Woods J M, Ricken J D, Druse M J
Department of Molecular and Cellular Biochemistry, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153, USA.
Alcohol Clin Exp Res. 1995 Oct;19(5):1331-7. doi: 10.1111/j.1530-0277.1995.tb01621.x.
The present study examined the hypothesis that chronic alcoholism augments the age-related loss of dopamine D1 receptors. This hypothesis was investigated because previous studies reported that both aging and chronic alcoholism produce significant changes in dopaminergic systems, and because chronic alcoholism potentiates some age-related CNS losses. In addition, this study investigated the effects of aging on D1 receptors in animals 1 and 7 days after withdrawal from chronic ethanol. Quantitative autoradiography was used to measure [3H]SCH 23390 binding to D1 receptors in brain areas associated with both the nigrostriatal and mesocorticolimbic dopamine systems. Receptors were assessed in 5-, 14-, and 24-month-old male Fischer 344 rats that were pair-fed a control or 6.6% (v/v) ethanol-containing liquid diet for 6 weeks. The results of these studies demonstrated that aging is associated with a significant decline in D1 receptors in the rostral and caudal striatum, and substantia nigra of both control and ethanol-fed rats. These receptor changes in the nigrostriatal system may be associated with motor abnormalities. In addition, there was an age-related decline in D1 receptors in two brain areas of the mesocorticolimbic system: the nucleus accumbens and frontal cortex. The latter findings may be important because of the involvement of this system with the rewarding properties of ethanol and other drugs of abuse. There were no age-related differences in the response of D1 receptors to ethanol withdrawal in the caudal and rostral striatum, substantia nigra, and nucleus accumbens.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究检验了慢性酒精中毒会加剧与年龄相关的多巴胺D1受体丧失这一假设。之所以研究该假设，是因为先前的研究报告称衰老和慢性酒精中毒都会使多巴胺能系统产生显著变化，还因为慢性酒精中毒会增强一些与年龄相关的中枢神经系统损伤。此外，本研究还调查了衰老对动物从慢性乙醇戒断1天和7天后D1受体的影响。采用定量放射自显影法来测量[3H]SCH 23390与黑质纹状体和中脑皮质边缘多巴胺系统相关脑区中D1受体的结合情况。在5个月、14个月和24个月大的雄性Fischer 344大鼠中评估受体，这些大鼠成对喂食对照或含6.6%（v/v）乙醇的液体饮食6周。这些研究结果表明，衰老与对照大鼠和乙醇喂养大鼠的吻侧和尾侧纹状体以及黑质中D1受体的显著下降有关。黑质纹状体系统中的这些受体变化可能与运动异常有关。此外，中脑皮质边缘系统的两个脑区——伏隔核和额叶皮质——中D1受体也出现了与年龄相关的下降。后一项发现可能很重要，因为该系统与乙醇和其他滥用药物的奖赏特性有关。在尾侧和吻侧纹状体、黑质以及伏隔核中，D1受体对乙醇戒断的反应不存在与年龄相关的差异。（摘要截选至250词）
