title: Decrease of phosphorylated CREB and ERK in nucleus accumbens is associated with the incubation of heroin seeking induced by cues after withdrawal.
abstract: cAMP response element binding protein (CREB) signaling is involved in the heroin reward, but whether the CREB signaling is involved in the incubation of heroin-seeking remains unknown. Here we aim to explore the expression of p-CREB and the p-ERK, an upstream molecular of CREB, in the nucleus accumbens (NAc) in the incubation of heroin-seeking induced by cue after withdrawal. First, rats were trained to self-administer heroin for 14 days, and then assessed heroin-seeking induced by context cue (CC)or by conditioned cues (CS)after 1 or 14 d withdrawal. We found that the active responses induced by CC or CS was higher after 14 d withdrawal than that after 1 d withdrawal, and the extent increased was more significant by CS than that by CC. Meanwhile, the expression of p-ERK decreased significantly when rats exposed to the CS, and decreased more after 14 d withdrawal. In contrast, reduction of the expression of p-CREB was more obvious with exposure to CS after 14 d withdrawal. Furthermore, microinjection of rolipram into the NAc decreased the heroin-seeking behavior induced by CS after 14 d withdrawal, which was correlated to an enhancement in the expression of p-CREB in the NAc. These findings suggest that the inactivation of CREB and ERK may be involved in the incubation of heroin-seeking induced by cues after prolonged withdrawal.
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, PR China; The Children's Hospital of Zhejiang University, School of Medicine, Hangzhou 310003, PR China.
authors.forename: Anna
authors.initials: A
authors.lastname: Sun
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, PR China.
authors.forename: Dingding
authors.initials: D
authors.lastname: Zhuang
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, PR China.
authors.forename: Huaqiang
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, PR China.
authors.forename: Miaojun
authors.initials: M
authors.lastname: Lai
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, PR China.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Chen
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, PR China.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, PR China.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, PR China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000818:Animals; D003463:Cues; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D058999:Drug-Seeking Behavior; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006556:Heroin Dependence / Q000378:metabolism* / Q000523:psychology; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000378:metabolism*; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000523:psychology; D013997:Time Factors
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D058988:Phosphodiesterase 4 Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D020889:Rolipram
keywords: Addiction; Opioid; Phosphodiesterase-4; Transcription factor; cAMP