DOPAMINE REGULATION OF TRANSCRIPTION FACTOR-TARGET INTERACTIONS IN RAT STRIATUM

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