Evidence for selective loss of brain dopamine- and histamine-stimulated adenylate cyclase activities in rabbits with aging.

Dopamine-stimulated adenylate cyclase activity in striatum and both dopamine- and histamine-stimulated adenylate cyclase activity in hypothalamus, frontal cortex and anterior limbic cortex declined by about 50% as rabbits aged from 5.5 months to 5.5 years of age. These changes were primarily in maximal response to amine although an additional component involving decreased affinity in the case of dopamine may also be present. In contrast, dopamine-stimulated adenylate cyclase of retina and both basal and guanyl-5'-yl-imidodiphosphate (Gpp(NH)p)-stimulated activity in these regions were not altered with age. There was no measurable decrease in the old animals in either dopamine or norepinephrine concentration in striatum, anterior limbic cortex or retina, or in choline acetylase activity or [3H]quinuclidinylbenzilate binding in striatum, anterior limbic cortex or frontal cortex. It is proposed that selective age-dependent decreases in transmitter receptors coupled to adenylate cyclases occur in the absence of or independent from neuronal cell loss, as evidenced by the retention of the other biochemical markers.