title: Role of the NO/sGC/PKG signaling pathway of hippocampal CA1 in morphine-induced reward memory.
abstract: Evidence suggests that the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP dependent protein kinase (PKG) signaling pathway plays a key role in memory processing, but the actual participation of this signaling cascade in the hippocampal CA1 during morphine-induced reward memory remains unknown. 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 (i.p.) injection of 4mg/kg morphine exhibited CPP, whereas rats treated with only 0.2mg/kg 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 4mg/kg morphine. Intra-CA1 injection of 7-NI blocked the consolidation of CPP induced by 4mg/kg 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 (0.2mg/kg, i.p.) 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 reward memory.
authors: Neuroscience Research Institute, Peking University, 38 Xueyuan Road, Beijing 100191, PR China.
authors: Fang
authors: F
authors: Shen
authors: Yi-Jing
authors: YJ
authors: Li
authors: Xiao-Jing
authors: XJ
authors: Shou
authors: Cai-Lian
authors: CL
authors: Cui
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012201:Reward; D015398:Signal Transduction / Q000502:physiology*; D000071756:Soluble Guanylyl Cyclase; D019966:Substance-Related Disorders / Q000503:physiopathology
chemical_list: D009294:Narcotics; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D009020:Morphine; D052248:Nitric Oxide Synthase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase