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青春期反复接触尼古丁对偏好酒精的AA大鼠和回避酒精的ANA大鼠的行为影响。

Behavioral consequences of repeated nicotine during adolescence in alcohol-preferring AA and alcohol-avoiding ANA rats.

作者信息

Kemppainen Heidi, Hyytiä Petri, Kiianmaa Kalervo

机构信息

Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland.

出版信息

Alcohol Clin Exp Res. 2009 Feb;33(2):340-9. doi: 10.1111/j.1530-0277.2008.00838.x. Epub 2008 Nov 19.

Abstract

BACKGROUND

Epidemiological studies suggest that exposure to nicotine at adolescent age is associated with increased potential to use alcohol and that genetic predisposition may further increase the risk. The present study addressed adolescent vulnerability to repeated nicotine exposure and its influence on subsequent ethanol self-administration by investigating interactions between nicotine-induced behavioral sensitization and voluntary ethanol consumption in alcohol preferring AA (Alko Alcohol) and alcohol nonpreferring ANA (Alko Non-Alcohol) rat lines selected for differential ethanol intake.

METHODS

Adolescent and adult rats received 10 injections of nicotine (0.5 mg/kg s.c.), given every second day from postnatal day (Pnd) 27 and 75, respectively. Nicotine-induced (0.5 mg/kg) locomotor activity was measured acutely after the first injection, and after the repeated treatment with nicotine on Pnds 52 and 86 in the adolescent groups and on Pnd 99 in the adult groups. After this, acquisition of voluntary ethanol (10% v/v) consumption as well as nicotine-induced (0.5 mg/kg) ethanol intake was measured in the AA rats.

RESULTS

Adolescent AA rats were more sensitive than adolescent ANA rats to the locomotor effects of nicotine. They were also stimulated more than adult AA rats, but such a difference was not found among ANA rats. Adolescent and adult rats did not differ in their susceptibility to nicotine-induced behavioral sensitization. Genetic predisposition to ethanol self-administration did not interact with development of behavioral sensitization in either adolescents or adults. Acquisition of ethanol intake was enhanced in the adolescent groups relative to the adult groups in a manner that was independent of the nicotine treatment. An increase in ethanol intake was found after challenging animals with nicotine, and this effect was enhanced in the nicotine-treated adolescent group.

CONCLUSIONS

These findings provide no or little support for the views that adolescent animals are more sensitive to the neurobehavioral effects of repeated exposure to nicotine and that exposure to nicotine in adolescence may contribute to enhanced vulnerability to ethanol abuse. Furthermore, genetic predisposition to high or low ethanol self-administration does not seem to be a factor that influences individual vulnerability to the neurobehavioral effects of repeated administration of nicotine.

摘要

背景

流行病学研究表明,青少年时期接触尼古丁与增加饮酒可能性有关,而且遗传易感性可能会进一步增加这种风险。本研究通过调查尼古丁诱导的行为敏化与自愿乙醇摄入之间的相互作用,探讨了青少年对反复接触尼古丁的易感性及其对随后乙醇自我给药的影响,该研究选用了对乙醇摄入量有差异的酒精偏好型AA(阿尔科酒精)大鼠品系和酒精非偏好型ANA(阿尔科非酒精)大鼠品系。

方法

青少年大鼠和成年大鼠分别从出生后第27天和第75天开始,每隔一天接受10次尼古丁注射(0.5毫克/千克,皮下注射)。在首次注射后以及青少年组在出生后第52天和第86天、成年组在出生后第99天用尼古丁重复处理后,急性测量尼古丁诱导的(0.5毫克/千克)运动活动。在此之后,测量AA大鼠自愿摄入乙醇(10%体积/体积)的情况以及尼古丁诱导的(0.5毫克/千克)乙醇摄入量。

结果

青少年AA大鼠比青少年ANA大鼠对尼古丁的运动效应更敏感。它们也比成年AA大鼠受到的刺激更大,但在ANA大鼠中未发现这种差异。青少年大鼠和成年大鼠对尼古丁诱导的行为敏化的易感性没有差异。乙醇自我给药的遗传易感性在青少年或成年期均未与行为敏化的发展相互作用。相对于成年组,青少年组乙醇摄入量的获得以一种与尼古丁处理无关的方式得到增强。用尼古丁刺激动物后发现乙醇摄入量增加,并且这种效应在尼古丁处理的青少年组中增强。

结论

这些发现几乎没有支持以下观点,即青少年动物对反复接触尼古丁的神经行为效应更敏感,以及青少年接触尼古丁可能导致对乙醇滥用的易感性增加。此外,高或低乙醇自我给药的遗传易感性似乎不是影响个体对反复给予尼古丁的神经行为效应易感性的因素。

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