The corticosterone synthesis inhibitor metyrapone decreases dopamine D1 receptors in the rat brain.
Experiments were performed to examine the effect of metyrapone, an inhibitor of corticosterone synthesis, on the level of dopamine D1 receptors and their transcripts in the caudate-putamen, nucleus accumbens and olfactory tubercle of the rat brain. The binding to dopamine D1 receptors was measured by receptor autoradiography using the specific D1 receptor antagonist [3H]SCH 23390. The level of dopamine D1 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 D1 receptor-specific binding in the studied areas of the rat brain. In the caudate putamen, the decrease in [3H]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 D1 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 D1 receptor level in the rat brain. since metyrapone (which inhibits the synthesis of these hormones) decreases the messenger RNA encoding D1 receptor synthesis, as well as the specific binding to this receptor.
Czyrak
A
A
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Wedzony
K
K
Michalska
B
B
Fijał
K
K
Dziedzicka-Wasylewska
M
M
Maćkowiak
M
M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects*; D003345:Corticosterone / Q000378:metabolism; D008297:Male; D008797:Metyrapone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects*
D017447:Receptors, Dopamine D1; D003345:Corticosterone; D008797:Metyrapone