Barbier Estelle, Pierrefiche Olivier, Vaudry David, Vaudry Hubert, Daoust Martine, Naassila Mickaël
Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l'Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, Faculté de Pharmacie, 1 rue des Louvels, 80000 Amiens, France.
Neuropharmacology. 2008 Dec;55(7):1199-211. doi: 10.1016/j.neuropharm.2008.07.030. Epub 2008 Jul 31.
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.
生命早期接触乙醇会对大脑功能以及后期对成瘾药物的反应产生长期影响。本研究在大鼠中调查了产前和产后（生命早期）乙醇暴露对药物消费/奖赏以及可能与这些行为改变相关的分子靶点的长期影响。由于已证明药物摄入量增加与对药物诱导的运动活动/敏感化、抗焦虑作用的易感性之间存在关联，我们在对照动物和生命早期乙醇暴露动物中测试了这些行为反应，具体取决于所使用的药物。我们的结果表明，生命早期接触乙醇的后代在条件性位置偏爱试验中显示出乙醇溶液消耗量增加以及对可卡因奖赏作用的敏感性增加。接触乙醇的后代对乙醇的抗焦虑作用更敏感，这种增加的敏感性至少可以部分解释因乙醇抗焦虑作用导致的乙醇消耗量改变。此外，生命早期乙醇暴露并未改变对乙醇低温效应和乙醇代谢的敏感性。生命早期乙醇暴露后对可卡因（20毫克/千克）和苯丙胺（1.2毫克/千克）的敏感化增加，并且可以部分解释精神兴奋剂奖赏特性的增加。基因表达分析显示，参与成瘾药物强化作用的脑区中大量基因的表达发生了改变。多巴胺能受体和转运体结合位点在乙醇暴露后代的纹状体中也下调。递质系统的这种长期神经化学改变以及对乙醇和其他成瘾药物的行为反应可能会使暴露后代的成瘾易感性增加。
