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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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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. |
format | Online Article Text |
id | pubmed-3501362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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