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Although the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP dependent protein kinase (PKG) pathway in hippocampus has been shown to be important for long term learning and memory, little is known about its role in drug-induced reward memory.In the present study, we firstly investigated the possible involvement of PKG in the acquisition, expression and consolidation of conditioned place preference (CPP) induced by morphine in male SD rats.Results showed that Rp-8-Br-PET-cGMPs, a PKG inhibitor, selectively impaired the consolidation of morphine CPP when it was microinjection into CA1 region of the hippoeampus immediately after each conditioning session.However, Rp-8-Br-PET-cGMPs had no effect on the acquisition or expression of morphine CPP when it was microinjection into the CA1 region before each conditioning session or before the test of morphine CPP.Furthermore, pharmacological intervention of NO and sGC in the CA1 region using NO synthase (NOS) inhibitor (7-NI) and sGC inhibitor (ODQ) also significantly blocked the consolidation of morphine CPP.The present study for the first time show that the NO/sGC/PKG signaling pathway in the hippocampal CA1 region may play a critical role in the consolidation of morphine induced reward memory.