Jiao X, Paré W P, Tejani-Butt S M
Department of Pharmacology and Toxicology (Box 118), University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104, USA.
Brain Res. 2006 Feb 16;1073-1074:175-82. doi: 10.1016/j.brainres.2005.12.009. Epub 2006 Feb 2.
Even though animal and human studies show alterations in dopamine transporter (DAT) sites after alcohol withdrawal, the role of DAT in influencing either alcoholic or depressive behavior has not been examined extensively. Given that the Wistar-Kyoto (WKY) rat is a putative animal model of depressive behavior, the present study examined the effects of chronic alcohol consumption on DAT sites in WKY versus Wistar (WIS) rats. Brains from both strains were sectioned for autoradiographic analysis of [3H]-GBR12935 binding to DAT sites after 24 days of alcohol exposure. The results indicated that WKY rats consumed a greater amount of alcohol (P < 0.001) than WIS rats did throughout the experiment. Autoradiographic analyses of discrete brain regions indicated that alcohol consumption increased DAT sites in a greater number of brain areas in WKY compared to WIS rats. In WKY rats, the binding of [3H]-GBR12935 to DAT sites was increased in the basolateral, central and lateral nuclei of the amygdala, lateral nucleus of the hypothalamus, olfactory tubercle, caudate-putamen, nucleus accumbens and substantia nigra (P < 0.05) and decreased in the ventromedial nucleus of the hypothalamus and the CA1 region of the hippocampus. In WIS rats, alcohol consumption increased DAT sites in the CA1 region of the hippocampus, basolateral nucleus of the amygdala, ventral tegmental area and substantia nigra, and decreased DAT sites in the lateral and ventromedial hypothalamus and dentate gyrus. These results indicate a strain dependent alteration in DAT sites which may be related to altered dopamine neurotransmission in select brain regions following alcohol consumption.
尽管动物和人体研究表明，戒酒会使多巴胺转运体（DAT）位点发生改变，但DAT在影响酗酒或抑郁行为方面的作用尚未得到广泛研究。鉴于Wistar-Kyoto（WKY）大鼠被认为是抑郁行为的动物模型，本研究考察了长期饮酒对WKY大鼠与Wistar（WIS）大鼠DAT位点的影响。在酒精暴露24天后，对两种品系大鼠的大脑进行切片，以放射自显影分析[3H]-GBR12935与DAT位点的结合情况。结果表明，在整个实验过程中，WKY大鼠比WIS大鼠摄入的酒精量更多（P < 0.001）。对离散脑区的放射自显影分析表明，与WIS大鼠相比，饮酒使WKY大鼠更多脑区的DAT位点增加。在WKY大鼠中，[3H]-GBR12935与杏仁核基底外侧核、中央核和外侧核、下丘脑外侧核、嗅结节、尾状核-壳核、伏隔核和黑质中DAT位点的结合增加（P < 0.05），而在下丘脑腹内侧核和海马CA1区则减少。在WIS大鼠中，饮酒使海马CA1区、杏仁核基底外侧核、腹侧被盖区和黑质的DAT位点增加，而使下丘脑外侧核和腹内侧核以及齿状回的DAT位点减少。这些结果表明，DAT位点存在品系依赖性改变，这可能与饮酒后特定脑区多巴胺神经传递的改变有关。
