite concurrent use frequently reported among women of childbearing age. Such comorbid gestational drug exposure may increase susceptibility to acquiring cigarette smoking (i.e., nicotine self-administration), a major gateway drug.

OBJECTIVES

We developed a noninvasive rat model for exposure to both nicotine (2-6 mg kg(-1) day(-1)) and EtOH (4 g/kg gavage) that continued throughout pregnancy and postnatal (P) days 2-12, the rodent equivalent of the human third trimester, a critical brain developmental period. Offspring with this full gestational exposure to both drugs (Nic+EtOH) were compared to controls: nicotine alone, EtOH alone, pair-fed (comparable nutrition and handling), and ad libitum chow-fed. At P60-90, offspring had unlimited chronic access to acquire i.v. nicotine self-administration.

RESULTS

There were no differences in gender ratio, stillbirths, birth weights, righting reflex, eye opening age, or weight gain. However, Nic+EtOH offspring of both genders acquired nicotine self-administration (15 or 30 microg kg(-1) injection(-1)) more rapidly, at a higher percentage, and at a higher level than offspring in the other cohorts.

CONCLUSION

Full gestational Nic+EtOH exposure produced no overt alterations in standard postnatal measures but resulted in an enhanced acquisition of nicotine self-administration in young adult offspring.

摘要

原理

流行病学证据表明,母亲吸烟或饮酒与后代随后的药物使用行为之间存在正相关。然而,尽管育龄妇女中经常报告同时使用这两种药物,但尚未通过实验研究整个孕期暴露于这两种药物的后果。这种合并的孕期药物暴露可能会增加对吸烟(即尼古丁自我给药)的易感性,吸烟是一种主要的入门药物。

目的

我们开发了一种非侵入性大鼠模型,使其在整个孕期和出生后第2至12天(相当于人类妊娠晚期,即关键的脑发育时期)暴露于尼古丁(2 - 6毫克/千克/天)和乙醇(4克/千克灌胃)。将这种在整个孕期暴露于两种药物的后代(Nic+EtOH)与对照组进行比较:单独使用尼古丁、单独使用乙醇、配对喂养(可比的营养和处理方式)以及自由摄食普通饲料喂养。在出生后第60至90天,后代可无限制地长期进行静脉注射尼古丁自我给药。

结果

在性别比例、死产、出生体重、翻正反射、睁眼年龄或体重增加方面没有差异。然而,与其他组的后代相比,两种性别的Nic+EtOH后代更快、以更高的百分比且在更高的水平上获得了尼古丁自我给药(15或30微克/千克注射量)。

结论

整个孕期暴露于Nic+EtOH对标准产后指标没有明显改变,但导致年轻成年后代对尼古丁自我给药的获得增强。

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