THE CORTICOSTERONE SYNTHESIS INHIBITOR METYRAPONE DECREASES DOPAMINE D-1 RECEPTORS IN THE RAT-BRAIN

Experiments were performed to examine the effect of metyrapone, an inh ibitor of corticosterone synthesis, on the level of dopamine D-1 recep tors and their transcripts in the caudate-putamen, nucleus accumbens a nd olfactory tubercle of the rat brain. The binding to dopamine D-1 re ceptors was measured by receptor autoradiography using the specific D- 1 receptor antagonist [H-3]SCH 23390. The level of dopamine D-1 recept or messenger RNA was determined by in situ hybridization histochemistr y. 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 studie d 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 lat eral part (24-27%). Decreases similar to those in the caudate-putamen were observed in the nucleus accumbens (21%) and olfactory tubercle (3 2%). Furthermore, metyrapone decreased the level of dopamine D-1 recep tor 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 t he synthesis of these hormones) decreases the messenger RNA encoding D -1 receptor synthesis, as well as the specific binding to this recepto r. (C) 1997 IBRO.