Regulation of dopamine D 1 receptors by chronic administration of structurally different D 1 receptor antagonist: A quantitative autoradiographic study

Abstract

The effects of chronic treatment (18 days) with the novel D 1 antagonists, the benzonaphthaepine SCH 39166 (2 mg/kg per day) and the tetrahydroisoquinoline A-69024 (10 mg/kg per day), on D 1 and D 2 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 D 1 antagonist and agonist, respectively, were also included in the experiment. Chronic treatment with SCH 23390 increased D 1 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 D 1 receptor binding in the brain areas studied. Interestingly, chronic treatment with SCH 39166 increased D 1 receptor binding in the anterior caudatus-putamen but not in the nucleus accumbens. In contrast, chronic treatment with A-69024 did not alter D 1 receptor binding in the brain areas studied. Treatment with SCH 23390, SCH 39166, A-69024 or SKF 38393 failed to alter D 1 receptor binding in the posterior caudatus-putamen and the tuberculum olfactorium. Neither the D 1 antagonists nor the D 1 agonist investigated altered D 2 receptor binding, studied with [ 125I]sulpiride, in the caudatus-putamen and nucleus accumbens. In summary, the benzonaphthazepine D 1 antagonist, SCH 39166, as well as the benzazepine D 1 antagonist, SCH 23390, can increase D 1 receptor binding,without influencing D 2 receptor binding. However, a tetrahydroisoquinoline, A-69024, failed to increase D 1 receptor binding, suggesting a differential regulation of D 1 receptors after treatment with this putative D 1 antagonist. In addition, there appear to be differences between D 1 receptors in the anterior and posterior caudatus-putamen in their sensitivity to chronic D 1 blockade.