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 receptor antagonist, SCH 23390, on the steady-state densities and turnover rates of these receptors were investigated in the striatum and substantia nigra of the rat. To this aim, we assessed the repopulation kinetics of [H-3]SCH 23390 binding sites after irreversible inactivation of dopamine D1 receptors induced by a single dose of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 mg/kg s.c.) in rats chronically treated with SCH 23390. The receptor repopulation was analyzed using a theoretical model that assumes a constant rate of receptor production and a first-order receptor degradation rate. The repeated administration of SCH 23390 (0.05 mg/kg s.c., thrice daily for 21 days) enhanced the steady-state density of dopamine D1 receptors in the striatum (+30%) and substantia nigra (+24%). This treatment also increased the production rates of dopamine D1 receptors in the striatum (+44%) and substantia nigra (+54%). By contrast, the rate constants of dopamine D1 receptor degradation were unchanged in both brain areas. These results suggest that the up-regulation of dopamine D1 receptors induced by chronic treatment with SCH 23390 is determined by modifications in the processes that control the rate of receptor production but not of receptor degradation.