The NO/sGC/PKG signaling pathway in the NAc shell is necessary for the acquisition of morphine-induced place...

There is evidence that the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP-dependent protein kinase (PKG) signaling pathway in the basal lateral amygdala and hippocampus plays a key role in memory processing, but it is not known if this NO signaling pathway in the nucleus accumbens (Gomes et al., 2006), a known pivotal region in reward memory, is essential for drug-associated reward memory. We therefore investigated the effect of the NO/sGC/PKG signaling pathway in the nucleus accumbens (NAc) on morphine-induced conditioned place preference (CPP). Results showed that a preconditioning microinjection of the NO synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) into the NAc shell, but not into the core, significantly blocked the acquisition of morphine CPP. The blockage effect of L-NAME on the acquisition of CPP was imitated by the neuronal NOS inhibitor 7-nitroindazole, 3-bromo-, sodium salt (7-NI), the sGC inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), and the PKG inhibitor Rp-8Br-PET-cGMPS. The 7-NI- or ODQ-induced effect was reversed by premicroinjection of the sGC activator YC-1 or the PKG activator 8-Br-cGMP in the NAc shell. However, microinfusion of 7-NI, ODQ, or Rp-8Br-PET-cGMPS into the NAc shell or the core had no effect on the expression of morphine CPP. These findings indicate that the NO/sGC/PKG signaling pathway in the NAc shell is critical for the acquisition of morphine-induced place preference, whereas the same signaling pathway in the NAc shell or core is not involved in the retrieval of morphine-induced place preference.