Collins M A, Ung-Chhun N, Cheng B Y, Pronger D
Department of Biochemistry and Biophysics, Loyola University of Chicago, Maywood, Illinois 60153.
J Neurochem. 1990 Nov;55(5):1507-14. doi: 10.1111/j.1471-4159.1990.tb04932.x.
Brain concentrations of salsolinol (SAL), a simple tetrahydroisoquinoline (sTIQ) condensation product of dopamine (DA) and acetaldehyde, are reported to increase in chow-fed rats drinking ethanol/H2O ad libitum. However, our analyses showed that rat chow contains traces of SAL and, as previously reported, appreciable 3,4-dihydroxyphenylalanine (DOPA), a sTIQ precursor. To examine the effect of consumption of ethanol in a DOPA- and SAL-free diet on endogenous sTIQs, we analyzed two brain regions and blood plasma of rats undergoing prolonged intake (3 weeks and 23 weeks) of liquid diet containing 6.6% ethanol or isocaloric carbohydrate. SAL and three other DA-related sTIQs were quantitated using capillary gas chromatography/mass spectrometry in the selected ion mode with deuterated standards. In accord with studies on ethanol/chow-fed rats, sTIQ concentrations in hypothalamus were elevated after 3 weeks of ethanol, although after 23 weeks, hypothalamic sTIQs were either unchanged or reduced (O-methylated SAL). Furthermore, sTIQ concentrations in corpus striatum and, with one exception, plasma were not altered by ethanol ingestion for either duration. (However, 23 weeks of ethanol intake significantly reduced the striatal concentrations of DA and its acid metabolite, presumably reflecting neurotoxicity.) Reasoning that DOPA in diet might underlie the reported ethanol-dependent increases in striatal sTIQs, we found that L-DOPA supplementation (500 micrograms/rat/day) of EtOH/liquid diet-fed rats for 13 weeks tended to increase striatal SAL. Overall, the data indicate that elevations in endogenous sTIQ concentrations due to prolonged ethanol intake depend on the brain region, duration of intake, and even associated dietary constituents. In that regard, the higher striatal SAL concentrations in rats drinking ethanol ad libitum could have been facilitated by DOPA and perhaps SAL consumed in lab chow.
据报道，随意饮用乙醇/水的正常饮食大鼠脑中的salsolinol（SAL）浓度会升高，SAL是多巴胺（DA）和乙醛的一种简单四氢异喹啉（sTIQ）缩合产物。然而，我们的分析表明，大鼠食物中含有微量的SAL，并且如先前报道的那样，还含有可观的3,4-二羟基苯丙氨酸（DOPA），一种sTIQ前体。为了研究在无DOPA和SAL的饮食中摄入乙醇对内源性sTIQ的影响，我们分析了长期摄入（3周和23周）含6.6%乙醇或等热量碳水化合物的流质饮食的大鼠的两个脑区和血浆。使用毛细管气相色谱/质谱联用仪在选择离子模式下，以氘代标准品对SAL和其他三种与DA相关的sTIQ进行定量。与对乙醇/正常饮食大鼠的研究一致，乙醇摄入3周后下丘脑的sTIQ浓度升高，尽管在23周后，下丘脑的sTIQ要么没有变化，要么降低（O-甲基化SAL）。此外，在两个时间段内，乙醇摄入均未改变纹状体中的sTIQ浓度，血浆中的sTIQ浓度除一个例外也未改变。（然而，摄入乙醇23周显著降低了纹状体中DA及其酸性代谢物的浓度，这可能反映了神经毒性。）由于推测饮食中的DOPA可能是所报道的纹状体sTIQ乙醇依赖性增加的基础，我们发现，给饮用乙醇/流质饮食的大鼠补充左旋多巴（500微克/大鼠/天）13周往往会增加纹状体中的SAL。总体而言，数据表明，长期摄入乙醇导致的内源性sTIQ浓度升高取决于脑区、摄入持续时间，甚至相关的饮食成分。在这方面，随意饮用乙醇的大鼠纹状体中较高的SAL浓度可能是由食物中摄入的DOPA以及可能的SAL促成的。
