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NAc Shell Arc/Arg3.1 Protein Mediates Reconsolidation of Morphine CPP by Increased GluR1 Cell Surface Expression: Activation of ERK-Coupled CREB is Required.
Int J Neuropsychopharmacol. 2015 Mar 06; 18(9)IJ

Abstract

BACKGROUND

Relapse into drug abuse evoked by reexposure to the drug-associated context has been a primary problem in the treatment of drug addiction. Disrupting the reconsolidation of drug-related context memory would therefore limit the relapse susceptibility.

METHODS

Morphine conditioned place preference (CPP) was used to assess activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and correlative molecule expression in the Nucleus accumbens (NAc) shell during the reconsolidation of morphine CPP. U0126 and Arc/Arg3.1 antisense oligodeoxynucleotide were adapted to evaluate the role and the underlying mechanism of Arc/Arg3.1 during the reconsolidation.

RESULTS

The retrieval of morphine CPP in rats specifically increased the Arc/Arg3.1 protein level in the NAc shell, accompanied simultaneously by increases in the phosphorylation of extracellular signal-regulated kinase1/2 (pERK1/2), the phosphorylation of Cyclic Adenosine monophosphate (cAMP) response element-binding (pCREB), and the up-regulation of the membrane α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors GluR1 subunit level. Intra-NAc shell infusion U0126, an inhibitor of the Mitogen-activated protein kinase kinase (MEK), prevented the retrieval-induced up-regulation of pERK1/2, pCREB, Arc/Arg3.1, and membrane GluR1 immediately after retrieval of morphine CPP. The effect of disrupting the reconsolidation of morphine CPP by U0126 could last for at least 14 days, and could not be evoked by a priming injection of morphine. Furthermore, the specific knockdown of Arc/Arg3.1 in the NAc shell decreased the membrane GluR1 level, and impaired both the reconsolidation and the reinstatement of morphine CPP.

CONCLUSIONS

Arc/Arg3.1 in the NAc shell mediates the reconsolidation of morphine-associated context memory via up-regulating the level of membrane of GluR1, for which the local activation of the ERK-CREB signal pathway, as an upstream mechanism of Arc/Arg3.1, is required.

Authors+Show Affiliations

Neuroscience Research Institute, Peking University (Drs Lv, Sun, Cui, and Han); Department of Neurobiology, School of Basic Medical Sciences, Peking University (Drs Lv, Sun, Cui, and Han); Key Laboratory for Neuroscience of the Ministry of Education and the Ministry of Public Health, Beijing, China (Drs Lv, Sun, Cui, and Han); Basic Medical Research Centre, Medical School of Nantong University, Nantong, China (Dr Lv).Neuroscience Research Institute, Peking University (Drs Lv, Sun, Cui, and Han); Department of Neurobiology, School of Basic Medical Sciences, Peking University (Drs Lv, Sun, Cui, and Han); Key Laboratory for Neuroscience of the Ministry of Education and the Ministry of Public Health, Beijing, China (Drs Lv, Sun, Cui, and Han); Basic Medical Research Centre, Medical School of Nantong University, Nantong, China (Dr Lv).Neuroscience Research Institute, Peking University (Drs Lv, Sun, Cui, and Han); Department of Neurobiology, School of Basic Medical Sciences, Peking University (Drs Lv, Sun, Cui, and Han); Key Laboratory for Neuroscience of the Ministry of Education and the Ministry of Public Health, Beijing, China (Drs Lv, Sun, Cui, and Han); Basic Medical Research Centre, Medical School of Nantong University, Nantong, China (Dr Lv) clcui@bjmu.edu.cn.Neuroscience Research Institute, Peking University (Drs Lv, Sun, Cui, and Han); Department of Neurobiology, School of Basic Medical Sciences, Peking University (Drs Lv, Sun, Cui, and Han); Key Laboratory for Neuroscience of the Ministry of Education and the Ministry of Public Health, Beijing, China (Drs Lv, Sun, Cui, and Han); Basic Medical Research Centre, Medical School of Nantong University, Nantong, China (Dr Lv).

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25746394

Citation

Lv, Xiu-Fang, et al. "NAc Shell Arc/Arg3.1 Protein Mediates Reconsolidation of Morphine CPP By Increased GluR1 Cell Surface Expression: Activation of ERK-Coupled CREB Is Required." The International Journal of Neuropsychopharmacology, vol. 18, no. 9, 2015.
Lv XF, Sun LL, Cui CL, et al. NAc Shell Arc/Arg3.1 Protein Mediates Reconsolidation of Morphine CPP by Increased GluR1 Cell Surface Expression: Activation of ERK-Coupled CREB is Required. Int J Neuropsychopharmacol. 2015;18(9).
Lv, X. F., Sun, L. L., Cui, C. L., & Han, J. S. (2015). NAc Shell Arc/Arg3.1 Protein Mediates Reconsolidation of Morphine CPP by Increased GluR1 Cell Surface Expression: Activation of ERK-Coupled CREB is Required. The International Journal of Neuropsychopharmacology, 18(9). https://doi.org/10.1093/ijnp/pyv030
Lv XF, et al. NAc Shell Arc/Arg3.1 Protein Mediates Reconsolidation of Morphine CPP By Increased GluR1 Cell Surface Expression: Activation of ERK-Coupled CREB Is Required. Int J Neuropsychopharmacol. 2015 Mar 6;18(9) PubMed PMID: 25746394.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NAc Shell Arc/Arg3.1 Protein Mediates Reconsolidation of Morphine CPP by Increased GluR1 Cell Surface Expression: Activation of ERK-Coupled CREB is Required. AU - Lv,Xiu-Fang, AU - Sun,Lin-Lin, AU - Cui,Cai-Lian, AU - Han,Ji-Sheng, Y1 - 2015/03/06/ PY - 2015/3/10/entrez PY - 2015/3/10/pubmed PY - 2016/5/27/medline KW - Activity regulated cytoskeleton-associated protein/activity-regulated gene 3.1 KW - GluR1 KW - cAMP response element-binding protein KW - conditioned place preference KW - extracellular signal-regulated kinase KW - reconsolidation JF - The international journal of neuropsychopharmacology JO - Int J Neuropsychopharmacol VL - 18 IS - 9 N2 - BACKGROUND: Relapse into drug abuse evoked by reexposure to the drug-associated context has been a primary problem in the treatment of drug addiction. Disrupting the reconsolidation of drug-related context memory would therefore limit the relapse susceptibility. METHODS: Morphine conditioned place preference (CPP) was used to assess activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and correlative molecule expression in the Nucleus accumbens (NAc) shell during the reconsolidation of morphine CPP. U0126 and Arc/Arg3.1 antisense oligodeoxynucleotide were adapted to evaluate the role and the underlying mechanism of Arc/Arg3.1 during the reconsolidation. RESULTS: The retrieval of morphine CPP in rats specifically increased the Arc/Arg3.1 protein level in the NAc shell, accompanied simultaneously by increases in the phosphorylation of extracellular signal-regulated kinase1/2 (pERK1/2), the phosphorylation of Cyclic Adenosine monophosphate (cAMP) response element-binding (pCREB), and the up-regulation of the membrane α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors GluR1 subunit level. Intra-NAc shell infusion U0126, an inhibitor of the Mitogen-activated protein kinase kinase (MEK), prevented the retrieval-induced up-regulation of pERK1/2, pCREB, Arc/Arg3.1, and membrane GluR1 immediately after retrieval of morphine CPP. The effect of disrupting the reconsolidation of morphine CPP by U0126 could last for at least 14 days, and could not be evoked by a priming injection of morphine. Furthermore, the specific knockdown of Arc/Arg3.1 in the NAc shell decreased the membrane GluR1 level, and impaired both the reconsolidation and the reinstatement of morphine CPP. CONCLUSIONS: Arc/Arg3.1 in the NAc shell mediates the reconsolidation of morphine-associated context memory via up-regulating the level of membrane of GluR1, for which the local activation of the ERK-CREB signal pathway, as an upstream mechanism of Arc/Arg3.1, is required. SN - 1469-5111 UR - https://www.unboundmedicine.com/medline/citation/25746394/NAc_Shell_Arc/Arg3_1_Protein_Mediates_Reconsolidation_of_Morphine_CPP_by_Increased_GluR1_Cell_Surface_Expression:_Activation_of_ERK_Coupled_CREB_is_Required_ L2 - https://academic.oup.com/ijnp/article-lookup/doi/10.1093/ijnp/pyv030 DB - PRIME DP - Unbound Medicine ER -