Amazwana: UNora Volkow uyinhloko ye-NIDA. Lokhu kuhlanganisa indima ye-dopamine (D2) receptors kanye nokwehliswa kwemali ekugqilazweni.
I-Volkow ingaba nempendulo engatholakali yokuphendula umlutha
Izindaba ze-Psychiatric June 4, i-2004
Inombolo ye-39 11 Ikhasi 32
UJim Rosack
Izinkinga zokulutha zingaba “wukushintsha kwemitha” lapho imikhuba ejwayelekile ingasaziwa njengebalulekile, kepha imiphumela yezidakamizwa zokuhlukumeza ohlelweni lobuchopho lwe-dopamine ibaluleke kakhulu, umqondisi weNIDA ukholelwa ukuthi.
UNora Volkow, MD, ufunde ucwaningo ngempendulo yobuchopho bomuntu ezintweni eziluthayo cishe iminyaka engama-25. Manje, ngemuva kwayo yonke leyo minyaka yokubhekwa nokwenziwa kocwaningo, usebenzisa isikhundla sakhe njengomqondisi weNational Institute on Drug Abuse (NIDA) ukuthola impendulo yombuzo oyisisekelo: kungani ubuchopho bomuntu buba umlutha?
Ngempela, ngemva kwekota lesine leminyaka ezindla ngalolo mbuzo olula, uVolkow-esebenzisa ucwaningo lwakhe kanye nabanye abacwaningi bokulutha-manje ukholelwa ukuthi insimu isendleleni eya empendulo.
Ngaphansi kokuqondiswa kwakhe, abacwaningi abaxhaswe yi-NIDA bafuna impendulo eshisayo. Ngenyanga edlule, uVolkow wabelana ngemicabango yakhe nesixuku esasichichima ngesikhathi sesifundo esivelele sodokotela bengqondo emhlanganweni waminyaka yonke we-APA eNew York City.
Ucwaningo olunzulu lukhombisile ukuthi zonke izidakamizwa zokulutha umlutha zandisa umsebenzi we-dopamine ohlelweni lomzimba wobuchopho bomuntu. Kodwa, uVolkow wagcizelela, “yize lokhu kwanda kwe-dopamine kubalulekile ukudala ukulutha, akuchazi empeleni ukulutha. Uma unikeza noma ubani umuthi wokuhlukumeza, amazinga awo e-dopamine ayanda. Kodwa iningi aliluthwa imilutha. ”
Kule minyaka eyishumi eyedlule, ucwaningo lwe-brain-imaging lubonise ukuthi ukwanda kwe-dopamine ehlobene nezidakamizwa zokuhlukunyezwa kungaphansi kwalabo abayisidakwa kunalowo ongeyena umlutha. Kodwa kulabo abasengozini yokulutha umlutha, lokhu ukwanda okuncane kakhulu kwamazinga e-dopamine kuholela ngesifiso esibucayi sokufuna isidakamizwa sokuhlukunyezwa kaningi.
Ingabe i-dopamine idlala indima kulolu shintsho? ” Kubuza uVolkow. “Yini empeleni eholela ekuphoqelweni ukuthatha umuthi wokuhlukumeza? Yini ebhebhethekisa ukwehluleka ukulawula umlutha? ”
Ukucabanga Kugcwalisa Ngamanye Ama-Blanks
Ukuthuthuka kwamasu okucabanga ubuchopho kuvumele abacwaningi ukuthi basebenzise izimpawu ezahlukahlukene zamakhemikhali ukubheka izingxenye zohlelo lwe-dopamine-i-dopamine transporter kanye ne-dopamine receptors (okungenani izinhlobo ezine ezahlukahlukene ze-dopamine receptors zikhonjwe kuze kube yimanje). Ngaphezu kwalokho, abacwaningi manje sebekwazi ukubheka izinguquko ekuguqulweni kwengqondo emzimbeni ngokuhamba kwesikhathi, besebenzisa izimpawu zebhayoloji ye-glucose, ukubona ukuthi izidakamizwa zokuhlukumeza ziyithinta kanjani leyo metabolism.
Le ntuthuko isivumele ukuthi sibheke izidakamizwa ezahlukahlukene zokuhlukumeza nokuthi yimiphi imiphumela kanye nezinguquko ezithile [ohlelweni lwe-dopamine] ezihambisana nenye yazo, ”kuchaza uVolkow. "Okumele sikwazi ukuthi yimiphi imiphumela nezinguquko ezivamile kuzo zonke izidakamizwa zokuhlukumeza."
”Kuqale ukubonakala ekuqaleni ukuthi ezinye izidakamizwa zokuhlukumeza zibonakala zithinta umthuthi we-dopamine, kanti ezinye azenzanga kanjalo. Ucwaningo lube selugxila kuma-dopamine receptors nase-metabolism ukuthola imiphumela ejwayelekile, kuchaza uVolkow. Esinye sezifundo zakhe kuma-1980s sikhombise ukwehla okungaguquguquki kokuhlushwa kwe-dopamine receptor, ikakhulukazi kwi-ventral striatum, yeziguli eziyimilutha ye-cocaine, uma kuqhathaniswa nezihloko zokulawula. UVolkow wahlatshwa umxhwele ukuthola ukuthi lokhu kuncipha kuhlala isikhathi eside, ngaphezu kwesinqumo sokuhoxiswa okunamandla ku-cocaine.
"Ukwehliswa kwe-dopamine yohlobo lwe-2 receptors akucaciswanga ukulutha kwe-cocaine kuphela," kuqhubeka uVolkow. Olunye ucwaningo luthole imiphumela efanayo ezigulini eziyimilutha yotshwala, i-heroin, ne-methamphetamine.
"Ngakho-ke, kusho ukuthini, lokhu kwehla okuvamile kuma-D2 receptors ekuluthweni?" Kubuza uVolkow.
Ukusetha kabusha iMetal Salience
"Ngiqala njalo ngezimpendulo ezilula, futhi uma zingasebenzi, ngivumela ingqondo yami ukuba idideke," kuphawula uVolkow, kwajabulisa isixuku.
Isistimu ye-dopamine, esho, isabela kwisenzo esinqunyiwe-into enokuthakazelisa, ebalulekile, noma efanelekile ukunaka. Ezinye izinto zingabonakala kahle, njengezintandokazi noma isimiso esingalindelekile noma isitatimende esichazayo lapho besongela emvelweni.
"Ngakho-ke i-dopamine isho ngempela," Bheka, naka lokhu-kubalulekile, "kusho uVolkow. "I-Dopamine ikhombisa ubuhlakani."
Kepha, uqhubeke wathi, i-dopamine imvamisa ihlala ngaphakathi kwe-synapse isikhathi esifushane kuphela — ngaphansi kwama-microseconds angama-50 — ngaphambi kokuba iphinde isetshenziswe kabusha ngumthuthi we-dopamine. Ngakho-ke ngaphansi kwezimo ezijwayelekile, ama-dopamine receptors kufanele abe maningi futhi azwele uma ezokunaka ukuqhuma okuncane kwe-dopamine okuhloswe ukuhambisa umyalezo, "Naka!"
Ngokunciphisa ama-receptor e-D2 ahlobene nokulutha, umuntu ngamunye wehla ukuzwela ekusebenziseni okunamandla okusebenza njengama-reinforcers yemvelo yokuziphatha.
"Izidakamizwa eziningi zokuhlukumeza," kusho uVolkow, "zivimba umthuthi we-dopamine kumasekethe wemiklomelo yobuchopho, avumela i-neurotransmitter ukuthi ihlale ku-synapse kuze kube phakade. Lokhu kubangela umvuzo omkhulu futhi ohlala njalo, noma ngabe umuntu anciphise izinombolo zama-receptors.
"Ngokuhamba kwesikhathi, imilutha ifunda ukuthi izinto ezishukumisayo zemvelo azisekho," kugcizelela uVolkow. "Kodwa umuthi wokuhlukumeza unjalo."
Ngakho-ke, wabuza, “Sazi kanjani ukuthi iyiphi inkukhu nokuthi yiliphi iqanda?” Ngabe ukusetshenziswa okuqhubekayo kwesidakamizwa sokuhlukumeza kuholela ekwehleni kuma-receptors e-D2, noma ingabe inani eliphansi labamukeli liholela ekubeni umlutha?
Ucwaningo manje lukhuluma ngalowo mbuzo, uVolkow uqinisekise. Futhi kubonakala sengathi lokhu kungase kube impendulo. Kubantu abangenakunqatshelwe abangakaze bavezwe izidakamizwa zokuhlukunyezwa, kunezinhlobo ezihlukahlukene kakhulu zezingxenyana ze-D2 receptor. Ezinye izihloko zokulawula ezivamile zinamazinga e-D2 aphansi njengezinye zezihloko ezinobuthi be-cocaine.
Kulolu cwaningo oluthile, uVolkow uthe, abacwaningi banikeza imithi ye-methylphenidate kubantu abangewona umlutha futhi bacela ukuba bahlole ukuthi izidakamizwa zabenza bazizwa kanjani.
"Labo abanamazinga aphezulu ezamukeli ze-D2 bathi kuyabheda, futhi labo abanamazinga aphansi ezamukeli ze-D2 kungenzeka ukuthi bathi kubenze bazizwa kahle," kubika iVolkow.
“Manje,” eqhubeka, “lokhu akusho ukuthi labo bantu abanamazinga aphansi ezamukeli ze-D2 basengozini yokuba umlutha. Kepha kungasho ukuthi abantu abanamazinga aphezulu we-D2 receptors bagcina benempendulo enamandla kakhulu ekwandeni okukhulu kwe-dopamine ebonwe ezidakamizweni zokuhlukumeza. Okuhlangenwe nakho kuwukungawuthandi, okungenzeka kubavikela ekuluthekeni. ”
Ngokombono, uphakamise, uma abacwaningi bezokwelapha umlutha bengathola indlela yokubangela ukwanda kwama-D2 receptors ebuchosheni, "ungakwazi ukuguqula labo bantu abanamazinga aphansi e-D2 futhi wenze indlela yokuphindisela ekuphenduleni izidakamizwa zokuhlukunyezwa."
Ukuthola kwakamuva komunye wabafundi abacwaninga nge-postdoctoral kaVolkow kukhombisile ukuthi kungenzeka kumagundane ukwethula ebuchosheni i-adenovirus enofuzo lokukhiqizwa kwe-D2 receptor, okudala ukwanda kokuhlushwa kwe-D2 receptor. Ukuphendula, amagundane ngokufanayo anciphisa ukuphuza kwabo utshwala. Abanye abacwaningi basanda kuphindaphinda okutholakele nge-cocaine.
“Kodwa,” kuxwayisa uVolkow, “udinga okungaphezu nje kwezinga eliphansi lama-receptors e-D2.” Ukucabanga ngezifundo ze-glucose metabolism kukhombisile ukuthi imetabolism incipha kakhulu kwi-orbital frontal cortex (OFC) kanye ne-cingate gyrus (CG) ekuphenduleni i-cocaine, utshwala, i-methamphetamine, nensangu kulabo abayimilutha, uma kuqhathaniswa nezihloko zokulawula. Futhi, wanezela, lokhu kwehla kwe-metabolism kuhambelana kakhulu namazinga anciphile ama-D2 receptors.
UVolkow ubhale ukuthi ukungasebenzi kahle e-OFC naku-CG “kubangela ukuthi abantu bangabe besakwazi ukwahlulela ubungako besidakamizwa — bathatha umuthi wokuhlukumeza ngenkani, nokho awubaniki injabulo futhi, ezimweni eziningi, kunemiphumela emibi. ” Noma kunjalo, abakwazi ukuyeka ukusebenzisa lesi sidakamizwa.
Olunye ucwaningo lubonisa ukuthi ukuvimbela ukuvimbela; umvuzo, ukugqugquzela, nokushayela; futhi ukufunda nezifunda zezinkumbulo konke okuvamile kubantu abanezinkinga zokulutha umlutha, usho kanje. Ngenxa yalokho, ukwelashwa kwezidakamizwa kudinga indlela edidiyelwe, izinhlelo.
"Akekho umuntu okhetha ukuba umlutha," kuphetha uVolkow. "Ngokuqondakalayo abakwazi ukukhetha ukungabi imilutha."
;