Iingxelo: UNora Volkow uyintloko ye-NIDA. Oku kubandakanya indima ye-dopamine (D2) kunye ne-desensitization kwi-addiction.
I-Volkow Mhlawumbi ingayifumanga Impendulo yokuLungisa umlutha
Iindaba zeengqondo zeJuni 4, i-2004
Umqulu 39 Inani 11 Page 32
UJim Rosack
Ukuphazamiseka okuluthayo kunokuba "lutshintsho kwimitha yokuma" apho inkuthazo yesiqhelo ayisaziwa njengeyona ibalulekileyo, ukanti iziphumo zeziyobisi zokuxhatshazwa kwinkqubo yengqondo ye-dopamine zibaluleke kakhulu, umlawuli we-NIDA ukholelwa.
UNora Volkow, MD, uye wafunda impendulo yengqondo yomntu kwizinto ezichasayo phantse iminyaka engama-25. Ngoku, emva kwayo yonke loo minyaka yoqwalaselo lweklinikhi kunye nophando, usebenzisa isikhundla sakhe njengomlawuli weZiko leSizwe lokuSetyenziswa gwenxa kweziyobisi (i-NIDA) ukufumana impendulo yombuzo osisiseko: kutheni le nto ingqondo yomntu iba likhoboka?
Enyanisweni, emva kwekota yeshumi leminyaka becingisisa lo mbuzo onobuqili, uVolkow-esebenzisa uphando lwakhe kunye nabanye abaphandi abanomlutha-ngoku bakholelwa ukuba intsimi ihamba ngendlela eya kwimpendulo.
Ngaphantsi kwesikhokelo sakhe, abaphandi abafumana inkxaso-mali kwi-NIDA basukela impendulo. Kwinyanga ephelileyo, uVolkow wabelane ngeengcinga zakhe nesihlwele esiphuphumayo ngexesha lesifundo esaziwayo segqirha kwintlanganiso yonyaka ye-APA kwisiXeko saseNew York.
Iqela elibanzi lophando libonakalisile ukuba onke amachiza okulutha akonyusa umsebenzi we-dopamine kwinkqubo ye-limbic yengqondo yomntu. Kodwa, uVolkow wagxininisa, “lo gama ukonyuka kwe-dopamine kubalulekile ekudaleni iziyobisi, akuchazi ukuba likhoboka. Ukuba unika ichiza lokuxhatshazwa kuye nabani na, amanqanaba abo e-dopamine ayonyuka. Ukanti uninzi alukhotyokiswa zizo. ”
Kule minyaka elishumi edlulileyo, uphando lwezobuchopho-mfanekiso lubonise ukuba ukwanda kwe-dopamine ehambelana neziyobisi kakubi kakhulu kulabo abanomlutha kunabo abangenalo umlutha. Nangona kunjalo kulabo abasengozini yokuxhatshazwa, oku kancinci ukwanda kwinqanaba le-dopamine kubangela umnqweno omkhulu wokufuna ukusetyenziswa kweziyobisi zokusetyenziswa kakubi ngokuphindaphindiweyo.
Ngaba idopamine idlala indima kolu tshintsho? ” UVolkow wabuza. “Yintoni ekhokelela ekunyanzelweni ukuba uthathe iziyobisi? Yintoni ebangela ukuba ilahleko iphulukane nolawulo? ”
Ukucinga Kuzalisa Kwezinye Iibhloko
Inkqubela phambili kubuchule bokucinga ngengqondo buye bavumela abaphandi ukuba basebenzise iziphawuli ezahlukeneyo zebhayoloji ukujonga izinto zenkqubo ye-dopamine-umthuthi we-dopamine kunye ne-dopamine receptors (ubuncinci ezine zineentlobo ezahlukeneyo zedopamine receptors ezichongiweyo ukuza kuthi ga ngoku). Ukongeza, abaphandi ngoku bayakwazi ukujonga utshintsho kwimetabolism yengqondo ngokuhamba kwexesha, basebenzise iziphawuli ze-biochemical kwi-glucose, ukubona indlela iziyobisi zokuxhatshazwa ezichaphazela ngayo imetabolism.
Le nkqubela phambili isivumele ukuba sijonge kumachiza ohlukeneyo okuphathwa gadalala kwaye zeziphi iziphumo kunye notshintsho [kwinkqubo yedopamine] enxulunyaniswa nenye yazo, ”ucacise watsho uVolkow. "Into ekufuneka siyazi ziziphumo kunye notshintsho oluqhelekileyo kuwo onke amachiza okuphatha gadalala."
”Kwacaca kwangoko kwangoko ukuba amanye amachiza okuphatha gadalala abonakala echaphazela umthuthi we-dopamine, kanti abanye khange benze njalo. Uphando emva koko lujolise kwii-dopamine receptors kunye nemetabolism ukufumana iziphumo ezifanayo, utshilo uVolkow. Esinye sezifundo zakhe kwii-1980s sabonisa ukwehla okungaguquguqukiyo koxinzelelo lwe-dopamine receptor, ngakumbi kwi-ventral striatum, yezigulana ezinomlutha wecocaine, xa kuthelekiswa nezifundo zolawulo. IVolkow yayinomdla wokufumanisa ukuba oku kuncipha kuhlala ixesha elide, ngaphezulu kwesisombululo sokurhoxa kwi-cocaine.
"Ukucuthwa kwe-dopamine yohlobo lwe-2 receptors ayichazwanga kubukhoboka be-cocaine kuphela," uqhubeke watsho uVolkow. Olunye uphando lufumene iziphumo ezifanayo kwizigulana ezinxila, i-heroin, kunye ne-methamphetamine.
"Ithetha ntoni ke le nto, ukunciphisa okuqhelekileyo kwii-receptors ze-D2?" UVolkow wabuza.
Ukusetha kwakhona iMeter Meter
"Ndihlala ndiqala ngeempendulo ezilula, kwaye ukuba azisebenzi, ndivumela ingqondo yam ukuba idideke," utshilo uVolkow, kwisihlwele sonwabile.
Inkqubo ye-dopamine, uthe, uyaphendula kwisisombululo esithile-into enokuyolisayo, ebalulekileyo, okanye ukulungelelwa ingqalelo. Ezinye izinto zinokuthi zilungele ngokunjalo, njenge-novel okanye i-stimuli engalindelekanga okanye i-stimuli xa isongela kwimvelo.
"Ke i-dopamine isithi," Jonga, nikela ingqalelo kule-kubalulekile, "utshilo uVolkow. "IDopamine ibonisa ubungqongqo."
Kodwa, uqhubeke, i-dopamine ihlala ihlala ngaphakathi kwe-synapse ixesha elifutshane-ngaphantsi kwe-50 microseconds-ngaphambi kokuba iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde yenzeke kwakhona. Ke phantsi kweemeko eziqhelekileyo, ii-dopamine receptors kufuneka zibe zininzi kwaye zinobuntununtunu ukuba ziya kuthathela ingqalelo ugqabhuko olufutshane lwedopamine ejolise ekuhambiseni umyalezo, "Nika ingqalelo!"
Ngenxa yokunciphisa ama-receptors e-D2 anxulumene nomlutha, umntu unomnono wokuhlawulela kwisistim esichukumisayo esisebenza njengabaqinisi bemvelo ngokuziphatha.
"Uninzi lweziyobisi zokuxhatshazwa, nangona kunjalo," utshilo uVolkow, "vimba umthuthi we-dopamine kwimijikelezo yomvuzo wobuchopho, evumela i-neurotransmitter ukuba ihlale kwi-synapse yobomi obungunaphakade. Oku kukhokelela kumvuzo omkhulu nohlala uhleli, nangona umntu eye wanciphisa inani lamamkeli.
"Ngokuhamba kwexesha, iziyobisi ziye zafunda ukuba izinto zendalo azisasebenzi," wagxininisa uVolkow. "Kodwa sisiyobisi gwenxa."
Ubuzile, “Sazi njani ukuba yeyiphi inkukhu kwaye leliphi iqanda?” Ngaba ukuqhubeka kokusebenzisa iziyobisi gwenxa kukhokelela ekunciphiseni kwii-receptors ze-D2, okanye ngaba inani elisezantsi labamkeli likhokelela ekubeni likhoboka?
Uphando ngoku uphendula loo mbuzo, uVolkow uqinisekisile. Kwaye kubonakala ngathi oku kulandelayo kungaba yimpendulo. Kubantu abangenakunyanisekanga abangazange bavelele kwiziyobisi zokusetyenziswa gadalala, kukho uluhlu olubanzi olubanzi lwe-D2 receptor concentrations. Ezinye izifundo zokulawula eziqhelekileyo zinamanqanaba e-D2 aphantsi njengezifundo ezinobungozi be-cocaine.
Kwisifundo esithile, uVolkow uthe, abaphandi banikezela i-methylphenidate engenazo izidakamizwa ezingenabuthi kwaye bacela ukuba bahlole ukuba izidakamizwa zenza bazive njani.
"Abo banamazinga aphezulu e-D2 receptors bathi kwakubi, kwaye abo banamazinga aphantsi e-D2 receptors babekho amathuba okuba bathi babenza bazive kakuhle," kusho uVolkow.
Uqhubeke wathi, "oku akuthethi ukuba abo bantu banamanqanaba asezantsi e-D2 receptors basengozini yokuba likhoboka. Kodwa oko kunokuthetha ukuba abantu abanamanqanaba aphezulu e-D2 receptors baphela benempendulo enkulu kakhulu kukonyuka okukhulu kwe-dopamine ebonwa kwiziyobisi zokuphathwa gadalala. Ngokwenene amava ayabathintela, anokuwakhusela kubukhoboka. ”
Kwithiyori, wacebisa, ukuba abaphandi kunyango lweziyobisi banokufumana indlela yokubangela ukonyuka kwee-receptors ze-D2 kwingqondo, "unganakho ukubaguqula abo bantu banamanqanaba asezantsi e-D2 kwaye wenze isimilo esiphikisayo ekuphenduleni iziyobisi."
Iziphumo zamva nje ezivela komnye wabafundi baseVolkow emva kophando zibonise ukuba kunokwenzeka kwiimpuku ukwazisa kwingqondo i-adenovirus kunye nofuzo kwimveliso ye-D2 receptor, ebangela ukonyuka koxinzelelo lwe-D2 receptor. Ukuphendula, iimpuku ngokufanayo zinciphisa ukuzilawula kwabo kotywala. Abanye abaphandi kutsha nje baphindaphinde iziphumo kunye necocaine.
"Kodwa," watsho uVolkow, "udinga ngaphezulu kwenqanaba eliphantsi lee-receptors ze-D2." Ukulinganisa izifundo zeswekile ye-glucose kubonise ukuba imetabolism iyancipha ngokubonakalayo kwi-orbital frontal cortex (OFC) kunye ne-cingate gyrus (CG) ekuphenduleni icocaine, utywala, imethamphetamine, kunye nentsangu kwezi ziyobisi, xa kuthelekiswa nezifundo zolawulo. Kwaye, wongeze, oku kuncipha kwimetabolism kuhambelana kakhulu namanqanaba anciphileyo e-D2 receptors.
UVolkow uxele ukuba ukungasebenzi kakuhle kwi-OFC nakwi-CG "kubangela ukuba abantu bangabinako ukugweba ubukho beziyobisi-bathatha iziyobisi ngokunyanzelwa, kodwa oko akubaniki lonwabo kwaye, kwiimeko ezininzi, kuneziphumo ezibi. ” Okwangoku, abanakuyeka ukusebenzisa iyeza.
Olunye uphando lubonisa ukuba ukulawulwa kwe-inhibitory; ukuvuza, ukukhuthaza, nokuqhuba; kunye nokufunda kunye neesekhondi zeememori ziyinto engavamile kubantu abaneengxaki zomlutha, wathi. Ngenxa yoko, unyango lomlingo lufuna indlela edibeneyo, inkqubo.
"Akukho mntu ukhetha ukuba likhoboka," ugqibile uVolkow. "Ngokucacileyo abakwazi ukukhetha ukungabinamakhoboka eziyobisi."
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