抑郁症研究的动物模型基础01级陈瑶瑶Iamdepressed.Metoo.Whyweneedanimalmodels?Thesortsofanimalmodels.Thefuturedevelopmentofanimalmodels.TheusesofanimalmodelsAntidepressantsscreening.Mechanismstudying神经生化功能改变模型应激模型条件性饲养模型基因工程动物模型获得性无助模型(learnedhelpless)慢性温和应激模型(chronicmildstress)行为绝望模型(behavioraldespair)Gene-engineeringmiceConventionaltransgenicmiceConditionalgene-targetingmethodsAntisensetargeting5-HT1A受体敲除抗抑郁表型糖皮质激素受体基因损伤抗抑郁表型，焦虑相关的行为减少(有待进一步确定)5-HT1B受体敲除拮抗抗抑郁表型，对SSRI类抗抑郁药敏感性增加谷氨酸脱羧酶基因敲除抗抑郁表型DA-β-羟化酶基因敲除拮抗抗抑郁表型神经细胞黏附分子基因敲除抗抑郁表型α2A-肾上腺素能受体基因敲除抑郁表型，并拮抗抗抑郁表型TNFα基因敲除抗抑郁表型α2C-肾上腺素能受体基因敲除抗抑郁表型血管紧张素基因敲除抗抑郁表型α2C-肾上腺素能受体基因过表达抑郁表型腺苷受体基因敲除抗抑郁表型NE转运子基因敲除抗抑郁表型速激肽NK1受体基因敲除抗抑郁表型单胺氧化酶A基因敲除抗抑郁表型IL-6基因敲除拮抗抗抑郁表型单胺氧化酶B基因敲除抗抑郁表型多巴胺D5受体基因敲除抗抑郁表型μ阿片受体基因敲除抗抑郁表型DARPP基因敲除对盐酸氟西汀敏感性降低δ阿片受体基因敲除抑郁表型CREB突变抗抑郁表型Gα-G-蛋白敲除拮抗抗抑郁表型BDNF条件性基因敲除抗抑郁表型，对电击敏感性降低5-HT1A受体敲除抗抑郁表型TrkB基因敲除抗抑郁表型，对抗抑郁药敏感性降低展望实验动物模型是研究抑郁症必不可少的工具。随着基因工程技术的出现，实验模型的可操作性和多样性都大大改善了。虽然转基因技术仍存在很多问题，但其仍有着光明的前景。Reference___________________________________________________________________________________________1．JanneGrønlia,.,RobertMurisonb,d,BjørnBjorvatnc,d,EliSørensena,ChiaraM.Portasa,ReidunUrsina,d，Chronicmildstressaffectssucroseintakeandsleepinrats，BehaviouralBrainResearch150(2004)139–1472．JohnF.Cryan,DanielHoyer,andAthinaMarkou，WithdrawalfromChronicAmphetamineInducesDepressive-LikeBehavioralEffectsinRodents，BIOLPSYCHIATRY2003;54:49–583．AndrewHarkin*,JohnP.Kelly,BrianE.Leonard，Areviewoftherelevanceandvalidityofolfactorybulbectomyasamodelofdepression，ClinicalNeuroscienceResearch3(2003)253–2624.VijayakumarMavanjia,b,SubimalDattaa,*，Clomipraminetreatmentinneonatalratsaltersthebrainacetylcholinesteraseactivityinadulthood，NeuroscienceLetters330(2002)119–1215.RuthE.Grahna,*,S.E.Hammacka,M.J.Willb,K.A.O’Connora,T.Deakc,P.D.Sparksa,L.R.Watkinsa,S.F.Maiera,Blockadeofalpha1adrenoreceptorsinthedorsalraphenucleuspreventsenhancedconditionedfearandimpairedescapeperformancefollowinguncontrollablestressorexposureinrats,BehaviouralBrainResearch134(2002)387_/3926.PeterGassa,*,HolgerM.Reichardtb,TatyanaStrekalovaa,FritzHenna,FrancoisTroncheb,Micewithtargetedmutationsofglucocorticoidandmineralocorticoidreceptors:Modelsfordepressionandanxiety?Physiology&Behavior73(2001)811–8257.AlexandreUrani,SabineChourbaji,FritzA.Henn,PeterGass*，Modelingdepressionwithtransgenicmice:theneurotrophinhypothesisrevisited，ClinicalNeuroscienceResearch3(2003)263–2698．MarianneB.Mu¨ller*,MartinE.Keck，Geneticallyengineeredmiceforstudiesofstress-relatedclinicalconditions，JournalofPsychiatricResearch36(2002)53–769．EricJ.Nestler,ElizabethGould,HusseiniManji,MajaBucan,RonaldS.Duman,HowardK.Gershenfeld,ReneHen,SusanKoester,IsraelLederhendler,MichaelJ.Meaney,TrevorRobbins,LoisWinsky,andSteveZalcman,PreclinicalModels:StatusofBasicResearchinDepressi...
