title: The NO/sGC/PKG signaling pathway in the NAc shell is necessary for the acquisition of morphine-induced place preference.
abstract: 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.
authors.affiliation: Neuroscience Research Institute, Peking University.
authors.forename: Fang
authors.initials: F
authors.lastname: Shen
authors.affiliation: Neuroscience Research Institute, Peking University.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Neuroscience Research Institute, Peking University.
authors.forename: Chong
authors.initials: C
authors.lastname: Qi
authors.affiliation: Neuroscience Research Institute, Peking University.
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Neuroscience Research Institute, Peking University.
authors.forename: Cai-Lian
authors.initials: CL
authors.lastname: Cui
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D009020:Morphine; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase