Amazwana: Lokhu kungenxa yomphakathi jikelele, kodwa kungaba kancane kwezobuchwepheshe. Noma kunjalo, ingenye yezindaba ezihamba phambili neziphelele kakhulu ezibhalwe ekugqilazweni.
Ngu-Eric J. Nestler noRobert C. Malenka
February 09, 2004
Ukuhlukumeza izidakamizwa kuveza izinguquko zesikhathi esigcwele kumjikelezo womvuzo wengqondo. Ulwazi lwemininingwane yamaselula nolwazi lwamangqamuzana yalezi zimo ezizoshintshashintsha kungaholela ezithombeni ezintsha zokuziphatha okuphoqeleka okucindezelayo.
Imigqa emhlophe esibukweni. Inaliti nesipuni. Kubasebenzisi abaningi, ukubona isidakamizwa noma izinto ezihambisana naso kungabethusa injabulo yokulindela. Ngemuva kwalokho, ngokulungiswa, kuza ukugijimisana kwangempela: imfudumalo, ukucaca, umbono, ukukhululeka, umuzwa wokuba maphakathi nendawo yonke. Isikhathi esifushane, konke kuzwakala kulungile. Kodwa kukhona okwenzekayo ngemuva kokuchayeka kaningi ezidakamizweni zokuhlukumeza - kungaba i-heroin noma i-cocaine, iwhisky noma ijubane.
Inani elake laveza injabulo alisebenzi futhi, futhi abasebenzisi badinga ukudutshulwa noma ukukhipha ukuze bazizwe bejwayelekile; ngaphandle kwawo, bayacindezeleka futhi, ngokuvamile, bagule emzimbeni. Ngemuva kwalokho baqala ukusebenzisa lesi sidakamizwa ngokucindezela. Kuleli qophelo, basuke sebenomlutha, belahlekelwa ukulawula ukusetshenziswa kwabo futhi bahlupheka ngezifiso ezinamandla noma ngabe injabulo isiphelile futhi umkhuba wabo uqala ukulimaza impilo yabo, ezezimali kanye nobudlelwano bomuntu siqu.
Sekuyisikhathi eside izazi ze-Neurobiologists zazi ukuthi injabulo ebangelwa izidakamizwa zokuhlukumezeka ivela ngoba wonke la makhemikhali agcina ekwenyuseni umsebenzi wohlelo lomvuzo wobuchopho: isekethe eyinkimbinkimbi yamaseli ezinzwa, noma ama-neuron, aguquke ukusenza sizizwe siduduzekile ngemuva kokudla noma ucansi – izinto sidinga ukukwenza ukuze sisinde futhi sidlulise izakhi zethu zofuzo. Okungenani ekuqaleni, ukusebenzisa lolu hlelo kusenza sizizwe sihle futhi kusikhuthaza ukuthi siphinde noma imuphi umsebenzi osilethele injabulo enjalo.
Kepha ucwaningo olusha lukhombisa ukuthi ukusetshenziswa kwezidakamizwa ezingalapheki kudala izinguquko ekwakhiweni nasekusebenzeni kwama-neuron ohlelo ahlala amasonto, izinyanga noma iminyaka ngemuva kokulungiswa kokugcina. Lezi zinguquko, ngokuhlanekezela, zinciphisa imiphumela ejabulisayo yento ehlukunyezwayo engapheli kepha futhi zandisa izifiso ezibamba umlutha ekulimaleni kokusetshenziswa okwandayo nokwanda kokuwa emsebenzini nasekhaya. Ukuqonda okuthuthukile kwalokhu kuguqulwa kwe-neural kufanele kusize ukuhlinzeka ngokungenelela okungcono kokulutha, ukuze abantu ababa yizisulu zezidakamizwa ezenza imikhuba bakwazi ukubuyisa ubuchopho babo nezimpilo zabo.
Izidakamizwa Ukufa
Ukuqaphela ukuthi izidakamizwa ezihlukahlukene zokuhlukunyezwa ekugcineni ziholela ekugqilazweni ngokusebenzisa indlela evamile ezivela ikakhulukazi ezifundweni zezilwane zelabhutri eziqala cishe eminyakeni eyi-40 edlule. Njengoba kunikezwe ithuba, amagundane, amagundane kanye nezidakamizwa ezingezona ezomuntu zizokwenza izinto ezifanayo abantu abazisebenzisayo. Kulezi zivivinyo, izilwane zixhunywe emgqeni wokubamba iqhaza. Bese bafundiswa ukucindezela i-lever eyodwa ukuze bathole ukumnika kwezidakamizwa nge-IV, enye i-lever ukuthola isixazululo saline esingathandeki, kanye nesiphambano sesithathu sokucela i-pellet yokudla. Kungakapheli izinsuku ezimbalwa, izilwane ziphethwe yizinyosi: zikwazi ukuzilawula kalula i-cocaine, i-heroin, i-amphetamine nezinye izidakamizwa eziningi ezivamile.
Ngaphezu kwalokho, ekugcineni babonisa izindlela zokuziphatha eziluthayo. Izilwane ngazinye zizodla izidakamizwa ngokudela imisebenzi ejwayelekile njengokudla nokulala – ezinye kuze kube seqophelweni lokuthi zibulawe ukukhathala noma ukungondleki. Okwezinto eziluthayo kakhulu, njenge-cocaine, izilwane zizosebenzisa iningi lamahora azo okuvuka zisebenzela ukuthola okuningi, noma ngabe kusho ukucindezela isigwedlo amahlandla angamakhulu ngokushaya okukodwa. Futhi njengoba imilutha yabantu ihlangabezana nokufisa okukhulu lapho ihlangabezana nempahla yezidakamizwa noma izindawo lapho ithole khona amagoli, izilwane, nazo, zikhetha indawo eziyizihlanganisa nomuthi – indawo esehokweni lapho ukucindezela i-lever kuhlale kunikeza isinxephezelo samakhemikhali .
Lapho kususwa into leyo, izilwane ngokushesha ziyeka ukusebenza ukuze zanelise amakhemikhali. Kepha ubumnandi abukhohliwe. Igundane elihlale lihlanzekile - noma izinyanga - lizobuyela masinyane ekuziphatheni kwalo ngokucindezela ibha lapho linikezwa ukunambitheka nje kwecocaine noma lifakwe ehokweni elihambisana nomuthi ophakeme. Futhi izingcindezi ezithile ezingokwengqondo, ezinjengokushaywa yizinyawo ngezikhathi ezithile, okungalindelekile, kuzothumela amagundane egijimela emuva ezidakamizweni. Lezi zinhlobo ezifanayo zokuthambekela kokuchayeka kumithamo ephansi yezidakamizwa, izinkomba ezihlobene nezidakamizwa noma ukucindezelwa-okubangela ukulangazelela nokubuyela emilutha yabantu.
Besebenzisa le ndlela yokuzibusa kanye namasu ahlobene nalawa, abacwaningi benza imephu yezindawo zobuchopho ezilamula isimilo sokuziphatha futhi bathola indima ebalulekile yesekethe yomvuzo wobuchopho. Izidakamizwa zilawula lesi sifunda, zivuselela umsebenzi wazo ngamandla nokuphikelela okukhulu kunanoma yimuphi umvuzo wemvelo.
Ingxenye eyinhloko yomjikelezo womvuzo uhlelo lwe-mesolimbic dopamine: iqoqo lamangqamuzana ezinzwa avela endaweni ye-ventral tegmental area (VTA), eduze kwesisekelo sobuchopho, futhi athumele izilinganiso zokukhomba izifunda ezingaphambi kobuchopho- kakhulu ikakhulukazi esakhiweni esijule ngaphansi kwe-cortex engaphambili ebizwa nge-nucleus accumbens. Lawo ma-neurons we-VTA axhumana ngokuthumela i-chemical messenger (i-neurotransmitter) dopamine kusuka kumatheminali, noma amathiphu, wokuqagela kwawo okude kuma-receptors kuma-nucleus accumbens neurons. Indlela ye-dopamine esuka ku-VTA iye kuma-nucleus accumbens ibaluleke kakhulu ekuluthweni umlutha: izilwane ezinezilonda kulezi zifunda zobuchopho azisakhombisi intshisekelo ezintweni zokuhlukunyezwa.
I-Rheostat yomvuzo
Izindlela zomvuzo zindala ngokwendalo. Ngisho nesibungu esilula, esihlala emhlabathini, iCaenorhabditis elegans sinenguqulo evamile. Kulezi zimpethu, ukungasebenzi kwamangqamuzana e-dopamine aqukethe ezine kuya kweziyisishiyagalombili kubangela ukuthi isilwane silime siqonde sidlule inqwaba yamagciwane, ukudla esikuthandayo. Ezilwaneni ezincelisayo, isifunda somvuzo siyinkimbinkimbi ngokwengeziwe, futhi sihlanganiswe nezinye izifunda eziningi zobuchopho ezisebenzela ukufaka umbala kokuhlangenwe nakho ngokomzwelo futhi ziqondise impendulo yomuntu ngamunye ezintweni ezivuzayo, kufaka phakathi ukudla, ubulili nokuxhumana nabantu. I-amygdala, ngokwesibonelo, isiza ukuhlola ukuthi ngabe okuhlangenwe nakho kuyajabulisa noma kuyaphindisela – nokuthi kufanele kuphindwe noma kugwenywe – futhi kusize ekwakheni ukuxhumana phakathi kwesipiliyoni nezinye izinkomba; i-hippocampus ibamba iqhaza ekuqopheni izinkumbulo zesipiliyoni, kufaka phakathi ukuthi yenzeke kuphi futhi nini futhi nobani; kanye nezifunda ezingaphambili ze-cerebral cortex zihlanganisa futhi zicubungule lonke lolu lwazi futhi zinqume indlela yokuziphatha komuntu lowo. Indlela ye-VTA-accumbens, okwamanje, isebenza njenge-rheostat yomvuzo: "itshela" ezinye izikhungo zobuchopho ukuthi umsebenzi uzuzisa kanjani. Lapho umsebenzi uthatha umvuzo othathwa kakhulu, maningi amathuba okuthi umzimba uwukhumbule kahle bese uwuphinda.
Yize ulwazi oluningi lwemijikelezo yomvuzo wobuchopho luthathwe ezilwaneni, izifundo zokucabanga ngobuchopho ezenziwe eminyakeni eyishumi eyedlule ziveze ukuthi izindlela ezilinganayo zilawula imivuzo yemvelo nezidakamizwa kubantu. Kusetshenziswa ukuskena okusebenzayo kwe-magnetic resonance imaging (fMRI) noma i-positron emission tomography (PET) (amasu alinganisa izinguquko ekugelezeni kwegazi okuhambisana nomsebenzi we-neuronal), abacwaningi babuke i-nucleus accumbens kwizidakamizwa ze-cocaine ikhanya lapho inikezwa isifutho. Lapho imilutha efanayo ikhonjiswa ividiyo yomuntu osebenzisa i-cocaine noma isithombe semigqa emhlophe esibukweni, ama-accumbens aphendula ngokufanayo, kanye ne-amygdala nezinye izindawo ze-cortex. Futhi izifunda ezifanayo ziyasabela kubadlali abagembulayo abakhonjiswa izithombe zemishini ye-slot, okuphakamisa ukuthi indlela ye-VTA-accumbens path ineqhaza elibaluleke ngokufanayo ngisho nasekuluthweni kwezidakamizwa.
I-Dopamine, Sicela
Kungenzeka kanjani ukuthi izinto ezahlukahlukene eziluthayo – ezingenazo izici ezijwayelekile zokwakheka futhi ezinemiphumela ehlukahlukene emzimbeni - konke lokhu kuphakamisa izimpendulo ezifanayo kumjikelezo womvuzo wobuchopho? Kungenzeka kanjani ukuthi i-cocaine, isikhuthazi esenza inhliziyo igijime, ne-heroin, isidambisi esidambisa izinhlungu, ihluke kakhulu ngandlela-thile kepha ifane nasekuqondiseni uhlelo lwemivuzo? Impendulo ukuthi zonke izidakamizwa zokuhlukumeza, ngaphezu kwanoma yimiphi eminye imiphumela, zidala ukuthi i-nucleus accumbens ithole isikhukhula se-dopamine futhi kwesinye isikhathi futhi nezimpawu zokulingisa ze-dopamine.
Lapho ingqamuzana le-nerve ku-VTA lijabule, lithumela umlayezo kagesi ngokugijima ku-axon yalo- "umgwaqo omkhulu" ophethe isiginali onabela kuma-nucleus accumbens. Isiginali ibangela ukuthi kukhishwe i-dopamine ethiphu ye-axon iye esikhaleni esincane – i-synaptic cleft – ehlukanisa i-axon terminal ne-neuron kuma-nucleus accumbens. Ukusuka lapho, i-dopamine inamathisela ku-receptor yayo ku-accumbens neuron futhi idlulisele isinali layo esitokisini. Ukuvala isignali kamuva, i-VTA neuron isusa i-dopamine ku-synaptic cleft iphinde iyiphinde isetshenziswe ukuze isetshenziswe futhi lapho kudingeka.
I-Cocaine nezinye izikhuthazo zikhubaza okwesikhashana iphrotheni le-transporter elibuyisela i-neurotransmitter kuma-terminals e-VTA neuron, ngaleyo ndlela ishiya i-dopamine eyedlulele ukuba isebenze ku-nucleus accumbens.
I-Heroin namanye ama-opiates, ngakolunye uhlangothi, abopha ama-neurons ku-VTA avame ukuvala ama-neurons akhiqiza i-VTA neurons. Ama-opiate akhipha lolu cingo lweselula, ngaleyo ndlela akhulule amaseli wokufihla i-dopamine ukuthi athele i-dopamine eyengeziwe kuma-nucleus accumbens. Ama-opiates nawo angakhipha umlayezo oqinile "womvuzo" ngokusebenza ngqo kuma-nucleus accumbens.
Kodwa izidakamizwa zenza okungaphezu nje kokunikeza i-dopamine jolt eyenza u-euphoria futhi ahambisane nomvuzo wokuqala nokuqiniswa. Ngokuhamba kwesikhathi futhi ngokuchayeka ngokuphindaphindiwe, baqala ukulungiswa kancane kancane emkhatsini wesifundazwe sokuvuza okuholela ekulutha umlutha.
Isiyaluyalu Sizalwa
Izigaba zokuqala zokulutha zibonakaliswa ukubekezelelana nokuthembela. Ngemuva kokuphuza ngokweqile kwezidakamizwa, umlutha udinga okungaphezulu kwalokhu ukuze uthole umphumela ofanayo kumzwelo noma ekugxileni njalonjalo. Lokhu kubekezelelana bese kubhebhethekisa ukwanda kokusetshenziswa kwezidakamizwa okubangela ukuncika – isidingo esiveza ukuthi sibuhlungu ngokomzwelo futhi, kwesinye isikhathi, ukusabela komzimba uma ukufinyelela komuthi kunqanyuliwe. Kokubili ukubekezelelana nokuncika kwenzeka ngoba ukusetshenziswa kwezidakamizwa njalo kungenza, ngokuxakayo, ukucindezela izingxenye zesekethe lomvuzo wobuchopho.
Enhliziyweni yalokhu kukhwabanisa okunomthelela kukhona i-molecule eyaziwa ngokuthi i-CREB (i-cAMP impendulo ye-element-binding protein). I-CREB iyinhlangano ye-transcription, iphrotheni elawula inkulumo, noma umsebenzi, wezakhi zofuzo futhi ngaleyo ndlela ukuziphatha jikelele kwamaseli wegazi. Uma izidakamizwa zokuhlukunyezwa zilawulwa, i-dopamine ingxenyeni ye-nucleus accumbens ikhuphuka, ikhuthaza amangqamuzana e-dopamine-alamukele ukwandisa ukukhiqizwa kwe-molecule encane yokubonisa, i-AMP (i-cyclic) ye-cyclic, ephinde isebenze i-CREB. Ngemuva kokuthi i-CREB ishintshwe, ibophezela kwisethi ethile yezakhi zofuzo, okudala ukukhiqizwa kwamaprotheni lawo majezi e-encode.
Ukusebenzisa izidakamizwa ezingapheliyo kubangela ukusebenza okuqhubekayo kwe-CREB, okuthuthukisa ukukhulunywa kwegciwane layo, ezinye zazo ikhodi zamaphrotheni ezondeza umjikelezo wesifundazwe. Isibonelo, i-CREB ilawula ukukhiqizwa kwe-dynorphin, i-molecule yemvelo enemiphumela e-opium.
I-Dynorphin ihlanganiswa yi-subset ye-neurons kuma-nucleus accumbens abuyela emuva futhi avimbele ama-neurons ku-VTA. Ukungeniswa kwe-dynorphin yi-CREB ngaleyo ndlela kukhubaza ukujikeleza komvuzo wobuchopho, kubangele ukubekezelelana ngokwenza umthamo ofanayo wezidakamizwa ungabi nomvuzo omncane. Ukwanda kwe-dynorphin nakho kunomthelela ekuthembekeni, njengoba ukuvinjelwa kwayo kwendlela yomvuzo kushiya umuntu, lapho isidakamizwa singekho, ecindezelekile futhi engakwazi ukujabulela imisebenzi eyayijabulisa phambilini.
Kepha i-CREB iyingxenye yendaba kuphela. Lesi sici sokuloba sicishiwe kungakapheli izinsuku emva kokuyeka ukusetshenziswa kwezidakamizwa. Ngakho-ke i-CREB ayikwazi ukuphendula ngokubamba okuhlala isikhathi eside izinto ezihlukumezekile ezinakho ebuchosheni-ngokushintshwa kobuchopho okwenza imilutha ibuyele entweni noma ngabe sekuphele iminyaka noma amashumi eminyaka yokuyeka. Ukubuyela emuva okunjalo kuqhutshwa kakhulu ukuzwela, into lapho imiphumela yomuthi yengezwa khona.
Yize kungase kuzwakale kungaqondakali, umuthi ofanayo ungavusa kokubili ukubekezelelana nokuzwela.
Ngokushesha ngemuva kokushaya, umsebenzi we-CREB imithethonqubo ephezulu futhi yokubekezela: ngezinsuku ezimbalwa, umsebenzisi uzodinga inani elinyukayo lezidakamizwa ukuhambisa umjikelezo wokuvuza. Kodwa uma umlutha wehla, umsebenzi we-CREB wehla. Ngaleso sikhathi, ukubekezelelana kuhambisana nokugqugquzela ukufakaza, ukukhahlela ukufisa okukhulu okuhambisana nokuziphatha kwezidakamizwa zokucindezela izidakamizwa. Ukunambitha nje noma inkumbulo kungadonsela umlutha emuva. Ukulangazelela okungazelelwe kuyaphikelela ngisho nangemva kokuhlala isikhathi eside. Ukuze siqonde izimpande zokweluleka, kufanele sibheke izinguquko zamangqamuzana ezinde isikhathi eside kunezinsuku ezimbalwa. Omunye umuntu ozobhalwa ngumunye umuntu uyisici esithile sokubhala: i-delta FosB.
Umgwaqo wokubuyela emuva
I-Delta FosB ibonakala isebenza ngendlela ehluke kakhulu ekulweni komlutha kune-CREB. Ucwaningo lwamagundane namagundane lubonisa ukuthi ekuphenduleni ukusetshenziswa kabi kwezidakamizwa ezingapheli, izingxube ze-delta ze-FosB zikhula kancane kancane futhi kancane kancane kule nucleus accumbens nezinye izifunda zobuchopho. Ngaphezu kwalokho, ngenxa yokuthi amaprotheni azinzile ngokweqile, ihlala isebenza kulezi zisele zamagciwane amasonto kuya ezinyangeni emva kokulawulwa kwezidakamizwa, ukuphikelela okuyokwenza ukuba kugcinwe izinguquko kwisitatimende sofuzo isikhathi eside ngemuva kokuba izidakamizwa ziphelile.
Izifundo zamagundane aguqukayo akhiqiza inani eliningi ngokweqile le-delta FosB kuma-nucleus accumbens akhombisa ukuthi ukufakwa isikhathi eside kwaleli molekyuli kudala ukuthi izilwane zizwele kakhulu kuzidakamizwa. Lezi gundane zazithambekele kakhulu ekubuyeleni emuva ngemuva kokuhoxiswa kwezidakamizwa futhi kamuva zenziwa zatholakala – okutholakele okusho ukuthi ukugxila kwe-delta FosB kungaba nomthelela ekwandeni kwesikhathi eside ekuzweleni ezindleleni zomvuzo zabantu. Kuyathakazelisa ukuthi i-delta FosB nayo ikhiqizwa kuma-nucleus accumbens kumagundane ekuphenduleni imivuzo ephindaphindwayo yezidakamizwa, njengokusebenzisa amasondo ngokweqile nokusetshenziswa koshukela. Ngakho-ke, ingahle ibe nendima ejwayelekile ekwakhiweni kokuziphatha okucindezelayo kububanzi obuningi bezinto ezivuzayo.
Ubufakazi bamuva busikisela indlela yokuthi ukuzwela kungaphikelela kanjani noma ngemuva kokugxila kwe-delta FosB kubuyela kokujwayelekile. Ukuvezwa okungapheli kwe-cocaine nezinye izidakamizwa zokuhlukumeza kuyaziwa ukuthi kuvuse amagatsha athola isignali we-nucleus accumbens neurons ukuze ahlume amahlumela angeziwe, abizwa ngama-dendritic spines, aqinisa ukuxhumana kwamaseli namanye ama-neurons. Kumagundane, lokhu kuhluma kungaqhubeka izinyanga ezithile ngemuva kokuphela kwezidakamizwa. Lokhu kutholakala kusikisela ukuthi i-delta FosB ingahle ibhekane nezinsipho ezengeziwe.
I-extrapolation ecacile kakhulu kusuka kule miphumela iphakamisa ukuthi kungenzeka ukuthi ukuxhumeka okwengeziwe okwenziwe ngumsebenzi we-delta FosB kukhulisa ukusayina phakathi kwamaseli axhunyiwe iminyaka futhi ukuthi ukubonakaliswa okuphakeme kungabangela ubuchopho ukuba bukhumbule emaceleni ahlobene nezidakamizwa. Izinguquko ze-dendritic, ekugcineni, zingaba ukulungiswa okuyisihluthulelo okubika ukungaxhunyiwe kwemithi.
Ukulutha Umlutha
Kuze kube manje sigxile kuzinguquko ezibangelwa izidakamizwa ezihlobene ne-dopamine ohlelweni lomvuzo wobuchopho. Khumbula, noma kunjalo, ukuthi ezinye izifunda zobuchopho – okungukuthi, i-amygdala, i-hippocampus ne-frontal cortex-zibandakanyekile ekuluthweni nasekuxhumaneni naphambili ne-VTA kanye ne-nucleus accumbens. Zonke lezo zifunda zikhuluma ngendlela yomvuzo ngokukhulula i-neurotransmitter glutamate. Lapho izidakamizwa zokuhlukumeza zanda ukukhishwa kwe-dopamine kusuka ku-VTA kuya kuma-nucleus accumbens, ziphinde ziguqule ukuphendula kwe-VTA kanye ne-nucleus accumbens ku-glutamate izinsuku.
Ukuhlolwa kwezilwane kubonisa ukuthi ukuguqulwa kobuzwe obuthakathaka ku-glutamate endleleni yomvuzo kuthuthukisa kokubili ukukhululwa kwe-dopamine kusuka ku-VTA nokuphendula ku-dopamine ku-nucleus accumbens, ngaleyo ndlela kukhuthazwa umsebenzi we-CREB no-delta FosB nemiphumela engathandeki yalezi zimvukuzane.
Ngaphezu kwalokho, kubonakala sengathi lokhu kuzwela kwe-glutamate uzwela kuqinisa izindlela ze-neuronal ezihlanganisa ukukhumbula okuhlangenwe nakho kwezidakamizwa nomvuzo ophezulu, ngaleyo ndlela kudla isifiso sokufuna isidakamizwa.
Indlela izidakamizwa eziguqula ngayo ukuzwela kwe-glutamate kuma-neuron endlela yomvuzo ayikaziwa ngokuqinisekile, kepha i-hypothesis esebenzayo ingenziwa ngokuya ngokuthi i-glutamate ithinta kanjani ama-neurons ku-hippocampus. Kukhona izinhlobo ezithile zesikhuthazo sesikhashana esifushane ezingakhulisa ukuphendula kweseli ku-glutamate ngaphezu kwamahora amaningi. Lo mkhuba, obizwa ngokuthi amandla wesikhathi eside, usiza izinkumbulo ukwakheka futhi kubukeka sengathi kuqondaniswe nokuvalwa kwamaprotheni athile e-glutamate-binding receptor avela ezitolo ze-intracellular, lapho engasebenzi khona, kulwelwesi lwe-nerve cell, lapho angaphendula khona ku-glutamate ikhishwe ku-synapse. Izidakamizwa zokuhlukumeza zithonya ukuvaleka kwama-glutamate receptors endleleni yomvuzo. Okunye okutholakele kusikisela ukuthi bangathonya futhi ukuhlanganiswa kwama-receptors athile e-glutamate.
Ukuhlanganiswa ndawonye, zonke izinguquko ezibangelwa izidakamizwa esifundeni sokuvuza esizixoxile ekugcineni sikhuthaze ukubekezelelana, ukuxhomeka, ukufisa, ukubuyela emuva kanye nokuziphatha okunzima okuhambisana nokulutha.
Imininingwane eminingi ihlala iyimfihlakalo, kepha singasho ezinye izinto ngokuqiniseka. Ngesikhathi sokusetshenziswa kwezidakamizwa isikhathi eside, futhi ngemuva nje kokusetshenziswa kuphelile, izinguquko ekugxileni kwe-AMP ejikelezayo kanye nomsebenzi we-CREB kuma-neuron endleleni yomvuzo kudlangile. Lezi zinguquko zibangela ukubekezelelana nokuncika, kunciphisa ukuzwela kumuthi futhi kunikeze umlutha ucindezelekile futhi untula ugqozi. Ngokuzigcina isikhathi eside, izinguquko emsebenzini we-delta FosB kanye nokusayinwa kwe-glutamate kudlangile. Lezi zenzo zibukeka sengathi yizona ezidonsela umlutha emuva kokuningi – ngokwandisa ukuzwela emiphumeleni yomuthi uma isetshenziswa futhi ngemuva kokuphelelwa yisikhathi nangokuvusa izimpendulo ezinamandla ezinkumbulweni zamaphuzu adlule kanye nezimpawu eziletha lezo zinkumbulo engqondweni.
Ukubuyekezwa ku-CREB, i-delta i-FosB ne-glutamate ukubonisa kuyimbangela yokulutha, kodwa ngokuqinisekile akuyona indaba yonke. Njengoba ucwaningo luqhubeka, izazi ze-neuroscientists zizovula ezinye izimo ezibalulekile ze-molecular and cell in the circuit reward and ezindaweni eziphathelene nobuchopho ezizokhanyisa uhlobo lweqiniso lomlutha.
Isifo Esivamile?
Ngaphandle kokuthuthukisa ukuqonda kwesisekelo semvelo sokulutha izidakamizwa, ukutholakala kwalezi zinguquko zamangqamuzana kunikeza izinhloso ezintsha zekwelashwa kwamakhemikhali kwalesi sifo. Futhi isidingo sokwelapha okusha sikhulu kakhulu. Ngaphandle kokulimala okusobala ngokomzimba nangokwengqondo, lesi simo siyimbangela ehamba phambili yokugula kwezokwelapha. Izidakwa zijwayele ukuqina kwesibindi, ababhemayo bangenwa umdlavuza wamaphaphu, kanti imilutha ye-heroin isabalalisa i-HIV uma yabelana ngezinaliti. Inani lomlutha wezempilo nokukhiqiza e-US lilinganiselwe ngaphezu kwamadola ayizigidi eziyizinkulungwane ezingama- $ 300 ngonyaka, okwenza kube ngenye yezinkinga ezinkulu kakhulu umphakathi obhekene nazo. Uma incazelo yokulutha inwetshiwe ifaka phakathi ezinye izinhlobo zokuziphatha okuphoqelela ngokweqile, njengokudla ngokweqile nokugembula, izindleko ziphakeme kakhulu. Imishanguzo engalungisa ukusabela okungahambi kahle, okuluthayo kwisikhuthazo esivuzayo — noma ngabe i-cocaine noma i-cheesecake noma injabulo yokuwina ku-blackjack – inganikeza inzuzo enkulu emphakathini.
Izindlela zokwelapha zanamuhla zehluleka ukwelapha iningi lemilutha. Eminye imishanguzo ivimbela ukuthi umuthi ungafinyeleli lapho ubheke khona. Lezi zinyathelo zishiya abasebenzisi "benobuchopho obuyimilutha" nokulangazelela okukhulu kwezidakamizwa. Okunye ukungenelela kwezokwelapha kulingisa imiphumela yesidakamizwa futhi ngaleyo ndlela kunciphise ukulangazelela isikhathi eside ngokwanele ukuba umlutha ugxume lo mkhuba. Lezi zinto ezithatha amakhemikhali, noma kunjalo, zingavele zishintshe umkhuba owodwa ziye komunye. Futhi yize izindlela zokwelapha ezingezona ezokwelapha, ezinjengezinyathelo eziyishumi nambili ezithandwayo – zisiza abantu abaningi ukubhekana nokulutha kwabo, ababambiqhaza basabuyela ezingeni eliphezulu.
Behlome ngokuqonda nge-biology yokulutha, abacwaningi ngelinye ilanga bangakwazi ukuklama imithi ephikisana noma ekhokhela imiphumela yesikhathi eside yezidakamizwa zokuhlukumeza ezifundeni zemiklomelo ebuchosheni. Amakhemikhali asebenzisana ngqo nama-receptors abopha i-glutamate noma i-dopamine kuma-nucleus accumbens, noma amakhemikhali avimbela i-CREB noma i-delta FosB ekusebenzeni kwezakhi zofuzo zazo kuleyo ndawo, kungahle kukhulule ukubamba kwezidakamizwa kumlutha.
Ngaphezu kwalokho, kudingeka sifunde ukuqaphela labo bantu abajwayele ukubheja. Nakuba izici ezingokwengqondo, ezenhlalakahle nezemvelo zibalulekile, ukucwaninga emindenini ekhungethweyo kubonisa ukuthi kubantu mayelana namaphesenti angu-XNUM weengozi yokulutha izidakamizwa i-genetic. Izakhi zofuzo ezithintekayo azikakabonakali, kepha uma abantu abathintekayo bekwazi ukuqashelwa kusenesikhathi, ukungenelela kungabhekiselwa kulaba bantu abasengozini.
Ngoba izici ezingokomzwelo nezenhlalo zisebenza ekuluthekeni, asinakulindela ukuthi imishanguzo izokwelapha ngokuphelele i-syndrome yokulutha. Kodwa singathemba ukuthi izindlela zokwelashwa zesikhathi esizayo zizonciphisa amandla amakhulu ezinto eziphilayo – ukuncika, izifiso - okuqhuba ukulutha futhi ngaleyo ndlela kuzokwenza ukungenelela kwengqondo nokusebenza ngempumelelo kusize ekwakheni kabusha umzimba nengqondo yomlutha.
U-ERIC J. NESTLER noROBERT C. MALENKA bacwaninga ngezibalo zemithi yokulutha izidakamizwa. U-Nestler, uprofesa kanye nosihlalo wophiko lwengqondo eYunivesithi yaseTexas Southwestern Medical Center eDallas, wakhethwa e-Institute of Medicine e-1998. UMalenka, uprofesa wezifo zengqondo nezokuziphatha eStanford University School of Medicine, wajoyina inhlangano lapho ngemuva kokukhonza njengomqondisi weCentral for the Neurobiology of Addiction eNyuvesi yaseCalifornia, eSan Francisco. NjengoSteven E. Hyman, manje e-Harvard University, uNestler noMalenka babhala incwadi ethi Molecular Basis of Neuropharmacology (McGraw-Hill, 2001).
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