The corticosterone synthesis inhibitor metyrapone decreases dopamine D-1 receptors in the rat brain

Experiments were performed to examine the effect of metyrapone, an inhibitor of corticosterone synthesis, on the level of dopamine D-1 receptors and their transcripts in the caudate-putamen, nucleus accumbens and olfactory tubercle of the rat brain. The binding to dopamine D-1 receptors was measured by receptor autoradiography using the specific D-1 receptor antagonist [H-3]SCH 23390. The level of dopamine D-1 receptor messenger RNA was determined by in situ hybridization histochemistry. The results obtained have shown that metyrapone (two injections of 150 and 50 mg/kg; i.p., given 20 and 3 h before killing, respectively) induced a decrease in the D-1 receptor-specific binding in the studied areas of the rat brain. In the caudate-putamen, the decrease in [H-3]SCH 23390 binding was stronger in the medial (31-39%) than in the lateral part (24-27%). Decreases similar to those in the caudate-putamen were observed in the nucleus accumbens (21%) and olfactory tubercle (32%). Furthermore, metyrapone decreased the level of dopamine D-1 receptor messenger RNA in the caudate-putamen (17-28%), nucleus accumbens (20%) and olfactory tubercle (18%). In conclusion, our study indicates that glucocorticoids might be involved in the regulation of dopamine D-1 receptor level in the rat brain, since metyrapone (which inhibits the synthesis of these hormones) decreases the messenger RNA encoding D-1 receptor synthesis, as well as the specific binding to this receptor. (C) 1997 IBRO.