Role of the NO/sGC/PKG signaling pathway of hippocampal CA1 in morphine-induced reward memory

Although evidence suggests that the nitric oxide(NO)/soluble guanylyl cyclase(sGC)/cGMP dependent protein kinase(PKG) signaling pathway in the hippocampal CA1 region plays a key role in memory processing,it remains unclear whether this signaling cascade is involved in drug-induced reward memory.In this study,we investigated the role of the NO/sGC/PKG signaling pathway in the CA1 on morphine-induced reward memory using a conditioned place preference(CPP) paradigm.We found that rats receiving an intraperitoneal(ip) injection of 4 mg·kg-1 morphine exhibited CPP,whereas rats treated with only 0.2 mg·kg-1 morphine failed to produce CPP.Intra-CA1 injection of the neuronal NO synthase(nNOS) inhibitor 7-NI,the sGC inhibitor ODQ or the PKG inhibitor Rp-8-Br-PET-cGMPS had no effect on the acquisition of CPP by 4 mg·kg-1 morphine.Intra-CA1 injection of 7-NI blocked the consolidation of CPP induced by 4 mg·kg-1 morphine,and this amnesic effect of 7-NI was mimicked by ODQ and Rp-8-Br-PET-cGMPS.Intra-CA1 injection of the NOS substrate L-arg or the sGC activator YC-1 with an ineffective dose of morphine(2 mg·kg-1,ip) elicited CPP.This response induced by L-arg or YC-1 was reversed by pre-microinjection of Rp-8-Br-PET-cGMPS in the CA1.These results indicated that the activation of the NO/sGC/PKG signaling pathway in the CA1 is necessary for the consolidation of morphine-related memory.