Altered dopamine receptor mediated signal transmission in the striatum of aged rats

Abstract

Striatal membranes of very old (40 months) as against young (3 months) female Wistar rats were used. Binding saturation experiments with [ 3H]SCH 23390 at the dopamine (DA) D 1 receptor (D 1) and [ 3H]spiperone at the DA D 2 receptor (D 2) revealed no change in the affinity ( K d) but a significant decrease in the density ( B max) of D 1 (−31%, P < 0.005) and of D 2 (− 22%, P < 0.05), respectively, in the aged vs. young striata. Displacement of either [ 3H]SCH 23390 or [ 3H]spiperone binding by DA displayed biphasic curves. The Hill coefficient (nH) was significantly increased in the senescent compared with the young of D 1 (0.72 ± 0.04 vs.0.61 ± 0.03, P < 0.025) but unchanged of D 2 (0.49 ± 0.04 vs.0.51 ± 0.02). The proportion of the high-affinity agonist binding state ( R high) was significantly decreased ( P < 0.025) in the older (20.9 ± 3.2%) in comparison with the young (30.6 ± 2.0%) in D 1 but increased non-significantly in D 2 (47.9 ± 2.6 vs.40.5 ± 5.1%). Calculating the resulting B max from Scatchard and displacement analyses of each single aged and young animal revealed a highly significant reduction ( P < 0.001) of the high-affinity agonist binding state of D 1 (−53%) as well as a non-significant reduction of D 2 (−8%) in the older. Simultanously, a significant 57% decrease ( P < 0.01) in the adenylate cyclase (AC) activity stimulated by 10 μM DA in the senescent compared with the young animals was monitored. The DA stimulation of AC was reversed in both cases by the addition of 200 nM of the D 1 antagonist SCH 23390.