Regulation of dopamine D1 receptors by chronic administration of structurally different D1 receptor antagonists: a...

The effects of chronic treatment (18 days) with the novel D1 antagonists, the benzonaphthazepine SCH 39166 (2 mg/kg per day) and the tetrahydroisoquinoline A-69024 (10 mg/kg per day), on D1 and D2 receptor binding in the rat brain were studied by quantitative receptor autoradiography. The benzazepine derivatives, SCH 23390 (0.5 mg/kg per day) and SKF 38393 (20 mg/kg per day), the prototype D1 antagonist and agonist, respectively, were also included in the experiment. Chronic treatment with SCH 23390 increased D1 receptor binding, studied with [3H]SCH 23390, in the nucleus accumbens and in all subregions of the anterior caudatus-putamen. However, chronic treatment with SKF 38393 did not alter D1 receptor binding in the brain areas studied. Interestingly, chronic treatment with SCH 39166 increased D1 receptor binding in the anterior caudatus-putamen but not in the nucleus accumbens. In contrast, chronic treatment with A-69024 did not alter D1 receptor binding in the brain areas studied. Treatment with SCH 23390, SCH 39166, A-69024 or SKF 38393 failed to alter D1 receptor binding in the posterior caudatus-putamen and the tuberculum olfactorium. Neither the D1 antagonists nor the D1 agonist investigated altered D2 receptor binding, studied with [125I]sulpiride, in the caudatus-putamen and nucleus accumbens. In summary, the benzonaphthazepine D1 antagonist, SCH 39166, as well as the benzazepine D1 antagonist, SCH 23390, can increase D1 receptor binding without influencing D2 receptor binding. However, a tetrahydroisoquinoline, A-69024, failed to increase D1 receptor binding, suggesting a differential regulation of D1 receptors after treatment with this putative D1 antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)