Imikhwa yeHypacol Sci. Umbhalo obhaliweyo ifumaneka kwi-PMC 2015 Jun 1.
Ishicilelwe kwifomu yokugqibela ehleliweyo njenge:
- Imikhwa yeHypacol Sci. I-2014 Jun; I-35 (6): 268-276.
- Ipapashwe kwi-intanethi 2014 Aprili 30. doi: I-10.1016 / j.tips.2014.04.002
PMCID: PMC4041845
I-NIHMSID: I-NIHMS585222
UMarco Leyton, Ph.D.1,2,3,4,* kwaye Paul Vezina, Ph.D.5,6
Inguqulelo yokugqibela yomhleli yeli nqaku iyafumaneka apha Imikhwa yeHypacol Sci
Bona amanye amanqaku ku-PMC Wisdom nqaku epapashwe.
Abstract
Iziyobisi zihlala zilungiswa ziingxaki ebuntwaneni nasebusheni. Kubantu abaninzi oku kuqala ngenkcazo yokuqala yokuthatha ingozi yomngcipheko, ubuntu ekuhlaleni kunye nokuziphatha okuchaseneyo. Sicebisa apha ukuba ezi zibonakaliso zahluka-hlukeneyo ezahluka-hlukeneyo zibonakalise amandla aphakamileyo emvakalelo yokuvuselelwa kwesimo somoya ukwenza indlela ye-dopamine ikhuthaze indlela yokuziphatha. Ukuba ukusetyenziswa kweziyobisi kuqalisiwe, olu lutsha olusemngciphekweni lunokuhlakulela iimpendulo eziphakamileyo kwimikhwa ehambelana neziyobisi. Ngokwemo yokubonakalisa imeko kunye nokuvuselelwa kweziyobisi, ezi ziphumo ziyomeleza kwaye ziqokelele, zikhokelela kwiimpendulo ezigqitha ezo ziveliswe ngamanye umvuzo. Kwangelo xesha, ii-cards ezingabotshwanga ngamachiza zinxulunyaniswa nokukhululwa kwe-dopamine esezantsi, zisandisa umohluko phakathi kwembuyekezo ngamachiza kunye neziyobisi ezingekho iziyobisi. Ngokudibeneyo, ezi nkqubo zokuphucula kunye nokuthintela ziqhubela phambili ukuba semngciphekweni okhoyo wokukhathazeka ngokuchaseneyo neziyobisi kunye nokukhuthaza okunxulumene neziyobisi. Iziphumo zokuthintela kunye nonyango zixutyushwa.
Imodeli yokudibanisa ye-neurodevelopmental yokuphazamiseka kokusetyenziswa kweziyobisi
Ukulutha kweziyobisi yeyona nto ixhaphakileyo ekuphazamiseni isifo se-neuropsychiatric esichaphazela uluntu namhlanje. Iindleko zentlalo, zonyango nezoqoqosho zikhulu, kusetyenziswa iziyobisi kufaka isandla kwi-12% yokufa emhlabeni [1] kunye nokuxabisa urhulumente wase-US kuphela kuqikelelwa i- $ 400 yezigidigidi ngonyaka [2-3].
Kungenxa yokuba bambalwa kakhulu abantu abazama iziyobisi zokusebenzisa gwenxa ukuphucula imeko yokusetyenziswa kweziyobisi (SUD), kwenziwa imizamo yokuchonga iimpawu ezixelwe kwangaphambili ze-neurobiological. Enye yeengcinga ezinde eziqwalaselwayo kukuba ukwanda kokunganyangekiyo kubonakalisa ubuzaza bokubhenkceka kwinkqubo ye-mesolimbic dopamine [4]. Kusaphikiswana ngayo nokuba ingaba le ntuthuko iyaziveza njengokwehla komsebenzi we-dopamine, njengakwinkqubo yeqela eliphikisayo nakwimodeli yokushokoxeka komvuzo [5-6], okanye bandisa umsebenzi we-dopamine, njengakwimodeli yokukhuthaza uvakalelo [7-8]. Imodeli ekhoyo ye-neurodevelopmental idibanisa nganye yezi mpawu. Iyayithathela ingqalelo indima yazo zonke izinto ezenziwa hypo- kunye ne-hyper-in mesolimbic dopamine system, kwaye icacisa indlela nganye enokuthi ibizwe ngayo ngokukodwa emngciphekweni.
Njengoko kushwankathelwe ngezantsi, ukuguqula ubungqina obuvela kwizifundo kwizifundo zolutsha, abantu abadala, kunye nezilwanyana zaselabhoratri zibonisa ukuba ulutsha lubonisa iimpendulo zedopamine eziphakamisayo kwiimvakalelo ezinamandla akhulayo ekuzibandakanyeni kokuziphatha okungafaniyo, kokufuna umvuzo. Nangona ezi ndlela zokuziphatha zinokuthi kuqala zibangele ukutshintsha okungafaniyo kweziyobisi, ukuqaliswa kokusetyenziswa kweziyobisi kuthoba ukuphakama kwakhona kwe-dopamine kwimikhwa enxulumene neziyobisi, kukhokelela kwimeko yokusetyenziswa kweziyobisi kunye nokuziva. Ezi ziphumo zenza ngakumbi iimpendulo zedopamine yengqondo kumachiza nakwimikhwa eyenzakaliswa iziyobisi, oko kusenza ukugxila kugxile kubantu abasemngciphekweni kwezi zinto zibangelwa kukufumana ichiza. Ngenxa yokuba ii-cices ezingabhangwanga iziyobisi ngaxeshanye zinxulunyaniswa ngokuthe ngqo neempendulo ze-dopamine, isiphumo sisiphumo sokuziphatha okuxineneyo, ukubeka kwinqanaba lokuqhubeka nokuthatha iziyobisi kunye ne-SUD.
Le modeli imele ukusuka kwinto enye yeengcinga zokusetyenziswa gwenxa kweziyobisi (1 Table). Ngokudibanisa ukusebenza kwe-hypo- kunye ne-hyper-dopamine, kunye nokudibanisa oku kunye nezinto ezichazayo ezichaziweyo, imodeli ekhoyo ye-neurodevelopmental ibonelela ngobalo-mali olubanzi lwenkqubo yokulutha. Kukwakhona, sicebisa ukuba, sikwindawo entle ukwazisa ngokuphuhliswa kweendlela ezisebenzayo zonyango.
Ukonyuka kokufuna umvuzo ngokungxamisekileyo kunye nokuphendula kwe-dopamine ngaphambi kokusebenzisa iziyobisi
Uthotho lwamva nje olwokuthathwa komntwana ongamzalanga abe yedwa, amawele, kunye nokulandela ulwaziso oluxhasayo luxhase isiphelo esihambelana ngokugqibeleleyo: uninzi lwee-SUD zibonisa isiphumo 'sokukhipha' imeko yomntu ophawulwa kukufuna umngcipheko, ukuthanda intombazana, kunye notyekelo oluchasayo ebuntwaneni nasebusheni [9-19]. Iinkqubo eziphambili ezingaphantsi kwesi siphakamiso kucingelwa ukuba zibandakanya ukuziva okungaphezulu nangaphantsi kovakalelo lokuvuza kunye nezohlwayo ezinxulumene,20-22]. Umzekelo, ulutsha olunemikhwa ephezulu yokukhuphelela ngaphandle yenza ukhetho olunobungozi, lukhetha umvuzo ophakamileyo kakhulu nokuba ilahleko iphezulu [23-25].
Umahluko okhoyo okwahlukileyo ekusebenziseni iziyobisi uyabonakala nakwizilwanyana zaselabhoratri, kwaye ayizizo zonke eziphuhlisa ukuzilawula ngokuziphatha kweziyobisi [26]. Enye yezona ntlobo zichazwe kwangaphambili zokuba sesichengeni sokufumana ukuzilawula kwiziyobisi ngumkhwa omkhulu wokuphonononga imeko yenoveli [26-29]. Phakathi kwezo zilwanyana ezifumana ukuzilawula ngokwamachiza, kuphela isistim esiya kutshintshela ekusebenziseni ngokunyanzelekileyo, njengoko kuchazwa kukuvuma ukusebenza ngakumbi ngechiza, sinyamezele izigigaba ezinokuphinda sizifumane, kwaye siqhubeke nokufuna iziyobisi ixesha elingaphezulu komndilili [30-31]. Ezi "zixinzelelo" ezisebenzisa iziyobisi zisebenzisa umahluko okhethekileyo kunye nezinto ezinokubangela ukuba uzenze, njengokuphendula kwangaphambi kwexesha32].
Iimpawu zokuziphatha ezichaza ukusetyenziswa kwendlela yokuziphatha kweziyobisi ziyahluka-hlukana nomkhwa wokuzibandakanya nezinye iimvuselelo ezonwabisayo kunye nokwahluka komntu ngamnye ekuphenduleni kweseli dopamine. Kwigundane, i-dopamine yeseli ephezulu idubula kwisiseko kunye nokukhululwa ekuphenduleni kwimingeni eyahlukeneyo ibikezela ukuphononongwa okutsha kokutsha [29,33], iswekile enkulu yokutya [29,34], ukuqhubela phambili ukufunda [35], kunye nokufumana ngokukhawuleza iziyobisi ngokwakho4,29,36-38]. Ubungqina bungaphezulu kokulungelelana. I-dopamine agonists yonyusa iimpendulo zangaphambi kwexesha ngexesha lokuvavanywa kokunyanzelwa kwaye uluhlu olubanzi lweemeko zokuziphatha ezixhomekeke kumvuzo kubandakanya ukufuna iziyobisi (Ibhokisi 1).
Ibhokisi 1
Dopamine kunye nomvuzo
Izifundo zezilwanyana zibonisa ukuba iindlela ezinobungozi, zokufuna umvuzo zinempembelelo dopamine. Izinto ezahlukileyo kwezi zinto zinokuchaphazeleka. Esona sifundo sihamba phambili kukuzimisela ukusondela kwaye uzinzise umzamo wokufumana umvuzo, isimilo esiphenjelelwa ngokusondeleyo kukhutshelo lwe-dopamine kwi-ventral striatum, i-amygdala, kunye ne-anterior cingulate [7-8,39-44]. I-Dopamine ichaphazela imeko yokuphendula kwangaphambi kwexesha kwiimbuyekezo zembuyekezo [45], ibonisa iimpembelelo kwi-striatum [46], ukuvuma ukunyamezela ukulibaziseka komvuzo omkhulu, kubonakalisa iimpembelelo kwi-amygdala kunye ne-orbitofadal cortex [42-43,47], kunye nolawulo lokuzibandakanya kuthengo kunye nomsebenzi, lubonisa iziphumo zecortex ye-orbitofrontal [47]. Ubunzima bobungqina bucebisa ukuba i-dopamine ayihambelani ngokusondeleyo nolonwabo [7,48].
Kubantu kakhulu umahluko okhoyo kwindlela yokuziphatha yangaphandle inokuba inxulumene nokwahluka kwempendulo ye-dopamine. Kubantu abaselula abasempilweni, ukuphendula kwe-dopamine enkulu kwimpendulo yohluka-kunye nokufuna izinto ezingaqhelekanga [49-50] kunye nezinye iimpawu ezinxibelelekayo zokunxulumana50-52]. Kwizifundo ze-fMRI, iziphumo ezifanayo ziyabonakala. Olona luvo luphezulu lokuphendula kumvuzo wemali, kokukhona kuthambekela ekuziphatheni okuyingozi [53-55]. Ngaphezulu kokuphendula okuqinisekileyo kokulindelwa komvuzo wolwazelelo, kokukhona kuphakanyiswa amanqaku okuphendula afanelekileyo [56]. Okukhulu ekuphenduleni kokuzinza kweentambo ezihonjiswe ngemifanekiso engaqhelekanga, kokukhona ziya kukhethwa kwiinyanga ezimbini kamva [57]. Kwaye kokukhulu ukuphendula okuqinisekileyo kwimifanekiso yokutya kunye nokwabelana ngesondo, kokukhona uya kuba mkhulu umthamo wokufumana ubunzima kunye nezokwabelana ngesondo ngokulandela emva kweenyanga ezintandathu [58].
Le mibutho ingentla ebantwini icingelwa ukuba ibonakalisa iimpembelelo zesiphumo ukusasazeka kokuhambisa usasazelelo lwedopamine eguqula uninzi lweenkqubo ezifanayo [59-61]. Ukuhanjiswa kwe-dopamine ephantsi ephazamisa ukuphazamiseka kwendlela yokusebenza kwe-corticostriatal [62], ulawulo oluphezulu olusezantsi lwe-cortex kunye nokukwazi kwembuyekezo enxulumene nomvuzo ukuvula i-striatum [63-64]. Ezi ziphumo ze-neurophysiological zinxulunyaniswa nokuziphatha okucothayo kokuphendula ngokukhethekileyo kwimbuyekezo [65-67], kunye nokuzimisela okunciphileyo kokuzinza umzamo wokufumana umvuzo, kubandakanya notywala [68], icuba [69] kunye nemali [70]. Umsebenzi we-dopamine ophakanyisiweyo, ngokuthelekisa, wandisa amandla emisebenzi enxulumene nomvuzo ukukhokela ukhetho lokuziphatha [65], inciphisa amandla okwenza umahluko phakathi kwexabiso eliphantsi nelisezantsi lembuyekezo [71], kwaye yenza ukuba isaphulelo esijikelezayo sexeshana, uhlobo lokungxengxeza luchazwe ngokukhetha imbuyekezo emitsha ngokukhawuleza ngaphezulu kwento enkulu, engakumbi esecaleni [72]. Kwindawo ekuhlalwa kuyo iklinikhi, abaguli abane-schizophrenia - abaqwalaselwa sisifo sehyper-dopamine- banemilinganiselo ephezulu kakhulu yeengxaki zokusebenzisa iziyobisi [73] ngelixa abo banesifo sikaParkinson, ukuba kukho nantoni na, banciphise amazinga okusebenzisa gwenxa iziyobisi [60]. Ewe, ukuphatha izigulana zikaParkinson amayeza e-dopamine agonist amayeza kunokubangela isifo sokudakumba esibonakaliswa ziingxaki ezahlukeneyo zokulawula impembelelo, kubandakanya ukugembula komzimba, ukulala ngesondo kunye nokusebenzisa gwenxa iziyobisi [60].
Umsebenzi we-Hyper- kunye ne-hypo-dopamine kulandela ukuqaliswa kokusetyenziswa kweziyobisi
Nje ukuba ukusetyenziswa kweziyobisi kuqalile, ezinye zeziphumo zinokubakho; okt, Iidosi eziphantsi ezazingasebenzi ngokufanelekileyo ngoku zinokuvelisa impendulo kwaye iidosi ezisebenzayo zangaphambili zenze iimpendulo ezinkulu. Kwizilwanyana zaselebhu, iirejimeni zokulawulwa kwamachiza eziphindaphindiweyo zinokukhokelela ekunyukeni okuqhubekekayo kwendlela yokuziphatha yokuphembelela yokusetyenziswa kweziyobisi, ukuzimisela okukhulu kokuzinza umzamo wokufumana umvuzo wamachiza, kunye nokukhululwa kweedopamine kwezamachiza [7-8].
Iimeko ekunokwenzeka ukuba zivelise ubuntu zifana neepateni zokusetyenziswa kwangoko kweziyobisi ebantwini: Ukuchazwa okuninzi ukuya kumthamo omkhulu ukuya kwiintsuku eziphezulu kuthathwe iintsuku ngokwahlukeneyo kukhuthazo lokusingqongileyo. Xa le meko sele yenziwe kuPhando lomntu, uvakalelo olwenziwe iziyobisi lubonakalisiwe kubandakanya ukukhutshwa kwe dopamine enkulu yeziyobisi kunye nefuthe elinamandla [74-76]. Oku kuqatshelwe, naphantsi kwazo nje ezi meko, ayizizo zonke izifundo ezibonisa iimpendulo eziqinisekisiweyo. Kumagundane, ubuntununtunu kunokwenzeka ukuba uphuhle kwezo zibonakalisa ukuphinda wenze okuphezulu kwimimandla yenoveli [27,33]. Emntwini, uvakalelo lwe-dopamine lwalukhulu ngakumbi kwezo zinamanani aphezulu okufuna amanqaku [74].
Ukulawulwa kwamachiza okuphindaphindiweyo kunokukhokelela kwimiphumo ebekiweyo; okt, okusingqongileyo okushukumiseka okuhambelana nesichiza kunokubangela iziphumo ezininzi ezifanayo njengechiza ngokwalo, kubandakanya nokusebenza ngokuziphatha, ukukhutshwa kwe-dopamine kunye nokufuna umvuzo [77-81]. Iimeko ezifanelekileyo zokuvelisa ezi mphumo zinemeko ziyafana nezo zokuphakamisa uvakalelo. Ngapha koko, umahluko ngamnye ubonakala [82]. Okokugqibela, ukuphononongwa okuphezulu kwamagundwane kubandakanyeka ngakumbi kwimicimbi ye-cocaine, kwaye zichaphazeleka ekubuyiselweni komdla wokufuna iziyobisi emva kwenkqubo yokutshabalalisa [83].
Nasebantwini, iitshiphu ezihanjiswe ngokusetyenziswa kweziyobisi zinokuza neziphumo ezininzi ezifanayo neziyobisi, kubandakanya ukwanda komvuzo [84], ukhetho lwendawo ekhethiweyo [85-86], umnqweno omkhulu weziyobisi ophenjelelwa ziziyobisi [87], kunye dopamine indlela yendlela yokusebenza [88-89]. Ukwahluka komntu ngamnye kwi-cue-indased dopamine [88] kwaye iimpendulo ezinqwenelekayo ziyabonakala [21], kwaye obunye ubungqina bucebisa ukuba oku kunokubonakalisa uphawu [21].
Iziphumo ezibonakalisiweyo ze-cue zibonakala ziphawulwa ikakhulu kwizifundo ezisemngciphekweni wokulutha. Kwiziselo ezinxilisayo ezisengozini yokuphazamiseka kwotywala, i-cices ezinxulumene notywala zibangela umqondiso ophakamileyo we-electroencephalogram (i-EEG) umqondiso weP300, isalathiso sendlela yokunyusa [90]. Kwizifundo ze-fMRI, ukwenza ulutsha oluphezulu lubonise iimpendulo ezinkulu kwisaziso semivuzo yemali kunakwizifundo zolawulo kwi-ventral striatum [54]. Ngokufanayo, xa kuthelekiswa nolawulo olusempilweni, izifundo ezinembali yosapho yokuphazamiseka kokusetyenziswa kotywala zibonisa iimpendulo ezikhulu kwiziselo ezinxulumene notywala kwi-nucleus accumbens kunye nezinye izinto zesekethe ye-mesocorticolimbic [91-93]. Ewe, kuphando olukhulu lwabantu abasele kakhulu (n = 326), okukhona banzi ubungqulu beengxaki zokusetyenziswa kotywala, kokukhona kuthi kusebenze ngakumbi ukwenziwa kotywala [94-95]. Okokugqibela, ubungqina bokuqala obumangalisayo bucebisa ukuba incasa yecuba ye-subpharmacological ye-bio ikhokelela ekuphenduleni okubalulekileyo kwe-dopamine kubathathi-nxaxheba abanembali yosapho yokuphazamiseka kotywala, kodwa hayi kwiziselo ezinobungozi obuphantsi [96].
Ubukho vs. ukungabikho kwemeko enxulumene neziyobisi kunye nemeko inokuguqula ukulungela ukuphendula kwezinye izehlo [76,97-99]. Ukuba umvuzo wendalo ubonelelwe kwindawo ebuphethwe ngaphambili ngamachiza, isilwanyana siya kubonisa ukubandakanyeka okunyanzelisiweyo ngalo mvuzo wendalo [82,100]. Ukuba, ngokwesiqhelo, imikhondo yamachiza inikezelwa ngokunxulumana nethuba lokufumana iziyobisi, indlela yokuziphatha efuna iziyobisi iyanyanzeleka [77,81,101]; ukuba ichiza lilawulwa, ukubonakaliswa kwe-dopamine [101] kunye novakalelo lokuziphatha102-103]. Kwelinye icala, ii-cues zibhangqwe ngokucacileyo ngokungabikho komvuzo wamachiza zinokuba nefuthe elinokubakho, kunciphisa ukukhutshwa kwe-dopamine [104], ukusebenza kwendlela yokuziphatha [97,102-103,105-106] kunye nokuthatha iziyobisi kunye nokubuyiselwa endaweni [107-108].
Iziphumo zokuvuselelwa okubhalwe ngokucacileyo ngokungabikho komvuzo weziyobisi azifundiswanga kakuhle ebantwini. Nangona kunjalo, ubungqina bamuva bucebisa ukuba iinkqubo zesithintelo zinokubanjwa. Umzekelo, xa abo bangatshayiyo abangaxhomekekanga baboniswa ngemigudu yokutshaya, amanqaku abonisa umnqweno akhuphuka ngokuphezulu kunesiseko; Ukuboniswa kweekharethi ezibini ezichazwe ngokucacileyo ukungabikho kwecuba, ngokuthelekisa, kunciphise kakhulu umnqweno ongezantsi:109]. Ubungqina bezi ziphumo zinciphile bungabonakala nasezingqondweni. Izifundo ezinobungozi obuphezulu abaqalise ukusebenzisa iziyobisi zibonisa iimpendulo ezincinci ze-EEG P300 kwiimpendulo ezilungileyo ezingezizo ezinxulumene nezinto ezifana ne-erotica kuneempawu ezinxulumene neziyobisi [90]. Izifundo ze-fMRI zixhasa isiphelo esifanayo: xa kuthelekiswa nolawulo olusempilweni, izifundo ezisemngciphekweni zibonisa iimpendulo ezincinci ze-striatal-limbic to cices ezahlukeneyo ezingaxutywanga neziyobisi, mhlawumbi ezo zibambekayo.110-112; cf, 55].
Ubukho vs. ukungabikho kweempawu ezinxulumene neziyobisi kunokuchaphazela ukukulungela kweeseli zedopamine ekuphenduleni ebantwini. Umzekelo, xa abasebenzisi abangaxhomekekanga kuhlobo lweziyobisi bangenisa i-cocaine phambi kwezinto ezinxulumene neziyobisi (inxitywa kwi-Microen mazingira eyaziwayo yokulungiselela kunye nokuphefumla umgubo wecocaine) [113], ukuba likhulu ngakumbi imbali yobomi bokusetyenziswa kwesiyobisi esivuselelayo, kokukhona iba nempendulo enkulu kakhulu ekufumaneni iziyobisi dopamine. Xa kuthelekiswa, kubasebenzisi abangakathembisiyo abasebenzisi bokuvuselela abavavanywayo ukungabikho kwesikhutshelo esinxulumene neziyobisi, iimbali zobomi obukhulu bokusetyenziswa kweziyobisi zinxulunyaniswa neempendulo ezincinci ezibangelwa kukusetyenziswa kweziyobisi dopamine [114] (Umzobo 1). Enye inkcazo yezi ziphumo kukuba ukungabikho kweempawu ezinxulumene neziyobisi dampens dopamine cell reactivity (Umzobo 2).
Ngokudibeneyo, ezi zifundo zingasentla zicebisa ukuba ukudluliselwa kwe-dopamine ephantsi ngokungabikho kweempawu ezinxulumene neziyobisi kunokubangelwa ziinkqubo ezimbini. Eyokuqala yinkqubo evulekileyo apho uthumelo lwedopamine luphantsi xa kuthelekiswa neempendulo ezibonakalayo xa ikho imixholo yamachiza. Okwesibini yinkqubo esebenzayo, ebonisa ukuthintelwa kwimeko (Ibhokisi 2). Ngapha koko, ayisiyi kuphela le misebenzi ingekho iziyobisi inokuthi inyanzeleke ngexesha lomsebenzi ophantsi we-dopamine kunye nenkuthazo, ukungabikho kwabo umtsalane akunakukhuphisana ngokutsala kwezona zixhobo zihamba neziyobisi. Ezi ziphumo zinokuba neempembelelo zokuziphatha ngexesha lokurhoxa, kwaye, eneneni, ukuphakama kokunyanzeleka kokufuna kunye nokusebenzisa iziyobisi xa ukurhoxiswa kweziyobisi kunokubonakalisa iinkqubo ezifanayo. Kanye njengokuba amazwe anqongopheleyo anokulonyusa ixabiso lokukhuthaza lendlela yomvuzo wendalo, njengokutya [116], ubungqina obuqinisekileyo bokuthi ukujonga iziyobisi kujongwe ngexesha lokurhoxiswa kweziyobisi kunokubonakalisa ukuphakama kwesikhuseli sokulungiswa kweziyobisi kunokuba kuthintele ukurhoxa [117-119]. Ke, ukusetyenziswa kweziyobisi ngexesha lokurhoxa kunokubonisa izinto ezinokubakho kunokuba kuqinisekiswe ngeendlela ezimbi. Ngezi ndlela, imikhondo engafakwanga ichiza inokubaluleka ekuphuhlisweni kweempawu ezimbini ezixineneyo ze-SUD: ukuchetywa okuqhubayo komdla kwiinkqubo ezinxulumene neziyobisi kunye nokuthatha iziyobisi kunye nomdla oncitshisiweyo wokulandela iinjongo ezingahambelani neziyobisi ezifanelekileyo ukuze uphumelele.
Ibhokisi 2
Iimpawu zokusingqongileyo kunye nomvuzo
Khawube nomfanekiso-ngqondweni usenyuka intaba. Ukuba amava exesha elidlulileyo akufundise ukuba umvuzo wokutsala usemantla, inkuthazo yakho yokuqhubekeka iya kuba phezulu, kwaye iindlela ezibonakalisa ukuba umvuzo ozayo uza kukhulisa kwaye uxhase idrive yakho. Ezi ndawo zikhuthazayo zihambelana ngokusondeleyo notshintsho ekuhanjisweni kweedopamine; okt, Iimeko ezihanjiswa ngumvuzo zandisa ukulungela kwamaseli e-dopamine ukugqabhuka umlilo ukuphendula ii-crete ezibini ezenziwe ngomvuzo [44,98,115]. Xa uthelekisa, iimeko ezihamba nebala ngokucacileyo ukungabikho komvuzo zinokufumana iipropathi ze-inhibitor enekhowudi [99] kunye nokukwazi ukukuthintela ngenkuthalo ukulungela ukusebenza kwe-dopamine kunye nokukwazi ukuphendula kwimivuzo kunye nezinto ezihambelana nomvuzo [76,104]. Ngokudibeneyo, oku kudityaniswa kweziphumo kuvelisa ukhetho olomeleleyo lweendawo ezixhonywe ngamachiza kunye nemikhwa, ukubamba abantu kude nemisebenzi engeyiyo neziyobisi.
Izifundo ezibini zamva nje zibonisa ukuba izifundo ezisengozini enkulu yee-SUDs zinokuchaphazeleka ikakhulu kwezi ziphumo (Umzobo 3). Okokuqala, impendulo ekhethekileyo eyahlukileyo ye-dopamine yabonwa kubasebenzisi beziyobisi abanganyanzelekanga besengozini ephezulu yokulutha, xa kuthelekiswa nabasebenzisi abasemngciphekweni, xa bevavanywa ngezidakamizwa ezikhoyo (utywala obungene kukubona kwesiselo, ukunuka, ukungcamla kunye nokuchukumisa) [120]. Okwesibini, ngokwahlukileyo okwahlukileyo, ukukhutshwa kwe-dopamine enexabiso eliphantsi kwabonwa kubasebenzisi bezinto ezinganyanzelekanga besengozini yokufumana iziyobisi xa kuvavanywa ngaphandle kweziyobisi ezikhoyo.d-amacwecwe amacwecwe afihlwe kwi-nondescript gelcaps) [114]. Kuzo zozibini ezi zifundo, umahluko weqela uye waphikelela emva kolawulo lokusetyenziswa kwesiyobisi ebomini babo bonke. Ewe, kwaba basebenzisi bengozi enkulu, iimpendulo ze-dopamine ngokungabikho kwezixhobo ezinxulumene neziyobisi zazisezantsi kakhulu kunale zibonwa kwizifundo ezinomngcipheko ophantsi ohambelana nembali yokusetyenziswa kwesiyobisi [114]. Ukuqwalaselwa okunje kuphakamisa amathuba okuba, kwezi zininzi zinengozi ephezulu, kulawulwe imeko ekuphenduleni kwimivuzo ikhula ngokukhawuleza okanye ngakumbi. Ngokudibeneyo, iziphumo eziqwalaselweyo apha zibonisa ukuba indibaniselwano yokuziva uziva ngamachiza, imeko, kunye nokwahluka komntu ekuthatheni inxaxheba kwezi ziphumo kunokuza kumngcipheko wolutsha olusemngciphekweni ngokusetyenziswa rhoqo kweziyobisi, ukubeka kwinqanaba le-SUD.
Iziphumo zokuthintela nokunyanga
Ngokungafaniyo nembono enye yokulutha egxile nakweyiphi na into eyenziwayo ye-hyper- okanye ye-hypo-mesolimbic dopamine, imodeli yokudibanisa ecetywayo apha idibanisa amanqaku omabini, ngaloo ndlela inika inqaku lokuqalisa kwenqaku le-neurobiological yezicwangciso zokungenelela, kubandakanya ukuthintela (Ibhokisi 3). Umsebenzi wamva nje unika isizathu sokuba nethemba. Umzekelo, ukukwenza ulutsha lube lulutsha olunikezwe uqeqesho lokulawula oko kungafuneki lubonise iingxaki ezimbalwa zokusebenzisa iziyobisi emva kweminyaka emibini [129].
Ibhokisi 3
Dopamine kunye nokuziphatha okungxamisekileyo
Ubudlelwane phakathi kokuziphatha okunganyanzelekanga, ukukhutshwa okuphakamileyo kwe-dopamine, kunye nokuchaphazeleka okukhulu kokusetyenziswa gwenxa kweziyobisi kunokusasaza kwisizukulwana ngasinye. Ukongeza ekusasazeni ngemikhwa ekhulayo, iintonga ezinganyanzelekanga zibonisa ukunakekelwa okuncinci koomama [121], ezikhokelela ekunyanzelisweni okukhulu, ukuvuza imizwa ye-cue, ukukhutshwa kwe-dopamine, kunye nokuziphethe-ngokwabo kweziyobisi kwinzala yabo [122-124]. Kwimeko yendalo, ezi zilwanyana zinokuba nakho ukunxulumana nemicimbi engentle. Ezi zixinzelelo zikwabangela ukukhutshwa kwe-dopamine, kwaye zikhokelele ekuziphatheni okungapheliyo kunye nokuthambeka kokudibeneyo kwe-dopaminergic kwiziyobisi zokuphathwa gadalala [125-127], eyandisa ngakumbi imikhwa yangaphambili. Iziphumo ezifanayo zinokwenzeka nakwabantu. Ewe, abantwana abakhulela kwiintsapho ezibonakala ngokuziphatha kwangaphandle basengozini ephezulu yoxinzelelo, ukwenzakala nokungahoyi, ukubabeka emngciphekweni ophezulu wee-SUDs [128].
Kuya kuhlala kucingelwa ukuba ngaba iinkqubo ezichazwe apha ngasentla (ukukhupha iimpawu, ukusebenza kwe-hyper- kunye ne-hypo-dopamine function) zisemthethweni kanye xa sele kuphuhliswe umlutha omkhulu. Kwelinye icala, iicustoms ezinxulumene neziyobisi zihlala zenza ukuba kusebenze amandla okunyanzelwa kwabantu abanokunganyaniseki okwangoku, ezi zenzo zinkulu kunezo zibonwa kulawulo olusempilweni, kwaye umahluko ngamnye kubungakanani bempendulo zamachiza ezidalwe ngu-due.76]. Ngokusekwe kolu hlolisiso, sicebisa ukuba kungaphambi kwexesha ukwala ukuhanjiswa dopamine njengenjongo yonyango.
Kwangelo xesha, abantu abanee-SUDs zangoku baxelwa ngokulandelelana ukuba banciphise ukukhutshwa kwe-striatal dopamine, ngokuthelekiswa nolawulo olusempilweni, xa becelomngeni ne-amphetamine [61]. Amanqaku amabini anomdla apha. Kuqala, kuzo zonke kodwa zonke kwezi zifundo [130], i-amphetamine yenziwa ngaphandle kwezinto ezinxulumene neziyobisi zikhona (Ibhokisi 4). Okwesibini, ayingabo bonke abantu abanee-SUDs ezibonisa ukunciphisa ukukhutshwa kwe-dopamine ye-amphetamine xa kuvavanywa ukungabikho kwezixhobo ezibini ezenziwa ngamachiza. Le mpendulo yomahluko ibonakala inokubaluleka kweklinikhi: i-50% ephantsi yezifundo ebonisa impendulo eqhelekileyo ye-dopamine phantsi kwale meko ikwaphendula ngcono kwizimo zokuziphatha ezomeleleyo zokuziphatha, ziphakamisa amathuba achukumisayo okuba izigulana ezinokuthi zivakalise impendulo kwi-dopamine ukungabikho kweendlela ezinxulumene neziyobisi kukwazile ukufunda indlela yokuziphatha enxulumene nomvuzo [138-139]. Kuya kuhlala kungacacanga ukuba ngaba ukukhutshwa kwe-dopamine ephantsi okubonakalayo kwenye yezigulana kuxhomekeke kwinto engahambelani neziyobisi, ukungafani komngcipheko kwimiphumela ye-neurotoxic yokusetyenziswa gwenxa kweziyobisi, umkhwa obukhoyo ngaphambili, i-dopamine D2 yangaphambi kunye ne-post-synaptic receptor super -Ubuzwe, okanye indibaniselwano yezi zinto. Ngokungafaniyo, uMartinez noogxa bakhe [138] Inomdla wokwazi ukuba aba bantu banokubonisa i-biomarker ebonisa ukuba bangazuza bhetele kwiindlela zokuziphatha ukuba bebelashwa kwangoko kunye neearhente ezonyusa umsebenzi we-presynaptic dopamine, njenge L-DOPA [140].
Ibhokisi 4
Dopamine kunye "neziyobisi"
Ubungqina beempendulo ze-dopamine ezingagugi phambi kobukho beempawu ezinxulumene nomlutha zibonwe ngokungaguqukiyo kubantu 'abanokungaziphathi kakuhle'. Xa kuthelekiswa nolawulo olusempilweni, abantu abanezinto ezingalunganga ezinento yokwenza 'nokuziphatha gwenxa' (ukuHamba ngePathological, iBinge Eating Disorder) bonisa ubungqina beempendulo zedopatri ye-dopamine ekhutshiweyo yokutya, imbuyekezo yemali kunye namacwecwe e-amphetamine angachazwanga [131-134; cf, 135]. Ngaphezulu kokukhululwa kwe-dopamine ephambili, kokukhona iba nzima ngakumbi iingxaki zekliniki [132,134,136-137]. Ukukhutshwa kwe-dopamine ephantsi akuchazanga ukuba kuxelwa. Nangona kunjalo, uncwadi lwe-fMRI lokungcakaza lonxibelelwano lwengxelo lwengxelo luyanda kwaye luyancipha ekusebenzeni kwe-striatal, kwaye ezi mpendulo zahlukileyo zibonakala zibonakalisa ubukhulu bobukho vs. ukungabikho komdlalo onxulumene nokungcakaza ocacileyo [76].
Ezinye iindlela zonyango ezisisiseko se-dopamine nazo ziphantsi kophuhliso. I-Dopamine D1 kunye ne-D2 receptor ligands zibonise ukungasebenzi kakuhle kodwa ii-D3 receptor antagonists ziye zabonisa ukubakho [141]. Ezinye i-receptor subtypes (D4, D5) ezingekavavanywa. Okokugqibela, ekubeni iziyobisi zibonakala zinamava e-dopamine xa kuphendulwa iziyobisi kunye nemipu xa amakhonkco engekho, imodulators zedopamine zinokubonelela ngonyango lwenoveli olungahambelaniyo nemodeli yangoku. Isindululo kukuba ezi khompawundi ziya kunciphisa ukunyuka kwe-dopamine ebuyisela ukukhangela iziyobisi ngaphandle kokukhusela konke ukuhanjiswa kwe-dopamine kunye nokuvelisa ilahleko egcweleyo yomdla [142].
Ukuqukumbela intetho
Imodeli yangoku idibanisa umbono we-neurodevelopmental kunye nobungqina bokuba ubukho vs. ukungabikho kweendlela ezinxulumene neziyobisi kunokuza kulawula ukwenziwa kwe-dopamine, ukuqondisa iinkqubo ezishukumisayo kunye nokumisela inqanaba lokuqhubeka nokusebenzisa iziyobisi rhoqo kunye ne-SUD. Olu luvo luhlanganisiweyo lubonisa isithembiso sokukhokela iindlela zokuthintela ungenelelo kwangethuba, kwaye licebisa ukuba indlela ekhokelela kweziqhamo kwiindlela zekhemesti zonyango inokuba kukuphuhlisa imijikelezo ekhuthaza amandla okugcina umdla kwizinto ezinxulumene neziyobisi. Ukomeleza ukubhenela kwezi njongo kunokunceda abo bane-SUD ukuba baphephe kwimikhombandlela enxulumene neziyobisi kunye nokuzimasa ngcono kwezona ziyimfuneko ebomini.
Iimbalasane
- Iziyobisi zihlala zilungiswa ziimpawu zokuziphatha ebuntwaneni
- Ukutshutshiswa kunokubonakalisa iimpendulo ezandileyo ze-dopamine kwizigameko ezothusayo
- Iziyobisi zixhapha iimpendulo dopamine, zikhokelela ekuziphatheni ngokukhethekileyo kwiziyobisi
- Izehlo ezingezizo iziyobisi ziba ngaphantsi kwesidima, kwaye zingabi namandla okwenza kusebenze i-dopamine
- Umdla oshiyekileyo uphuhlisa, ubeka inqanaba lokusetyenziswa rhoqo kweziyobisi kunye neziyobisi
Imibulelo
Olu hlaziyo lwenziwe lwabakho ngenxa yezibonelelo ezivela kwiCanadian Institutes yoPhando lwezeMpilo (i-MOP-36429 kunye neMOP-64426, ML) kunye neZiko lezeMpilo leSizwe (DA09397, PV).
Imihlathi
Iphepha elichazayo ukuba awusenanto oyifunayo: Le fayili yeFayile yombhalo wesandla ongabhalwanga owamkelwe ukushicilelwa. Njengenkonzo kumakhasimende ethu sinika le ngcaciso yokuqala kwincwadi yesandla. Umbhalo wesandla uza kufumana ukukopishwa, ukufakela, nokuphonononga ubungqina obunokubakho ngaphambi kokuba kukhutshwe kwifomu yayo yokugqibela. Nceda uqaphele ukuba ngexesha lokuveliswa kweeprogram ezinokuthi zifumaneke ezinokuthi ziphazamise umxholo, kunye nazo zonke izisemthethweni ezichasayo ezisetyenziswa kwiphephancwadi.
Ucaphulo