动机与成瘾

MotivationandAddictionNeuroscienceExploringtheBrainChapter16Thelong-termregulationoffeedingbehaviorbymotivation(1)EnergyBalance(2)hormonal,hypothalamicregulationofbodyfat,feeding(3)bodyfatandfoodconsumption(4)thehypothalamusandfeeding(5)theeffectsofdecreasedleptinlevelonthehypothalamus(6)theeffectsofelevatedleptinlevelonthehypothalamus(7)thecontroloffeedingbylateralhypothalamicpeptides吴鎏桢基础Loadingandemptyingthebody'senergyreserves.(a)Afterameal,whenweareintheprandialstate,excessenergyisstoredasglycogenorastriglycerides.吴鎏桢基础(b)Betweenmeals,whenweareinthepostabsorptivestate,theglycogenandtriglyceridesarebrokendown(catabolized)intosmallermoleculesthatcanbeusedasfuelbythecellsofthebody.吴鎏桢基础Energybalanceandbodyfat.(a)Normalenergybalanceleadstonormaladiposity.(b)Prolongedpositiveenergybalanceleadstoobesity,(c)Prolongednegativeenergybalanceleadstostarvation.吴鎏桢基础Maintenanceofbodyweightaroundasetvalue.Bodyweightisnormallystable.Ifananimalisforce-fed,itwillgainweight.Theweightislost,however,assoonastheanimalcanregulateitsownfoodintake.Similarly,weightlostduringaperiodofstarvationisrapidlygainedwhenfoodisfreelyavailable.吴鎏桢基础Ob:obesityBarHarborJacksonLabs吴鎏桢基础Regulationofbodyfatbyacirculatinghormone.Ifageneticallyobeseob/obmouseissurgicallyfusedwithanormalmousesothatbloodbomesignalsarenowsharedbetweentheanimals,theobesityoftheob/obmouseisgreatlymoderated.吴鎏桢基础Alteredfeedingbehaviorandbodyweightresulteingfrombilaterallesionsoftherathypothalamus.(a)Thelateralhypothalamicsyndrome,characterizedbyanorexia,iscausedbylesionsofthelateralhypothatamus.(b)Theventromedialhypothalamicsyndrome,characterizedbyobesity,iscausedbylesionsoftheventromedialhypothalamus.(LHA)(VMH)吴鎏桢基础Hypothalamicnucleiimportantforthecontroloffeeding.(a)Amidsagittalviewofthehumanbrain,showingthelocationofthehypothalamus(b)Acoronalsectionofthehumanbrain,showing,inpart,threeimportantnucleiforthecontroloffeeding:thearcuatenucleus,theparaventricularnucleus,andthelateralhypothalamicarea(PVN)(ARC)吴鎏桢基础吴鎏桢基础吴鎏桢基础吴鎏桢基础Responsetoelevatedleptinlevels.AriseinleptinlevelsinthebloodisdetectedbyneuronsinthearcuatenucleusthatcontainthepeptidesαMSHandCART.Theseneuronsprojectaxonstothelowerbrainstemandspinalcord,theparaventricularnucleiofthehypothalamus,andthelateralhypothalamicarea.Eachoftheseconnectionscontributestothecoordinatedhumoral,visceromotor,andsomaticmotorresponsestoincreasedleptinlevels.(Source:AdaptedfromSawchenko,1998,p.437.)Anorecticpeptides吴鎏桢基础Responsetodecreasedleptinlevels.AreductioninbloodlevelsofleptinisdetectedbyneuronsinthearcuatenucleusthatcontainthepeptidesNPYandAgRP.ThesearcuatenucleusneuronsinhibittheneuronsintheparaventricularnucleithatcontrolthereleaseofTSHandACTHfromthepituitary.Inaddition,theyactivatetheneuronsinthelateralhypothalamusthatstimulatefeedingbehavior.Someoftheactivatedlateralhypothalamicneuronscontainthepeptidesmelaninconcentratinghormone(MCH)andorexin.orexigenicpeptides吴鎏桢基础CompetitionforactivationoftheMC4receptor,OnewaythatαMSH,ananorecticpeptide,andAgRP,anorexigenicpeptide,exertoppositeeffectsonmetabolismandfeedingbehaviorisviaaninteractionwiththeMC4receptoronsomehybothalamicneurons,WhileαMSHstimulatestheMC4receptor,AgRPblockstheactionofαMSHatthereceptor.吴鎏桢基础Neuronsthatstimulatefeedingintheratlateralhypothalamus.Inthisphot-omicrograph,neuronscontainingmesse-ngerRNAfororexinappearbrightonadarkbackground.Orexinisoneofthelateralhypothalamicpeptidesthatstim-ulatesfeedingbehaviorAswewillseeinChapter19,thesamecellsplayanimportantroleinthecontrolofsleepandwakefulness.RememberthatleptinlevelsrisewhenbodyfatisincreasedandtheyfallwhenbodyfatisdecreasedAriseinleptinlevelsincreasesα-MSHandCARTinarcuatenucleusneurons.Theseanorecticpeptidesactonthebraintoinhibitfeedingbehaviorandincreasemetabolism.AfallinleptinlevelsincreasesNPYandAgRPinthearcuatenucleusandMCHandorexininthelateralhypothalamicarea.Theseorexigenicpeptidesactonthebraintostimulatefeedingbehavioranddecreasemetabolism.Theshort-termregulationoffeedingbehaviorbymotivation(1)gastricdistension(2)cholecystokininCCK(3)InsulinOthermotivatedbehaviors(1)drinking(2)temperatureregulation吴鎏桢基础Hypotheticalmodelfortheshort-termregulationoffeedingbehavior.Thisgraphshowsapossiblemeansofregulatingfoodconsumptionbysatietysignals,whichriseinresponsetofeeding.Whensatietysignalsarehigh,foodconsumptionisinhibited.Whenthesatietysignalsfalltozero,theinhibitioniseliminated,andfoodconsumptionensues.SynergisticactionofgastricdistensionandCCKonfeedingbehavior.Bothsignalsconvergeonaxonsinthevagusnervethattriggersatiety.吴鎏桢基础Changesinbloodinsulinlevelsbefore,during,andafterameal.(Source:AdaptedfromWoodsandStricker,1999,p.1094)吴鎏桢基础吴鎏桢基础Mesocorticolimbicdopaminesystem（MLDS）.Animalsaremotivatedtobehaveinwaysthatstimulatethereleaseofdopamineinthebasalforebrainarea.(VTA)吴鎏桢基础Changinhypothalamicserotoninlevelsbeforeandduringameal.Themoodelevatingeffectsofeatingarebelievedtoberelatedtothereleaseofserotonininthebrain.(Soure:AdaptedfromSchwartzetal,1990)吴鎏桢基础Pathwaystriggeringvolumetricthirst.Hypovolemiaisdetected