Time-Dependent Exposure of Nicotine and Smoke Modulate Ultrasubcellular Organelle Localization of Dopamine D-1 and D-2 Receptors in the Rat Caudate-Putamen

Abstract

The correlation of the subcellular localization of dopamine D-1 and D-2 receptors (DA D-1 R, DA D-2 R) with nicotine addiction has not been studied. We demonstrated the ultrasubcellular organelle localization of DA D-1 and D-2 Rs in the caudate-putamen (CPu) area of rat brain in vivo exposed to nicotine (3 mg/day; oral) and passive cigarette smoking (500 ml each; 3 times/day) for 1, 4, and 12 weeks, respectively. Our results revealed DA D-1 R localization in the presynaptic and postsynaptic dendrites, endocytic vesicles, and secretory granules, and DA D-2 R localization in the presynaptic dendrites and vesicles. DA D-1 R immunogold particles were highly decreased in the secretory granules of CPu, and increased in the postsynaptic area and vesicles after prolonged nicotine and smoking exposures, suggesting the strong influence of long time smoking and nicotine exposures on DA D-1 R subcellular organelle localization. DA D-2 R immunoreactivity was comparatively less changed than that of the DA D-1 R. Western blot analysis also showed the differential expression of DA D-1 and D-2 R proteins upon nicotine and smoking exposures as compared to the untreated controls. Taken together, the results for the first time suggests the execution of addictive behavior of nicotine through modulation of mesolimbic dopaminergic system targeting subcellular organelle of DA D-1 and D-2 Rs in the CPu of adult rat brain that may lead to novel therapeutic approaches related to nicotine's neuropsychological disorders including drug addiction. Synapse 63:847-854, 2009. (C) 2009 Wiley-Liss, Inc.