the-modified-hole-board-measuring-behavior-cognition-social

The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure ...

Utrecht University

Brain Center Rudolf Magnus

The aim of this study was to investigate the in vivo relationship between reelin and NMDA receptor function in schizophrenia. We assessed the effect of reelin deficiency in behavioral models of aspects of this illness, NMDA receptor subunit levels, and NMDA receptor, dopamine D₂ receptor, and dopamine transporter density. Male, but not female, reelin heterozygous mice showed significantly enhanced MK-801-induced locomotor hyperactivity compared to wildtype controls (7.4-fold vs. 5.2-fold effect of MK-801 over saline, respectively) but there were no genotype differences in the response to amphetamine. Both male and female reelin heterozygous mice showed enhanced effects of MK-801 on startle, but not prepulse inhibition (PPI) of startle. There were no group differences in the effect of apomorphine on startle or PPI. The levels of NMDA receptor subunits were not altered in the striatum. In the frontal cortex, male and female reelin heterozygous mice showed significant up-regulation of NR1 subunits, but down-regulation of NR2C subunits, which was associated with significantly elevated NR1/NR2A and NR1/NR2C ratios. However, there were no differences in [³H]MK-801 binding density in the nucleus accumbens or caudate nucleus, nor in the density of [³H]YM-09151 or [³H]GBR12935 in these brain regions. The enhanced effects of MK-801 in reelin heterozygous mice in this study could be reflective of the role of reelin deficiency in schizophrenia. This genotype effect was male-specific for locomotor hyperactivity, a model of psychosis, but was seen in male and female mice for startle, which could be an indication of changes in anxiety. Changes in NMDA receptor subunit levels and ratios were also seen in both male and female mice. These results suggest that the role of reelin deficiency in schizophrenia may be particularly mediated by altered NMDA receptor responses, with some of these effects being strictly sex-specific.

Altered N-methyl-D-aspartate receptor function in reelin heterozygous mice: male-female differences and comparison with dopaminergic activity.

[11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats.

&#x672C;&#x7814;&#x7A76;&#x7684;&#x76EE;&#x7684;&#x662F;&#x8C03;&#x67E5;&#x5982;&#x679C;&#x897F;&#x5C3C;&#x8840;&#x8111;&#x5C4F;&#x969C;&#x8FD0;&#x8F93;&#x548C;&#x7ED1;&#x5B9A;&#x5230;&#x82EF;&#x4E8C;&#x6C2E;&#x5353;&#x7C7B;&#x7F51;&#x7AD9;&#x4E0A;&#x7684; &gamma;-&#x6C28;&#x57FA;&#x9178; A (GABA(A)) &#x53D7;&#x4F53;&#x590D;&#x6742;&#x6539;&#x53D8;&#x766B;&#x75EB;&#x7684;&#x5B9E;&#x9A8C;&#x6A21;&#x578B;&#x4E2D;&#xFF0C;&#x968F;&#x540E;&#xFF0C;&#x7814;&#x7A76;&#x5982;&#x679C;&#x66F4;&#x6539;&#x4E2D; P-&#x7CD6;&#x86CB;&#x767D; (p-gp)-&#x897F;&#x5C3C;&#x5728;&#x8840;&#x8111;&#x5C4F;&#x969C;&#x7684;&#x4ECB;&#x5BFC;&#x7684;&#x5C04;&#x6D41;&#x53EF;&#x80FD;&#x6DF7;&#x6DC6; (11) C &#x897F;&#x5C3C; PET &#x5728;&#x766B;&#x75EB;&#x4E2D;&#x7684;&#x89E3;&#x91CA;&#x3002;

&#x6539;&#x53D8; GABAA &#x53D7;&#x4F53;&#x5BC6;&#x5EA6;&#x548C;&#x4E2D;&#x6D77;&#x4EBA;&#x9178;&#x766B;&#x75EB;&#x6A21;&#x578B;&#x7684;&#x4E0D;&#x53D8;&#x7684;&#x8840;&#x8111;&#x5C4F;&#x969C;&#x8FD0;&#x8F93;&#xFF1A; &#x4F7F;&#x7528; 11 C &#x897F;&#x5C3C;&#x548C;&#x94F6;&#x9F99;&#x5728;&#x4F53;&#x5185;&#x5916;&#x7814;&#x7A76;

The aim of the present study was to investigate if flumazenil blood-brain barrier transport and binding to the benzodiazepine site on the Î³-aminobutyric acid A (GABA(A)) receptor complex is altered in an experimental model of epilepsy and subsequently to study if changes in P-glycoprotein (P-gp)-mediated efflux of flumazenil at the blood-brain barrier may confound interpretation of (11)C-flumazenil PET in epilepsy.

Altered GABAA Receptor Density and Unaltered Blood-Brain Barrier Transport in a Kainate Model of Epilepsy: An In Vivo Study Using 11C-Flumazenil and PET.

La pr&eacute;sente &eacute;tude visait &agrave; d&eacute;terminer si le transport de barri&egrave;re h&eacute;mato - enc&eacute;phalique flumaz&eacute;nil et liaison &agrave; la benzodiaz&eacute;pine site sur A acide &gamma;-aminobutyrique (complexe GABA(A)) r&eacute;cepteur est alt&eacute;r&eacute;e dans un mod&egrave;le exp&eacute;rimental de l&#39;&eacute;pilepsie et d&#39;&eacute;tudier si modifie ensuite dans la P-glycoprot&eacute;ine (P-gp)-m&eacute;diation efflux de flumaz&eacute;nil &agrave; la barri&egrave;re h&eacute;mato - enc&eacute;phalique peut confondre interpr&eacute;tation de (11) C-flumaz&eacute;nil PET dans l&#39;&eacute;pilepsie.

Modifi&eacute; la densit&eacute; des r&eacute;cepteurs GABAA et inchang&eacute;e de barri&egrave;re h&eacute;mato - enc&eacute;phalique Transport dans un mod&egrave;le de Kainate d&#39;&eacute;pilepsie : une &eacute;tude In Vivo 11c-flumaz&eacute;nil et PET.

Ziel der vorliegenden Studie war zu untersuchen, wenn Flumazenil Blut - Hirn-Schranke Transport und Bindung an die Benzodiazepin am &gamma;-Aminobutyric Acid A site (GABA(A))-Rezeptor-Komplex in einem experimentellen Modell der Epilepsie ver&auml;ndert und anschlie&szlig;end &Auml;nderungen vornimmt, wenn studieren in P-Glykoprotein (P-Gp)-vermittelten Efflux von Flumazenil an der Blut - Hirn-Schranke kann unversehens Interpretation (11) C-Flumazenil-PET bei Epilepsie.

Ge&auml;ndert von GABAA-Rezeptordichte und unver&auml;nderte Blut - Hirn-Schranke-Transport in einem Kainate-Modell der Epilepsie: eine In Vivo-Studie mit 11 C-Flumazenil und PET.

Lo scopo del presente studio era di indagare se flumazenil barriera emato - encefalica trasporto e vincolante per le benzodiazepine sito sulla A acido &gamma;-amminobutirrico (GABA(A)) complesso recettoriale &egrave; alterata in un modello sperimentale di epilessia e successivamente a studiare se cambia in P-glicoproteina (P-gp)-efflusso mediata del flumazenil presso la barriera emato - encefalica pu&ograve; confondere l&#39;interpretazione del PET C-flumazenil (11) nell&#39;epilessia.

Alterato trasporto inalterato barriera emato - encefalica in un modello Kainato dell&#39;epilessia e densit&agrave; del recettore GABAA: uno studio Vivo In utilizzando 11 C-Flumazenil e PET.

&#x672C;&#x7814;&#x7A76;&#x306E;&#x76EE;&#x7684;&#x306F;&#x3001;&gamma;-&#x30A2;&#x30DF;&#x30CE;&#x916A;&#x9178;&#x306E; A &#x30B5;&#x30A4;&#x30C8; &#x30D5;&#x30EB;&#x30DE;&#x30BC;&#x30CB;&#x30EB;&#x8840;&#x6DB2;&#x8133;&#x95A2;&#x9580;&#x8F38;&#x9001;&#x304A;&#x3088;&#x3073;&#x30D0;&#x30A4;&#x30F3;&#x30C7;&#x30A3;&#x30F3;&#x30B0;&#x3001;&#x30D9;&#x30F3;&#x30BE;&#x30B8;&#x30A2;&#x30BC;&#x30D4;&#x30F3;&#x3092;&#x5834;&#x5408;&#x3092;&#x691C;&#x8A0E;&#x3057;&#x305F; (GABA(A)) &#x53D7;&#x5BB9;&#x4F53;&#x8907;&#x5408;&#x4F53;&#x304C;&#x3066;&#x3093;&#x304B;&#x3093;&#x306E;&#x5B9F;&#x9A13;&#x30E2;&#x30C7;&#x30EB;&#x3067;&#x5909;&#x66F4;&#x3057;&#x3001;&#x305D;&#x306E;&#x5F8C;&#x5834;&#x5408;&#x306F;&#x52C9;&#x5F37;&#x3059;&#x308B; P (P gp) &#x7CD6;&#x86CB;&#x767D;&#x8CEA;&#x5909;&#x66F4;-&#x30D5;&#x30EB;&#x30DE;&#x30BC;&#x30CB;&#x30EB;&#x3001;&#x8840;&#x6DB2;&#x8133;&#x95A2;&#x9580;&#x306E;&#x4EF2;&#x4ECB;&#x3055;&#x308C;&#x305F;&#x6D41;&#x51FA; (11) C &#x30D5;&#x30EB;&#x30DE;&#x30BC;&#x30CB;&#x30EB; &#x30DA;&#x30C3;&#x30C8;&#x3066;&#x3093;&#x304B;&#x3093;&#x306B;&#x304A;&#x3051;&#x308B;&#x306E;&#x89E3;&#x91C8;&#x3092;&#x6DF7;&#x540C;&#x53EF;&#x80FD;&#x6027;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;

&#x5909;&#x66F4; GABAA &#x53D7;&#x5BB9;&#x4F53;&#x5BC6;&#x5EA6;&#x3068;&#x3066;&#x3093;&#x304B;&#x3093;&#x306E;&#x30AB;&#x30A4;&#x30CB;&#x30F3;&#x9178;&#x30E2;&#x30C7;&#x30EB;&#x306B;&#x304A;&#x3051;&#x308B;&#x4E0D;&#x5909;&#x8840;&#x6DB2;&#x8133;&#x95A2;&#x9580;&#x8F38;&#x9001;: In Vivo 11 C &#x30D5;&#x30EB;&#x30DE;&#x30BC;&#x30CB;&#x30EB;&#x3084; PET &#x3092;&#x7528;&#x3044;&#x305F;&#x7814;&#x7A76;

&#xD604;&#xC7AC;&#xC758; &#xC5F0;&#xAD6C;&#xC758; &#xBAA9;&#xC801;&#xC740; &#xB9CC;&#xC57D; flumazenil &#xD608;&#xC561;-&#xB1CC; &#xC7A5;&#xBCBD; &#xAD50;&#xD1B5;&#xACFC; benzodiazepine &#xBC14;&#xC778;&#xB529; &#xC0AC;&#xC774;&#xD2B8; &gamma;-aminobutyric acid A&#xC5D0; &#xC870;&#xC0AC; &#xD558;&#xB294; (GABA(A)) &#xC218;&#xC6A9; &#xCCB4; &#xBCF5;&#xC7A1; &#xD55C; &#xAC04; &#xC9C8;&#xC758; &#xC2E4;&#xD5D8; &#xBAA8;&#xB378;&#xC5D0;&#xC11C; &#xBCC0;&#xACBD; &#xD558; &#xACE0; &#xC774;&#xD6C4;&#xC5D0; &#xACF5;&#xBD80; &#xD558;&#xB294; &#xACBD;&#xC6B0; P-&#xB2F9;&#xB2E8;&#xBC31;&#xC9C8; (P-gp) &#xBCC0;&#xACBD;-&#xD608;&#xC561;-&#xB1CC; &#xC7A5;&#xBCBD;&#xC5D0;&#xC11C; flumazenil &#xC911;&#xC7AC; &#xACBD;&#xACFC; &#xAC04; &#xC9C8;&#xC5D0;&#xC11C; (11) C flumazenil PET&#xC758; &#xD574;&#xC11D; &#xD63C;&#xB3D9; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

GABAA &#xC218;&#xC6A9; &#xCCB4; &#xBC00;&#xB3C4; &#xBC0F; &#xAC04; &#xC9C8;&#xC758; Kainate &#xBAA8;&#xB378;&#xC5D0;&#xC11C; &#xBCC0;&#xACBD; &#xB418;&#xC9C0; &#xC54A;&#xC740; &#xD608;&#xC561;-&#xB1CC; &#xC7A5;&#xBCBD; &#xC804;&#xC1A1; &#xBCC0;&#xACBD;: &#xC2DC;&#xB0B4; Vivo &#xC5F0;&#xAD6C; 11 C Flumazenil &#xBC0F; &#xC560;&#xC644; &#xB3D9;&#xBB3C;&#xC744; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC;

El objetivo del presente estudio fue investigar si sitio flumazenil barrera blood - brain transporte y enlace a la benzodiazepina en el &aacute;cido &gamma;-aminobut&iacute;rico (complejo del receptor GABA(A)) se altera en un modelo experimental de epilepsia y posteriormente estudiar si los cambios en la P-glicoprote&iacute;na (P-gp)-mediada emanaci&oacute;n de flumazenil en la barrera blood - brain puede confundir la interpretaci&oacute;n de (11) C-flumazenil PET en epilepsia.

Alteraciones de la densidad de receptores GABAA y transporte barrera hemato - encef&aacute;lica en un modelo de kainato de epilepsia: un estudio de Vivo en con 11C-Flumazenil y PET.

To analyse the impact of both epilepsy and pharmacological modulation of P-glycoprotein on brain uptake and kinetics of positron emission tomography (PET) radiotracers [(11)C]quinidine and [(11)C]laniquidar.

Article	Year
Altered N-methyl-D-aspartate receptor function in reelin heterozygous mice: male-female differences and comparison with dopaminergic activity. Progress in neuro-psychopharmacology & biological psychiatry\| PubMed ID: 22361156	2012
[11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats. EJNMMI research\| PubMed ID: 22747744	2012
Altered GABAA Receptor Density and Unaltered Blood-Brain Barrier Transport in a Kainate Model of Epilepsy: An In Vivo Study Using 11C-Flumazenil and PET. Journal of nuclear medicine : official publication, Society of Nuclear Medicine\| PubMed ID: 23143088	2012
[11C]quinidine and [11C]laniquidar PET imaging in a chronic rodent epilepsy model: impact of epilepsy and drug-responsiveness. Nuclear medicine and biology\| PubMed ID: 23827307	2013

Maaike Labots

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