Age-related changes in the regulation of behavior by D-1:D-2 dopamine receptor interactions

Functional interactions between D-1 and D-2 dopamine receptor systems appear important in the regulation of psychomotor behavior, and may alter with aging. Male Sprague-Dawley rats of 5 and 20–24 months were challenged with the selective D-2 agonist LY 163502 alone or following pretreatment with the selective D-1 antagonist SCH 23390. Typical sniffing and locomotor responses to LY 163502 alone were significantly reduced in aged animals. Pretreatment with SCH 23390 blocked these typical responses in both young and aged animals, consistent with their regulation by cooperative D-1:D-2 interactions; however, SCH 23390 released a significant excess of atypical limb/body jerking to LY 163502 in aged animals, a response which appears to have its basis in oppositional D-1:D-2 interactions. These results suggest that the net effect of aging on dopaminergic transmission is to reduce tonic activity through D-1 receptors to a greater extent than that occurring through D-2 receptors. As the present aged animals showed a selective loss of striatal D-2 but not of D-1 receptors in radioligand binding studies, such a reduction of D-1-mediated transmission with aging would seem to involve loss of presynaptic function or of postsynaptic mechanisms beyond the D-1 recognition site.