Forskolin increases phosphorylated-CREB and fos immunoreactivity in rat striatum.

Promoter regions of the preproenkephalin, preprodynorphin, and c-fos genes contain cyclase response elements (CREs) as well as AP-1 sites. Activation of the adenylate cyclase cascade leads to phosphorylation of cyclase response element binding proteins (P-CREBs) which then bind CREs in these genes and induce transcription. In this experiment, semi-quantitative immunocytochemistry was used to examine striatal CREB-, P-CREB-, and Fos-like immunoreactivity (IR) 1 h following intracerebroventricular injection of H2O-soluble forskolin. Although forskolin did not alter CREB-IR, forskolin did induce striatal P-CREB-IR and Fos-IR by 2.5- and 10-fold, respectively. These data support a role for P-CREB and/or Fos in regulating opioid peptide gene transcription following direct in vivo activation of adenylate cyclase.