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Chemical Senses 20: 257-260,
© 1995

research-article

Dopamine Regulation of Transcription Factor-Target Interactions in Rat Striatum

Steven E. Hyman1,2,3,, Rebecca L. Cole1,2, Christine Konradi1,3 and Barry E. Kosofsky1,4

1Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital CNY-2, 149 13th St, Charlestown MA 02129 2Program in Neuroscience, Harvard Medical School Boston, MA 02115 3Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School Boston, MA 4Department of Neurology, Massachusetts General Hospital and Harvard Medical School Boston, MA, USA

Correspondence to be sent to: S.E. Hyman, Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, CNY-2, 149 13th St, Charlestown, MA 02129, USA

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.


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