Effects of Age on Selective Antagonist Binding to Muscarinic Receptors in Rat Striatum

The objective of the present study was to investigate the effect of senescence on the binding properties of muscarinic receptors in the neostriatum of young (3 months), middle-aged (18 months) and aged (33 months) male Fischer 344 x Brown Norway hybrid rats by employing direct binding of selective radiolabeled antagonists. Using the selective M, muscarinic receptor antagonist, $[^3H]$AF-DX384, as the ligand, no significant difference in the maximal receptor density (Bmax) was observed in the neostriatum among any age-groups. In contrast, with the selective M, receptor antagonist, $[^3H]$4-DAMP, a significant increase in the number of muscarinic receptors was observed in neostriatal membrane fractions prepared from the aged animals relative to that observed in the young rats. For each ligand there was no age-related change in its affinity (Kd) for the muscarinic receptors. These results indicate that the observed age-related changes in the muscarinic receptor density may not be necessarily decremuntal and depend upon the muscarinic receptor subtype examined.