IZIMVO: Uxinzelelo lunokonyusa umngcipheko wokuba likhoboka. 
Uxinzelelo olungapheliyo, ukusetyenziswa kweziyobisi, kunye nokuba sesichengeni sokulutha
Rajita Sinha Ann NY Acad Sci. Umbhalo-ngqangi wombhali; ifumaneka kwi-PMC 2009 ngo-Agasti 26. Ipapashwe kwifom yokugqibela ehleliweyo njenge: Ann NY Acad Sci. 2008 Okthobha; 1141: 105–130. doi: 10.1196/annals.1441.030. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA Idilesi yembalelwano: Rajita Sinha, Ph.D., uNjingalwazi, iSebe Psychiatry, uMlawuli, Yale Interdisciplinary Stress Centre, Yale University School of Medicine, 2 Church Stress Emazantsi, iSuite 209, iNew Haven, CT 06515. Izwi: +203−974−9608; ifeksi: +203−974−7076. I-imeyile: [imeyile ikhuselwe]
Abstract
Uxinzelelo yinto eyaziwayo yomngcipheko ekuphuhliseni umlutha kunye nokuba sesichengeni sokuphinda ubuyele ekubeni likhoboka. Uluhlu lwezifundo ezisekelwe kuluntu kunye ne-epidemiological zichonge uxinzelelo oluthile kunye noguquko lwenqanaba lomntu ngamnye oluqikelelwayo lokusetyenziswa kweziyobisi nokusetyenziswa kakubi. Uphando lwangaphambili lukwabonisa ukuba ukuvezwa koxinzelelo kuphucula ukuzilawula kwechiza kwaye kubuyisele ukufuna ichiza kwizilwanyana ezinamava ngamachiza. Iziphumo ezibi zoxinzelelo kubomi bangaphambi kwexesha, ukuphathwa kakubi kwabantwana, kunye nobunzima obuqokelelweyo kutshintsho lwe-corticotropin ekhupha into kunye ne-hypothalamic-pituitary-adrenal axis (CRF/HPA), i-CRF ye-extrahypothalamic, i-autonomic arousal, kunye ne-central noradrenergic systems nazo zibonisiwe. . Iziphumo zolu tshintsho kwindlela ye-corticostriatal-limbic yenkuthazo, yokufunda, kunye nohlengahlengiso olubandakanya i-mesolimbic dopamine, i-glutamate, kunye ne-gamma-amino-butyric acid (GABA) iindlela zixoxwa njenge-pathophysiology esisiseko ehambelana nomngcipheko onxulumene noxinzelelo. Iimpembelelo zokusetyenziswa kweziyobisi rhoqo kunye nezingapheliyo kwiinguqu kwezi nkqubo zoxinzelelo kunye nokukhuthaza zibuye zihlaziywe, ingqwalasela eyodwa kwimpembelelo yolu lungelelaniso kulawulo loxinzelelo, ukulawulwa kwempembelelo, kunye nokunyanzeliswa kokufuna iziyobisi ezinyanzelekileyo kunye nokuphinda kuthinteke. Okokugqibela, izikhewu zophando ekuqhubeleni phambili ukuqonda kwethu unxulumano phakathi koxinzelelo kunye nokukhotyokiswa zibonisiwe, ngethemba lokuba ukujongana nale mibuzo ingaphendulwanga kuya kuba nefuthe elibonakalayo kuthintelo olutsha kunye nezicwangciso zonyango zokujongana nokuba sesichengeni sokuba likhoboka.
intshayelelo
Uxinzelelo kudala lusaziwa njengonyusa umngcipheko wokuba likhoboka. Le minyaka ilishumi idlulileyo ikhokelele ekunyukeni okumangalisayo kokuqonda iindlela ezisisiseko zalo mbutho. Ukuziphatha kunye ne-neurobiological correlates ichongiwe, kwaye ubungqina obuthile beenguqu ze-molecular kunye neeselula ezinxulumene noxinzelelo olungapheliyo kunye nokulutha buchongiwe. Izifundo zabantu zixhamle ekuveleni kwezixhobo ezintsonkothileyo zokucinga ngengqondo kunye novavanyo olunqamlezayo lweendlela ezenziwe zelabhoratri zoxinzelelo kunye nomnqweno kunye nokunxibelelana kwazo kwimimandla ethile yobuchopho ehambelana nomvuzo kunye nomngcipheko wokuba likhoboka. Eli phepha lijolise ikakhulu kumanyano phakathi koxinzelelo kunye nokulutha ebantwini kodwa likwatsalwa kuncwadi olubanzi lwezilwanyana ukuxhasa iingcamango ezicetywayo. Inkcazo yoxinzelelo kunye ne-neural underpinnings inikezelwa ngokugxininiswa okuthe ngqo kwimiphumo yayo ekukhuthazeni nasekuziphatheni. Kumxholo wobungqina obuqinileyo be-epidemiological obunxibelelanisa ubuntwana kunye nobunzima obudala kunye nomngcipheko wokuba likhoboka, iziphumo zophando olusisiseko kunye nolwabantu olukhomba iindlela zokubeka eziphantsi kolu manyano ziyachazwa. Indima ebalulekileyo ibonwa kwiisekethe zangaphambili ezibandakanyekayo ekufundeni okuguquguqukayo kunye nomsebenzi wesigqeba, kubandakanya nokulawula uxinzelelo kunye neminqweno / iimpembelelo, kumanyano phakathi koxinzelelo kunye nomngcipheko wokulutha. Nangona kunjalo, imibuzo emininzi ihlala ingaphendulwanga ekuqondeni umngcipheko wokulutha onxulumene noxinzelelo, kwaye ezi ziyaphononongwa ukuze zazise uphando lwexesha elizayo. Okokugqibela, iziphumo zokusetyenziswa kweziyobisi ezingapheliyo kuxinzelelo kunye neendlela zokuvuza ngakumbi ngokubhekisele kumngcipheko wokuphinda zihlolwe. Izikhokelo zexesha elizayo ekujonganeni nomngcipheko wokuphinda ubuyele kwimeko yoxinzelelo kwizicwangciso zeklinikhi nazo ziyaxoxwa.
Uxinzelelo, iiMvakalelo, kunye nokuziphatha okuziqhelanisayo
Igama elithi "uxinzelelo" libhekisela kwiinkqubo ezibandakanya ukuqonda, ukuvavanywa, kunye nokuphendula kwiziganeko ezinobungozi, ezisongelayo, okanye ezicela umngeni okanye i-stimuli.1-3 Amava oxinzelelo anokuba ngumngeni ngokweemvakalelo okanye ngokwasemzimbeni kwaye asebenze iimpendulo zoxinzelelo kunye neenkqubo zokulungelelanisa ukuze kubuyiselwe i-homeostasis.2,4, 6–1 Imizekelo yoxinzelelo lweemvakalelo ibandakanya impixano phakathi kwabantu, ukuphulukana nobudlelwane, ukuswelekelwa lilungu losapho elisondeleyo, kunye nokulahlekelwa ngumntwana. Uxinzelelo oluqhelekileyo lomzimba yindlala okanye ukunqongophala kokutya, ukungalali okanye ukuphuthelwa, i-hyper- okanye i-hypothermia egqithisileyo, kunye namazwe okurhoxa kweziyobisi. Ukongeza, ukusetyenziswa rhoqo kunye nokuzinkcinkca kwamachiza amaninzi asebenza ngengqondo kusebenza njengoxinzelelo lwe-pharmacological. Olu hlobo lwengqiqo luvumela ukuqwalaselwa okwahlukileyo (2) kweziganeko zangaphakathi nangaphandle okanye izivuseleli ezenza iimfuno okanye umthwalo kumzimba; (3) iinkqubo ze-neural ezivavanya iimfuno kunye nokuvavanya ukufumaneka kwezixhobo zokulungelelanisa ukuhlangabezana neemfuno (uvavanyo); (4) i-subjective, ukuziphatha, kunye nomsebenzi we-physiological obonisa uxinzelelo kumzimba; (5) i-neuroadaptations kwiinkqubo zengqondo zengqondo kunye nezikhuthazayo ezinxulumene noxinzelelo olungapheliyo; kunye (XNUMX) nokuziphatha, ukuqonda, kunye nokulungelelanisa umzimba ekuphenduleni uxinzelelo.
Ngelixa uxinzelelo luhlala lunxulunyaniswa nefuthe elibi kunye noxinzelelo, lunokubandakanya "uxinzelelo olulungileyo" olusekwe kwimpembelelo yangaphandle kunye nengaphakathi enzima / enomngeni ophakathi kodwa inqunyelwe ixesha kwaye iphumela kwiimpendulo zokuqonda kunye nokuziphatha ezivelisa ingqondo kunye nokuqonda. ukufezekiswa, kwaye kunokubonwa njengento eyonwabileyo kwaye inomdla.1,3,6,7 Iimeko ezinjalo zithembele ekusebenzeni okwaneleyo kokukhuthaza kunye nokulawula ukuphumeza iziphumo ezijoliswe kwiinjongo kunye ne-homeostasis.3,6,8 Nangona kunjalo, ixesha elide, eliphindaphindiweyo, okanye Uxinzelelo olungapheliyo-umzekelo, amazwe ahambelana nokunyuka koxinzelelo okanye ukuzingisa koxinzelelo-okukhona ukungalawuleki kunye nokungazicingeli kwemeko yoxinzelelo, kuthoba imvakalelo yokulawula okanye ukuguquguquka, kunye nobukhulu bempendulo yoxinzelelo kunye nomngcipheko wokuzingisa kwe-homeostatic dysregulation. .1,6,9–11 Ke ngoko, imilinganiselo yokuqina, ukulawuleka, ukuqikelelwa, ukomelela, kunye nokulungelelana kubalulekile ekuqondeni indima yoxinzelelo ekwandeni komngcipheko wokuziphatha kakubi njengokukhobokisa.
Umbono kunye novavanyo loxinzelelo luxhomekeke kwimiba ethile yokubonisa yangaphandle okanye yangaphakathi, iimpawu zobuntu, ukufumaneka kwemithombo yangaphakathi (kubandakanywa nemeko yempilo yomntu), imeko yangaphambili yeemvakalelo (kubandakanya iinkolelo kunye nezinto ezilindelekileyo), kunye nemimandla ethile yobuchopho elamla Uvavanyo lwezivuseleli njengoxinzelelo, kunye nesiphumo somzimba, ukuziphatha, kunye namava ovakalelo kunye neempendulo eziguqukayo. Imimandla yobuchopho efana ne-amygdala, i-hippocampus, i-insula, kunye ne-orbitofrontal, i-medial prefrontal, kunye ne-cingulate cortices zibandakanyeka ekuboneni nasekuvavanyeni i-stimuli yeemvakalelo kunye noxinzelelo, kunye nesiqu sobuchopho (i-locus ceruleus kunye nemimandla ehambelana nokuvusa), i-hypothalamus, i-thalamus, imimandla yokubetha, kunye ne-limbic ibandakanyeka kwiimpendulo zomzimba kunye neemvakalelo. Ngokudibeneyo le mimandla inegalelo kumava onxunguphalo. Iimpendulo ze-Physiological zibonakaliswa ngeendlela ezimbini eziphambili zoxinzelelo, ezizezi, i-corticotropin releasing factor (CRF) ekhutshwe kwi-nucleus ye-paraventricular (PVN) ye-hypothalamus, evuselela i-hormone ye-adrenocorticotrophin evela kwi-pituitary yangaphambili, ethi emva koko ivuselele ukukhuselwa kwe-corticosterone / i-corticosterone. i-adrenal glands, kunye nenkqubo ye-nervous autonomic, ehambelana neenkqubo ze-sympathoadrenal medulary (SAM).4,12
Ukongeza, iCRF inempembelelo enkulu kwimimandla ye-extrahypothalamic kuyo yonke imimandla ye-corticostriatal-limbic kwaye idlala indima ebalulekileyo ekumodareyitheni impendulo yoxinzelelo lwengqondo kunye nokuziphatha. indawo ye-ventral tegmental okanye i-VTA, i-nucleus accumbens [NAc], kunye nemimandla ye-prefrontal ye-medial [mPFC] imimandla) ebalulekileyo ekulawuleni uxinzelelo, ukusebenzisa ingqondo kunye nokulawulwa kokuziphatha, kunye nokuxoxisana ngeempendulo zokuziphatha kunye neengqondo ezibalulekileyo zokulungelelanisa kunye ne-homeostasis.13, 8,14,15 Iindlela ze-CRF ze-hypothalamic kunye ne-extrahypothalamic CRF kunye neecatechoamines ezisembindini zijolise kwiindlela ezikhuthazayo zobuchopho ezichaphazela kakhulu iinkqubo zokuguquguquka kunye ne-homeostatic. Ngokomzekelo, iinxalenye ezahlukeneyo ze-cortex ye-medial prefrontal cortex ibandakanyeka kwimisebenzi ephezulu yokuqonda okanye yokulawula ukulawula, njengokulawula kunye nokuthintela iimpembelelo, ukulawula uxinzelelo, ukugxila kunye nokutshintsha ingqalelo, ukubeka iliso kwindlela yokuziphatha, ukudibanisa ukuziphatha kunye nemiphumo ekuhambeni kwexesha, ukuqwalasela ezinye iindlela ngaphambi kokuba usebenze, kunye neempendulo zokwenza izigqibo.16,17 Izazinzulu zengqondo kunye nokuziphatha ziye zabonisa ngokugqithiseleyo ukuba ngokunyuka kwamanqanaba oxinzelelo lwengqondo kunye nomzimba okanye impembelelo embi, kukho ukuncipha kolawulo lokuziphatha kunye nokwanda kokunyanzeliswa, kunye nokwanda kwamanqanaba oxinzelelo, kunye nokungapheliyo. yoxinzelelo, umngcipheko omkhulu wokuziphatha kakubi.18-27 Ubungqina be-Neurobiological bubonisa ukuba ngokunyuka kwamanqanaba oxinzelelo, kukho ukuncipha kokusebenza kwangaphambili kunye nokunyuka kwe-limbic-striatal level response, eqhubela phambili ukuziphatha okuphantsi kunye nokulawulwa kwengqondo.28,29 Ngaloo ndlela. , iindlela zobuchopho ezikhuthazayo zezona kujoliswe kuzo kwiikhemikhali zoxinzelelo lwengqondo kwaye zibonelela ngendlela ebalulekileyo enokuthi ngayo uxinzelelo luchaphazele ukuba sesichengeni sokulutha.
Ukuxinezeleka kunye noPhuhliso lweZimilo eziLuthayo
Kukho uncwadi oluninzi kunxulumano olubalulekileyo phakathi koxinzelelo oluqatha kunye nolungapheliyo kunye nenkuthazo yokusebenzisa kakubi izinto ezikhobokisayo (jonga30 ukuze uphonononge). Uninzi lweethiyori eziphambili zokulutha zikwachonga indima ebalulekileyo yoxinzelelo kwiinkqubo zokulutha. Ezi zivela kwiimodeli zengqondo zokulutha ezijonga ukusetyenziswa kweziyobisi kunye nokusetyenziswa kakubi njengeqhinga lokujongana noxinzelelo, ukunciphisa uxinzelelo, ukunyanga ngokwakho, kunye nokunciphisa uxinzelelo olunxulumene nokurhoxa, i-31-37 ukuya kwiimodeli ze-neurobiological eziphakamisa ukukhuthaza kunye noxinzelelo. Iikhonsepthi ze-allostasis ukucacisa indlela i-neuroadaptations kumvuzo, ukufunda, kunye neendlela zoxinzelelo kunokunyusa umnqweno, ukulahleka kolawulo, kunye nokunyanzeliswa, amacandelo aphambili kutshintsho olusuka kusetyenziso oluqhelekileyo lwezinto ukuya ekungakwazini ukuyeka ukusetyenziswa okungapheliyo ngaphandle kwemiphumo emibi, eyona nto ibalulekileyo. yokukhotyokiswa.38–40 Kweli candelo, sijonga kwakhona imigca yobungqina obuguqukayo obukhomba indima ebalulekileyo edlalwa luxinzelelo ekwandiseni ukuba sesichengeni sokukhobokisa.
Ubunzima obuNgapheliyo kunye nokuNyuleka koMngcipheko wokusetyenziswa kweziyobisi
Kukho ubungqina obuninzi obuvela kwizifundo ezisekelwe kuluntu kunye nezonyango ezixhasa unxulumano oluhle phakathi kobunzima bengqondo, impembelelo embi, kunye noxinzelelo olungapheliyo kunye nokuba sesichengeni sokulutha. Ubungqina kule ndawo bunokwahlulwa ngokweendidi ezintathu ezibanzi. Eyokuqala ibandakanya izifundo ezilindelekileyo ezibonisa ukuba ulutsha olukwishumi elivisayo olujongene neziganeko ezimbi kakhulu zamva nje lubonisa amanqanaba awonyuka okusetyenziswa kweziyobisi kunye nokusetyenziswa kakubi kweziyobisi.41–55 Iziganeko zobomi ezimbi ezifana nokulahlekelwa ngumzali, uqhawulo-mtshato lwabazali kunye neengxabano, inkxaso ephantsi yabazali, ubundlobongela ngokomzimba kunye nokuxhatshazwa, ngokweemvakalelo. impatho-gadalala nokungahoywa, ukubekwa ikheswa kunye nobudlelwane obutenxileyo, kunye nolwakhiwo losapho olunomzali omnye zonke zinxulunyaniswa nomngcipheko owandisiweyo wokusetyenziswa gwenxa kweziyobisi.
Uhlobo lwesibini lobungqina lunxulumano phakathi kokwenzakala kunye nokuphathwa kakubi, impembelelo embi, uxinzelelo olungapheliyo, kunye nomngcipheko wokusetyenziswa kakubi kweziyobisi. Kukho ubungqina obuninzi bobudlelwane obandileyo phakathi kokuphathwa gadalala ngokwesondo kunye nokuphathwa gadalala ngokwasemzimbeni kunye nokwanda kokusetyenziswa kweziyobisi kunye nokwanda kokusetyenziswa kweziyobisi.56-60 Kukho nobungqina bokuba iziganeko zamva nje zobomi kunye nokuxhatshazwa ngokwasemzimbeni nangokwesondo nganye ibeka umngcipheko othile ozimeleyo wokuba sesichengeni sokulutha.58 Ukongeza kuxhatshazo ngokwesondo kunye nomzimba, iimpembelelo ezingalunganga kunye noxinzelelo olungapheliyo zixela kwangaphambili ukuba sesichengeni somlutha. Iziphumo zibonisa ukuba impembelelo embi, kubandakanywa nemvakalelo engathandekiyo yomsindo, ihambelana nobungozi bokusetyenziswa kakubi kweziyobisi.61-67 Izifundo ezininzi ziye zabonisa ubudlelwane obubalulekileyo phakathi kokuxhaphaka kweemvakalelo kunye nokukhathazeka kokukhathazeka, kubandakanywa ukuphazamiseka kwengxaki emva kokuphazamiseka (PTSD), iingxaki zokuziphatha. kunye nomngcipheko okhulayo wokuphazamiseka kokusetyenziswa kweziyobisi.68-78 Njengoko uxinzelelo luhambelana kakhulu nokuxhaphaka kwemizwelo kunye nokukhathazeka okuxhalabisayo kunye nokukhathazeka okungapheliyo kwengqondo, i-79,80 le mibutho iphakamisa umba wokuba ingaba izifo zengqondo ezicatshangelwa njengezimo ezixinzelelekileyo zinokuthi zibangele Unxulumano olubalulekileyo phakathi koxinzelelo kunye nokuphazamiseka kokusetyenziswa kweziyobisi.
Kudidi lwesithathu lobungqina obuvela kwizifundo zabemi, uphando lwakutsha nje luye lwavavanya ukuvezwa kobomi bonke kuxinzelelo kunye nefuthe lobunzima obukhulayo kumngcipheko wokulutha emva kokubala inani lezinto zolawulo ezinjengobuhlanga / ubuhlanga, isini, imeko yentlalontle, ukusetyenziswa kakubi kweziyobisi kwangaphambili, ukuxhaphaka kwezifo zengqondo, imbali yentsapho yokusetyenziswa kweziyobisi, kunye neengxaki zokuziphatha kunye nokuziphatha.81,82 Ubunzima obuninzi okanye uxinzelelo lwavavanywa ngokusebenzisa indlela yokuhlola uluhlu kunye nokubala inani leziganeko ezahlukeneyo eziye zafunyanwa kwixesha elithile ngexesha lokuphila. Imiphumo ye-distal (iziganeko ezenzeka ngaphezu konyaka we-1 ngaphambili) kunye namava oxinzelelo olusondeleyo (iziganeko ngexesha lamva nje le-1-year), kunye nemiphumo yazo kwiinkqubo zokuhlangana zokuphazamiseka kokusetyenziswa kweziyobisi nazo zavavanywa. Iziphumo zibonisa ukuba inani elongezelekayo leziganeko ezicinezelayo laliqikelele kakhulu ukuxhomekeka kotywala kunye neziyobisi ngendlela exhomekeke kwidosi, nasemva kokubalwa kwezinto zolawulo. Zombini iziganeko ezikude kunye nezisondele kakhulu kwaye ngokuzimeleyo zichaphazele ukuba sesichengeni somlutha. Ngaphaya koko, iziphumo ezixhomekeke kumthamo woxinzelelo olongezelekayo olusemngciphekweni wokuba likhoboka zikho kuzo zombini izini kunye neCaucasian, i-African-American, kunye ne-Hispanic uhlanga / amaqela eentlanga. Iindidi zeziganeko ezimbi ezinxulunyaniswa kakhulu nokuba sesichengeni kuqhawulo-mtshato lwabazali okanye ungquzulwano, ukulahlwa, ukunyanzelwa ukuba bahlale ngaphandle kwabazali, ukuphulukana nomntwana ngenxa yokufa okanye ukususwa, ukungathembeki kwezinye izinto ezibalulekileyo, ukulahlekelwa likhaya ngenxa yentlekele yendalo, ukufa komntu osondeleyo. , ukuxhatshazwa ngokwasemphefumlweni okanye ukungahoywa, ukuxhatshazwa ngokwesondo, ukudlwengulwa, ukuphathwa gadalala ngokwasemzimbeni ngumzali, umkhathaleli, ilungu losapho, iqabane, okanye enye into ebalulekileyo, ixhoba lokudutyulwa kwemipu okanye ezinye izenzo zobundlobongela, kunye nokubona ukuphathwa kakubi. Ezi zimele iziganeko ezicinezela kakhulu kunye nezicinezelekileyo ngokwasemoyeni, ezidla ngokungalawulekiyo nezingalindelekanga ngokwendalo. Itheyibhile yoku-1 ishwankathela iintlobo zeziganeko zobomi, uxinzelelo olungapheliyo, ukuphathwa gadalala, kunye neziguquko zenqanaba lomntu ngamnye ezinxulumene nomngcipheko wokulutha.
ISIBHILE 1
Iindidi zeZiganeko zoBomi eziMandundu, ukuNcunula, ukuXinezeleka okuNgapheliyo, kunye neZiguquguquko zeNqanaba loMntu ngamnye uKuqikelelwa koMngcipheko wokulutha
Ukubonakaliswa koxinzelelo kukwandisa ukuqaliswa kunye nokunyuka kokuzilawula kweziyobisi
Kukho ubungqina obuvela kwizifundo zezilwanyana ukuxhasa ingcamango yokuba ukuvezwa ngokukrakra kuxinzelelo kwandisa ukuqaliswa kunye nokunyuka kokusetyenziswa kweziyobisi kunye nokusetyenziswa kakubi (jonga i-30,83 yokuhlaziywa). Umzekelo, kwiimodeli zezilwanyana, uxinzelelo lwentlalontle, ukwahlukaniswa kwezentlalo, umva kunye nokungcangcazela kweenyawo, uxinzelelo lokuzibamba, kunye noxinzelelo lwento entsha kwaziwa ngokunyusa ukufunyanwa kwe-opiates, utywala, kunye nolawulo lwe-psychostimulant, kunye nemiqolomba enxulumene nohlobo loxinzelelo, imfuza. imvelaphi yezilwanyana, kunye nokwahluka ngokohlobo lweziyobisi (jonga i-84–87 yophononongo). Kwakhona, nangona kukho iziphumo ezibi, obunye ubungqina bubonisa ukuba uxinzelelo lobomi bokuqala, ukusetyenziswa kweenkqubo ezifana nokuhlukaniswa kwe-neonatal okanye ukwahlukana komama, kunye noxinzelelo olude kunye noluphindaphindiweyo olumele amava oxinzelelo olungapheliyo, kuphucula ukuzilawula kwe-nicotine, i-psychostimulants, kunye notywala kunye / okanye iziphumo zabo zokuziphatha ezibukhali.88-93 Ngokucacileyo, isondo sidlala indima ebalulekileyo kwimvakalelo enxulumene noxinzelelo kwimpembelelo yokuqinisa iziyobisi kunye nokunyusa uxinzelelo lwe-self-administration.93-97 Kubantu, kukho ubungqina obuninzi obuvela kubantu Izifundo ezinde zokuxhasa iziphumo zoxinzelelo ekuqaliseni ukusetyenziswa kweziyobisi kunye nokunyuka kwabafikisayo kunye nabantu abadala. izifundo ezivavanya iziphumo zokuvezwa koxinzelelo ekusetyenzisweni kweziyobisi zilinganiselwe kwiziyobisi ezisemthethweni ezinjengotywala kunye nenikotini, ngenxa yezizathu zokuziphatha. Nangona kunjalo, kukho ubungqina bokuba uxinzelelo lukwandisa ukusela kunye nokutshaya i-nicotine (jonga i-24,98 yokuhlaziywa), kodwa iziphumo zembali yokusela, imbali yobunzima, uxinzelelo lwentlalo kunye nokulindela kwaziwa ngokudlala indima kwezi zifundo zovavanyo.
IiNdlela eziSebenzayo eziSesikweni iimpembelelo zoxinzelelo kubuSechengeni boMkhwa
Njengobungqina obusebenzisa iindlela ezahlukeneyo buye baqokelela ukuxhasa isiphumo esibalulekileyo soxinzelelo kumngcipheko wokuba likhoboka, eli candelo liphonononga uphando kumakhonkco e-neurobiological phakathi koxinzelelo kunye neendlela zomvuzo ezenziwa ziziyobisi ezixhaphazayo. Kuyaziwa ukuba iipropathi zokuqinisa iziyobisi zokusetyenziswa kakubi zibandakanya ukusebenza kwazo iindlela ze-mesolimbic dopaminergic (DA), ezibandakanya i-dopamine neurons evela kwindawo ye-ventral tegmental kunye nokwandisa kwi-ventral striatum kunye ne-prefrontal cortex (PFC) .115- I-117 Le ndlela ikwabandakanyeka ekunikeni ubukhali kwi-stimuli, ekuqhubeni umvuzo, nasekufundeni nasekuziqhelaniseni.14,118 Izifundo zokucinga ngengqondo yomntu zikwaxhasa indima yezi nkqubo kumvuzo weziyobisi, njenge-psychostimulants, utywala, i-opioids, kunye ne-nicotine zonke zisebenza Iinkqubo ze-DA ze-mesolimbic, ngokukodwa, i-ventral kunye ne-dorsal striatum, kwaye umsebenzi onjalo unxulunyaniswa nokulinganiswa kweziyobisi eziphezulu okanye zolonwabo kunye nokunqwenela.119-126
Nangona kunjalo, ukubonakaliswa koxinzelelo kunye nokunyuka kwamanqanaba e-glucocorticoids (GC) kwakhona kuphucula ukukhululwa kwe-dopamine kwi-NAc.127-132 Ukunyanzeliswa kwe-GC nge-adrenalectomy kunciphisa amanqanaba e-extracellular ye-dopamine phantsi kweemeko ze-basal kunye neempendulo zoxinzelelo kunye neengqondo. I-DA synthesis kunye ne-turnover kwi-NAc, i-131,133 ebonisa ukuba utshintsho kwi-hypothalamic-pituitary-adrenal (HPA) axis kunye ne-glucocorticoids inokuchaphazela kakhulu ukuhanjiswa kwe-DA. Kukho ubungqina bokuba, njengeziyobisi zokuxhatshazwa, uxinzelelo kunye nokunyuka okuhambelanayo kwi-CRF kunye ne-glucocorticoids yokwandisa umsebenzi we-glutamate kwi-VTA, ethi ikhulise umsebenzi we-dopaminergic neurons. kwi-cortisol inxulunyaniswa nokuqokelelwa kwe-dopamine kwi-ventral striatum, i-134 kwaye obunye ubungqina bubonisa ukuba ukunyuka kwe-amphetamine-induced kwi-cortisol kunxulunyaniswa nokubotshwa kwe-dopamine kwi-ventral striatum kunye nokulinganisa kwe-amphetamine-induced euphoria.135 Ngenxa yokuba zombini uxinzelelo kunye iziyobisi zokuxhatshazwa zisebenzisa iindlela ze-mesolimbic, akumangalisi ukuba umphumo ngamnye kwi-synaptic adaptations kwi-VTA dopamine neurons kunye noshintsho lwe-morphological kwi-medial prefrontal cortex.138
Ukongeza kwindima emvuzweni, umzimba okhulayo wezifundo zokucinga zabantu kunye nedatha ye-preclinical ibonisa ukuba i-ventral striatum ibandakanyeka kwimeko ye-aversive, kumava e-aversive, i-stimuli yentlungu, kunye nokulindela i-aversive stimuli.143-146 Ubungqina obunjalo. ikhomba indima yeendlela ze-mesolimbic dopamine ngaphaya kokusetyenzwa komvuzo, kwaye enye ebandakanya ngokubanzi inkuthazo kunye nokuqwalaselwa kwempendulo yokuziphatha ngexesha leziganeko ezinqabileyo (ezichaseneyo okanye ezinomdla). umvuzo, ukufunda, kunye nokulungelelanisa kunye nokuziphatha okujoliswe kuyo yi-amygdala, i-hippocampus, i-insula, kunye nemimandla ye-corticolimbic ehambelana nayo. ukuthathwa kwezigqibo, nakwiimpawu ezikhobokisayo zeziyobisi zokuxhatshazwa.147
IiNdlela zoxinzelelo eziBandakanywe ekuFumaneni ukuZilawula kweZiyobisi
Uphando luye lwavavanya ukuba ukonyuka okunxulumene noxinzelelo ekufumaneni ukuzilawula kweziyobisi kulamlwa yi-corticosterone (i-cortisol ebantwini). Iziphumo zibonisa ukuba ukukhutshwa kwe-corticosterone e-HPA kubalulekile ekufumaneni ukuzilawula kweziyobisi.131,153-155 Ulawulo lweCorticosterone lukwaququzelela iziphumo ze-psychomotor stimulant ye-cocaine kunye ne-morphine.156 Ngapha koko, abachasi be-GC receptor bafakwe kwi-VTA ethotyiweyo, ukunciphisa umsebenzi we-VTA. 157 ecebisa ukuba umsebenzi we-GC receptors kwi-VTA unokulamla iziphumo zokuziphatha ezixhomekeke kwi-dopamine. Iimpuku ngokucinywa kofuzo lwe-GR zibonisa ukuhla okuxhomekeke kwithamo kwinkuthazo ekuzilawuleni i-cocaine.158 Ezi datha zibonisa ukuba ukukhutshwa kwe-corticosterone enxulumene ne-HPA kungangenelela ngokuyinxenye ukonyuka kwe-dopamine okubonwa emva kolawulo lwechiza.
Nangona kwiiprimates ezingengomntu unxibelelwano phakathi kwe-cortisol, i-dopamine, kunye nokuzilawula kweziyobisi akukhange kuxelwe, kukho ubungqina bokuba uxinzelelo olunxulumene nokuthotyelwa kwentlalontle lunxulunyaniswa namanqanaba asezantsi e-D2 receptors kunye nolawulo oluphezulu lwe-cocaine.159 Ebantwini, ilungile. Izifundo ze-emission tomography (PET) zisebenzisa i- [11C] i-raclopride zibonisa ukuba ukuvezwa koxinzelelo olubukhali kwandisa ukukhutshwa kwe-dopamine kwi-ventral striatum (VS). Umzekelo, kuphononongo oluncinci lwesampulu, uPruessner kunye noogxa (2004)139 bafumanisa ukuba abantu abasempilweni abanokhathalelo lukamama olusezantsi kubomi bokuqala babonisa ukukhutshwa okukhulu kwe-dopamine kwi-ventral striatum ngexesha loxinzelelo olunzima lwengqondo xa kuthelekiswa nabo banembali ukhathalelo lukamama kubomi baselula. Ngaphaya koko, impendulo ye-cortisol ngexesha lomsebenzi woxinzelelo yadityaniswa kakhulu (r = .78) kwi-VS dopamine release. U-Oswald kunye noogxa (2005) 125 baphinde babonisa ukuba iimpendulo ze-amphetamine ezihambelana nomngeni "eziphezulu" kunye nokunyuka okuhambelanayo kwe-dopamine kwi-VS nganye yayinxulunyaniswa kakhulu neempendulo ze-cortisol ezenziwe yi-amphetamine. Ngoku kutshanje, iqela elifanayo liye labonisa ubudlelwane obubalulekileyo phakathi kwamanqanaba e-cortisol kunye nokukhululwa kwe-dopamine kwi-VS usebenzisa umsebenzi woxinzelelo lwengqondo. kumsebenzi we-VS okanye ukubopha i-dopamine kunye nomngcipheko wokuziphatha okukhobokisayo kuyafuneka ukuseka ngokuthe ngqo unxibelelwano phakathi koxinzelelo, i-mesolimbic dopamine, kunye nomngcipheko wokulutha.
Ubomi bokuqala kunye noxinzelelo olungapheliyo, iiNkqubo zeDopamine, kunye noLawulo lokuSelf-Administration
Kukho ubungqina obukhulayo obuvela kwizifundo zesayensi ezisisiseko zokuba uxinzelelo lobomi bokuqala kunye noxinzelelo olungapheliyo luchaphazela kakhulu iindlela ze-mesolimbic dopamine kwaye zidlala indima ekuzilawuleni kweziyobisi. Ukuboniswa okuphindaphindiweyo kunye nexesha elide lokuhlukana komama (MS) kwiimpuku ezisanda kuzalwa kuguqula kakhulu uphuhliso lweendlela zeCRF ezingundoqo.11 Ezi zilwanyana njengabantu abadala zibonisa i-HPA ebaxiweyo kunye neempendulo zokuziphatha kuxinzelelo. i-PVN, yandisa i-CRF-efana ne-immunoreactivity kwi-locus ceruleus (LC), kunye nokwandisa amanqanaba e-CRF receptor kwi-LC kunye ne-raphe nuclei.160,161 Izilwanyana ezikhulileyo zikwabonisa ukuncipha kwempendulo engathandekiyo kwi-glucocorticoids, i-11 kwaye olu tshintsho luhamba kunye nokunciphisa i-GC. ukubonakaliswa kwe-receptor kwi-hippocampus kunye ne-cortex yangaphambili.162 Ukunciphisa amanqanaba e-GABA ye-receptor kwimimandla ye-noradrenergic ye-cell cell kwi-LC kunye nokunciphisa i-benzodiazepine (CBZ) amanqanaba e-receptor kwi-LC kunye ne-amygdala nayo ixeliwe.11,163 Okubaluleke ngakumbi, iigundane ze-MS zibonisa kakhulu. Iimpendulo eziphakamileyo ze-DA kuxinzelelo olunzima kunye nokwanda koxinzelelo-olubangelwa kukuchaphazeleka kokuziphatha kunye nokuvuselelwa kokuziphatha okunamandla kulawulo lwengqondo. Iindawo zokuthutha i-DA ezithintekayo, kunye nokunciphisa iindawo zokubopha i-D164 receptor kunye namanqanaba e-mRNA kwigobolondo le-NAc.11,143,165-3 Ukongezelela, ukusilela okungapheliyo kwe-norepinephrine kubangela ukuba utshintsho olufana novelwano olunokuthi luhambelane nokuguqulwa kweendlela ze-DA-signaling.166
Uxinzelelo lobomi bokuqala kunye noxinzelelo olude kunye noluphindaphindiweyo luchaphazela kakubi uphuhliso lwe-prefrontal cortex, ummandla oxhomekeke kakhulu kumava okusingqongileyo ukuze ukhule. kunye neempendulo ezizimeleyo zoxinzelelo kunye nokulawula ezi mpendulo.171 Ngokomzekelo, izilonda ze-PFC ze-ventromedial ziphumela ekuphuculeni i-HPA kunye neempendulo ezizimeleyo zoxinzelelo. Amanqanaba aphezulu e-glucocorticoid receptors nawo afunyenwe kwi-PFC, kwaye unyango olungapheliyo lwe-GC lukhokelela ekuhlengahlengisweni okumangalisayo kwe-dendritic ye-PFC neurons efana naleyo ibonwa kwi-hippocampus. I-PFC kunye noxinzelelo olutshintshileyo lwe-DA kunye ne-serotonin (i-171-HT) i-terminals kuyo yonke i-PFC.172,173 ye-Social ukoyiswa kwengcinezelo iphinda iguqule impendulo evela kwi-PFC kwaye ifake isandla ekuziphatheni kweziyobisi. kunye nokuguqulwa kobungakanani kunye nomthamo wemimandla yangaphambili, ithalamic, kunye ne-cerebellar ehambelana nokuphathwa kakubi kunye nokuqaliswa kokulutha.5 Ngokudibeneyo, idatha eboniswe kweli candelo igxininisa ukubaluleka kwemiphumo yoxinzelelo kwimimandla ye-mesolimbic kunye ne-prefrontal ebandakanyeka kukuziphatha okunxulumene noxinzelelo. ulawulo.
Uxinzelelo, Ukuzithiba, kunye nokuba sesichengeni sokuba likhoboka
Uxinzelelo oluphezulu lweemvakalelo luhambelana nokulahlekelwa kolawulo kwiimpembelelo kunye nokungakwazi ukuthintela ukuziphatha okungafanelekanga kunye nokulibazisa ukukholisa. I-20,177,178 Kukwakho ubungqina obukhulayo bokuba ulutsha olukwishumi elivisayo olusemngciphekweni wokusetyenziswa gwenxa kweziyobisi oluye lwafumana uxinzelelo oluninzi oludweliswe kwiThebhile 17,28,179 lubonakala lubonisa ukuncipha kolawulo lweemvakalelo kunye nokuziphatha, kwaye ukuncipha kokuzithiba kunxulunyaniswa nomngcipheko wokusetyenziswa gwenxa kweziyobisi kunye. ezinye iindlela zokuziphatha ezingafanelekanga.1 Ulutsha olukwishumi elivisayo olusemngciphekweni wokusetyenziswa gwenxa kweziyobisi luyaziwa ngokuba lucuthe ukusebenza kakuhle, ukuziphatha okuphantsi kunye nolawulo lweemvakalelo, ukwenza izigqibo ezingalunganga, kunye namanqanaba aphezulu okuziphatha okutenxileyo kunye nokungabinamdla. ngokuthabatheka, ukwenza izigqibo, kunye nomngcipheko wokulutha, i-104,152,180,181 kwaye njengoko kuxoxiwe kumacandelo angaphambili, imimandla ethile yale ndlela, efana ne-VTA, NAc, PFC, kunye ne-amygdala, isesichengeni kakhulu kumqondiso onxulumene noxinzelelo kunye neplastiki ehambelana nokuqala- uxinzelelo lobomi kunye namava oxinzelelo olungapheliyo. Kuphononongo lokucinga lwe-PET lwakutsha nje, u-Oswald (24,152,182)184 uvavanye iziphumo zoxinzelelo olungapheliyo kunye nokunyanzeliswa kukukhutshwa kwe-amphetamine-induced striatal dopamine. Ezi ziphumo zibonise ukuba ukunyanzeliswa komgangatho ophezulu kwakunxulunyaniswa nokukhutshwa kwe-dopamine ye-VS. Nangona kunjalo, ezi ziphumo zatshintshwa yintsebenziswano ebalulekileyo kunye noxinzelelo lweziganeko zobomi obungapheliyo. Ngoxinzelelo oluphantsi ukuya koluphakathi, ukukhutshwa kwe-dopamine bekukukhulu kuphantsi kunezifundo ezingxamisekileyo, kodwa ngoxinzelelo oluphezulu, omabini amaqela abonisa ukukhutshwa okuphantsi kwe-DA. Ezi ziphumo zibonisa iziphumo ezibalulekileyo zoxinzelelo kunye nokunyanzeliswa kukuhanjiswa kwe-mesolimbic dopamine kwaye kuqaqambise inyani yokuba zombini ezi zinto kufuneka ziqwalaselwe ngononophelo ukuze kuqondwe ngokupheleleyo indima yoxinzelelo kunye nokungabinamdla kumngcipheko wokuba likhoboka.
Imodeli yeSchematic yeziphumo zoxinzelelo kwiziyobisi
Umzobo woku-1 ubonisa imodeli ecwangcisiweyo yeziphumo zoxinzelelo kumlutha. Iqaqambisa uvakalelo olunqamlezayo loxinzelelo kunye nokusetyenziswa gwenxa kweziyobisi kwiimpendulo ezithile zokuziphatha kunye ne-neurochemical kwaye ibonisa iindlela eziqhelekileyo ze-neurobiological apho zombini uxinzelelo kunye neziyobisi zokuxhatshazwa zisebenza. IKholam A idwelisa iindidi ezintathu zezinto ezinokuba sesichengeni: (1) izinto eziphuhlisayo/zomntu ngamnye ezifana nophuhliso lwangaphambili lomsebenzi olawulayo, iimvakalelo ezingalunganga, ukuziphatha/ukuzithiba, ukungashukumi, okanye ukuthatha umngcipheko, kunye nokutshintsha ubuntununtunu bokuqala kwiziphumo ezivuzayo zeziyobisi; (2) izinto ezinobungozi obunxulumene noxinzelelo ezifana neziganeko zobomi ezimbi kwangaphambili, ukwenzakala kunye namava okuphathwa kakubi kwabantwana, amava oxinzelelo olude kunye nolungapheliyo; kunye (3) neempembelelo zofuzo kunye nembali yentsapho ye-psychopathology kunye ne-addiction, ekungakhange kuxoxwe ngayo apha kodwa ibe nemiphumo ebalulekileyo yokunxibelelana kwingozi yokulutha kunye neemvakalelo kunye noxinzelelo lweempawu. kwiindlela ze-neurobiological ezibandakanyekayo kulawulo loxinzelelo kunye nokulawulwa kwengqondo kunye nokuziphatha (ikholamu B). Utshintsho oluthile lwe-synaptic kule mizila kumanqanaba eemolekyuli kunye neselula188 inika isiseko sendlela apho uxinzelelo kunye nezinto zomntu kunye nemfuza kwikholamu A isebenzisana nokwandisa umngcipheko wokuziphatha kakubi okumelelwe kwikholamu C. Umzekelo ucebisa ukuba amava oxinzelelo kwikholamu ubukho bezi zinto zisesichengeni zikhokelela kuxinzelelo lwe-maladaptive kunye neempendulo zokuzibamba ezinyusa umngcipheko wokuba likhoboka. Indlela ethile apho ukuphendula koxinzelelo lwe-maladaptive kwandisa lo mngcipheko kubandakanya ukungasebenzi kakuhle kwiisekethe zoxinzelelo lwengqondo, ngakumbi iinkqubo zeCRF kunye ne-NE, kunye nokusebenzisana kwazo kunye ne-mesocorticolimbicstriatal dopamine pathways kunye nokumodareyitha kwayo nge-glutamate kunye ne-GABA.194 Ngapha koko, ubungqina bamva nje bubonisa ukuba uxinzelelo iimolekyuli ezilawulayo, kuquka neuropeptides ezifana neuropeptide (NPY) endocannabinoids, kunye neuroactive steroids zidlala indima esengozini yokulutha.118,195-114,196,197
Umzobo 1(SIKHOYO)
Imodeli ecetyiweyo yeziphumo zoxinzelelo kumlutha, emele ukubonakaliswa komnqamlezo woxinzelelo kunye neziyobisi kwiimpendulo zokuziphatha kunye ne-neurochemical, elamlwa luxinzelelo kunye neendlela zomvuzo. UKholamu A udwelisa iindidi ezintathu zezinto ezinokuba sesichengeni: (1) izinto zophuhliso/zenqanaba lomntu ngamnye ezifana nophuhliso lwangaphambili lomsebenzi olawulayo, iimvakalelo ezingakhiyo, ukuziphatha/ukuzithiba, ukungxamiseka okanye ukuthatha umngcipheko, kunye nokutshintsha ubuntununtunu bokuqala kwiziphumo ezinomvuzo zamachiza; (2) izinto ezinobungozi obunxulumene noxinzelelo ezifana neziganeko zobomi ezimbi kwangaphambili, ukwenzakala kunye namava okuphathwa kakubi kwabantwana, amava oxinzelelo olude kunye nolungapheliyo; kunye (3) neempembelelo zofuzo kunye nembali yentsapho ye-psychopathology. Nganye kwezi zinto zichaphazela omnye nomnye ukuba zichaphazele kakhulu utshintsho kwiindlela ze-neurobiological ezibandakanyekayo kulawulo loxinzelelo kunye nokulawulwa kwengqondo kunye nokuziphatha (iKholamu B). Olo tshintsho luncinci ludibanisa iindlela apho uxinzelelo kunye nezinto zomntu kunye nemfuza kwikholamu A zinxibelelana ukwandisa umngcipheko wokuziphatha kakubi okuboniswa kwikholamu C xa umntu ejongene noxinzelelo okanye umngeni weemeko.
Ukusetyenziswa kweziyobisi kunye nokusetyenziswa kakubi kunye notshintsho kuxinzelelo kunye neendlela zomvuzo
Ukusetyenziswa kweziyobisi okuNgxamisekileyo kunye nokuNgapheliyo kunye noTshintsho kwiimpendulo zoxinzelelo
Ulawulo olubukhali lwezona ziyobisi zixhaphake kakubi ezinje ngotywala, inikotini, icocaine, iamphetamines, kunye nentsangu evuselela iindlela zomvuzo wobuchopho (inkqubo ye-mesocorticolimbic dopaminergic) ikwavula iindlela zoxinzelelo lwengqondo (CRF-HPA axis kunye ne-autonomic nervous system pathways) ngokunyuka I-plasma adrenocorticotropic hormone (ACTH) kunye ne-corticosterone, utshintsho kwizinga lentliziyo kunye noxinzelelo lwegazi, kunye neempendulo ze-skin conductance.204-217 Ngakolunye uhlangothi, ukuvezwa ngokukrakra kwi-opiates kunciphisa amanqanaba e-cortisol kubantu.218,219 Ukusetyenziswa rhoqo kunye nokungapheliyo kwezi ziyobisi nazo ezinxulumene nohlengahlengiso kwezi nkqubo zithe ngqo ngamachiza. Ngokomzekelo, utshintsho kwizinga lentliziyo kunye nokuhluka kwentliziyo (HRV) zichazwe ngokusetyenziswa rhoqo kunye nokungapheliyo kotywala. ye-morphine, i-nicotine, kunye ne-alcohol nayo ixeliwe.220-222 Le miphumo ngokuthe ngqo yeziyobisi zokusetyenziswa kakubi kumacandelo amakhulu empendulo yoxinzelelo lwe-physiological isekela ulwahlulo lwabo njengoxinzelelo lwe-pharmacological.
Amazwe okurhoxisa ngokukhawuleza ahambelana nokunyuka kwamanqanaba e-CRF kwi-CSF, i-plasma ACTH, i-cortisol, i-norepinephrine (NE), kunye namanqanaba e-epinephrine (EPI). impendulo kwimingeni ye-pharmacological and psychological in alcoholics and chronic smokes, ngelixa i-hyper-responsivity ye-HPA hormones ekuphenduleni i-metyrapone kuye kwabikwa kwi-opiate kunye ne-cocaine addicts.38,211,216,227-231 Ngapha koko, ukuhoxiswa kunye nokuyeka utywala obungapheliyo kukwanxulunyaniswa novelwano olutshintshileyo kunye iimpendulo ze-parasympathetic, i-232-236 kunye neempendulo ezitshintshileyo ze-noradrenergic kumngeni we-yohimbine ekuzikhwebuleni kwangaphambili kwi-cocaine nazo ziphawulwe.
Nangona ulawulo olubukhali lweziyobisi lunyusa i-mesolimbic dopamine, i-241 yokusetyenziswa rhoqo kunye nokungapheliyo kweziyobisi ezixhaphazayo kunye neendawo zokurhoxisa ngokukhawuleza zilawula iindlela ze-mesolimbic dopamine kunye nokuncipha kwe-basal kunye ne-dopamine evuselelweyo echazwe kwizifundo ezininzi zangaphambili. ukuguqula ngokumangalisayo iindlela ezingundoqo ze-noradrenergic kwi-ventral kunye ne-dorsal striatum, ezinye iindawo ze-fore-brain, kunye ne-ventromedial prefrontal cortex.242 Izifundo zokucinga ngengqondo yomntu zingqinela ezi datha zangaphambili, kunye nokunciphisa i-D251 receptors kunye nokuhanjiswa kwe-dopamine kwi-frontal kunye ne-ventral striatum. Imimandla enxilisayo kunye nabaxhaphazi be-cocaine ngexesha lokurhoxa kakhulu kunye nokurhoxa ixesha elide (ukuya kuthi ga kwiinyanga ezi-252,253-2) abaxhaphazi be-cocaine yabantu.3 Olu tshintsho luyafana neziphumo zoxinzelelo olude kunye noluphindaphindiweyo kwi-mesolimbic dopamine kunye nokusilela kwe-norepinephrine okuphawulwe kwicandelo langaphambili4 kwaye iphakamisa umbuzo wokuba ngaba iziphumo zeziyobisi ezingapheliyo kwi-extrahypothalamic CRF, noradrenergic, okanye iinkqubo zeglucocorticoid zinokuncinci. Lungisa ngokuyinxenye olu tshintsho lunxulumene ne-dopamine kwindlela ye-corticostriatal limbic dopamine.
Kwelinye icala, ukuba sesichengeni ngokuqatha, rhoqo, nangokungapheliyo kumachiza kukhokelela “ekuchukumiseni” okanye ekuphuculweni kokuziphatha kunye nokusabela kwe-neurochemical kumachiza nakuxinzelelo. Ukuguqulwa kwe-Synaptic kwi-VTA, i-NAc, kunye ne-PFC ephakathi emodareyithwe yimiphumo ye-glutamate kwi-dopamine neurons kunye ne-CRF kunye nemiphumo ye-noradrenergic kwi-DA kunye neendlela ezingezizo ze-DA zifaka isandla ekuziphatheni koxinzelelo kunye neziyobisi zokuxhatshazwa.210,259-262 Ukongeza, amanqanaba aphezulu Ubuchopho obufunyenwe kwi-neurotrophic factor (BDNF) kwimimandla ye-mesolimbic dopamine iye yanxulunyaniswa nokunyuka kokufuna iziyobisi ngexesha lokuziyeka ekusebenziseni iziyobisi ezingapheliyo. ngokukodwa i-VTA, i-NAc, kunye ne-amygdala, kwaye olo tshintsho lunegalelo ekufuneni iziyobisi ezinyanzelekileyo.263,264 Ngaloo ndlela, kukho ukuguqulwa okubalulekileyo kwe-physiological, neurochemical, kunye nokuziphatha kuxinzelelo kunye neendlela ze-dopaminergic ezinxulumene nokusetyenziswa kweziyobisi ezingapheliyo, ezinokuthi zithintele ukunqwenela kunye nokunyanzeliswa. ukufuna, ukugcinwa kokusetyenziswa kweziyobisi, kunye nomngcipheko wokubuyela umva. Akucaci ngokupheleleyo ukuba olu tshintsho luhlala ixesha elingakanani okanye ubungakanani bokubuyisela okanye ukuqhelaniswa kwezi ndlela kunye neempendulo kwiimpendulo ezisebenzayo ezinxulumeneyo.
Iimpendulo ezitshintshileyo zoxinzelelo kunye nokuKhanga kunye nokuSetyenziswa gwenxa kweziyobisi okuNgapheliyo
Iimpawu zeklinikhi zokucaphuka, ukuxhalaba, ukuxinezeleka ngokweemvakalelo, iingxaki zokulala, i-dysphoria, isimilo esindlongo-ndlongo, kunye nokunqwenela iziyobisi zixhaphakile ngexesha lokuyeka kwangoko utywala, i-cocaine, i-opiates, inikotini, kunye nentsangu. kulandela ukurhoxa, okuhambelana notshintsho kuxinzelelo kunye neendlela ze-dopamine.30,266 Ubunzima bezi mpawu buye banxulunyaniswa neziphumo zonyango, ngokuxhomekeka okukhulu kunye nokuqina kokuziyeka uqikelelo lweziphumo zonyango ezibi.269-37,197,250,270 Ukufuna iziyobisi okanye "ukufuna" kweziyobisi. ingqiqo yahluke kwezinye ixhala kunye neempawu ezichaphazela kakubi njengoko zivela "kumnqweno" okanye umnqweno we-hedonic stimulus. Nangona kunjalo, ngokusetyenziswa kweziyobisi ezingapheliyo, eli gama linxulunyaniswa nesidingo somzimba, indlala, kunye nenjongo eyomeleleyo yokufuna into efunwayo, ngaloo ndlela imele imiba enyanzelekileyo yokunqwenela kunye nokufuna iziyobisi ezichongiweyo ngabaguli abakhobokileyo.271-274 , ukulangazelela kunye nokufuna okunyanzelekileyo kubonakaliswa ngamandla kumxholo wokuvezwa koxinzelelo, iindlela ezinxulumene neziyobisi, kunye neziyobisi ngokwazo kwaye zinokuba sisiqalo esinamandla sokuphinda sibuyele.274-277 Iimodeli ezininzi zamva nje zokulutha zibonise umbono wokuba oku kwandisa umnqweno okanye ukufuna. ichiza kukubonakaliswa kokuziphatha kweemolekyuli kunye neenguqu zeselula kuxinzelelo kunye neendlela ze-dopamine ezixoxwe kwicandelo elidlulileyo. Ngenene enye inkxaso yolu luvo iphuma kwilabhoratri kunye nezifundo zokucinga ezishwankathelweyo ngezantsi.
Kwilabhoratri yam, siye savavanya iziphumo zoxinzelelo kunye neendlela ezinxulumene neziyobisi ekunqweneleni iziyobisi kwiziselo ezinxilisayo, abantu abaxhomekeke kwi-cocaine, kunye nabantu abanyangwa nge-naltrexone, abaxhomekeke kwi-opiate ukuze baphile. Ukukhanga iziyobisi kunye neempendulo zoxinzelelo zavavanywa kunyango, abantu abangenayo, abantu abanomlutha abaye bavezwa kwiimeko ezixinzelelekileyo kunye nezingenaxinzelelo zeziyobisi kunye neemeko zokuphumla ezingathathi hlangothi, kusetyenziswa iinkqubo zemifanekiso ekhokelwa ngumntu njengendlela yokungeniswa.282 Iziphumo zethu zokuqala zibonise ukuba kumlutha. abantu ngabanye, imifanekiso yoxinzelelo ibangele iimvakalelo ezininzi zoloyiko, usizi, nomsindo xa kuthelekiswa noxinzelelo lokuthetha esidlangalaleni, nto leyo ebangele ukwanda koloyiko kodwa kungekho msindo okanye lusizi. Ukongeza, imifanekiso yoxinzelelo lomntu yavelisa ukwanda okukhulu kwinkanuko ye-cocaine, ngelixa ukuthetha esidlangalaleni akuzange kwenzeke.283-285 Ukonyuka okubonakalayo kwisantya sentliziyo, i-cortisol yamathe, ukunqwenela iziyobisi, kunye nokuxhalaba kuye kwabonwa kunye nokuvezwa kwemifanekiso kuxinzelelo kunye noxinzelelo lweziyobisi. xa kuthelekiswa nezinto zokuphumla ezingathathi hlangothi kubantu abaxhomekeke kwi-cocaine.285 Kutshanje, siye sabonisa ukuba uxinzelelo kunye notywala / iziyobisi ezinxulumene neziyobisi zinyusa inkanuko, ukuxhalaba, iimvakalelo ezingathandekiyo, kunye neempendulo zomzimba kwiziselo ezinxilisayo kunye nakwi-naltrexone-treat, opiate. -abantu abasebenzisa iziyobisi.
Kuvavanyo olubanzi ngakumbi lwempendulo yoxinzelelo lwebhayoloji kubantu abasandul 'ukuyeka i-cocaine-amakhoboka e-cocaine, siye sanika ingxelo yokuba ukuvezwa okufutshane kuxinzelelo kunye neziyobisi xa kuthelekiswa nokuphumla okungathathi hlangothi kusebenze i-axis ye-HPA (kunye nokonyuka kwe-ACTH, i-cortisol, kunye namanqanaba eprolactin. ) kunye neenkqubo ze-sympthoadrenomedullary, njengoko kulinganiswe ngamanqanaba e-plasma norepinephrine kunye ne-epinephrine.282 Ngaphezu koko, sifumene ubungqina obuncinane bokubuyisela okanye ukubuyela kwisiseko kwi-ACTH, NE, kunye namanqanaba e-EPI nangaphezulu kwe-1 h emva kokubonakaliswa kwemifanekiso ye-5-min. . Ezi ziphumo zongezwa ukuze kuthelekiswe ngokuthe ngqo abantu abaxhomekeke kwi-cocaine kunye neqela elihambelana nenani labantu abasela utywala ekuhlaleni, kusetyenziswa umntu ngamnye olungelelaniswe noxinzelelo lweemvakalelo kunye nemifanekiso enxulumene neziyobisi / utywala xa kuthelekiswa nemifanekiso engathathi hlangothi. Iziphumo zibonise ukuba izigulana ze-cocaine zibonise uvakalelo oluphuculweyo kuxinzelelo lweemvakalelo kunye nokuvuswa komzimba kunye namanqanaba aphezulu okunqwenela iziyobisi kuzo zombini uxinzelelo kunye nokuvezwa kweziyobisi xa kuthelekiswa nolawulo. Iziselo ezinxilisayo ezibuyelayo kwiiveki ezi-291 zokuziyeka zibonise amanqanaba amakhulu esantya sentliziyo esisiseko kunye namanqanaba e-salivary cortisol xa kuthelekiswa nokulawula abasela. Phezu koxinzelelo kunye nokuvezwa kwe-alcohol-cue exposure, babonisa uxinzelelo oluqhubekayo, ukunqwenela utywala, kunye neempendulo zoxinzelelo lwegazi, kodwa izinga lentliziyo elicinezelweyo kunye nempendulo ye-cortisol xa kuthelekiswa nolawulo. ukuba sesichengeni seziyobisi, ngelixa abaselayo baxela amanqanaba asezantsi okuchaphazeleka okungalunganga kunye nokuxhalaba kunye nokuvezwa kotywala. Ezi datha zibonelela ngobungqina obuthe ngqo bokunqwenela iziyobisi eziphezulu kunye neempendulo ze-hedonic ezitshintshileyo kuzo zombini uxinzelelo kunye neziyobisi kubantu abanomlutha xa kuthelekiswa nabasela bentlalontle (bona umfanekiso 4). Bakwabonisa ukuba utshintsho kwiimpendulo zoxinzelelo lwe-physiological lunxulunyaniswa namanqanaba aphezulu oxinzelelo-olunyanzeliswayo kunye ne-cue-induced craving and distress states. Ubume botshintsho luphawulwa kuxinzelelo lweemvakalelo okwandisiweyo, ukunyuka kwenkanuko, ukuguqulwa kweempendulo ezisisiseko, kunye neempendulo ezingacacanga okanye ezicinezelekileyo ngokwasemzimbeni kubantu abangamakhoboka otywala xa kuthelekiswa nabasela utywala ekuhlaleni.
Umzobo 2 (AKUKHOYO)
Iimpazamo ezithetha kunye neziqhelekileyo zokunqwenela okuphezulu kunye noxinzelelo ngexesha lokuvezwa kuxinzelelo, iimpawu zeziyobisi, kunye neemeko zemifanekiso engathathi hlangothi. (A) Ukuthanda okuphezulu kuphezulu kakhulu kwiziselo ezinxilisayo kunye nezigulana ze-cocaine xa kuthelekiswa nabasela ekuhlaleni (P <0.0001). (B) Umgangatho wokuxhalaba ophakamileyo uphezulu kakhulu kwiziselo ezinxilisayo kunye nezigulana ze-cocaine xa kuthelekiswa nabasela ekuhlaleni (P <0.001). (Iinkcukacha-manani zinikwe kwiFox et al.291 kunye noSinha et al.239)
Izifundo ezininzi zikwavavanye imimandla yobuchopho enxulumene nokunqwenela kubantu abakhobokileyo. Ukuvezwa kwiimpawu zeziyobisi ezaziwa ngokunyusa ukunqwenela kwandisa umsebenzi kwi-amygdala kunye nemimandla ye-cortex yangaphambili, i-292-294 kunye nokwahlukana ngokwesini kumsebenzi we-amygdala kunye nempendulo ye-cortex yangaphambili kubantu abaxhomekeke kwi-cocaine. i-opiates iphinda isebenze imimandla ye-prefrontal cortex, i-amygdala, i-hippocampus, i-insula, kunye ne-VTA (jonga i-Ref. 295,296). Njengoko uxinzelelo lukwanyusa ukunqwenela iziyobisi, siye savavanya ukusebenza kwengqondo ngexesha loxinzelelo kunye nemifanekiso engathathi hlangothi kuphononongo olusebenzayo lwemagnethi resonance imaging (fMRI). Nangona ulawulo olusempilweni kunye nabantu abaxhomekeke kwi-cocaine babonise amanqanaba afanayo oxinzelelo kunye notshintsho lwepulse ngexesha lokuvezwa koxinzelelo, ukuphendula kwengqondo kuxinzelelo lweemvakalelo kwimimandla yeparalimbic efana ne-anterior cingulate cortex, ihippocampus, kunye nemimandla yeparahippocampal yayinkulu kulawulo olusempilweni ngexesha loxinzelelo, ngelixa icocaine. Izigulana zibonise ukungabikho okumangalisayo kolu hlaselo.297 Ngokwahlukileyo koko, abaguli be-cocaine baye banyusa umsebenzi kwingingqi ye-caudate kunye ne-dorsal striatum ngexesha loxinzelelo olwalunxulunyaniswa kakhulu noxinzelelo-olubangela umnqweno we-cocaine.
Izifundo zamva nje ze-PET zikwabonise ulungelelwaniso olubalulekileyo phakathi kwe-dorsal striatum kunye ne-drug cue-induced cocaine craving.299,300 Ezi ziphumo ziyahambelana nezifundo zokucinga kunye nezigulana ezinxilisayo ezibonisa ukonyuka kobudlelwane phakathi kwemimandla ye-dorsal striatum kunye nokukhanukela kotywala ekuphenduleni ukunikezelwa kwento enxulumene notywala. stimuli.301,302 Ukusebenzisa i-PET imaging kunye nezinxila kunye nezigulane ze-cocaine, uphando lubonise ubudlelwane obubalulekileyo phakathi kwe-dopamine D2 receptor ebophayo kwi-VS kunye nokukhanga kweziyobisi kunye nokukhuthaza ukuzilawula. imisebenzi yesigqeba, kubandakanywa nokulawulwa kwempembelelo, ukwenza izigqibo, kunye nokuseta ukutshintshwa, kubonise ukusilela komsebenzi olawulayo kunye neempendulo ze-hypofrontal kubantu abanomlutha xa kuthelekiswa namavolontiya okulawula.124,303,304-305 Ngokudibeneyo, ezi ziphumo zibonisa ukuba ukwanda koxinzelelo kunye nokukhanga okubangelwa yi-cue kunye nokunyanzeliswa kweziyobisi- Ukufuna amazwe kubantu abakhobokileyo kunxulunyaniswa nomsebenzi omkhulu kwi-striatum, kodwa wehla umsebenzi kwimimandla ethile ye-cingulate kunye ne-prefrontal cortex kunye nemimandla ehambelana nayo ebandakanyekayo ekulawuleni iimpembelelo kunye neemvakalelo.
UkuBuyiselwa koxinzelelo-olunyanzelwayo lokuFumana iziyobisi kunye nokuBuyisela kwakhona
Ngelixa uninzi lweendlela zonyango olusebenzayo kunye nonyango lwezonyango kunyango lokulutha lukhona, kuyaziwa ukuba amazinga okuphinda abuyele ekukhotyokisweni ahlala ephezulu.30,313,314 Ukutyhileka kuxinzelelo, isivuseleli esinxulumene neziyobisi, kunye neziyobisi ngokwazo zibuyisela isimilo sokufuna iziyobisi kwizilwanyana kwaye siphinde siphinde sibuyele. Ukuba sesichengeni kubantu abakhobokileyo.274,315–317 Ulwazi olunjalo lugxininisa imfuneko yoqwalaselo oluthe ngqo ekuchaphazelekeni okungapheliyo njengenjongo kuphuhliso lonyango.
Kwiminyaka elishumi edlulileyo, inani elikhulu lophononongo lwangaphambili lubonise ukuba ingqondo yeCRF, i-noradrenergic, kunye ne-glutamatergic pathways inegalelo ekubuyiselweni ekufuneni ichiza.86,316-320 Neuroadaptations ezinxulumene nokusetyenziswa kweziyobisi ezingapheliyo ziquka ingqondo egqithisileyo yeCRF kunye neendlela zeglutamatergic, ezitshintshileyo iimpendulo ezizimeleyo, kunye neenkqubo ezingasebenziyo ze-dopamine kunye ne-GABA, kwaye olu tshintsho lunokuhamba kunye namazwe aphezulu okunqwenela kunye nokuphinda kuhlawulwe ukuchaphazeleka okuhambelana nobume obungapheliyo bokulutha. I-118,196,197,274,313,321-adrenergic agonists, kwaye kutsha nje, ii-glutamatergic agents zibalulekile ekunciphiseni uxinzelelo-olubangelwa ukufuna kwizilwanyana zaselabhoratri ezinomlutha (bona2-316,317,322). Ezi datha ziyahambelana neziphumo zomntu eziphononongiweyo kwicandelo langaphambili elibonisa ukuba utshintsho kuxinzelelo kunye neendlela ze-dopaminergic zihamba noxinzelelo oluphezulu kunye nokunqwenela amazwe kunye neempendulo ezifipheleyo zomzimba kunye ne-neural ezibalulekileyo kulawulo loxinzelelo, ukunqwenela, kunye nolawulo lwempembelelo.
Uphando lwabantu luye lwaqala ukuchonga iimpawu zoxinzelelo kunye nomnqweno wokufuna ukuxela kwangaphambili iziphumo zokubuyela kwakhona. Ukuqonda ngokupheleleyo ukuba ukonyuka koxinzelelo kunye nemeko yokunqwenela iziyobisi kuqikelelo lokuphinda ubuyele, silandele unyango lwe-cocaine- kunye nabantu abaxhomekeke etywaleni kwizifundo zethu ezichazwe kumacandelo angaphambili emva kokukhutshwa kunyango lweentsuku ezingama-90 ukuvavanya iziphumo zokubuyela kwakhona. . Kwiqela le-cocaine, sifumene ukuba uxinzelelo lwe-cocaine olunqwenela kwilabhoratri yaxela kwangaphambili ixesha lokuphinda i-cocaine. Ngelixa iimpendulo ezibangelwa uxinzelelo lwe-ACTH kunye neempendulo ze-cortisol zingadityaniswanga nexesha lokubuyela umva, ezi mpendulo zaziqikelelwa ngezixa ze-cocaine ezisetyenzisiweyo ngexesha lokulandelwa. Ulungelelwaniso phakathi koxinzelelo kunye neziyobisi-okubangelwa ukunqwenela iziyobisi kunye noxinzelelo kunye neempendulo ze-HPA ezenziwe ngeziyobisi. Ezi datha zibonisa ukuba ubuncinci kwimeko yokuxhomekeka kwe-cocaine, uxinzelelo kunye noxinzelelo olubangelwa yiziyobisi luvelisa imeko efanayo yokufuna iziyobisi ehambelana nokuba sesichengeni sokuphinda. Kwiizidakwa, isimo sengqondo esibi, uxinzelelo olubangelwa uxinzelelo lotywala, kunye nokuxinzezeleka koxinzelelo kunye neempendulo ze-cortisol ezibangelwa yi-cue-induced cortisol ziye zadibaniswa neziphumo zokubuyela kotywala. kunye neempendulo zoxinzelelo lwegazi kuxinzelelo kodwa ukunyuka kwe-nicotine ukurhoxiswa kunye namanqaku okunqwenela, kwaye ezi mpendulo zaziqikelele iziphumo zokuphinda zibuyele kwi-nicotine. Uxinzelelo kunye nenkuthazo enyanzelekileyo yeziyobisi (umnqweno) kunye neempendulo ezingalunganga zolawulo loxinzelelo (ingxelo etshintshiweyo yeglucocorticoid okanye ukonyuka kwe-noradrenergic arousal) kukhokelela ekuchaphazelekeni okuphuculweyo kokuphinda umlutha.
Iziphumo ezivela kwisiseko sesayensi kunye nelebhu yabantu kunye neziphumo zeklinikhi zichonga iithagethi ezininzi zonyango lwe-pharmacological ukujongana noxinzelelo-olunyanzelwa ukubuyiswa kweziyobisi kunye nokuba sengozini yokubuyela kwakhona. Idatha esisiseko yesayensi ibonisa ukuba abachasi beCRF, i-alpha-2 adrenergic agonists, kunye neearhente zeglutamatergic zinokuthembisa ekujonganeni nokubuyela umva okunxulumene noxinzelelo. Izifundo zaselabhoratri zabantu ziyafuneka eziya kuhlola ezi arhente ukuvavanya isithembiso sazo malunga nabamakishi abaphakathi bokungabinako ukuphinda babuyele kuxinzelelo olunxulumene noxinzelelo. Uphononongo olunjalo luya kujolisa uxinzelelo- kunye ne-cue-induced drug craving, ixhala elinxulumene nomnqweno, imilinganiselo ye-HPA, kunye nesantya sentliziyo okanye ukuguquguquka kwentliziyo kunye neempendulo kwimimandla ethile yengqondo.297 Ngokomzekelo, kwi-laboratory yokuqala kunye neziphumo zokufunda zeklinikhi, siye sabonisa ukuba i-lofexidine, i-agonist ye-alpha-2 ye-adrenergic, iyancipha kakhulu i-opiate ebangelwa uxinzelelo kunye nokunyanzeliswa komsindo, ngelixa iphinda iphucule iziphumo zokuphindaphinda i-opiate kwi-naltrexone ephathwayo, abantu abaxhomekeke kwi-opiate.330 Ngokufanayo, izicwangciso zokuziphatha ezinciphisa i-opiate. ukuxhalaba kunye noxinzelelo olunxulumene nokunqwenela iziyobisi kunye nokulungelelanisa iimpendulo zoxinzelelo ukuze kube nokuphendula okuguquguqukayo kwiimeko ezinomngeni omkhulu kunokuba luncedo ekunciphiseni iziphumo zoxinzelelo ekufuneni iziyobisi kunye nokubuyela umva. Ngokomzekelo, ukucutha uxinzelelo olusekelwe kwingqondo (MBSR) lusebenza kakuhle ekunciphiseni ukuphindaphinda ukudakumba okukhulu, kwaye ukulungelelaniswa kwezi zicwangciso kunokuba luncedo ukujongana nomngcipheko wokuphinda ube likhoboka.274
Isishwankathelo kunye nemiyalelo yexesha elizayo
Olu phononongo lujolise kubungqina obuninzi obuvela kwizifundo zangaphambi kweklinikhi, zeklinikhi, kunye nezifundo zabantu ukuba iimeko ezinoxinzelelo kakhulu kunye noxinzelelo olungapheliyo zonyusa ukuba sesichengeni somlutha, oko kukuthi, zombini umngcipheko wokuba likhoboka kunye nomngcipheko wokuphinda ubuyele. Iindidi zoxinzelelo ezandisa umngcipheko wokulutha zichongiwe kwiThebhile 1. Abacinezeli bavame ukuba neemvakalelo eziphezulu, iziganeko eziphazamisayo ezingalawulekiyo kunye nezingalindelekanga kubantwana nakubantu abadala. Imixholo isusela kwilahleko, ubundlobongela, nobundlongo-ndlongo ukuya kwinkxaso engekho mgangathweni, ungquzulwano phakathi kwabantu, ukuba likheswa, kunye nokwenzakala. Kukwakho nobungqina bobudlelwane obuxhomekeke kwithamo phakathi kobunzima obuqokelelweyo kunye nomngcipheko wokulutha-okukhona inani elikhulu lezinto zoxinzelelo umntu atyhileka kuzo, kokukhona umngcipheko wokuba likhoboka. Izixinzelelo ezinxulumene nomsebenzi zinenkxaso ebuthathaka, kodwa izinto eziguquguqukayo zomntu ngamnye ezifana nophawu olubi lweemvakalelo kunye nokungazithibi kakuhle (okunokwenzeka kufana nomsebenzi ophantsi wolawulo) zibonakala zinegalelo elikhethekileyo kumngcipheko wokuba likhoboka. Ukuvezwa koxinzelelo olunjalo kwasekuqaleni kobomi kunye nokuqokelelana koxinzelelo (ixesha elide) kubangela i-neuroendocrine, i-physiological, isimilo, kunye notshintsho oluphathekayo oluhlala luhlala ixesha elide kwaye luchaphazela kakubi uphuhliso lweenkqubo zobuchopho ezibandakanyekayo ekufundeni, ekukhuthazeni, nakwindlela yokuziphatha ehambelana noxinzelelo. . Uphando olujongene ngqo noxinzelelo olunxulumene notshintsho lwe-neurobiological kunye nonxulumano lwabo neziphumo zokuziphatha lufuneka kakhulu. Ubungqina bokucacisa igalelo loxinzelelo kutshintsho kwimisebenzi ye-mesolimbic dopamine kunye nokunxulumana nokusetyenziswa kweziyobisi nako kuyafuneka. Umzobo we-1 ubonisa imodeli yeskimu yemibutho exhaswe kuphando, kunye nezithuba eziseleyo.
Uphononongo lobungqina obubonisa iziphumo zokusetyenziswa kweziyobisi kunye nokuxhatshazwa kwiimpendulo zoxinzelelo kunye nokuhanjiswa kwe-dopamine kubonisiwe, kunye neempendulo ezitshintshileyo ngokweemvakalelo kunye nenkuthazo ezinxulumene nokunqwenela kunye nokubuyela ekusebenziseni iziyobisi. Ngelixa ukusetyenziswa kakubi kweziyobisi kukhokelela kutshintsho kuxinzelelo kunye neendlela ze-dopaminergic ezibandakanyeka kwinkuthazo, ukuzilawula, kunye neenkqubo eziguqukayo eziyimfuneko ukuze uphile, ubungqina bokuba olo tshintsho luyakwandisa ukufuna iziyobisi okanye ukunqwenela kunye nokuziphatha kokusetyenziswa kweziyobisi buyanqongophala. Umzekelo, uphononongo lokuba ukuvezwa kwangaphambili kweziyobisi ezingekho mthethweni kunye nezingekho mthethweni kuyaluguqula unxulumano phakathi koxinzelelo kunye nokuzilawula kweziyobisi kunqabile. Ngelixa kukho i-neuroadaptations ethile kumvuzo kunye nemimandla ehambelana nayo, kukwabalulekile ukuvavanya ukuba loluphi olu tshintsho lubandakanyekayo ekwandiseni ukuthathwa kweziyobisi kunye nenkxaso yeenkqubo zokulutha ezinjengokulahleka kolawulo, ukuzingisa komnqweno, kunye nokunyuka kokuzilawula kweziyobisi. Njengoko uxinzelelo lukwanyusa umngcipheko weemvakalelo kunye nokuphazamiseka kokuxhalaba okudityaniswa kakhulu nokulutha, kubalulekile ukujonga ukuba ngaba kukho izinto ezithile ezinxulumene noxinzelelo ezinegalelo kumngcipheko wokuphazamiseka kweemvakalelo kunye noxinzelelo kunye nomngcipheko wokuba likhoboka. Oko kukuthi, zeziphi izinto zokomelela ezikhusela iseti yesigulo kodwa zisesichengeni kwenye. Ukuphononongwa konxibelelwano lwemfuza nokusingqongileyo kunokuba luncedo ngakumbi ekuphenduleni imibuzo enjalo.
Uphononongo lophononongo lwakutsha nje malunga nokubuyiselwa okubangelwa luxinzelelo ekufuneni iziyobisi, ukunqwenela iziyobisi, kunye nokuba sesichengeni sokuphinda kunikezelwe. Iimpembelelo zeklinikhi ziquka ukuphuhliswa kweenkqubo zovavanyo olutsha kunye namanqaku aya kuba luncedo ekuchongeni abo basengozini ethile yokuxhatshazwa kwengcinezelo kunye nokuvavanya i-novel pharmacological therapies ezijolise kwikhonkco phakathi koxinzelelo kunye nomngcipheko wokubuyela kwakhona. Njengoko kubonisiwe kuMfanekiso 2, abantu abakhobokileyo babonisa uvakalelo olongeziweyo lokunqwenela kunye nokuxhalaba okukhulu kuxinzelelo- kunye neemeko ezinxulumene neziyobisi, kodwa ukuba ezo mpendulo zitshintshiweyo zibonisa utshintsho ngenxa yokusetyenziswa kweziyobisi ezingapheliyo okanye iimeko zoxinzelelo olungapheliyo kufuneka ziphinde zihlolwe. Uphando malunga neendlela apho uxinzelelo olungapheliyo kunye nokusetyenziswa kweziyobisi kuguqula imisebenzi yesigqeba esibandakanyekayo kwiimpendulo zokuziphatha eziguqukayo ezifunekayo. Unyango olusebenzayo lokuziphatha lujolise ekuphuculeni impendulo yokumelana. Nangona kunjalo, ukubonakaliswa koxinzelelo kunye noxinzelelo olungapheliyo kunciphisa uxinzelelo kunye neendlela zokujongana, kwaye ke ngoko unyango olujolise ekomelezeni ukujamelana noxinzelelo lusenokungafaneleki kwabo banemingcipheko enxulumene noxinzelelo. Ukuphuhliswa kongenelelo olutsha olujolise ekuzithibeni, ngakumbi kumxholo woxinzelelo olufunekayo. Uphando olucwangcisiweyo kule mibuzo luya kukhokelela ekuqondeni ngakumbi ukuba uxinzelelo luhambelana njani nokubuyela kwakhona. Ngaphaya koko, olo phando lunokubaluleka ekuphuhliseni iithagethi zonyango olutsha ukuze kuncitshiswe ukubuyela umva, kokubini kwindawo yophuhliso lwamayeza kunye nasekuphuhliseni unyango lokuziphatha olujolise ngokukodwa kwiziphumo zoxinzelelo ekuqhubekeni nokusetyenziswa kweziyobisi kunye nokubuyela kumlutha.
Imibulelo
Ukulungiswa kolu hlaziyo kuxhaswe ngezibonelelo ezivela kwiiNational Institutes of Health, i-P50-DA165556, i-R01-AA13892, i-R01-DA18219, kunye ne-U01-RR24925.
Imihlathi
Iimbambano Zomdla
Umbhali akabhengeza nakuphi na ukungqubana komdla.
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