Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure
Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure
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DOI：
10.1016/j.neuropharm.2008.07.030
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发表时间：
2008-12-01
影响因子：
4.7
通讯作者：
Naassila, Mickael
中科院分区：
文献类型：
--
作者：
Barbier, Estelle;Pierrefiche, Olivier;Naassila, Mickael
在生命早期接触乙醇可能会对大脑功能和以后生活中滥用药物的反应产生长期影响。本研究在大鼠身上研究了出生前和出生后(早期)酒精暴露对药物消费/奖励的长期影响，以及与这些行为变化潜在相关的分子靶点。由于药物摄入量的增加与对药物诱导的运动活动/敏化、焦虑的敏感性之间的关系已经被证明，我们测试了这些行为反应，依赖于药物，在对照组和早期生命酒精暴露的动物中。我们的结果表明，暴露于早期生命乙醇的子代表现出更多的乙醇溶液消耗量，并在条件性位置偏好测试中对可卡因奖励效应的敏感度增加。接触乙醇的后代对乙醇的抗焦虑作用更敏感，这种敏感性的增加至少部分解释了乙醇的抗焦虑作用在消费方面的变化。此外，早期接触酒精并不改变对乙醇和乙醇代谢的低温效应的敏感性。在生命早期接触酒精后，对可卡因(20 mg/kg)和苯丙胺(1.2 mg/kg)的敏感度增加，这可以部分解释精神刺激剂奖赏特性的增加。基因表达分析显示，在参与药物滥用强化作用的大脑区域，大量基因的表达发生了变化。在酒精暴露的子代中，纹状体中的多巴胺能受体和转运体结合部位也下调。递质系统以及对乙醇和其他滥用药物的行为反应中的这种长期神经化学变化，可能会增加暴露在这种环境中的后代成瘾的可能性。(C)2008爱思唯尔有限公司。保留所有权利。
Exposure to ethanol early in life can have long-lasting implications on brain function and drug of abuse response later in life. The present study investigated in rats, the long-term consequences of pre- and postnatal (early life) ethanol exposure on drug consumption/reward and the molecular targets potentially associated with these behavioral alterations. Since a relationship has been demonstrated between heightened drugs intake and susceptibility to drugs-induced locomotor activity/sensitization, anxiolysis, we tested these behavioral responses, depending on the drug, in control and early life ethanol-exposed animals. Our results show that progeny exposed to early life ethanol displayed increased consumption of ethanol solutions and increased sensitivity to cocaine rewarding effects assessed in the conditioned place preference test. Offspring exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and the increased sensitivity could, at least in part, explain the alteration in the consumption of ethanol for its anxiolytic effects. In addition, the sensitivity to hypothermic effects of ethanol and ethanol metabolism were not altered by early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and, could partly explain, an increase in the rewarding properties of psychostimulants. Gene expression analysis revealed that expression of a large number of genes was altered in brain regions involved in the reinforcing effects of drugs of abuse. Dopaminergic receptors and transporter binding sites were also down-regulated in the striatum of ethanol-exposed offspring. Such long-term neurochemical alterations in transmitter systems and in the behavioral responses to ethanol and other drugs of abuse may confer an increased liability for addiction in exposed offspring. (C) 2008 Elsevier Ltd. All rights reserved.