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The α7nACh–NMDA receptor complex is involved in cue-induced reinstatement of nicotine seeking

Smoking is the leading preventable cause of disease, disability, and premature death. Nicotine, the main psychoactive drug in tobacco, is one of the most heavily used addictive substances, and its continued use is driven through activation of nicotinic acetylcholine receptors (nAChRs). Despite harmf...

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Detalles Bibliográficos
Autores principales: Li, Shupeng, Li, ZhaoXia, Pei, Lin, Le, Anh D., Liu, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501362/
https://www.ncbi.nlm.nih.gov/pubmed/23091164
http://dx.doi.org/10.1084/jem.20121270
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author Li, Shupeng
Li, ZhaoXia
Pei, Lin
Le, Anh D.
Liu, Fang
author_facet Li, Shupeng
Li, ZhaoXia
Pei, Lin
Le, Anh D.
Liu, Fang
author_sort Li, Shupeng
collection PubMed
description Smoking is the leading preventable cause of disease, disability, and premature death. Nicotine, the main psychoactive drug in tobacco, is one of the most heavily used addictive substances, and its continued use is driven through activation of nicotinic acetylcholine receptors (nAChRs). Despite harmful consequences, it is difficult to quit smoking because of its positive effects on mood and cognition that are strong reinforcers contributing to addiction. Furthermore, a formidable challenge for the treatment of nicotine addiction is the high vulnerability to relapse after abstinence. There is no currently available smoking cessation product able to achieve a >20% smoking cessation rate after 52 wk, and there are no medications that directly target the relapse process. We report here that the α7nAChR forms a protein complex with the NMDA glutamate receptor (NMDAR) through a direct protein–protein interaction. Chronic nicotine exposure promotes α7nAChR–NMDAR complex formation. Interestingly, administration of an interfering peptide that disrupts the α7nAChR–NMDAR complex decreased extracellular signal-regulated kinase (ERK) activity and blocked cue-induced reinstatement of nicotine seeking in rat models of relapse, without affecting nicotine self-administration or locomotor activity. Our results may provide a novel therapeutic target for the development of medications for preventing nicotine relapse.
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spelling pubmed-35013622013-05-19 The α7nACh–NMDA receptor complex is involved in cue-induced reinstatement of nicotine seeking Li, Shupeng Li, ZhaoXia Pei, Lin Le, Anh D. Liu, Fang J Exp Med Brief Definitive Report Smoking is the leading preventable cause of disease, disability, and premature death. Nicotine, the main psychoactive drug in tobacco, is one of the most heavily used addictive substances, and its continued use is driven through activation of nicotinic acetylcholine receptors (nAChRs). Despite harmful consequences, it is difficult to quit smoking because of its positive effects on mood and cognition that are strong reinforcers contributing to addiction. Furthermore, a formidable challenge for the treatment of nicotine addiction is the high vulnerability to relapse after abstinence. There is no currently available smoking cessation product able to achieve a >20% smoking cessation rate after 52 wk, and there are no medications that directly target the relapse process. We report here that the α7nAChR forms a protein complex with the NMDA glutamate receptor (NMDAR) through a direct protein–protein interaction. Chronic nicotine exposure promotes α7nAChR–NMDAR complex formation. Interestingly, administration of an interfering peptide that disrupts the α7nAChR–NMDAR complex decreased extracellular signal-regulated kinase (ERK) activity and blocked cue-induced reinstatement of nicotine seeking in rat models of relapse, without affecting nicotine self-administration or locomotor activity. Our results may provide a novel therapeutic target for the development of medications for preventing nicotine relapse. The Rockefeller University Press 2012-11-19 /pmc/articles/PMC3501362/ /pubmed/23091164 http://dx.doi.org/10.1084/jem.20121270 Text en © 2012 Li et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Li, Shupeng
Li, ZhaoXia
Pei, Lin
Le, Anh D.
Liu, Fang
The α7nACh–NMDA receptor complex is involved in cue-induced reinstatement of nicotine seeking
title The α7nACh–NMDA receptor complex is involved in cue-induced reinstatement of nicotine seeking
title_full The α7nACh–NMDA receptor complex is involved in cue-induced reinstatement of nicotine seeking
title_fullStr The α7nACh–NMDA receptor complex is involved in cue-induced reinstatement of nicotine seeking
title_full_unstemmed The α7nACh–NMDA receptor complex is involved in cue-induced reinstatement of nicotine seeking
title_short The α7nACh–NMDA receptor complex is involved in cue-induced reinstatement of nicotine seeking
title_sort α7nach–nmda receptor complex is involved in cue-induced reinstatement of nicotine seeking
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501362/
https://www.ncbi.nlm.nih.gov/pubmed/23091164
http://dx.doi.org/10.1084/jem.20121270
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