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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Translational strategies for therapeutic development in nicotine addiction: Rethinking the conventional bench to bedside approach</title>
<author><name sortKey="Foll, Bernard Le" sort="Foll, Bernard Le" uniqKey="Foll B" first="Bernard Le" last="Foll">Bernard Le Foll</name>
<affiliation><nlm:aff id="A1">Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Alcohol Research and Treatment Clinic, Addiction Medicine Services, Ambulatory Care and Structured Treatments, Centre for Addiction and Mental Health, Toronto, ON, Canada</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Department of Family and Community Medicine, University of Toronto, Toronto, Canada</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A5">Department of Psychiatry and Institute of Medical Sciences, University of Toronto, Toronto, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pushparaj, Abhiram" sort="Pushparaj, Abhiram" uniqKey="Pushparaj A" first="Abhiram" last="Pushparaj">Abhiram Pushparaj</name>
<affiliation><nlm:aff id="A1">Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pryslawsky, Yaroslaw" sort="Pryslawsky, Yaroslaw" uniqKey="Pryslawsky Y" first="Yaroslaw" last="Pryslawsky">Yaroslaw Pryslawsky</name>
<affiliation><nlm:aff id="A1">Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Forget, Benoit" sort="Forget, Benoit" uniqKey="Forget B" first="Benoit" last="Forget">Benoit Forget</name>
<affiliation><nlm:aff id="A6">Integrative Neurobiology of Cholinergic Systems, Department of Neuroscience, Pasteur Institute, 25 rue du Dr. Roux, Paris 75724, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vemuri, Kiran" sort="Vemuri, Kiran" uniqKey="Vemuri K" first="Kiran" last="Vemuri">Kiran Vemuri</name>
<affiliation><nlm:aff id="A7">Center for Drug Discovery, Northeastern University, Boston, MA 02115-5005, United States</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115-5005, United States</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A9">Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115-5005, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Makriyannis, Alexandros" sort="Makriyannis, Alexandros" uniqKey="Makriyannis A" first="Alexandros" last="Makriyannis">Alexandros Makriyannis</name>
<affiliation><nlm:aff id="A7">Center for Drug Discovery, Northeastern University, Boston, MA 02115-5005, United States</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115-5005, United States</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A9">Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115-5005, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Trigo, Jose M" sort="Trigo, Jose M" uniqKey="Trigo J" first="Jose M." last="Trigo">Jose M. Trigo</name>
<affiliation><nlm:aff id="A1">Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">24140878</idno>
<idno type="pmc">4002666</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4002666</idno>
<idno type="RBID">PMC:4002666</idno>
<idno type="doi">10.1016/j.pnpbp.2013.10.009</idno>
<date when="2013">2013</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Translational strategies for therapeutic development in nicotine addiction: Rethinking the conventional bench to bedside approach</title>
<author><name sortKey="Foll, Bernard Le" sort="Foll, Bernard Le" uniqKey="Foll B" first="Bernard Le" last="Foll">Bernard Le Foll</name>
<affiliation><nlm:aff id="A1">Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Alcohol Research and Treatment Clinic, Addiction Medicine Services, Ambulatory Care and Structured Treatments, Centre for Addiction and Mental Health, Toronto, ON, Canada</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Department of Family and Community Medicine, University of Toronto, Toronto, Canada</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A5">Department of Psychiatry and Institute of Medical Sciences, University of Toronto, Toronto, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pushparaj, Abhiram" sort="Pushparaj, Abhiram" uniqKey="Pushparaj A" first="Abhiram" last="Pushparaj">Abhiram Pushparaj</name>
<affiliation><nlm:aff id="A1">Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pryslawsky, Yaroslaw" sort="Pryslawsky, Yaroslaw" uniqKey="Pryslawsky Y" first="Yaroslaw" last="Pryslawsky">Yaroslaw Pryslawsky</name>
<affiliation><nlm:aff id="A1">Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Forget, Benoit" sort="Forget, Benoit" uniqKey="Forget B" first="Benoit" last="Forget">Benoit Forget</name>
<affiliation><nlm:aff id="A6">Integrative Neurobiology of Cholinergic Systems, Department of Neuroscience, Pasteur Institute, 25 rue du Dr. Roux, Paris 75724, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vemuri, Kiran" sort="Vemuri, Kiran" uniqKey="Vemuri K" first="Kiran" last="Vemuri">Kiran Vemuri</name>
<affiliation><nlm:aff id="A7">Center for Drug Discovery, Northeastern University, Boston, MA 02115-5005, United States</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115-5005, United States</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A9">Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115-5005, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Makriyannis, Alexandros" sort="Makriyannis, Alexandros" uniqKey="Makriyannis A" first="Alexandros" last="Makriyannis">Alexandros Makriyannis</name>
<affiliation><nlm:aff id="A7">Center for Drug Discovery, Northeastern University, Boston, MA 02115-5005, United States</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115-5005, United States</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A9">Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115-5005, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Trigo, Jose M" sort="Trigo, Jose M" uniqKey="Trigo J" first="Jose M." last="Trigo">Jose M. Trigo</name>
<affiliation><nlm:aff id="A1">Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Progress in neuro-psychopharmacology & biological psychiatry</title>
<idno type="ISSN">0278-5846</idno>
<idno type="eISSN">1878-4216</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
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<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P1">Tobacco produces an impressive burden of disease resulting in premature death in half of users. Despite effective smoking cessation medications (nicotine replacement therapies, bupropion and varenicline), there is a very high rate of relapse following quit attempts. The use of efficient strategies for the development of novel treatments is a necessity. A `bench to bedside strategy' was initially used to develop cannabinoid CB<sub>1</sub>
receptor antagonists for the treatment of nicotine addiction. Unfortunately, after being tested on experimental animals, what seemed to be an interesting approach for the treatment of nicotine addiction resulted in serious unwanted side effects when tested in humans. Current research is focusing again on pre-clinical models in an effort to eliminate unwanted side effects while preserving the initially observed efficacy. A `bed side to bench strategy' was used to study the role of the insula (part of the frontal cortex) in nicotine addiction. This line of research started based on clinical observations that patients suffering stroke-induced lesions to the insula showed a greater likelihood to report immediate smoking cessation without craving or relapse. Subsequently, animal models of addiction are used to explore the role of insula in addiction. Due to the inherent limitations existing in clinical versus preclinical studies, the possibility of close interaction between both models seems to be critical for the successful development of novel therapeutic strategies for nicotine dependence.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8211617</journal-id>
<journal-id journal-id-type="pubmed-jr-id">6714</journal-id>
<journal-id journal-id-type="nlm-ta">Prog Neuropsychopharmacol Biol Psychiatry</journal-id>
<journal-id journal-id-type="iso-abbrev">Prog. Neuropsychopharmacol. Biol. Psychiatry</journal-id>
<journal-title-group><journal-title>Progress in neuro-psychopharmacology & biological psychiatry</journal-title>
</journal-title-group>
<issn pub-type="ppub">0278-5846</issn>
<issn pub-type="epub">1878-4216</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">24140878</article-id>
<article-id pub-id-type="pmc">4002666</article-id>
<article-id pub-id-type="doi">10.1016/j.pnpbp.2013.10.009</article-id>
<article-id pub-id-type="manuscript">NIHMS574726</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Translational strategies for therapeutic development in nicotine addiction: Rethinking the conventional bench to bedside approach</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Foll</surname>
<given-names>Bernard Le</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="aff" rid="A2">b</xref>
<xref ref-type="aff" rid="A3">c</xref>
<xref ref-type="aff" rid="A4">d</xref>
<xref ref-type="aff" rid="A5">e</xref>
<xref ref-type="corresp" rid="CR1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pushparaj</surname>
<given-names>Abhiram</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pryslawsky</surname>
<given-names>Yaroslaw</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Forget</surname>
<given-names>Benoit</given-names>
</name>
<xref ref-type="aff" rid="A6">f</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vemuri</surname>
<given-names>Kiran</given-names>
</name>
<xref ref-type="aff" rid="A7">g</xref>
<xref ref-type="aff" rid="A8">h</xref>
<xref ref-type="aff" rid="A9">i</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Makriyannis</surname>
<given-names>Alexandros</given-names>
</name>
<xref ref-type="aff" rid="A7">g</xref>
<xref ref-type="aff" rid="A8">h</xref>
<xref ref-type="aff" rid="A9">i</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Trigo</surname>
<given-names>Jose M.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>a</label>
Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada</aff>
<aff id="A2"><label>b</label>
Alcohol Research and Treatment Clinic, Addiction Medicine Services, Ambulatory Care and Structured Treatments, Centre for Addiction and Mental Health, Toronto, ON, Canada</aff>
<aff id="A3"><label>c</label>
Department of Family and Community Medicine, University of Toronto, Toronto, Canada</aff>
<aff id="A4"><label>d</label>
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada</aff>
<aff id="A5"><label>e</label>
Department of Psychiatry and Institute of Medical Sciences, University of Toronto, Toronto, Canada</aff>
<aff id="A6"><label>f</label>
Integrative Neurobiology of Cholinergic Systems, Department of Neuroscience, Pasteur Institute, 25 rue du Dr. Roux, Paris 75724, France</aff>
<aff id="A7"><label>g</label>
Center for Drug Discovery, Northeastern University, Boston, MA 02115-5005, United States</aff>
<aff id="A8"><label>h</label>
Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115-5005, United States</aff>
<aff id="A9"><label>i</label>
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115-5005, United States</aff>
<author-notes><corresp id="CR1"><label>*</label>
Corresponding author at: Translational Addiction Research Laboratory, Centre for Addiction and Mental Health Addiction (CAMH), University of Toronto, 33 Russell Street, Toronto, ON M5S 2S1, Canada. Tel.: +1 416 535 8501x4772; fax: +1 416 595 6922. <email>bernard.lefoll@camh.ca</email>
(B. Le Foll).</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>22</day>
<month>4</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>17</day>
<month>10</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="ppub"><day>3</day>
<month>7</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>03</day>
<month>7</month>
<year>2015</year>
</pub-date>
<volume>52</volume>
<fpage>86</fpage>
<lpage>93</lpage>
<pmc-comment>elocation-id from pubmed: 10.1016/j.pnpbp.2013.10.009</pmc-comment>
<permissions><copyright-statement>© 2013 Elsevier Inc. All rights reserved</copyright-statement>
<copyright-year>2013</copyright-year>
</permissions>
<abstract><p id="P1">Tobacco produces an impressive burden of disease resulting in premature death in half of users. Despite effective smoking cessation medications (nicotine replacement therapies, bupropion and varenicline), there is a very high rate of relapse following quit attempts. The use of efficient strategies for the development of novel treatments is a necessity. A `bench to bedside strategy' was initially used to develop cannabinoid CB<sub>1</sub>
receptor antagonists for the treatment of nicotine addiction. Unfortunately, after being tested on experimental animals, what seemed to be an interesting approach for the treatment of nicotine addiction resulted in serious unwanted side effects when tested in humans. Current research is focusing again on pre-clinical models in an effort to eliminate unwanted side effects while preserving the initially observed efficacy. A `bed side to bench strategy' was used to study the role of the insula (part of the frontal cortex) in nicotine addiction. This line of research started based on clinical observations that patients suffering stroke-induced lesions to the insula showed a greater likelihood to report immediate smoking cessation without craving or relapse. Subsequently, animal models of addiction are used to explore the role of insula in addiction. Due to the inherent limitations existing in clinical versus preclinical studies, the possibility of close interaction between both models seems to be critical for the successful development of novel therapeutic strategies for nicotine dependence.</p>
</abstract>
<kwd-group><kwd>Dependence</kwd>
<kwd>Nicotine</kwd>
<kwd>Reinstatement</kwd>
<kwd>Therapy</kwd>
<kwd>Treatment</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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