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Involvement of hippocampal jun-N terminal kinase pathway in the enhancement of learning and memory by nicotine

Involvement of hippocampal jun-N terminal kinase pathway in the enhancement of learning and memory by nicotine
Involvement of hippocampal jun-N terminal kinase pathway in the enhancement of learning and memory by nicotine
Despite intense scrutiny over the past 20 years, the reasons for the high addictive liability of nicotine and extreme rates of relapse in smokers have remained elusive. One factor that contributes to the development and maintenance of nicotine addiction is the ability of nicotine to produce long-lasting modifications of behavior, yet little is known about the mechanisms by which nicotine alters the underlying synaptic plasticity responsible for behavioral changes. This study is the first to explore how nicotine interacts with learning to alter gene transcription, which is a process necessary for long-term memory consolidation. Transcriptional upregulation of hippocampal jun-N terminal kinase 1 (JNK1) mRNA was found in mice that learned contextual fear conditioning (FC) in the presence of nicotine, whereas neither learning alone nor nicotine administration alone exerted an effect. Furthermore, the upregulation of JNK1 was absent in beta2 nicotinic receptor subunit knockout mice, which are mice that do not show enhanced learning by nicotine. Finally, hippocampal JNK activation was increased in mice that were administered nicotine before conditioning, and the inhibition of JNK during consolidation prevented the nicotine-induced enhancement of contextual FC. These data suggest that nicotine and learning interact to alter hippocampal JNK1 gene expression and related signaling processes, thus resulting in strengthened contextual memories
483-92
Kenney, Justin W.
a498bbd6-750d-4778-bd72-6ea336c883e8
Florian, Cédrick
46798905-58a3-454e-bb68-486490ad3287
Portugal, George S.
016470cf-55ba-4cf6-96ed-76758d51f71f
Abel, Ted
b2e82fcd-117d-45f3-8009-91adb0e9eac9
Gould, Thomas J.
de84ac91-2b6f-4524-b4d3-1f210047c57a
Kenney, Justin W.
a498bbd6-750d-4778-bd72-6ea336c883e8
Florian, Cédrick
46798905-58a3-454e-bb68-486490ad3287
Portugal, George S.
016470cf-55ba-4cf6-96ed-76758d51f71f
Abel, Ted
b2e82fcd-117d-45f3-8009-91adb0e9eac9
Gould, Thomas J.
de84ac91-2b6f-4524-b4d3-1f210047c57a

Kenney, Justin W., Florian, Cédrick, Portugal, George S., Abel, Ted and Gould, Thomas J. (2010) Involvement of hippocampal jun-N terminal kinase pathway in the enhancement of learning and memory by nicotine. Neuropsychopharmacology, 35 (2), 483-92. (doi:10.1038/npp.2009.153). (PMID:19776730)

Record type: Article

Abstract

Despite intense scrutiny over the past 20 years, the reasons for the high addictive liability of nicotine and extreme rates of relapse in smokers have remained elusive. One factor that contributes to the development and maintenance of nicotine addiction is the ability of nicotine to produce long-lasting modifications of behavior, yet little is known about the mechanisms by which nicotine alters the underlying synaptic plasticity responsible for behavioral changes. This study is the first to explore how nicotine interacts with learning to alter gene transcription, which is a process necessary for long-term memory consolidation. Transcriptional upregulation of hippocampal jun-N terminal kinase 1 (JNK1) mRNA was found in mice that learned contextual fear conditioning (FC) in the presence of nicotine, whereas neither learning alone nor nicotine administration alone exerted an effect. Furthermore, the upregulation of JNK1 was absent in beta2 nicotinic receptor subunit knockout mice, which are mice that do not show enhanced learning by nicotine. Finally, hippocampal JNK activation was increased in mice that were administered nicotine before conditioning, and the inhibition of JNK during consolidation prevented the nicotine-induced enhancement of contextual FC. These data suggest that nicotine and learning interact to alter hippocampal JNK1 gene expression and related signaling processes, thus resulting in strengthened contextual memories

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Published date: January 2010

Identifiers

Local EPrints ID: 168297
URI: http://eprints.soton.ac.uk/id/eprint/168297
PURE UUID: be937140-ae5d-40e7-a081-f9ca71746899

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Date deposited: 03 Dec 2010 09:15
Last modified: 14 Mar 2024 02:17

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Contributors

Author: Justin W. Kenney
Author: Cédrick Florian
Author: George S. Portugal
Author: Ted Abel
Author: Thomas J. Gould

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