Decrease of phosphorylated CREB and ERK in nucleus accumbens is associated with the incubation of heroin seeking induced by cues after withdrawal

• Published in: Neuroscience letters Vol. 591; pp. 166 - 170
• Main Authors: Sun, Anna, Zhuang, Dingding, Zhu, Huaqiang, Lai, Miaojun, Chen, Weisheng, Liu, Huifeng, Zhang, Fuqiang, Zhou, Wenhua
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 30.03.2015
• Subjects: Addiction; Animals; cAMP; Cues; Cyclic AMP Response Element-Binding Protein - metabolism; Drug-Seeking Behavior; Extracellular Signal-Regulated MAP Kinases - metabolism; Heroin Dependence - metabolism; Heroin Dependence - psychology; Male; Microinjections; Nucleus Accumbens - metabolism; Opioid; Phosphodiesterase 4 Inhibitors - pharmacology; Phosphodiesterase-4; Phosphorylation; Rats, Sprague-Dawley; Rolipram - pharmacology; Substance Withdrawal Syndrome - metabolism; Substance Withdrawal Syndrome - psychology; Time Factors; Transcription factor; CREB; Phosphodiesterase-4; Addiction; PDE4; aCSF; Opioid; cAMP; Transcription factor; ERK
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2015.02.048

•Expression of p-CREB protein decreased after prolonged withdrawal.•Expression of p-ERK decreased exposed to cues after withdrawal.•Intra-accumbens with rolipram enhanced expression of p-CREB and inhibited heroin seeking. 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.