Alterations in opiate receptor binding in the hippocampus of aged Long-Evans rats

Quantitative in vitro autoradiography was used to examine [³H]D-Ala², MePhe⁴, Gly-O1⁵ enkephalin (DAGO) (μ-agonist) and [³H]diprenorphine (general opiate antagonist) binding sites in the hippocampal formation of young (6-8 months) and aged (25-28 months) Long-Evans rats. Age-related changes in these binding sites were restricted to specific regions but were not generally dependent on the ligand used. No reliable age-related changes in opiate binding were observed in the CA1 field or subicular region. In contrast, a decrease in the density of binding was found in both dorsal and ventral hippocampus within the CA3 field of aged brains. An age-related decrease in opiate binding within the dentate gyrus differed in its topography at dorsal and ventral levels of the hippocampus. A uniform decrease of opiate receptor binding was found throughout the dorsal dentate gyrus, while a more localized decrease of these sites occurred in hilar and granular layers of the ventral dentate gyrus. These results indicate that a decrease of opiate binding in the hippocampal formation is largely localized to the CA3 region and dentate gyrus of aged rats. These findings are discussed with reference to age-related changes in hippocampal pathways containing opioid peptides. The implications for hippocampal opioid function in learning and age-related cognitive decline are also considered.