Reduced dopaminergic binding during aging in the rodent striatum

Abstract

[3H]Spiroperidol and [3H]ADTN ( 2-amino-l,7-dihydroxy-1,2,3,4-tetra hydronaphthalene) binding were used to assay for dopamine receptors in aged C57BL/6J mouse striatal membranes. [3H]spiroperidol binding declined linearly with age starting at 3 months. By 28 months, spiroperidol binding was only about 50% of the 3 month value. Dissociation constants dissociation rates and binding inhibition by (+)-butaclamol (antagonist) and apomorphine (agonist) were similar, suggesting that the age-related loss of spiroperidol binding was due to a loss in receptor number and not an alteration in binding affinity. [3H]ADTN binding also declined with age, but the losses tended to be about twice as large as those seen for spiroperidol. Consideration of possible mechanisms of receptor loss with age indicate that nigrostriatal denervation effects cannot explain all aging changes in striatal dopaminergic functions. The loss of receptors with age may derive from a loss of striatal neurones on which residue a population of dopaminergic binding sites.