Bustamante Diego, Quintanilla Maria Elena, Tampier Lutske, Gonzalez-Lira Victor, Israel Yedy, Herrera-Marschitz Mario
Programme of Molecular and Clinical Pharmacology, Faculty of Medicine, University of Chile, Santiago 7, Chile.
Eur J Pharmacol. 2008 Sep 4;591(1-3):153-8. doi: 10.1016/j.ejphar.2008.06.069. Epub 2008 Jun 24.
Several studies on the differences between ethanol-preferring versus non-preferring rat lines suggest an innate deficit in the mesolimbic dopaminergic system as an underlying factor for ethanol volition. Rats would try to overcome such deficit by engaging in a drug-seeking behaviour, when available, to drink an ethanol solution over water. Thus, in the present study we compared the effect of a single dose of ethanol (1 g/kg, i.p.) on the extracellular levels of monoamines measured by microdialysis in the shell of nucleus accumbens of University of Chile bibulous (UChB) and University of Chile Abstainer (UChA) rats, bred for 79 and 88 generations to prefer or reject ethanol, respectively. It is reported that under basal conditions extracellular dopamine levels are lower in the bibulous than in the abstainer rats, while ethanol induced a 2-fold greater increase of dopamine release in bibulous than in abstainer rats. The greater effect of ethanol in bibulous rats was not associated to differences in blood ethanol levels, since the concentration and elimination of ethanol were virtually identical in both rat lines, indicating that bibulous rats are more sensitive to the stimulation of dopamine release by ethanol than abstainer rats. No differences were observed in 5-hydroxytryptamine or metabolites measured simultaneously under basal or ethanol-stimulating conditions in bibulous and abstainer rats. Overall, the present results suggest that a low dopaminergic tone and a strong mesolimbic dopamine response to ethanol are concerted neurochemical features associated to an ethanol-seeking behaviour in rats.
几项关于嗜酒与不嗜酒大鼠品系差异的研究表明,中脑边缘多巴胺能系统的先天性缺陷是导致乙醇偏好的潜在因素。当有乙醇溶液可供选择时,大鼠会试图通过寻求药物的行为来克服这种缺陷,从而选择饮用乙醇溶液而非水。因此,在本研究中,我们比较了单次注射乙醇(1 g/kg,腹腔注射)对智利大学嗜酒(UChB)和智利大学戒酒(UChA)大鼠伏隔核壳中通过微透析测量的单胺细胞外水平的影响。这两种大鼠分别经过79代和88代选育,使其表现出对乙醇的偏好或排斥。据报道,在基础条件下,嗜酒大鼠的细胞外多巴胺水平低于戒酒大鼠,而乙醇诱导的嗜酒大鼠多巴胺释放增加幅度比戒酒大鼠大两倍。乙醇对嗜酒大鼠的更大影响与血液乙醇水平的差异无关,因为两种大鼠品系中乙醇的浓度和消除情况几乎相同,这表明嗜酒大鼠比戒酒大鼠对乙醇刺激多巴胺释放更敏感。在基础或乙醇刺激条件下,同时测量的嗜酒和戒酒大鼠的5-羟色胺或其代谢产物没有差异。总体而言,目前的结果表明,低多巴胺能张力和中脑边缘多巴胺对乙醇的强烈反应是与大鼠寻求乙醇行为相关的协同神经化学特征。