The cAMP signaling pathway appears to be essential in rodents for triggering sustained enhancement of synaptic transmission and for consolidation of spatial information into long-term storage. We and others have observed changes with aging in forms of hippocampal long term potentiation (LTP) that are mediated by the cAMP signal transduction pathway. These include age-related changes in L-LTP (Bach et al., PNAS 96:5280-5) and “chemLTP” induced by β-adrenergic receptor stimulation followed immediately by application of Mg++-free aCSF (Raskin et al., SFN Abstracts 2002). In this study we examined whether such changes in LTP are related to changes in basal and/or stimulated cAMP levels. Cyclic AMP production was assayed in hippocampal slices from young (6-week-old) and aged (22-month-old) F344 rats after exposure to isoproterenol (1 μM) paired with 10 mM Ca2+/0 Mg2+/30 mM K+ (ISO-chemLTP), or following direct stimulation of adenylate cyclase with forskolin (10 μM) paired with the Mg++-free depolarizing solutio...