Induction of immediate early genes by cyclic AMP in primary cultures of neurons from rat cerebral cortex

In this paper, we tested whether physiological activators of the cAMP second messenger pathway in primary cultures of neurons from rat cerebral cortex directly induce c-fos and other immediate early gene (IEG) transcription factors. We have found that brief (30 s to 2 min) stimulation of neurons with vasoactive intestinal peptide (VIP) and SKF-38393, a D₁-dopaminergic receptor agonist, potently increased mRNA levels for the IEGs c-fos, jun-B, and NGFI-A, with weaker increases for c-jun. This action was mimicked by forskolin and dibutyryl cAMP. IEG induction by VIP and dibutyryl cAMP was not blocked by excitatory amino acid receptor antagonists or by blockers of dihydropyridine-sensitive calcium channels. Moreover, calcium-free medium did not modify IEG induction by dibutyryl cAMP, suggesting that cAMP can directly regulate IEG expression in differentiated neurons independently of calcium.