Dopamine Regulation of Transcription Factor-Target Interactions in Rat Striatum

• Published in: Chemical senses 1995-04, Vol.20 (2), p.257-260
• Main Authors: Hyman, Steven E., Cole, Rebecca L., Konradi, Christine, Kosofsky, Barry E.
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry and metabolism; Biological and medical sciences; Central nervous system; Corpus Striatum - physiology; Dopamine - physiology; Dopamine Agonists - pharmacology; Dopamine Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Rats; Transcription Factors - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0379-864X; 1464-3553
• DOI: 10.1093/chemse/20.2.257

Transcriptional regulation is an important mechanism by which neurons adapt to environmental stimuli. The indirect dopamine agonists, amphetamine and cocaine have been shown to induce expression of immediate early genes, such as c-fos, and neuropeptide genes, such as prodynorphin in the rat striatum. Here we show that phosphorylation of transcription factor CREB is a critical early event coupling dopamine stimulation to gene regulation. CREB interacts with functional regulatory elements in both the c-fos and prodynorphin genes, and is phosphorylated in response to dopamine in a D1 dopamine receptor-dependent manner. In addition, we show by intra-striatal injection of antisense oligonucleotides directed against CREB mRNA, that CREB protein is required for c-fos induction by amphetamine.