EFFECTS OF CHRONIC ALCOHOL-CONSUMPTION AND AGING ON DOPAMINE D-2 RECEPTORS IN FISCHER-344 RATS

Aging and chronic alcohol consumption are each accompanied by signific ant changes in dopamine and dopamine receptors. This study extended pr evious work by investigating the combined effects of chronic alcoholis m and aging on total dopamine D-2 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 D-2 receptors and their conversion to the low-affinity form is included. Quantitative autoradiography was used to assess [H-3]spip erone-labeled D-2 receptors in tissue sections from 5- to 14- and 24-m onth Fischer 344 rats that were pair-fed a control or 6.6% (v/v) ethan ol-containing liquid diet for 6 weeks. In addition, D-2 receptors were determined in rats given the control liquid diet ad libitum, The resu lts of these experiments demonstrated age-related changes in the nigro striatal system, There was an age-related loss of total dopamine D-2 r eceptors in the rostral and caudal striatum (similar to 25% decrease i n B-max). This decline in D-2 receptors may be associated with changes in motor function, Despite the age-related decline in D-2 receptors, there were no significant differences in the proportion of striatal re ceptors in the high-affinity form or in their conversion to the low-af finity state, Both aging and chronic alcohol consumption produced sign ificant changes in the concentration of D-2 receptor, in brain areas a ssociated with the mesocorticolimbic system. That is, the specific bin ding of [H-3]spiperone was decreased in the frontal cortex of aged rat s, In addition, chronic alcoholism was associated with a significant i ncrease (similar to 20%) in the B-max for D-2 receptors in the nucleus accumbens, Nonetheless, neither age nor chronic alcohol consumption a ltered the proportion of high-affinity D-2 receptors in the nucleus ac cumbens or their conversion to the lower affinity state, The observed changes in D-2 receptors in the frontal cortex and nucleus accumbens a re of interest because of the involvement of the mesocorticolimbic dop amine areas in the rewarding properties of alcohol and other drugs of abuse, Although aging and chronic alcoholism both produced significant changes in dopamine D-2 receptor concentrations, alcohol did not acce ntuate the age-related loss of D-2 receptors, We cannot eliminate the possibility that a more prolonged exposure or higher ethanol dose may potentiate age-related changes in the dopaminergic system.