Variations in age-related decline in striatal D2-dopamine receptors in a variety of mouse strains

To determine the importance of inheritance on the age-associated decline in D2-dopamine receptor number, the binding of [3H]spiperone to mouse striatal membranes was measured in animals ranging from 7 to 104 weeks of age from 5 murine strains (C57BL/6J, C3/HeJ, A/J, SJL/J and DBA/1J). In young mice, receptor number (Bmax) was influenced by genetic background such that C57BL/6J less than SJL/J less than A/J = DBA/1J = C3H/HeJ. A 50-60% decline in Bmax with age was found in all strains except for C57BL/6J. Bmax in the C57BL/6J mice were lower than in the other strains of young animals (7-15 weeks) but remained relatively constant throughout life (measured up to 104 weeks of age). Furthermore, the maximal decline in receptor number was observed relatively early in life (16-30 weeks) and remained constant thereafter. Neither age nor genetic background influenced ligand affinity (Kd). Thus the results of this study suggest that the maximal decline in Bmax for the dopamine receptor occurs before the second half of life and that the magnitude of this decline is polymorphic.