Regulation of striatal dopamine receptors by corticosterone: an in vivo and in vitro study.
The effects of chronic corticosterone administration and adrenalectomy on the expression of brain dopamine receptors were studied in rats. In situ hybridization and receptor binding autoradiography were carried out to determine D1, D2 and D3 receptor expression in dorsal and ventral striata. Except for down-regulation of D2 mRNA in dorsal striatum after 2 week corticosterone treatment, no other significant changes were detected. In addition, the transcriptional regulation of D1 and D2 gene promoters by glucocorticoids was studied in neuroblastoma cell lines using transient transfections. While a small segment of the D2-promoter could be activated three-fold by dexamethasone, large fragments of neither D1 or D2 promoters were regulated by this treatment. Glucocorticoids do not appear to have direct overall effects on striatal dopamine receptor expression. The observed down-regulation of D2 receptor mRNA in the dorsal striatum in vivo is likely secondary to increased striatal dopamine release induced by corticosterone.
Lammers
C H
CH
Genetic Pharmacology Unit, Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, MSC 1406, Bethesda, MD 20892-1406, USA.
D'Souza
U M
UM
Qin
Z H
ZH
Lee
S H
SH
Yajima
S
S
Mouradian
M M
MM
D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic
D009419:Nerve Tissue Proteins; D011954:Receptors, Dopamine; D003345:Corticosterone