Cyclic 3',5'-adenosine monophosphate (cAMP) generation by neuronal activity and norepinephrine (NE) was studied in rat hippocampal slices. High-frequency perforant path stimulation increased cAMP levels 2.5-fold in the dentate gyrus 1 min, but not 30 min, post-stimulation. This increase was abolished by depletion of NE with 6-hydroxydopamine. NE (50 microM) also caused a 3-fold rise in cAMP in whole slices and this stimulation was not altered by NE depletion. These results are consistent with our previous data suggesting that cAMP production is involved in the expression of long-term potentiation and NE-induced long-lasting potentiation in the dentate gyrus.