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长期乙醇摄入对中脑边缘和黑质纹状体多巴胺系统的影响。

The effects of chronic ethanol consumption on the mesolimbic and nigrostriatal dopamine systems.

作者信息

Pellegrino S M, Druse M J

机构信息

Department of Molecular and Cellular Biochemistry, Loyola University of Chicago, Stritch School of Medicine, Maywood, IL 60153.

出版信息

Alcohol Clin Exp Res. 1992 Apr;16(2):275-80. doi: 10.1111/j.1530-0277.1992.tb01376.x.

Abstract

Both the mesolimbic dopamine system, which is involved with the rewarding properties of several drugs of abuse, and the nigrostriatal dopamine system, which is involved with motor function, appear to be sensitive to the effects of ethanol. In order to determine which components of the mesolimbic and nigrostriatal dopamine systems are adversely affected by chronic ethanol consumption, we assessed dopamine and DOPAC (3,4-dihydroxyphenylacetic acid) concentration and D1 and D2 receptors in several dopaminergic brain areas. These studies demonstrated that consumption of a 6.6% (v/v) ethanol-containing lipid diet for 1 month affected several components of the mesolimbic dopamine system in 3-month-old Fisher 344 rats and fewer components of the nigrostriatal dopamine system. Specifically, there was a 1.6- to 2.6-fold increase in the concentration of DOPAC in the nucleus accumbens (NA), frontal cortex (FCX), ventral tegmental area (VTA), and substantia nigra (SN). While the increase in DOPAC in the FCX and VTA was paralleled by a similar increase in dopamine, there was a significant deficiency of dopamine in the SN. These results suggest that there is an increase in dopamine turnover in the FCX, VTA, NA, and SN, which is accompanied by increased dopamine synthesis in the former two regions. Studies of dopamine receptors in control and ethanol-fed rats demonstrated a 25% loss of D1 receptors in the NA. No significant differences were found in D1 receptors in the striatum or globus pallidus. In addition, there were no differences in the number of total D2 receptors or in the conversion of the high to low affinity state of D2 receptors in the nucleus accumbens and striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

中脑边缘多巴胺系统与多种成瘾药物的奖赏特性有关,黑质纹状体多巴胺系统与运动功能有关,这两个系统似乎都对乙醇的作用敏感。为了确定中脑边缘和黑质纹状体多巴胺系统的哪些成分会受到慢性乙醇摄入的不利影响,我们评估了几个多巴胺能脑区的多巴胺和3,4-二羟基苯乙酸(DOPAC)浓度以及D1和D2受体。这些研究表明,给3个月大的Fisher 344大鼠喂食含6.6%(v/v)乙醇的脂质饮食1个月,会影响中脑边缘多巴胺系统的多个成分,而对黑质纹状体多巴胺系统成分的影响较少。具体而言,伏隔核(NA)、额叶皮质(FCX)、腹侧被盖区(VTA)和黑质(SN)中的DOPAC浓度增加了1.6至2.6倍。虽然FCX和VTA中DOPAC的增加与多巴胺的类似增加平行,但SN中多巴胺明显缺乏。这些结果表明,FCX、VTA、NA和SN中的多巴胺周转率增加,前两个区域的多巴胺合成也增加。对对照大鼠和乙醇喂养大鼠的多巴胺受体研究表明,NA中D1受体减少了25%。纹状体或苍白球中的D1受体未发现显著差异。此外,伏隔核和纹状体中D2受体总数或D2受体从高亲和力状态向低亲和力状态的转换数量没有差异。(摘要截断于250字)

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