Locomotor effects of imidazoline I2-site-specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway
Identifieur interne : 000007 ( Pmc/Curation ); précédent : 000006; suivant : 000008Locomotor effects of imidazoline I2-site-specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway
Auteurs : Nicholas Macinnes ; Susan DutySource :
- British Journal of Pharmacology [ 0007-1188 ] ; 2004.
Abstract
The present study examined the ability of the selective imidazoline I2-site ligands 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) and 2-[4,5-dihydroimidaz-2-yl]-quinoline (BU224) and selected monoamine oxidase (MAO) inhibitors to evoke locomotor activity in rats bearing a lesion of the nigrostriatal pathway. Male Sprague–Dawley rats were injected with 12.5 Intraperitoneal (i.p.) administration of the irreversible MAO-B inhibitor deprenyl (20 mg kg−1) or the imidazoline I2-site ligands BU224 (14 mg kg−1) and 2-BFI (7 and 14 mg kg−1) produced significant increases in ipsiversive rotations compared to vehicle controls totaling, at the highest respective doses tested, 521±120, 131±37 and 92.5±16.3 net contraversive rotations in 30 (deprenyl) or 60 (BU224 and 2-BFI) min. In contrast, the reversible MAO-A inhibitor moclobemide (2.5–10 mg kg−1) and the reversible MAO-B inhibitor lazabemide (2.5–10 mg kg−1) failed to instigate significant rotational behaviour compared to vehicle. Coadministration of lazabemide (10 mg kg−1), moclobemide (10 mg kg−1) or 2-BFI (14 mg kg−1) with These data suggest that I2-specific ligands have dual effects in the 6-OHDA-lesioned rat model of Parkinson's disease; a first effect associated with an increase in activity in the intact hemisphere, probably
Url:
DOI: 10.1038/sj.bjp.0706019
PubMed: 15545290
PubMed Central: 1575965
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000007
Links to Exploration step
PMC:1575965Curation
No country items
Nicholas Macinnes<affiliation><nlm:aff id="aff1"><sup>1</sup>
Wolfson Centre for Age-Related Diseases, G20 Wolfson Wing, Hodgkin Building, Guy's Campus, GKT School of Biomedical Sciences, King's College London, London SE1 1UL</nlm:aff>
<wicri:noCountry code="subfield">London SE1 1UL</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="aff1"><sup>1</sup>
Wolfson Centre for Age-Related Diseases, G20 Wolfson Wing, Hodgkin Building, Guy's Campus, GKT School of Biomedical Sciences, King's College London, London SE1 1UL</nlm:aff>
<wicri:noCountry code="subfield">London SE1 1UL</wicri:noCountry>
</affiliation>
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Locomotor effects of imidazoline I<sub>2</sub>
-site-specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway</title>
<author><name sortKey="Macinnes, Nicholas" sort="Macinnes, Nicholas" uniqKey="Macinnes N" first="Nicholas" last="Macinnes">Nicholas Macinnes</name>
<affiliation><nlm:aff id="aff1"><sup>1</sup>
Wolfson Centre for Age-Related Diseases, G20 Wolfson Wing, Hodgkin Building, Guy's Campus, GKT School of Biomedical Sciences, King's College London, London SE1 1UL</nlm:aff>
<wicri:noCountry code="subfield">London SE1 1UL</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Duty, Susan" sort="Duty, Susan" uniqKey="Duty S" first="Susan" last="Duty">Susan Duty</name>
<affiliation><nlm:aff id="aff1"><sup>1</sup>
Wolfson Centre for Age-Related Diseases, G20 Wolfson Wing, Hodgkin Building, Guy's Campus, GKT School of Biomedical Sciences, King's College London, London SE1 1UL</nlm:aff>
<wicri:noCountry code="subfield">London SE1 1UL</wicri:noCountry>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">15545290</idno>
<idno type="pmc">1575965</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1575965</idno>
<idno type="RBID">PMC:1575965</idno>
<idno type="doi">10.1038/sj.bjp.0706019</idno>
<date when="2004">2004</date>
<idno type="wicri:Area/Pmc/Corpus">000007</idno>
<idno type="wicri:Area/Pmc/Curation">000007</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Locomotor effects of imidazoline I<sub>2</sub>
-site-specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway</title>
<author><name sortKey="Macinnes, Nicholas" sort="Macinnes, Nicholas" uniqKey="Macinnes N" first="Nicholas" last="Macinnes">Nicholas Macinnes</name>
<affiliation><nlm:aff id="aff1"><sup>1</sup>
Wolfson Centre for Age-Related Diseases, G20 Wolfson Wing, Hodgkin Building, Guy's Campus, GKT School of Biomedical Sciences, King's College London, London SE1 1UL</nlm:aff>
<wicri:noCountry code="subfield">London SE1 1UL</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Duty, Susan" sort="Duty, Susan" uniqKey="Duty S" first="Susan" last="Duty">Susan Duty</name>
<affiliation><nlm:aff id="aff1"><sup>1</sup>
Wolfson Centre for Age-Related Diseases, G20 Wolfson Wing, Hodgkin Building, Guy's Campus, GKT School of Biomedical Sciences, King's College London, London SE1 1UL</nlm:aff>
<wicri:noCountry code="subfield">London SE1 1UL</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series><title level="j">British Journal of Pharmacology</title>
<idno type="ISSN">0007-1188</idno>
<imprint><date when="2004">2004</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p><list list-type="order"><list-item><p>The present study examined the ability of the selective imidazoline I<sub>2</sub>
-site ligands 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) and 2-[4,5-dihydroimidaz-2-yl]-quinoline (BU224) and selected monoamine oxidase (MAO) inhibitors to evoke locomotor activity in rats bearing a lesion of the nigrostriatal pathway.</p>
</list-item>
<list-item><p>Male Sprague–Dawley rats were injected with 12.5 <italic>μ</italic>
g 6-hydroxydopamine (6-OHDA) into the right median forebrain bundle to induce a unilateral lesion of the nigrostriatal tract. After 6 weeks, test drugs were administered either alone or in combination with <sc>L</sc>
-DOPA (<sc>L</sc>
-3,4-dihydroxyphenylamine) and the circling behaviour of animals was monitored as an index of anti-Parkinsonian activity.</p>
</list-item>
<list-item><p>Intraperitoneal (i.p.) administration of the irreversible MAO-B inhibitor deprenyl (20 mg kg<sup>−1</sup>
) or the imidazoline I<sub>2</sub>
-site ligands BU224 (14 mg kg<sup>−1</sup>
) and 2-BFI (7 and 14 mg kg<sup>−1</sup>
) produced significant increases in ipsiversive rotations compared to vehicle controls totaling, at the highest respective doses tested, 521±120, 131±37 and 92.5±16.3 net contraversive rotations in 30 (deprenyl) or 60 (BU224 and 2-BFI) min. In contrast, the reversible MAO-A inhibitor moclobemide (2.5–10 mg kg<sup>−1</sup>
) and the reversible MAO-B inhibitor lazabemide (2.5–10 mg kg<sup>−1</sup>
) failed to instigate significant rotational behaviour compared to vehicle.</p>
</list-item>
<list-item><p>Coadministration of lazabemide (10 mg kg<sup>−1</sup>
), moclobemide (10 mg kg<sup>−1</sup>
) or 2-BFI (14 mg kg<sup>−1</sup>
) with <sc>L</sc>
-DOPA (20 mg kg<sup>−1</sup>
) significantly increased either the duration or total number of contraversive rotations emitted over the testing period in comparison to <sc>L</sc>
-DOPA alone.</p>
</list-item>
<list-item><p>These data suggest that I<sub>2</sub>
-specific ligands have dual effects in the 6-OHDA-lesioned rat model of Parkinson's disease; a first effect associated with an increase in activity in the intact hemisphere, probably <italic>via</italic>
an increase in striatal dopamine content, and a secondary action which, through the previously documented inhibition of MAO-A and/or MAO-B, increases the availability of dopamine produced by <sc>L</sc>
-DOPA.</p>
</list-item>
</list>
</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-comment> Original-type: pa</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Pharmacol</journal-id>
<journal-title>British Journal of Pharmacology</journal-title>
<issn pub-type="ppub">0007-1188</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">15545290</article-id>
<article-id pub-id-type="pmc">1575965</article-id>
<article-id pub-id-type="pii">0706019</article-id>
<article-id pub-id-type="doi">10.1038/sj.bjp.0706019</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Papers</subject>
</subj-group>
</article-categories>
<title-group><article-title>Locomotor effects of imidazoline I<sub>2</sub>
-site-specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>MacInnes</surname>
<given-names>Nicholas</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Duty</surname>
<given-names>Susan</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="caf1">*</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<sup>1</sup>
Wolfson Centre for Age-Related Diseases, G20 Wolfson Wing, Hodgkin Building, Guy's Campus, GKT School of Biomedical Sciences, King's College London, London SE1 1UL</aff>
<author-notes><corresp id="caf1"><label>*</label>
Author for correspondence: <email xlink:href="mailto:susan.duty@kcl.ac.uk">susan.duty@kcl.ac.uk</email>
</corresp>
</author-notes>
<pub-date pub-type="epub"><day>15</day>
<month>11</month>
<year>2004</year>
</pub-date>
<pub-date pub-type="collection"><day>30</day>
<month>11</month>
<year>2004</year>
</pub-date>
<pub-date pub-type="ppub"><month>12</month>
<year>2004</year>
</pub-date>
<volume>143</volume>
<issue>8</issue>
<fpage>952</fpage>
<lpage>959</lpage>
<history><date date-type="received"><day>16</day>
<month>07</month>
<year>2004</year>
</date>
<date date-type="rev-recd"><day>01</day>
<month>09</month>
<year>2004</year>
</date>
<date date-type="accepted"><day>13</day>
<month>09</month>
<year>2004</year>
</date>
</history>
<copyright-statement>Copyright 2004, Nature Publishing Group</copyright-statement>
<copyright-year>2004</copyright-year>
<permissions><copyright-holder>Nature Publishing Group</copyright-holder>
</permissions>
<abstract><p><list list-type="order"><list-item><p>The present study examined the ability of the selective imidazoline I<sub>2</sub>
-site ligands 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) and 2-[4,5-dihydroimidaz-2-yl]-quinoline (BU224) and selected monoamine oxidase (MAO) inhibitors to evoke locomotor activity in rats bearing a lesion of the nigrostriatal pathway.</p>
</list-item>
<list-item><p>Male Sprague–Dawley rats were injected with 12.5 <italic>μ</italic>
g 6-hydroxydopamine (6-OHDA) into the right median forebrain bundle to induce a unilateral lesion of the nigrostriatal tract. After 6 weeks, test drugs were administered either alone or in combination with <sc>L</sc>
-DOPA (<sc>L</sc>
-3,4-dihydroxyphenylamine) and the circling behaviour of animals was monitored as an index of anti-Parkinsonian activity.</p>
</list-item>
<list-item><p>Intraperitoneal (i.p.) administration of the irreversible MAO-B inhibitor deprenyl (20 mg kg<sup>−1</sup>
) or the imidazoline I<sub>2</sub>
-site ligands BU224 (14 mg kg<sup>−1</sup>
) and 2-BFI (7 and 14 mg kg<sup>−1</sup>
) produced significant increases in ipsiversive rotations compared to vehicle controls totaling, at the highest respective doses tested, 521±120, 131±37 and 92.5±16.3 net contraversive rotations in 30 (deprenyl) or 60 (BU224 and 2-BFI) min. In contrast, the reversible MAO-A inhibitor moclobemide (2.5–10 mg kg<sup>−1</sup>
) and the reversible MAO-B inhibitor lazabemide (2.5–10 mg kg<sup>−1</sup>
) failed to instigate significant rotational behaviour compared to vehicle.</p>
</list-item>
<list-item><p>Coadministration of lazabemide (10 mg kg<sup>−1</sup>
), moclobemide (10 mg kg<sup>−1</sup>
) or 2-BFI (14 mg kg<sup>−1</sup>
) with <sc>L</sc>
-DOPA (20 mg kg<sup>−1</sup>
) significantly increased either the duration or total number of contraversive rotations emitted over the testing period in comparison to <sc>L</sc>
-DOPA alone.</p>
</list-item>
<list-item><p>These data suggest that I<sub>2</sub>
-specific ligands have dual effects in the 6-OHDA-lesioned rat model of Parkinson's disease; a first effect associated with an increase in activity in the intact hemisphere, probably <italic>via</italic>
an increase in striatal dopamine content, and a secondary action which, through the previously documented inhibition of MAO-A and/or MAO-B, increases the availability of dopamine produced by <sc>L</sc>
-DOPA.</p>
</list-item>
</list>
</p>
</abstract>
<kwd-group><kwd>2-BFI</kwd>
<kwd>deprenyl</kwd>
<kwd>imidazoline I<sub>2</sub>
site</kwd>
<kwd>rat</kwd>
<kwd><italic>in vivo</italic>
</kwd>
<kwd>lazabemide</kwd>
<kwd>moclobemide</kwd>
<kwd>monoamine oxidase</kwd>
<kwd>Parkinson's disease</kwd>
</kwd-group>
</article-meta>
</front>
<floats-wrap><fig id="fig1"><label>Figure 1</label>
<caption><p>Ability of i.p. administration of I<sub>2</sub>
-site ligands (2-BFI and BU224) and MAO inhibitors (moclobemide, lazabemide and deprenyl) to elicit ipsiversive rotations in rats bearing a unilateral 6-OHDA lesion. Rotational behaviour was measured for 30 or 60 min post drug or vehicle administration. Data are mean±s.e.m. (<italic>n</italic>
=7). <sup>*</sup>
<italic>P</italic>
<0.05 and <sup>**</sup>
<italic>P</italic>
<0.01 indicate a statistically significant difference from vehicle using either the Student–Newman–Keuls test after a significant one-way ANOVA or a paired <italic>t</italic>
-test (deprenyl alone).</p>
</caption>
<graphic mime-subtype="gif" xlink:href="143-0706019f1"></graphic>
</fig>
<fig id="fig2"><label>Figure 2</label>
<caption><p>Ability of the I<sub>2</sub>
-site ligand 2-BFI (14 mg kg<sup>−1</sup>
i.p.) or the MAO inhibitors, moclobemide (10 mg kg<sup>−1</sup>
i.p.) and lazabemide (10 mg kg<sup>−1</sup>
i.p.) to potentiate <sc>L</sc>
-DOPA (10 mg kg<sup>−1</sup>
i.p.)-induced contraversive rotations in rats bearing a unilateral 6-OHDA lesion. (a, b) Total number of rotations over 240 min are shown. <sup>*</sup>
<italic>P</italic>
<0.05 indicates a statistically significant difference between drug+<sc>L</sc>
-DOPA <italic>versus</italic>
vehicle+<sc>L</sc>
-DOPA using either a paired <italic>t</italic>
-test (a) or Dunnett's test after a significant two-way ANOVA (b). (c, d) Animals were administered test drugs in conjunction with benserazide (15 mg kg<sup>−1</sup>
) at time <italic>T</italic>
-30 min, with 10 mg kg<sup>−1</sup>
<sc>L</sc>
-DOPA being given 30 min later at time <italic>T</italic>
0. In (c), <sup>*</sup>
<italic>P</italic>
<0.05 indicates a statistically significant difference between 2-BFI+<sc>L</sc>
-DOPA <italic>versus</italic>
vehicle+<sc>L</sc>
-DOPA (paired <italic>t</italic>
-test; after a significant 2-way ANOVA). In (d), <sup>*</sup>
<italic>P</italic>
<0.05, and <sup>**</sup>
<italic>P</italic>
<0.01 indicate a statistically significant difference between lazabemide+<sc>L</sc>
-DOPA <italic>versus</italic>
vehicle+<sc>L</sc>
-DOPA; <sup>+</sup>
<italic>P</italic>
<0.05 indicates a statistically significant difference between moclobemide+<sc>L</sc>
-DOPA <italic>versus</italic>
vehicle+<sc>L</sc>
-DOPA (Dunnett's test after a significant two-way ANOVA). Data are mean±s.e.m. (<italic>n</italic>
=7). Abbreviations: Laz, lazabemide. Moc, moclobemide. Veh, vehicle.</p>
</caption>
<graphic mime-subtype="gif" xlink:href="143-0706019f2"></graphic>
</fig>
</floats-wrap>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Santé/explor/JankovicV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000007 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000007 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Santé |area= JankovicV1 |flux= Pmc |étape= Curation |type= RBID |clé= PMC:1575965 |texte= Locomotor effects of imidazoline I2-site-specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:15545290" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \ | NlmPubMed2Wicri -a JankovicV1
![]() | This area was generated with Dilib version V0.6.19. | ![]() |