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THE β-amyloid peptide (Aβ) has been known to activate microglia and to induce release of nitric oxide (NO). In this study, we examined the effect of cAMP on Aβ-induced microglial activation using cultured rat brain microglia. Dibutyryl-cAMP (dbcAMP) and 3-isobutyl-1-methylxanthine (IBMX) significantly potentiated Aβ(25–35)- or Aβ(1–42)-induced NO release in a dose-dependent manner. The increase in NO release was due to the increased expression of inducible nitric oxide synthase (iNOS). However, forskolin, an adenylate cyclase activator, weakly increased NO release at 10–50 μM but caused a decrease at 100 μM. These results suggest that increase in intracellular cAMP could potentiate microglial activation induced by Aβ.