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Updated: Jul 15, 2026

Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area
Published on: August 10, 2012
Functional interaction between dopamine receptor subtypes for the regulation of c-fos expression
Dong-Im Cho1, WenYing Quan, Min-Ho Oak
1Research Institute of Drug Development, College of Pharmacy, Chonnam National University, Kwang-Ju 500-757, Republic of Korea.
Abstract:
Dopaminergic drugs increase the expression of the proto-oncogene, c-fos, in the brain, which is involved in the coordination of neurobiological changes caused by repeated cocaine or amphetamine use. This study examined the roles of five dopamine receptor subtypes on the c-fos promoter activity. D(1)R or D(5)R significantly increased the expression of c-fos promoter by activating protein kinase A. However, D(2)R, D(3)R, or D(4)R did not show any noticeable effects. The co-expression of D(1)R/D(3)R or D(1)R/D(2)R synergistically activated the basal and agonist-induced expression of the c-fos promoter, respectively. The Ral guanine-nucleotide-dissociation-stimulator-like, which was found to interact with the 3rd cytoplasmic loop of D(3)R, mediated the inhibitory activity of D(3)R in c-fos expression. In summary, the expression of the c-fos promoter was increased by the D1-like receptors and enhanced synergistically by the D2-like receptors via the modulation of cellular cAMP. D(3)R inhibited the expression of the c-fos promoter through an interaction with RGL.
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