Cholinergic binding sites in rat brain: Analysis by age and cognitive status

Age-related alterations in the density of cholinergic receptor binding and reuptake sites were examined in discrete forebrain regions of behaviorally tested rats using quantitative autoradiography. Neurochemical changes associated with chronological age alone were distinguished from memory-dependent alterations by correlating density of binding sites with performance in the Morris water maze task. An initial analysis of tritium quenching indicated no reliable differential quenching in the study population. Modest age-related reductions in selected subtypes of cholinergic binding sites in basal forebrain, basal ganglia, and thalamus were observed. However, these reductions were not correlated with a spatial memory deficit. In contrast, no significant changes in the analysis by chronological age were detected for the density of [3H]hemicholinium binding to high affinity choline uptake sites or [3H]pirenzepine binding to M1 receptors in any brain region but strong correlations were found between behavioral performance of aged rats and density of these sites in dorsal hippocampal subfield CA3 and dentate gyrus. These findings indicate the value of combined neurobiological/behavioral assessment.