Age-related changes of dopamine D-1-like and D-2-like receptor binding in the F344/N rat striatum revealed by positron emission tomography and in vitro receptor autoradiography

To clarify age-related changes in dopamine D-1-like and D-2-like receptor b inding in the striatum, positron emission tomography (PET) and in vitro rec eptor autoradiography (in vitro ARG) were performed using F344/N rats of va rious ages (6, 12, 18, and 24 months). In the PET study, [C-11]SCH23390 and [C-11]raclopride were used to image dopamine D-1-like receptors and dopami ne D-2-like receptors, respectively, while [H-3]SCH23390 and [H-3]racloprid e were used for the in vitro ARG study. With PET, we calculated the binding potential ( = k(3)/k(4), B-max/K-d) of [C-11]SCH23390 and [C-11]raclopride in the striatum according to the curve fitting (CF) and the Logan plot (LP ) methods. The binding potential of [C-11]SCH23390 in the striatum. demonst rated significant decrease as a function of age (max. decrease -26%) by the LP method, while this was not observed in the data analyzed by the CF meth od. In contrast, the binding potential of [C-11]raclopride in the striatum decreased significantly with age by both the CF (max. decrease -28%) and th e LP (max. decrease -36%) methods. However, no significant difference by ei ther method was observed in rats between 6 and 12 months old using either l igand. In the in vitro ARG study, the specific binding (fmol/mg tissue) of [H-3]SCH23390 and [H-3]raclopride in the striatum were determined. Both [H- 3]SCH23390 and [H-3]raclopride binding declined considerably with age as no ted by comparing 12, 18, and 24-month-old rats against those 6 months old ( max. decrease -29% and -31%, respectively). The substantial difference in b inding shown in 12-month-olds in comparison with 6-month-olds using either ligand with in vitro ARG was in contrast with the PET results. These distin ctions between the PET and the in vitro ARG studies may be attributed to th e receptor microenvironment created under these experimental conditions. Th e results indicate that PET with LP analysis is useful in obtaining age-rel ated changes of D-1-like and D-2-like receptor binding in the striatum of l iving rats. (C) 2001 Wiley-Liss, Inc.