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Evidence for selective decreases in biogenic amine receptor function with age in the rabbit has been obtained. Dopamine-stimulated adenylate cyclase activity in the striatum (caudate-putamen) of rabbit brain declined by about 50 percent as rabbits aged from less than 1 to 4 to 5 years of age. Similar decreases in transmitter-stimulated adenylate cyclase activity were found for histamine as well as for dopamine and norepinephrine in hypothalamus, frontal cortex and anterior limbic cortex. Isoproterenol-stimulated activity was also decreased with age in frontal cortex. These changes appeared to represent decreases in maximal response and not alteration in affinity for amine. In contrast, dopamine-stimulated adenylate cyclase of retina and transmitter-independent (basal or Gpp(NH)p-stimulated) activity in each of the regions studied were not altered with age. Dopamine receptors in striatum directly assessed by measurement of [3H]-spiroperidol binding revealed a comparable decrease in the number of binding sites without change in ligand affinity. Preliminary data also indicated decreased spiroperidol binding sites in the cortical regions of older animals. These changes in striatum and cortex were evident in the absence of decreases in either dopamine content or choline acetylase activity, an activity presumed to be present in neurons containing dopamine receptors. It is proposed that selective age-dependent decreases in postsynaptic biogenic amine receptor content occur in the absence of, or independent from, neuronal cell loss, possibly by a mechanism involving receptor desensitization. These changes occur in the animal model in those brain regions which in man are thought to be of importance in the loss of cerebral function that is found with senscence.
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