Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Δ9-tetrahydrocannabinol
Identifieur interne : 002520 ( PascalFrancis/Curation ); précédent : 002519; suivant : 002521Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Δ9-tetrahydrocannabinol
Auteurs : A. A. Boucher [Australie, France] ; J. C. Arnold [Australie] ; L. Duffy [Australie] ; P. R. Schofield [Australie] ; J. Micheau [France] ; T. Karl [Australie]Source :
- Psychopharmacologia [ 0033-3158 ] ; 2007.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Rationale Cannabis use may precipitate schizophrenia especially if the individual has a genetic vulnerability to this mental disorder. Human and animal research indicates that neuregulin 1 (Nrg1) is a susceptibility gene for schizophrenia. Objectives The aim of this study was to investigate whether dysfunction in the Nrg1 gene modulates the behavioural effects of Δ9-tetrahydrocannabinol (THC), the major psychotropic component of cannabis. Materials and methods Heterozygous Nrg1 transmembrane-domain knockout mice (Nrg1 HET) were treated with acute THC (0, 5 or 10 mg/kg i.p.) 30 min before being tested using open field (OF), hole board (HB), light-dark (LD), elevated plus maze (EPM), social interaction (SI) and prepulse inhibition (PPI) tests. Results Nrg1 HET mice showed differences in baseline behaviour with regard to locomotor activity, exploration and anxiety. More importantly, they were more sensitive to the locomotor suppressant actions of THC compared to wild type-like (WT) mice. In addition, Nrg1 HET mice expressed a greater THC-induced enhancement in % PPI than WT mice. The effects of THC on anxiety-related behaviour were task-dependent, with Nrg1 HET mice being more susceptible than WT mice to the anxiogenic effects of THC in LD, but not in the EPM, SI and OF tests. Conclusions Nrg1 HET mice were more sensitive to the acute effects of THC in an array of different behaviours including those that model symptoms of schizophrenia. It appears that variation in the schizophrenia-related neuregulin 1 gene alters the sensitivity to the behavioural effects of cannabinoids.
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Boucher</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), 384 Victoria Street</s1><s2>Darlinghurst, NSW 2010</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Australie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Pharmacology, University of Sydney</s1><s2>Sydney, NSW 2006</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Australie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Laboratoire de Neurosciences Cognitives, Université Bordeaux I</s1><s2>33405 Talence</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Arnold, J C" sort="Arnold, J C" uniqKey="Arnold J" first="J. C." last="Arnold">J. C. 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Micheau</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Laboratoire de Neurosciences Cognitives, Université Bordeaux I</s1><s2>33405 Talence</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Karl, T" sort="Karl, T" uniqKey="Karl T" first="T." last="Karl">T. Karl</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), 384 Victoria Street</s1><s2>Darlinghurst, NSW 2010</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Australie</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">07-0306032</idno><date when="2007">2007</date><idno type="stanalyst">PASCAL 07-0306032 INIST</idno><idno type="RBID">Pascal:07-0306032</idno><idno type="wicri:Area/PascalFrancis/Corpus">003B68</idno><idno type="wicri:Area/PascalFrancis/Curation">002520</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Δ<sup>9</sup>-tetrahydrocannabinol</title><author><name sortKey="Boucher, A A" sort="Boucher, A A" uniqKey="Boucher A" first="A. A." last="Boucher">A. A. Boucher</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), 384 Victoria Street</s1><s2>Darlinghurst, NSW 2010</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Australie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Pharmacology, University of Sydney</s1><s2>Sydney, NSW 2006</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Australie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Laboratoire de Neurosciences Cognitives, Université Bordeaux I</s1><s2>33405 Talence</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Arnold, J C" sort="Arnold, J C" uniqKey="Arnold J" first="J. C." last="Arnold">J. C. Arnold</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), 384 Victoria Street</s1><s2>Darlinghurst, NSW 2010</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Australie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Pharmacology, University of Sydney</s1><s2>Sydney, NSW 2006</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Australie</country></affiliation></author><author><name sortKey="Duffy, L" sort="Duffy, L" uniqKey="Duffy L" first="L." last="Duffy">L. Duffy</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), 384 Victoria Street</s1><s2>Darlinghurst, NSW 2010</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Australie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Neuroscience Research Program, Garvan Institute of Medical Research</s1><s2>Sydney, NSW 2010</s2><s3>AUS</s3><sZ>3 aut.</sZ></inist:fA14><country>Australie</country></affiliation></author><author><name sortKey="Schofield, P R" sort="Schofield, P R" uniqKey="Schofield P" first="P. R." last="Schofield">P. R. Schofield</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), 384 Victoria Street</s1><s2>Darlinghurst, NSW 2010</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Australie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Prince of Wales Medical Research Institute</s1><s2>Sydney, NSW 2031</s2><s3>AUS</s3><sZ>4 aut.</sZ></inist:fA14><country>Australie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>University of New South Wales</s1><s2>Sydney, NSW 2052</s2><s3>AUS</s3><sZ>4 aut.</sZ></inist:fA14><country>Australie</country></affiliation></author><author><name sortKey="Micheau, J" sort="Micheau, J" uniqKey="Micheau J" first="J." last="Micheau">J. Micheau</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Laboratoire de Neurosciences Cognitives, Université Bordeaux I</s1><s2>33405 Talence</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Karl, T" sort="Karl, T" uniqKey="Karl T" first="T." last="Karl">T. Karl</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), 384 Victoria Street</s1><s2>Darlinghurst, NSW 2010</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Australie</country></affiliation></author></analytic><series><title level="j" type="main">Psychopharmacologia</title><title level="j" type="abbreviated">Psychopharmacologia</title><idno type="ISSN">0033-3158</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Psychopharmacologia</title><title level="j" type="abbreviated">Psychopharmacologia</title><idno type="ISSN">0033-3158</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term><term>Anxiety</term><term>Behavior</term><term>Cannabinoid</term><term>Drug of abuse</term><term>Gating</term><term>Knockout mouse</term><term>Neuregulin</term><term>Prepulse inhibition</term><term>Schizophrenia</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Neuréguline</term><term>Animal</term><term>Comportement</term><term>Cannabinol(6a,7,8,10a-tétrahydro)</term><term>Cannabinoïde</term><term>Schizophrénie</term><term>Angoisse anxiété</term><term>Inhibition préimpulsion</term><term>Gating</term><term>Substance toxicomanogène</term><term>Souris knockout</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Rationale Cannabis use may precipitate schizophrenia especially if the individual has a genetic vulnerability to this mental disorder. Human and animal research indicates that neuregulin 1 (Nrg1) is a susceptibility gene for schizophrenia. Objectives The aim of this study was to investigate whether dysfunction in the Nrg1 gene modulates the behavioural effects of Δ<sup>9</sup>-tetrahydrocannabinol (THC), the major psychotropic component of cannabis. Materials and methods Heterozygous Nrg1 transmembrane-domain knockout mice (Nrg1 HET) were treated with acute THC (0, 5 or 10 mg/kg i.p.) 30 min before being tested using open field (OF), hole board (HB), light-dark (LD), elevated plus maze (EPM), social interaction (SI) and prepulse inhibition (PPI) tests. Results Nrg1 HET mice showed differences in baseline behaviour with regard to locomotor activity, exploration and anxiety. More importantly, they were more sensitive to the locomotor suppressant actions of THC compared to wild type-like (WT) mice. In addition, Nrg1 HET mice expressed a greater THC-induced enhancement in % PPI than WT mice. The effects of THC on anxiety-related behaviour were task-dependent, with Nrg1 HET mice being more susceptible than WT mice to the anxiogenic effects of THC in LD, but not in the EPM, SI and OF tests. Conclusions Nrg1 HET mice were more sensitive to the acute effects of THC in an array of different behaviours including those that model symptoms of schizophrenia. It appears that variation in the schizophrenia-related neuregulin 1 gene alters the sensitivity to the behavioural effects of cannabinoids.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0033-3158</s0></fA01><fA02 i1="01"><s0>PSYPAG</s0></fA02><fA03 i2="1"><s0>Psychopharmacologia</s0></fA03><fA05><s2>192</s2></fA05><fA06><s2>3</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Δ<sup>9</sup>-tetrahydrocannabinol</s1></fA08><fA11 i1="01" i2="1"><s1>BOUCHER (A. A.)</s1></fA11><fA11 i1="02" i2="1"><s1>ARNOLD (J. C.)</s1></fA11><fA11 i1="03" i2="1"><s1>DUFFY (L.)</s1></fA11><fA11 i1="04" i2="1"><s1>SCHOFIELD (P. R.)</s1></fA11><fA11 i1="05" i2="1"><s1>MICHEAU (J.)</s1></fA11><fA11 i1="06" i2="1"><s1>KARL (T.)</s1></fA11><fA14 i1="01"><s1>Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), 384 Victoria Street</s1><s2>Darlinghurst, NSW 2010</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Pharmacology, University of Sydney</s1><s2>Sydney, NSW 2006</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></fA14><fA14 i1="03"><s1>Laboratoire de Neurosciences Cognitives, Université Bordeaux I</s1><s2>33405 Talence</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="04"><s1>Neuroscience Research Program, Garvan Institute of Medical Research</s1><s2>Sydney, NSW 2010</s2><s3>AUS</s3><sZ>3 aut.</sZ></fA14><fA14 i1="05"><s1>Prince of Wales Medical Research Institute</s1><s2>Sydney, NSW 2031</s2><s3>AUS</s3><sZ>4 aut.</sZ></fA14><fA14 i1="06"><s1>University of New South Wales</s1><s2>Sydney, NSW 2052</s2><s3>AUS</s3><sZ>4 aut.</sZ></fA14><fA20><s1>325-336</s1></fA20><fA21><s1>2007</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>1761</s2><s5>354000149659830030</s5></fA43><fA44><s0>0000</s0><s1>© 2007 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>2 p.1/2</s0></fA45><fA47 i1="01" i2="1"><s0>07-0306032</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Psychopharmacologia</s0></fA64><fA66 i1="01"><s0>DEU</s0></fA66><fC01 i1="01" l="ENG"><s0>Rationale Cannabis use may precipitate schizophrenia especially if the individual has a genetic vulnerability to this mental disorder. Human and animal research indicates that neuregulin 1 (Nrg1) is a susceptibility gene for schizophrenia. Objectives The aim of this study was to investigate whether dysfunction in the Nrg1 gene modulates the behavioural effects of Δ<sup>9</sup>-tetrahydrocannabinol (THC), the major psychotropic component of cannabis. Materials and methods Heterozygous Nrg1 transmembrane-domain knockout mice (Nrg1 HET) were treated with acute THC (0, 5 or 10 mg/kg i.p.) 30 min before being tested using open field (OF), hole board (HB), light-dark (LD), elevated plus maze (EPM), social interaction (SI) and prepulse inhibition (PPI) tests. Results Nrg1 HET mice showed differences in baseline behaviour with regard to locomotor activity, exploration and anxiety. More importantly, they were more sensitive to the locomotor suppressant actions of THC compared to wild type-like (WT) mice. In addition, Nrg1 HET mice expressed a greater THC-induced enhancement in % PPI than WT mice. The effects of THC on anxiety-related behaviour were task-dependent, with Nrg1 HET mice being more susceptible than WT mice to the anxiogenic effects of THC in LD, but not in the EPM, SI and OF tests. Conclusions Nrg1 HET mice were more sensitive to the acute effects of THC in an array of different behaviours including those that model symptoms of schizophrenia. It appears that variation in the schizophrenia-related neuregulin 1 gene alters the sensitivity to the behavioural effects of cannabinoids.</s0></fC01><fC02 i1="01" i2="X"><s0>002B18C06A</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Neuréguline</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Neuregulin</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Neuregulina</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Animal</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Animal</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Animal</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Comportement</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Behavior</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Conducta</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Cannabinol(6a,7,8,10a-tétrahydro)</s0><s2>NK</s2><s2>FX</s2><s5>04</s5><s6>Cannabinol(«6a,7,8,10a»-tétrahydro)</s6></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Cannabinoïde</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Cannabinoid</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Canabinoide</s0><s5>05</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Schizophrénie</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Schizophrenia</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Esquizofrenia</s0><s5>06</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Angoisse anxiété</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Anxiety</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Angustia ansiedad</s0><s5>07</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Inhibition préimpulsion</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Prepulse inhibition</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>inhibición prepulso</s0><s5>08</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Gating</s0><s5>09</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Gating</s0><s5>09</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Gating</s0><s5>09</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Substance toxicomanogène</s0><s5>23</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Drug of abuse</s0><s5>23</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Sustancia toxicomanógena</s0><s5>23</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Souris knockout</s0><s4>CD</s4><s5>96</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>Knockout mouse</s0><s4>CD</s4><s5>96</s5></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Ratón knockout</s0><s4>CD</s4><s5>96</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Psychose</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Psychosis</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Psicosis</s0><s5>37</s5></fC07><fN21><s1>197</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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