Amagqabantshintshi e-YBOP: Oku kuluntu ngokubanzi, kodwa kunokuba bubuchwephesha noko. Nangona kunjalo, lelinye lawona manqaku abalaseleyo kwaye agqibeleleyo abhalwe kumlutha.
Ngu-Eric J. Nestler noRobert C. Malenka
Februwari 09, 2004
Ukusetyenziswa kakubi kweziyobisi kuvelisa utshintsho lwexesha elide kumasekethe omvuzo wengqondo. Ulwazi lweeselula kunye neenkcukacha zee molecular ezi zinto zikhokelela ekutheni unyango olutsha luqhube ukuziphatha okunyanzelisayo.
Imigca emhlophe esipilini. Inaliti kunye necephe. Kubasebenzisi abaninzi, ukubona iziyobisi okanye izinto ezinxulumene nazo kunokubangela ukungcangcazela kukonwaba okulindelekileyo. Emva koko, ngokulungiswa, kuza ukukhawuleza kwangempela: ukufudumala, ukucaca, umbono, ukukhululeka, ukuvakalelwa kukuba usembindini wendalo yonke. Okwexeshana, yonke into iziva ilungile. Kodwa into eyenzekayo emva kokubhengeza iziyobisi gwenxa- nokuba yi-heroin okanye icocaine, iwhiskey okanye isantya.
Isixa esakha savelisa imincili asisebenzi kakuhle, kwaye abasebenzisi badinga ukudutyulwa okanye ukuncwina ukuze bazive beqhelekileyo; ngaphandle kwayo, bayadandatheka kwaye, bahlala begula emzimbeni. Emva koko baqala ukusebenzisa iyeza ngokunyanzelwa. Okwangoku, bangamakhoboka, baphulukana nolawulo ekusebenziseni kwabo kunye nokubandezeleka kweminqweno enamandla nasemva kokuba ulonwabo lungasekho kwaye umkhwa wabo uqala ukonakalisa impilo yabo, iimali kunye nolwalamano lomntu.
Iingcali ze-Neurobiologists kudala zazi ukuba imincili ebangelwa ngamachiza okuphathwa gadalala ivela kuba zonke ezi khemikhali zigqibezela ukonyusa umsebenzi wenkqubo yomvuzo wobuchopho: isekethe entsonkothileyo yeeseli zemithambo-luvo, okanye ii-neurons, eziguquke ukuze zisenze sizive sigungxula emva kokutya okanye ngokwesondo- izinto Kufuneka siyenze ukuze siphile kwaye sidlule kwimfuza yethu. Ubuncinci ekuqaleni, ukuyikhupha le nkqubo kusenza sizive silungile kwaye kusikhuthaza ukuba siphindaphinde nawuphi na umsebenzi osizisele olo lonwabo.
Kodwa uphando olutsha lubonisa ukuba ukusetyenziswa gwenxa kweziyobisi kubangela utshintsho kulwakhiwo kunye nokusebenza kwenkqubo ye-neurons ehlala iiveki, iinyanga okanye iminyaka emva kokulungiswa kokugqibela. Olu hlengahlengiso, olugwenxa, luthomalalisa iziphumo ezonwabisayo zento engaphathwa gadalala kodwa ikwonyusa iminqweno ebambisa umlutha kukutshabalalisa ukusetyenziswa okunyukayo nokwanda kokuwa emsebenzini nasekhaya. Ukuqonda okuphuculweyo kolu tshintsho lwe-neural kufuneka kuncede ukubonelela ngongenelelo olungcono lweziyobisi, ukuze abantu ababa lixhoba leziyobisi ezenza imikhwa bakwazi ukubuyisa iingqondo zabo kunye nobomi babo.
Iidakamizwa Ukufa
Ukuqonda ukuba iziyobisi ezahlukahlukeneyo zokusetyenziswa gadalala ekugqibeleni zikhokelela ekugqithiseni umzila ngendlela eqhelekileyo ezivela ngokubanzi kwiziphumo zezilwanyana zebhoratri ezaqala malunga ne-40 kwiminyaka edlulileyo. Ukunikezelwa ithuba, amagundane, iigundane kunye neengqungquthela ezingezizo zomntu ziya kuzilawula izinto ezifanayo zokuxhaphazwa kwabantu. Kule mizingo, izilwanyana zixhunyiwe kumgca we-intravenous. Baye bafundiswe ukuba bacinezele i-lever enye ukuze bafumane ukuxhamla kwezilwanyana nge-IV, enye i-lever ukuze ifumane isisombululo esinomdla esingathandekiyo, kunye ne-lever yesithathu ukucela i-pellet yokutya. Kwiintsuku ezimbalwa, izilwanyana zixakeke: zikwazi ukulawula i-cocaine, i-heroin, i-amphetamine kunye nezinye izinto eziqhelekileyo zokuzenza iziyobisi.
Ngapha koko, ekugqibeleni babonisa isimilo sokuziphatha. Isilwanyana ngasinye siza kuthatha amachiza sidlalisa imisebenzi yesiqhelo njengokutya nokulala – ezinye zide zibulawe kukudinwa okanye ukungondleki. Kwezona zinto zinomlutha, ezinje ngecocaine, izilwanyana ziya kuchitha iiyure zazo zivuka zisebenza ukufumana ezinye, nokuba oko kuthetha ukucofa i-lever kangangezihlandlo ezilikhulu ukubetha kube kanye. Njengokuba abantu abakhobokisayo benqwenela kakhulu xa befumana iziyobisi okanye iindawo apho bafumene amanqaku khona, izilwanyana nazo, ziye zikhethe indawo ezinxulumana nayo neziyobisi-indawo esekhayeni apho uxinzelelo lwe-lever luhlala lubonelela ngembuyekezo yemichiza. .
Xa kuthathwe into leyo, izilwanyana ziyeka ngokukhawuleza ukusebenza ukuze zanelise imichiza. Kodwa ulonwabo alulityalwa. Umlingo ohleli ucocekile-nokuba ziinyanga-uya kubuyela kwangoko kwindlela aziphethe ngayo xa enikwa incasa yecocaine okanye ebekwe kwikheji enxulumana nesiyobisi. Kwaye uxinzelelo oluthile lwengqondo, njengamaxesha ngamaxesha, ukothuka okungalindelekanga kweenyawo, luya kuthumela iigundane zibaleke zibuyele kwiziyobisi. Ezi ntlobo ezifanayo zokukhuthazwa kukuvezwa kweedosi ezisezantsi zamachiza, imikhwa enxulumene neziyobisi okanye uxinzelelo- lokuvuselela umnqweno kunye nokuphinda ubuye kwiziyobisi zabantu.
Sebenzisa olu setyenziso lokuzilawula kunye neendlela ezinxulumene noko, abaphandi benza imephu yemimandla yobuchopho elawula isimilo sokuziphatha kwaye bafumanisa eyona ndima iphambili yesekethe yomvuzo wobuchopho. Iziyobisi zilawula le sekethe, zivuselela umsebenzi wayo ngamandla kunye nokuzingisa okukhulu kunawo nawuphi na umvuzo wendalo.
Elona candelo liphambili lomjikelezo womvuzo yinkqubo ye-mesolimbic dopamine: iseti yeeseli zemithambo-luvo ezivela kwindawo yecandelo le-ventral tegmental (VTA), kufutshane nesiseko sobuchopho, kwaye ithumele uqikelelo ekujoliseni imimandla ngaphambili kwengqondo- kakhulu Ngokuqaphelekayo kulwakhiwo olunzulu ngaphantsi kwecortex engaphambili ebizwa ngokuba yi-nucleus accumbens. Ezo VTA neurons zinxibelelana ngokusasaza isithunywa semichiza (i-neurotransmitter) dopamine evela kwiitheminali, okanye iingcebiso, zoqikelelo lwabo olude kwii-receptors kwi-nucleus accumbens neurons. Indlela ye-dopamine esuka kwi-VTA ukuya kwi-nucleus accumbens ibaluleke kakhulu kumlutha: izilwanyana ezinesilonda kule mimandla yobuchopho ayisabonisi mdla kwizinto zokuxhatshazwa.
Rheostat of Reward
Iindlela zomvuzo zezakudala zendalo. Nditsho nomsundulu olula, umhlaba ohlala eCaenorhabditis elegans une-rudimentary version. Kwezi ntshulube, ukungasebenzi kweesine ukuya kwezisibhozo eziphambili zine-dopamine kubangela ukuba isilwanyana silime ngqo sidlule kwimfumba yebhaktiriya, ukutya esikuthandayo. Kwizilwanyana ezanyisayo, isekethe yomvuzo inzima ngakumbi, kwaye idityanisiwe neminye imimandla yobuchopho esebenza ukubala amava kunye neemvakalelo kwaye iqondise impendulo yomntu kukhuthazo olunomvuzo, kubandakanya ukutya, isini kunye nokunxibelelana kwezentlalo. I-amygdala, umzekelo, iyanceda ukuvavanya ukuba amava ayamnandi na okanye ayaphindiswa – kwaye kufuneka aphindaphindwe okanye aphetshwe – kwaye incede ukwenza unxibelelwano phakathi kwamava kunye nezinye iindlela; hippocampus ithatha inxaxheba ekurekhodeni iinkumbulo zamava, kubandakanya indawo kwaye nini kwaye yenzeke nabani; kunye nemimandla engaphambili yecortex yecereal ilungelelanisa kwaye isebenze lonke olu lwazi kwaye ichonge indlela yokuziphatha komntu. Indlela ye-VTA-accumbens, okwangoku, isebenza njenge-rheostat yomvuzo: "uxelela" amanye amaziko obuchopho indlela onomvuzo ngayo umsebenzi. Umsebenzi onomvuzo uthathwa njengesiqhelo, kokukhona kunokwenzeka ukuba umzimba uwukhumbule kakuhle kwaye uwuphinda-phinde.
Nangona uninzi lolwazi lokujikeleza komvuzo kuthathwe kwizilwanyana, izifundo zokucinga ngengqondo ezenziwa kule minyaka ili-10 idlulileyo zichaze ukuba iindlela ezilinganayo zilawula umvuzo wendalo kunye neziyobisi ebantwini. Sebenzisa i-imagination magontic resonance imaging (fMRI) okanye i-positron emission tomography (PET) iskena (ubuchule obulinganisa utshintsho ekuhambeni kwegazi okunxulunyaniswa nomsebenzi we-neuronal), abaphandi bajonge i-nucleus accumbens kwizidakamizwa ze-cocaine ezikhanyayo xa zinikwa umhlola. Xa kwa ezo zilingo ziboniswa ividiyo yomntu osebenzisa icocaine okanye ifoto yemigca emhlophe kwisipili, ii-accumbens ziphendula ngokufanayo, kunye ne-amygdala kunye neendawo ezithile zecortex. Kwaye kwalemimandla minye iyasabela kukungcakaza okunyanzelekileyo okuboniswa imifanekiso yoomatshini bokungcakaza, iphakamisa ukuba indlela ye-VTA-eqokeleleneyo inendima ebaluleke ngokufanayo nakwimilutha yeziyobisi.
Dopamine, Nceda
Kungenzeka njani ukuba izinto ezahlukeneyo zokulutha-ezingenazo izinto ezifanayo zesakhiwo kwaye zinemiphumo eyahlukeneyo emzimbeni- zonke zenza iimpendulo ezifanayo kwisekethe yomvuzo wobuchopho? Ingenzeka njani icocaine, into evuselelayo ebangela intliziyo ukubaleka, kunye neheroin, ethomalalisa ukuthomalalisa iintlungu, inokuba yahluke ngandlela thile kwaye ngokufanayo ijolise kwinkqubo yomvuzo? Impendulo kukuba onke amachiza okuphatha gadalala, ukongeza kuyo nayiphi na eminye imiphumo, ibangela ukuba i-nucleus iqokelele ukuba ifumane umkhukula we-dopamine kwaye ngamanye amaxesha ikwayi-dopamine-elingisa imiqondiso.
Xa iseli yemithambo-luvo kwi-VTA inemincili, ithumela umyalezo wombane obaleka ecaleni kwe-axon yayo-umgaqo-ophethe "uhola wendlela" ofikelela kwi-nucleus accumbens. Isiginali ibangela ukuba kukhutshwe i-dopamine kwincam ye-axon iye kwisithuba esincinci-i-synaptic cleft-eyahlula i-axon terminal ukusuka kwi-neuron kwi-nucleus accumbens. Ukusuka apho, i-dopamine latches kwi-receptor yayo kwi-accumbens neuron kwaye igqithise uphawu lwayo kwiseli. Ukuvala umqondiso kamva, i-VTA neuron isusa i-dopamine kwi-synaptic cleft kwaye iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde iphinde
I-Cocaine kunye nezinye izikhuthazo zikhubaza okwesikhashana iphrotheni ye-transporter ebuyisela i-neurotransmitter kwii-terminals ze-neuron ze-VTA, ngaloo ndlela zishiya i-dopamine engaphezulu ukuba isebenze kwi-nucleus accumbens.
IHeroin kunye nezinye ii-opiates, kwelinye icala, zibopha ii-neurons kwi-VTA edla ngokuvala i-dopamine evelisa i-VTA neurons. Ii-opiates zikhupha olu qhekeko lweselfowuni, yiyo loo nto zikhulula iiseli ezifihlakeleyo zedopamine ukuze zigalele i-dopamine eyongezelelweyo kwi-nucleus accumbens. Ii-opiates zinokuvelisa umyalezo "owomeleleyo" ngokusebenza ngokuthe ngqo kwi-nucleus accumbens.
Kodwa iziyobisi zenza okungaphezulu nje ukubonelela nge-dopamine jolt eyenza ukunyuka kwe-humidity kwaye idibanise umvuzo wokuqala kunye nokuqiniswa. Ngokuhamba kwexesha kunye nokuvelela ngokuphindaphindiweyo, baqalisa ukulungelelaniswa ngokuthe ngcembe kwinqanaba leesekethe ezenza umlutha.
Umlutha Uzalwe
Amanqanaba okuqala okulutha abonakaliswa kukunyamezelana nokuxhomekeka. Emva kokuzinkcinkca ngeziyobisi, likhoboka leziyobisi lifuna into eninzi ukuze lifumane umphumo ofanayo kwimood okanye uxinzelelo njalonjalo. Ukunyamezelana emva koko kuphembelela ukwanda kokusetyenziswa kweziyobisi okubangela ukuxhomekeka- imfuno ebonakalisa ukuba buhlungu ngokweemvakalelo kwaye, ngamanye amaxesha, ukusabela komzimba ukuba ukufikelela kwichiza kunqunyanyisiwe. Zombini ukunyamezelana kunye nokuxhomekeka kwenzeka ngenxa yokuba ukusetyenziswa gwenxa kweziyobisi kunokuthi, ngokungathandekiyo, kucinezele iinxalenye zesekethe yomvuzo wobuchopho.
Kwintliziyo yale ntshutshiso ekhohlakeleyo i-molecule ebizwa ngokuba yi-CREB (i-cAMP respond-element protein). I-CREB yinto yombhalo, iprotheyini elawula intetho, okanye umsebenzi, weejeni kwaye ngoko ke ukuziphatha ngokubanzi kweeseli zesisindo. Xa izidakamizwa zokusetyenziswa gadalala zilawulwa, i-dopamine i-concentrations inucley accumcums, ikhupha iiseli eziphendulayo ukwenzela ukwandisa imveliso ye-molecule encinci, i-AMP (i -AMP), eyenza i-CREB isebenze. Emva kokuba i-CREB ishintshiwe, ibophelela kwisethi ethile yeendiza, okubangela ukuveliswa kweeprotheni ezo zidizadi zekhowudi.
Ukusetyenziswa kweziyobisi ezingapheliyo kubangela ukusetyenziswa okuqhubekayo kwe-CREB, ekhuthaza ukubonakaliswa kwezakhi zofuzo ezijoliswe kuyo, ezinye zazo ikhowudi yeeprotheyini eziye zanciphise i-circuitry reward. Umzekelo, i-CREB ilawula ukuveliswa kwedynorphin, i-molecule yendalo kunye nemiphumo efana ne-opium.
I-Dynorphin idityaniswe yi-subset yee-neurons kwii-nucleus accumbens ezibuyela umva kwaye zithintele ii-neurons kwi-VTA. Ukwenziwa kwe-dynorphin yi-CREB ngaloo ndlela kuthintela ukujikeleza kwengqondo komvuzo, kubangela ukunyamezelana ngokwenza idosi efanayo yakudala yeziyobisi ibe nomvuzo omncinci. Ukonyuka kwe-dynorphin kukwa negalelo ekuxhomekekeni, njengoko kuthintelwa kwendlela yomvuzo kushiya umntu, ekungabikho kwesiyobisi, edandathekile kwaye engakwazi ukonwaba kwimisebenzi eyonwabisayo yangaphambili.
Kodwa i-CREB sisiqwengana sebali. Inqaku lokukhutshelwa licinyiwe phakathi kweentsuku emva kokuyeka ukusetyenziswa kweziyobisi. Ke i-CREB ayinakho ukuphendula ngokubamba ixesha elide okusetyenzisiweyo kweziyobisi kwingqondo- zotshintsho kwingqondo ezibangela ukuba iziyobisi zibuyele kwinto leyo nasemva kweminyaka okanye amashumi eminyaka yokuyeka. Ukubuyela umva kwakhona kuqhutywa ubukhulu becala yimvakalelo, into ethi inyuse isiphumo seziyobisi.
Nangona kungathi kunokubakho okungafaniyo, isicatshulwa esifanayo singavusa ukunyamezela kunye nokukhuthaza.
Kungekudala emva kwesigxina, umsebenzi we-CREB uphakamiso oluphezulu kunye nokunyamezela: iintsuku eziliqela, umsebenzisi uya kufuna iimali ezandayo zezilwanyana ukuhambisa isiphaluka somvuzo. Kodwa ukuba umlutha uyayeka, umsebenzi we-CREB uyancipha. Ngelo xesha, ukunyamezela kunye nokukhuthaza ukubeka, ukukhaba isifiso esinzulu esingaphantsi kokunyanzeliswa kwezidakamizwa. Ingumnandi nje okanye imemori inokutsala umlutha emva. Ukulangazelela okungapheliyo kuqhubeka nangona emva kwexesha elide lokungabikho. Ukuqonda iingcambu zokukhuthaza, kufuneka sibheke utshintsho lweey molecular ezinde ixesha elide kuneentsuku ezimbalwa. Omnye umgqatswa ungumgqwetha omnye umzobo wokubhala: i-delta FosB.
Indlela yokubuyela kwiNkundla
I-Delta iFosB ibonakala isebenza ngokuhlukileyo kumlutha kune-CREB. Uphononongo lweeigundane kunye neengcongolo lubonisa ukuba ekuphenduleni ukusetyenziswa kakubi kweziyobisi, iziphumo ze-delta ze-FosB zikhula ngokuthe ngcembe kwaye zihamba kancane kwi-nucleus accumbens nakwezinye iindawo zengqondo. Ngaphezu koko, ngenxa yokuba iprotheni yomelelekile, ihlala isebenzayo kulezi zisele kwiiveki emva kweenyanga emva kokulawulwa kwezidakamizwa, ukunyamezela okuza kwenza ukuba kugcinwe utshintsho kwimbonakalo yegazi emva kwexesha emva kokuba izidakamizwa ziphelile.
Izifundo zeempuku eziguqukayo ezivelisa ubungakanani obugqithisileyo be-delta FosB kwi-nucleus accumbens ibonisa ukuba ukwenziwa ixesha elide kwale molekyuli kubangela ukuba izilwanyana zibe novakalelo oluvakalayo kwiziyobisi. Ezi iimpuku beziqhelekile ukubuyela umva emva kokuba amayeza erhoxisiwe kwaye kamva enziwe afumaneka- ukufumanisa okuthetha ukuba ukugxila kwe-FosB kunganegalelo kukonyuka kwexesha elide kubuntununtunu kwiindlela zomvuzo wabantu. Into enomdla kukuba, i-delta FosB ikwaveliswa kwi-nucleus eqokelelene kwiimpuku ukuphendula imbuyekezo ephindaphinda yemivuzo, njengokubaleka kwevili okugqithisileyo kunye nokusetyenziswa kweswekile. Yiyo loo nto inokuba nenxaxheba ngokubanzi kuphuhliso lokuziphatha okunyanzelekileyo kuluhlu olubanzi lokukhuthaza.
Ubungqina bamva nje buchaza indlela yokwenza uvakalelo luqhubeke nasemva kokugxininiswa kwe-FosB kubuyela esiqhelweni. Ukuvezwa okungapheliyo kwi-cocaine kunye namanye amachiza okuphatha gadalala kuyaziwa ngokunyusa amasebe afumana umqondiso we-nucleus eqokelela ii-neurons ukuze kuhlume amahlumelo ongezelelweyo, abizwa ngokuba ziintambo zedendritic, ezomeleza unxibelelwano lweeseli nezinye ii-neurons. Kwiimpuku, oku kuhluma kunokuqhubeka kangangeenyanga ezithile emva kokupheliswa kweziyobisi. Oku kufumanisa kuphakamisa ukuba i-delta FosB inokuba noxanduva lokongezwa kweentlobo.
Uphuhliso olongezelelweyo olusenyongweni kulezi ziphumo luphakamisa ukuba ukuxhamla okongezelelweyo okuveliswa ngumsebenzi we-delta yeFosB kukhulisa ukubonakaliswa phakathi kwamaseli anxulumene neminyaka kwaye ukubonakaliswa okuphakamileyo kunokubangela ukuba ingqondo iphosakele kwiinkalo ezinxulumene neziyobisi. Utshintsho lwe-dendritic, ekugqibeleni, lube yinto engundoqo yokwenza ukuba i-intransience of addiction.
UkuLungiswa kokuFunda
Ukuza kuthi ga ngoku sigxile kutshintsho olwenziwe ngamachiza olunxulumene ne-dopamine kwinkqubo yomvuzo wobuchopho. Khumbula, nangona kunjalo, ukuba eminye imimandla yobuchopho- eyile, i-amygdala, i-hippocampus kunye ne-cortex yangaphambili-bayabandakanyeka kumlutha kwaye banxibelelana ngapha nangapha kunye ne-VTA kunye ne-nucleus accumbens. Zonke ezo ngingqi zithetha kwindlela yomvuzo ngokukhupha i-neurotransmitter glutamate. Xa iziyobisi zokuxhatshazwa zisonyusa ukukhutshwa kwe-dopamine kwi-VTA ukuya kwi-nucleus accumbens, zikwatshintsha ukuphendula kwe-VTA kunye ne-nucleus accumbens kwi-glutamate kangangeentsuku.
Izilwanyana zezilwanyana zibonisa ukuba utshintsho kwintlupheko ku-glutamate kwindlela yokuvuza luphucula kokubili ukukhululwa kwe-dopamine kwi-VTA kunye nokuphendula kwi-dopamine kwi-nucleus accumbens, ngaloo ndlela kukhuthaza i-CREB kunye ne-delta FosB kunye nemiphumo engathandekiyo yale milekyuli.
Ukongezelela, kubonakala ukuba oku kuguqulwa kwentswelo ye-glutamate kuqinisa iindlela ze-neuronal ezidibanisa iinkumbulo zamagunya athatha amayeza kunye nomvuzo ophezulu, ngaloo ndlela unondla umnqweno wokufuna iziyobisi.
Indlela ezisebenzisa ngayo iziyobisi ukuguqula ubuntununtunu kwi-glutamate kwii-neuron zendlela yomvuzo ayikaziwa ngokuqinisekileyo, kodwa i-hypothesis esebenzayo inokwenziwa ngokusekwe kwindlela i-glutamate echaphazela ngayo ii-neurons kwihippocampus. Kukho iintlobo ezithile zesikhuthazo sexesha elifutshane ezinokuphucula impendulo yeseli kwi-glutamate ngaphezulu kweeyure ezininzi. Le nto, ibizwa ngokuba lixesha elide, inceda iinkumbulo ukuba zenze kwaye zibonakala ngathi zingenwe kukucinywa kweeproteni ezithile ze-glutamate-binding receptor ezivela kwiivenkile ze-intracellular, apho zingasebenzi khona, kwi-membrane yeseli ye-nerve, apho banokuphendula khona kwi-glutamate ikhutshwe kwisinxibelelanisi. Iziyobisi zokuxhatshazwa zinefuthe lokuvalwa kwee-glutamate receptors kwindlela yomvuzo. Ezinye iziphumo zibonisa ukuba banokuchaphazela ukuhlanganiswa kwee-receptors ezithile ze-glutamate.
Kuthathwe ndawonye, zonke iinguqu ezenziwe ngamachiza kwisiphaluji somvuzo esiye saxoxa ngazo ekugqibeleni zikhuthaza ukunyamezela, ukuxhomekeka, ukuthanda, ukubuyela kwakhona kunye nokuziphatha okulukhuni oluhamba noxinzelelo.
Iinkcukacha ezininzi zihlala ziyimfihlakalo, kodwa ezinye izinto singazithetha ngesiqinisekiso. Ngexesha lokusetyenziswa gwenxa kweziyobisi, kwaye kungekudala emva kokuba ukusetyenziswa kuyekile, utshintsho kwi-cyclic AMP kunye nomsebenzi we-CREB kwii-neurons kwindlela yomvuzo iphambili. Olu tshintsho lubangela ukunyamezelana kunye nokuxhomekeka, kunciphisa ubuntununtunu kwichiza kwaye kunike umlutha uxinzelelo kunye nokuswela amandla. Ngokuthabatha ixesha elide ngakumbi, utshintsho kwimisebenzi ye-delta ye-FosB kunye ne-glutamate signaling iphambili. Ezi ntshukumo zibonakala ngathi zezizo ezitsala umlutha ukubuyela ngaphezulu- ngokwandisa ubuntununtunu kwiziphumo zeziyobisi ukuba zisetyenziswa kwakhona emva kokuphelelwa ngamandla nangokukhuthaza iimpendulo ezinamandla kwimemori yeendawo eziphakamileyo ezidlulileyo kunye neziqulatho ezizisa ezo nkumbulo engqondweni.
Ukuhlaziywa kwe-CREB, i-delta yeFosB kunye nokubonakaliswa kwe-glutamate kukuphambili kwimiba, kodwa ngokuqinisekileyo akuyiyo ibali elipheleleyo. Njengoko uphando luqhubela phambili, izazinzulu ziza kutyhila ezinye iimodeli ezibalulekileyo kunye neeselungelelanisi kwisekethe yomvuzo kunye nakwiindawo ezinengqondo ezidibeneyo eziza kukhanyisa ukunyaniseka kwezilwanyana.
Uphulo oluqhelekileyo?
Ngaphandle kokuphucula ukuqonda kwesiseko sebhayiloji yeziyobisi, ukufunyanwa kwezi nguqulelo zeemolekyuli kubonelela ngeethagethi zonyango lwonyango lokuphazamiseka kwesi sifo. Kwaye isidingo sonyango esitsha sikhulu kakhulu. Ukongeza kumonakalo ocacileyo womzimba kunye nengqondo, imeko sesona sizathu siphambili sokugula. Utywala buthanda ukuqina kwesibindi, abantu abatshayayo bachaphazeleka ngumhlaza wemiphunga, kwaye iziyobisi zeheroin zisasaza i-HIV xa besabelana ngenaliti. Umrhumo wokulutha kwezempilo kunye nemveliso e-US uqikelelwe ngaphezulu kwe- $ 300 yezigidigidi ngonyaka, okwenza ukuba ibe yenye yezona ngxaki zijamelene noluntu. Ukuba inkcazo yokulutha iye yandiswa ukuba ibandakanye ezinye iindlela zokuziphatha okunyanzelekileyo, njengokutya kakhulu nokungcakaza, iindleko ziphezulu kakhulu. Unyango olunokulungisa ukungahambelani, ukusabela okuluthayo kwisikhuthazo esinomvuzo-nokuba yi-cocaine okanye i-cheesecake okanye uvuyo lokuphumelela kwi-blackjack-lunokubonelela ngesibonelelo esikhulu kuluntu.
Unyango lwanamhlanje luyasilela ukunyanga uninzi lweziyobisi. Amanye amayeza athintela ichiza ukuba lingafikeleli kwithagethi. La manyathelo ashiya abasebenzisi "benomlutha wobuchopho" kunye nokunqwenela iziyobisi. Olunye ungenelelo lonyango lilinganisa ifuthe leziyobisi kwaye ngaloo ndlela kunciphisa umnqweno omde ngokwaneleyo wokuba likhoboka lingakhaba umkhwa. Ezi zinto zithatha indawo yamachiza, nangona kunjalo, zinokuthi zitshintshe umkhwa omnye endaweni yomnye. Kwaye nangona kungenanyango, unyango lokubuyisela kwisimo sangaphambili-njengeenkqubo ezithandwayo ezinamanyathelo ali-12- kunceda abantu abaninzi ukuba balwe neziyobisi zabo, abathathi-nxaxheba basabuyela kwinqanaba eliphezulu.
Bexhotyiswe ngengqondo kwi-biology yeziyobisi, abaphandi ngenye imini banokwazi ukuyila amayeza aphikisayo okanye ahlawule iziphumo zexesha elide zeziyobisi zokuxhatshazwa kwimimandla yomvuzo kwingqondo. Iimpawu ezisebenzisana ngokuthe ngqo kunye ne-receptors ezibophelela kwi-glutamate okanye i-dopamine kwi-nucleus accumbens, okanye iikhemikhali ezithintela i-CREB okanye i-delta FosB ekusebenzeni kwiijethi ezijolise kuyo kuloo ndawo, zinokuthi zikhulule ukubambelela kweziyobisi kwikhoboka.
Ukongezelela, kufuneka sifunde ukuqaphela abo bantu banomdla wokulutha. Nangona iimeko zengqondo, ezentlalo nakwimeko yendalo zibalulekile, uphando kwiintsapho ezinokukhuphaza lubonisa ukuba kubantu malunga neepesenti ze-50 zengozini yokuxhatshazwa kweziyobisi ziyimfuza. Iizityalo ezithile ezibandakanyekayo azange zenziwe zichongwe, kodwa ukuba abantu abanokuthi bangakwazi ukuqwalaselwa kwangaphambili, ukungenelela kungabhekiselwa kula bantu abasengozini.
Kungenxa yokuba iimvakalelo kunye nezentlalo zisebenza kubukhoboka, asinakulindela ukuba amayeza anyange ngokupheleleyo isifo sokulutha. Kodwa singathemba ukuba unyango lwexesha elizayo luya kuyinciphisa amandla amakhulu ebhayoloji- ukuxhomekeka, iminqweno – eqhuba ukuba likhoboka kwaye ngalo ndlela iyakwenza ungenelelo lwengqondo nolusebenzayo lusebenze ngakumbi ekuncedeni ukwakha umzimba nengqondo yomlutha.
U-ERIC J. NESTLER noROBERT C. MALENKA bafunda i-molecular of drug addiction. U-Nestler, uprofesa kunye nosihlalo weSebe lezengqondo kwiYunivesithi yaseTexas kwiSouth Medical Centre eDallas, wanyulwa kwiziko lezeMpilo kwi-1998. UMalenka, uprofesa wezifo zengqondo kunye nezobugcisa kwiSyunivesithi yeSyunivesithi yeSyunivesithi yaseStanford, wajoyina i-faculty emva kokukhonza njengomlawuli weziko le-Neurobiology of Addiction kwiYunivesithi yaseCalifornia, eSan Francisco. NgoSteven E. Hyman, ngoku eYunivesithi yaseHarvard, uNestler noMalenka babhala incwadi ethi Molecular Basis ye-Neuropharmacology (McGraw-Hill, 2001).
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