Activity-dependent and use-dependent regulation of dopamine-receptor clustering

In this study, fluorescence-conjugated ligands were employed to label dopam inergic D-1-like and D-2-like receptors, respectively, in neurons derived f rom the frontal cortex of embryonic rats. The receptor binding sites were v isualized and analyzed using confocal microscopy. Our results showed that f luorescently labeled receptors tended to form clusters with a diameter of a bout one micrometer and were distributed on both somata and dendrites. Chro nic treatment with tetrodotoxin reduced the number of fluorescent clusters of both D-1-like and D-2-like receptors, while chronic treatment with a hig h concentration of potassium increased the number of fluorescent clusters o f both D-1-like and D-2-like receptors. Further, chronic treatment with SCH 23390 up-regulated the number of D-1-like receptor clusters, whereas chroni c treatment with bromocriptine down-regulated the number of D-2-like recept or clusters. In addition, chronic treatment with spiperone downregulated th e number of D-1-like receptor clusters. These results suggest that both neu ronal activity and dopaminergic receptor occupancy are important factors th at determine dopaminergic receptor clustering which is an essential step to ward synaptogenesis during neuronal maturation process. (C) 2000 Lippincott Williams & Wilkins.