Epilepsyisoneofthemostcommonnervoussystemdis eases.However,themechanismofonsetisnotclear.Dizocilpine(MK 80 1 )isanon competitiveantagonistofN methyl D aspartate (NMDA )receptor,whichcaneasilypenetrateblood brainbarrier<1>.Ithasbeenknownthatepileptics eizureisrelatedtothebalancebetweenexcitatorytransmittersandinhibitorytransmitters<2,3 >.Inthisstudytheantiepilepticeffectofdizocil pineonamygdalakindlinginrats,whichresemblescomplexpartialepilepsywasinvestigated<2,4>.MaterialsandmethodsDrugs Dizocilpine,nicardipine,valproateandsemicarbazide (SCZ)werepurchasedfromSigma (StLous,USA) ;phenobarbitalfromMingtaiDrugCo .LtdinJilinprovince ;sodiumpenicillinfromHa’erbinDrugCo.Ltd ;sodiumpentobarbitalfrom (UnionCo.Ltd) .AlldrugsweredissolvedinsalineexceptnicardipinewhichwasdissolvedinMe2 SO .Animals Wistarrats (♀ ,weighing 1 90g± 1 0g)weresuppliedbytheAnimalCenter,QingdaoInstituteofDrugControl (CertificateNo.0 0 0 697,GradeII) .Theywerehousedinacontrolledenvironment (temperature 2 3±2℃ )ona 1 2hlight - 1 2hdarkcyclewithfreeaccesstofoodandwater.Kunmingmice (♂♀ ,weighing 2 0g± 2g)werealsofromtheAnimalCenter,QingdaoInstituteofDrugControl (CertificateNo.0 0 0 2 0 9,GradeII) .Experimentwasroutinelyperformedbetween 1 4∶0 0 - 1 7∶0 0inaquietlaboratory .Epilepsymodels Theratswereanesthetizedwithsodiumpentobarbital (40mg·kg- 1,ip)andabipolarelectrodewasstereotaxicallyi mplantedintoeachbasolateralnucleusoftheamygdala.Theelectrodewasmadeoftwopiecesoftwistedstainless steelwires (0 2 5mmindiameter)whichwereseparatedatthetipby 0 2 5mm .AccordingtothebrainatlasofK nigetal<5 >,thefollowingstereotaxiccoordinateswereused :AP 3 0mm ,L 4 8mm ,DV 8 8mm .Allcoordinatesweremeasuredfrombregma .Theelectrodepairwasanchoredtotheskullwithmi niaturescrewsanddentalcement.Afterelectrode implantation,theanimalsweretreatedwithsodiumpenicillinfor3dtopreventinfection<6>.Afterapostoperativerecoveryperiodof2weeks, allratsreceivedthekindlingstimulusoncedaily,whichconsistedofa1strainof60Hz,40 0 μAandmonophasicsquarewavepulsesattheintensitydescribedbelow<7,8>.Afterdischargeduration(ADD)wasthetotaltimeofspikesintheEEGrecordedfromthestimulation .Thedevelopmentofkindledseizureswasassessedb yusingamodificationofRacine’sstageasfollows<9>:stage0 ,noresponseorbehaviorarrest;stage 1 ,rhythmicmouthandfacialmovement;stage 2 ,rhythmicheadnodding;stage3 ,forelimbclonus;stage 4 ,rearingbilateralforelimbclonus;stage 5 ,rearingandfalling .Animalswhichdisplayed 3consecutiveseizuresonstages 5weredefinedaskindled.Inhibitoryeffectofdizo cilpineonpreviouslyamygdalakindledrats Thekindledratsweregivendizocilpine(0 0 5,0 1and 0 2 5mg·kg- 1,ip)atavolumeof2mL·kg- 1.TwohoursafteradministrationtheADDandRacine ’sstageofthedizocilpineonamygdalakindlingmodelswererecorded.Theratswerepreviouslygiventhesamevolumeofsa lineascontrol.Theintervalofexperimentswasat least4d.Effectsofdizocilpinecombinedwithphe nobarbital,valproateornicardipineonamygdalakindledrats Dizocilpine(0 0 5mg·kg- 1,ip )combinedwithineffectivedoseofphenobarbital (7 5mg·kg- 1,ip) ,valproate (2 0 0 0mg·kg- 1,po) <10 >,nicardipine (2 0mg·kg- 1,ip) ,ADDandRacine’sstagewererecordedaccordingtot heevaluationcriterion.Theratsreceivedthesam evolumeofsalineasselfcontrolbeforetheadmini strationofthemedicine.InfluenceofdizocilpineonSCZinducedseizureFortymiceweredividedrandomlyinto 4groupsandweregivensalineordizocilpine (0 0 5,0 1and 0 2 5mg·kg- 1,ip)atavolumeof 2 0mL·kg- 1.SCZ (1 50mg·kg- 1,iv)wereadministratedatavolumeof 1 0mL·kg- 1.Thelatencyofseizureandrateofonsetanddeathwererecorded 3hlater<11>.Statisticalanalysis Alldataobtainedwereexpressedas x±s.Intergroupdifferenceswereanalyzedusingpairedt test.EnumerationdatawereanalyzedbyChi squaretest.Results1 InhibitoryeffectofdizocilpineonamygdalakindledratsAsshowninTable 1 ,dizocilpinesignificantlysuppressedboththeseizurestageandADDinadose dependentmanner.Table 1 Inhibitoryeffectofdizocilpine (ip)onamygdalakindledratsDose mg·kg- 1ADD sVehicleDizocilpinetreatedRacine’sstageVehicleDizocilpinetreated0 .
More abstracts about the MK-801与抗癫痫药合用对大鼠杏仁核点燃的影响(英文)