CHRONIC TREATMENT WITH SCH-23390 INCREASES THE PRODUCTION-RATE OF DOPAMINE-D(1) RECEPTORS IN THE NIGRO-STRIATAL SYSTEM OF THE RAT

The effects of chronic treatment with the selective dopamine D1 recept or antagonist, SCH 23390, on the steady-state densities and turnover r ates of these receptors were investigated in the striatum and substant ia nigra of the rat. To this aim, we assessed the repopulation kinetic s of [H-3]SCH 23390 binding sites after irreversible inactivation of d opamine D1 receptors induced by a single dose of N-ethoxycarbonyl-2-et hoxy-1,2-dihydroquinoline (EEDQ, 10 mg/kg s.c.) in rats chronically tr eated with SCH 23390. The receptor repopulation was analyzed using a t heoretical model that assumes a constant rate of receptor production a nd a first-order receptor degradation rate. The repeated administratio n of SCH 23390 (0.05 mg/kg s.c., thrice daily for 21 days) enhanced th e steady-state density of dopamine D1 receptors in the striatum (+30%) and substantia nigra (+24%). This treatment also increased the produc tion rates of dopamine D1 receptors in the striatum (+44%) and substan tia nigra (+54%). By contrast, the rate constants of dopamine D1 recep tor degradation were unchanged in both brain areas. These results sugg est that the up-regulation of dopamine D1 receptors induced by chronic treatment with SCH 23390 is determined by modifications in the proces ses that control the rate of receptor production but not of receptor d egradation.