Effects of Chronic Alcohol Consumption and Aging on Dopamine D1 Receptors in Fischer 344 Rats

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Abstract
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. Consumption of the 6.6% (v/v) ethanol‐containing liquid diet for 6 weeks did not augment any of the age‐related losses of D, receptors. Nonetheless, we cannot eliminate the possibility that either a more prolonged ethanol exposure or consumption of a higher dose of ethanol would have had more pronounced effects on the young to aged rats.