Effects of Chronic Alcohol Consumption and Aging on Dopamine D2 Receptors in Fischer 344 Rats

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Abstract
Aging and chronic alcohol consumption are each accompanied by significant changes in dopamine and dopamine receptors. This study extended previous work by investigating the combined effects of chronic alcoholism and aging on total dopamine D2 receptors in brain areas associated with the nigrostriatal and mesocorticolimbic systems. In addition, the effects of chronic alcohol consumption and aging on the high-affinity state of D2 receptors and their conversion to the low-affinity form is included. Quantitative autoradiography was used to assess [3H]spiperone-labeled D2 receptors in tissue sections from 5- to 14- and 24-month Fischer 344 rats that were pair-fed a control or 6.6% (v/v) ethanol-containing liquid diet for 6 weeks. In addition, D2 receptors were determined in rats given the control liquid diet ad libitum. The results of these experiments demonstrated age-related changes in the nigrostriatal system. There was an age-related loss of total dopamine D2 receptors in the rostral and caudal striatum (∼25% decrease in Bmax). This decline in D2 receptors may be associated with changes in motor function. Despite the age-related decline in D2 receptors, there were no significant differences in the proportion of striatal receptors in the high-affinity form or in their conversion to the low-affinity state. Both aging and chronic alcohol consumption produced significant changes in the concentration of D2 receptors in brain areas associated with the mesocorticolimbic system. That is, the specific binding of [3H]spiperone was decreased in the frontal cortex of aged rats. In addition, chronic alcoholism was associated with a significant increase (∼20%) in the Bmax for D2 receptors in the nucleus accumbens. Nonetheless, neither age nor chronic alcohol consumption altered the proportion of high-affinity D2 receptors in the nucleus accumbens or their conversion to the lower affinity state. The observed changes in D2 receptors in the frontal cortex and nucleus accumbens are of interest because of the involvement of the mesocorticolimbic dopamine areas in the rewarding properties of alcohol and other drugs of abuse. Although aging and chronic alcoholism both produced significant changes in dopamine D2 receptor concentrations, alcohol did not accentuate the age-related loss of D2 receptors. We cannot eliminate the possibility that a more prolonged exposure or higher ethanol dose may potentiate age-related changes in the dopaminergic system.