Ngaba ikhonkco phakathi kokukhotyokiswa kweziyobisi ebudaleni kunye nokusetyenziswa kweziyobisi ekufikiseni kunokubangela ukufiphala kwemida phakathi kweenkqubo zenkuthazo kunye ne-hedonic? (2019)

UkuRehabil ukuSetyenziswa gadalala. I-2019; I-10: 33-46.

Ishicilelwe kwi-intanethi 2019 Jul 12. ikhonkco: 10.2147/SAR.S202996

PMCID: PMC6634303

PMID: 31372088

Fiona Kehinde,1 Opeoluwa Oduyeye,2 kwaye URaihan Mohammed1

Abstract

Kukho imvumelwano ebanzi yokuba uphuhliso lweziyobisi ebudaleni lunxibelelene ngokusondeleyo nokuqaliswa kokusetyenziswa kweziyobisi ebusheni. Nangona kunjalo, ubudlelwane phakathi kokuvezwa kweziyobisi ngexesha lokufikisa kunye nokuba sesichengeni okulandelayo ekubeni likhoboka ayikaqondwa ngokupheleleyo. Olu phononongo luya kuqala ukusebenzisa ubungqina obuvela kwizifundo zabantu abadala malunga nomvuzo kunye nokulutha ukuze unike indawo yesalathiso esexesheni yesiqhelo somvuzo-umjikelezo kunye notshintsho olubi oluthi lwenzeka kamva kubukhoboka. Oku kuya kuthi ke kuthelekiswe nobungqina bangoku obuvela kwizifundo zokufikisa kumjikelezo womvuzo. Ukufana phakathi kweenkqubo zomvuzo ezilawula iimpawu zokuziphatha ebusheni kunye neprofayili yomvuzo kumlutha wabantu abadala kunokunceda ukucacisa ukuba kutheni umngcipheko wokukhula umlutha wonyuka xa ukusetyenziswa kweziyobisi kuqaliswa ebusheni. Sithetha ukuba ubudala bokuqala bungumngcipheko omkhulu ekuphuhliseni ukusetyenziswa kweziyobisi ngenxa yokuphazamiseka kwemida phakathi kweenkqubo zokukhuthaza kunye ne-hedonic, eyenzeka ngexesha lokufikisa. Ukuqonda okunzulu kweenkqubo ezilamla oku kungacacanga kunokuvula iindlela ezintsha zothintelo kunye nonyango lwabantu abadala abangamakhoboka eziyobisi.

Internet: umlutha, i-dopamine, impulsive, isinyanzelo, i-opiate

intshayelelo

E-US, i-75% yabafundi besikolo samabanga aphakamileyo baye babika ukuba basebenzisa iziyobisi ezingekho mthethweni, basele utywala okanye batshaye icuba. Ngenxa yokuba izakhiwo zengqondo ngexesha lokufikisa ziyiplastiki ephezulu, eli nani liphezulu ngendlela eyothusayo. Ukufikisa lixesha lokukhula ekuthi (ubukhulu becala) kuvunyelwene ukuqala ngokufikisa kwiminyaka eyi-10 kwaye iphele xa ukuvuthwa ngokwesondo kunye nomzimba kugqityiwe malunga nobudala be-20., Ngokwendlela yokuziphatha, ukufikisa kuphawulwa lutshintsho olukhawulezileyo ekusebenzeni kwentlalo oluziswa kukukhula kokungafuneki, uvakalelo lokuvuza kunye nokufuna imvakalelo., Ukuvezwa kweziyobisi ngeli xesha lophuhliso olunovakalelo kunokukhokelela kutshintsho oluladaptive kwizakhiwo zobuchopho eziqhubeka nokuba ngumntu omdala kwaye zonyuse umngcipheko wokukhula kokuphazamiseka kwengqondo okufana nokuba likhoboka.

Umlutha uchazwa njengepatheni ye-maladaptive yokusetyenziswa kweziyobisi eqhubekayo nangona imiphumo emibi. Ibonakaliswa ngumnqweno onamandla wokuthatha iziyobisi, ubunzima bokulawula ukusetyenziswa kweziyobisi kunye nokuxhomekeka komzimba okanye kwengqondo. Ngenxa yokuba, ngokomndilili, mnye kuphela abasebenzisi abathandathu be-cocaine abakhula ngokuxhomekeka, kuyabonakala ukuba abanye abantu basesichengeni sokukhotyokiswa ziziyobisi kunabanye. Lo mngcipheko womntu ufunyenwe unxulunyaniswa nobukho okanye ukungabikho kweempawu zokuziphatha ezinjengokufuna imvakalelo, eqikelela ukuqaliswa kokusetyenziswa kwecocaine, impulsivity, eqikelela ukuba ufuna i-cocaine kunye nexhala, eliqikelela ukwanda kokusetyenziswa kwecocaine.

Ukuphazamiseka kokusetyenziswa kweziyobisi ekufikiseni kukwangunobangela omkhulu womngcipheko wokukhula kokukhotyokiswa ngumntu omdala. Ukuqonda okunzulu kwe-neurocircuitry esisiseko elawula inkuthazo yokuthatha iziyobisi ekufikiseni kunokucacisa oko kubeka umngcipheko kwabanye kunye nokomelela kwabanye. Oku kuqonda kunokugqamisa iindlela zokukhusela ezinokuthi zikhutshwe kwaye zisetyenziswe ukunqanda kunye nokunyanga ngokufanelekileyo umlutha xa umntu emdala.

Olu phononongo lujolise ekucazululeni i-neurocircuitry esisiseko yomvuzo ebusheni ukuze uqonde ngcono i-etiology yokukhotyokiswa kwabantu abadala xa ukusetyenziswa kweziyobisi kuqalwa kule minyaka. Iindlela zobuchopho zomvuzo zinokuhlelwa njengezinto ezilungiselelayo okanye ezigqibeleleyo ngokwendalo; le miba yomvuzo kucingelwa ukuba ixhomekeke kwinkuthazo edityanisiweyo kunye neenkqubo ze-hedonic, ngokulandelelanayo. Sijongana nombuzo othi "ingaba ikhonkco phakathi kokulutha kweziyobisi ebudaleni kunye nokusetyenziswa kweziyobisi ebusheni kubangelwa kukufiphala kwemida phakathi kweenkqubo zenkuthazo kunye ne-hedonic?" Isishwankathelo seziphumo eziphambili zophononongo sinokufumaneka 1 Table.

1 Table

Iziphumo eziphambili zophononongo

  • Kwixesha lokufikisa, zombini i-dopamine kunye ne-opioids idlala indima kwiinkqubo zenkuthazo kunye ne-hedonic; Ukwahlukana phakathi kweendima zezi zibini ze-neurotransmitter zingaphantsi kwekhonkrithi kunokuba bekucingwa.

  • Oku kufunyanisiweyo kunokukhuthaza iindlela ezintsha ze-pharmacological kunyango lokuphazamiseka kokusetyenziswa kweziyobisi.

  • Ukufiphala phakathi kwenkqubo yenkuthazo kunye ne-hedonic ebonwa nge-neurobiologically nayo ibonwa ngokuziphatha; kukho ukufiphala kwemida phakathi kweempawu zokuziphatha ezifuna imvakalelo kunye nokungxama.

  • Ezi mpawu zombini zinamakhonkco kuphuhliso lwamva lokukhotyokiswa ziziyobisi ebudaleni.

  • Inkqubo etshintshiweyo yokufunda ngomvuzo kunye nokuncipha kolawulo lwengqondo inokongeza kumngcipheko owongeziweyo wokuba likhoboka leziyobisi xa ukusetyenziswa kweziyobisi kuqalwa ebusheni.

  • Iziphumo ezithembisayo ziye zaphawulwa kungenelelo olusekwe ekuphuculeni ulawulo lwengqondo kwingqondo yabantu abadala abanengxaki yokusebenzisa iziyobisi kunye nabakwishumi elivisayo abasengozini enkulu yokuphuhlisa ukuphazamiseka kokusetyenziswa kweziyobisi.

Kuba sithatha kubungqina bezilwanyana kunye nezifundo zabantu (bona izixhobo ezongezayo), kufuneka sivume ukuba kukho izinto ezinciphisa ukusetyenziswa kunye nokuthembeka kwedatha kuzo zombini. Ezi zinto zibandakanya: iyantlukwano yezomthetho malunga nenqanaba ekufikelelwa kulo ubudala, ukukhokelela kwimisebenzi eyahlukeneyo evumelekileyo yentlalontle ebotshelelwa kweli xesha lophuhliso; ukuguquguquka komntu ngamnye malunga nokuba kufikelelwa nini ukufikisa (abantu abakubudala obufanayo banokungabikho kwinqanaba lophuhliso elifanayo); kunye nokuguquguquka komntu ngamnye kubukho beempawu ezaziwayo zokwandisa amathuba okuphazamiseka kokusetyenziswa kweziyobisi (ichazwe ngasentla). Ezi zinto zihlala zingalawulwa kwizifundo zabantu, zichaza ukuba kutheni ezininzi zivelisa iziphumo eziphikisanayo. Nangona iimodeli zezilwanyana zisenokungakucacisi ngokupheleleyo ukuntsonkotha kokufikisa kunye nokukhula kokukhotyokiswa ziziyobisi ebudaleni, zivumela ukusebenza ngcono kunye nolawulo oluthile kwizinto eziguquguqukayo, ezivumela uhlolo olungcono lwe-causality.

Okubalulekileyo, ukusilela kwinkalo yophando olubanzi ukufikelela kwimvumelwano malunga nenkcazo yamagama aphambili, anxulumene nomvuzo, kuthetha ukuba izifundo kulwakhiwo olufanayo zihlala zifunda izinto ezahlukeneyo kunye nezifundo "ezahlukeneyo" zakha ukufunda into enye. Ke ngoko, ngeenjongo zolu hlaziyo, amagama aphambili achazwe kwi 2 Table.

2 Table

Iinkcazo zamagama aphambili asetyenziswe kulo lonke olu hlaziyo

Ukufuna imvakalelo: Ukufuna amava anoveli.
Impulsivity: utyekelo lokwenza izinto ngokweempembelelo zokuziphatha ngaphandle kokuqwalaselwa kweziphumo.
Umvuzo-uvakalelo: ubuntununtunu kwiimpawu ezinomvuzo ze-stimuli, "ukuthanda".
Iinkqubo zenkuthazo: iindlela zengqondo kunye ne-neural yokufuna / indlela yokuziphatha. Ezi nkqubo azibotshelelwanga kuphela ekuqhubeni ukunciphisa kodwa endaweni yoko iminqweno kunye nenkuthazo yenkuthazo.
Iinkqubo ze-Hedonic: iindlela zengqondo kunye ne-neural zolonwabo.
Ibuyiselo: iziphumo ezinomvuzo wesivuseleli okanye ichiza lichaza uyolo oluphathekayo olubalelwa kweso sivuseleli okanye ichiza. Ulonwabo lwe-subjective luyintlanganisela yotshintsho kwi-sensory processing (iemvakalelo ezilungileyo) kunye/okanye naluphi na utshintsho kubume bendalo esingqongileyo.
Ukuqiniswa: ukuqiniswa kobudlelwane phakathi: i-stimulus ene-conditioned and unconditioned, i-stimulus kunye nempendulo, okanye isenzo kunye nesiphumo. I-positive reinforcers yandisa amathuba okuphendula okungalindelekanga kunye neziqinisekiso ezingalunganga, xa zishiywe, zandisa amathuba okuphendula okungalindelekanga.
Iziyobisi: iphethini ye-maladaptive yokusetyenziswa kweziyobisi eqhubekayo nangona iziphumo ezibi.
Umvuzo wokujikeleza: Izakhiwo ze-neural ezinoxanduva lokufuna/ukusondela kwindlela yokuziphatha, ukufunda ngokunxulumana kunye nolonwabo.,
Ulawulo lwengqondo: Ukulawulwa kweengcinga kunye nezenzo ukuze kuphunyezwe injongo.
Ukuhanjiswa kweDopaminergic: inkqubo ebandakanya ukukhutshwa kwe-dopamine kwii-terminals zangaphambi kwe-synaptic, umsebenzi wale dopamine kwezinye ii-neurons kunye nokuphinda kuthathwe le dopamine ngezinye iiseli.

Umjikelo womvuzo wabantu abadala

Ukuze uqonde ukuba kutheni ukusetyenziswa kweziyobisi ebusheni kwandisa umngcipheko wokukhula kwengxaki yokusetyenziswa kweziyobisi njengomntu omdala, Kuqala kubalulekile ukuhlekisa ngeendlela ekwahluke ngazo ukusetyenzwa komvuzo wokufikisa kwindlela yokuvuza yabantu abadala. Isishwankathelo esifutshane sokusetyenzwa komvuzo wabantu abadala siya kubonelela "ngesiseko" eliza kusetyenziswa leli phepha njengendawo yesalathiso ukuthelekisa nezifundo eziphanda ubume bokulungiswa komvuzo kulutsha. Umahluko obonakalayo uya kucaciswa kamva kwaye usetyenziselwe ukulungisa ikhonkco phakathi kokufikisa kokuthatha iziyobisi kunye nokuphuhlisa ingxaki yokusetyenziswa kweziyobisi.

Imbali emfutshane yokusetyenzwa komvuzo wabantu abadala: i-dopamine hypothesis yomvuzo

Ngo-1978, uRoy Wise ucebise i-dopamine hypothesis yomvuzo, eyathi ukuhanjiswa kwe-dopamine kulamla kuzo zonke iindlela zomvuzo. Ngelo xesha, i-hypothesis yabonakala ixhaswa bubungqina obuchaphazela indlela ye-mesolimbic dopamine kwindlela yokuziphatha ekhuthazayo. Indlela ye-mesolimbic idibanisa indawo ye-ventral tegmental (VTA) kwi-nucleus accumbens (NaC). Ukusebenza kwale ndlela kukhokelela ekonyukeni kokukhutshwa kwe-dopamine kwi-NaC. Oku kwanda kokukhutshwa kwe-dopamine konyusa ubungangamsha bemivuzo kunye nenkuthazo enxulumene nomvuzo ukuququzelela uqinisekiso, injongo ejolise kunye nokuziphatha ngokwesiqhelo. Indlela ye-nigrostriatal idibanisa i-substantia nigra kunye ne-dorsal striatum. Le ndlela ilawula ukuveliswa kwentshukumo, ekwabandakanyeka kwindlela yokuziphatha eqhelekileyo. Indlela ye-mesocortical idibanisa i-VTA kwi-prefrontal cortex (PFC). Le ndlela ibandakanyeka kulawulo lokuqonda kwaye ngaloo ndlela inxulumene ngokusondeleyo nendlela ye-mesolimbic. Ukongeza, i-dopamine kwi-basolateral amygdala (BLA) ilamla ukufuna kunye nokukhuthaza ukufunda.

I-Olds & Milner yafumanisa ukuba iimpuku zabantu abadala ezine-electrode ezifakwe kwiindawo ezahlukeneyo ngaphakathi kobuchopho bazo zinokucinezela i-lever ukuzivuselela, into eyaziwa ngokuba yi-intra-cranial self-stimulation (ICSS). Izifundo ezalandelayo zafumanisa ukuba i-electrode efakwe ecaleni kwendlela ye-mesolimbic dopamine iququzelele ukonyuka okukhulu kwe-ICSS. Ii-electrode ezikhuthazayo zifunyenwe ukuba zonyuse i-dopamine eyongeziweyo kule ndlela, ebonakale ngathi yomeleza i-lever-pressing kwiimpuku. Ke, idatha ye-ICSS inxibelelanisa i-dopamine kwiipropathi zokuqinisa imivuzo.

Ithiyori kaWise nayo yaxhaswa zizifundo ze-brain micro-dialysis. Kwiimpuku zamadoda amadala, iDi Chiara kunye ne-Imperato yafumanisa ukuba amanqanaba e-dopamine anda ngaphambi nangexesha lokuziphatha ngokwesondo kwi-NaC. Ukongeza, uPfaus et al wafumanisa ukuba iziyobisi ezidla ngokubandakanyeka kwingxaki yokusetyenziswa kweziyobisi ezifana ne-opiates, utywala kunye ne-amphetamine nazo zonyusa i-extracellular dopamine kwi-NaC yeempuku zabantu abadala. Obu bungqina bubonisa ukuba i-accumbal dopamine yayinxulunyaniswa nomvuzo.

Izifundo zokuzilawula zikwaxhasa ithiyori kaWise. Umzekelo, xa uHoebel et al efakela i-cannulas kwi-NaC yeempuku zabantu abadala kwaye walinganisa amazinga okuzilawula we-amphetamine kunye ne-saline, iimpuku zagcina amazinga aphezulu e-lever ecinezela ukuzilawula ngokwazo i-amphetamine. Ukongeza, uYokel & Wise wafumanisa ukuba neuroleptics (D2abachasi be-R) ukunciphisa amazinga e-amphetamine yokuzilawula ngokwakho kwiimpuku zabantu abadala. Ngaphantsi kweedosi eziphantsi ze-neuroleptics, iigundane zonyuse i-lever-pressing yazo ukoyisa inkcaso (i-right-ward shift kwi-dose-response curve). Kodwa, phantsi kweedosi eziphezulu ze-neuroleptics, iigundane zanciphisa kakhulu amaxabiso azo okuphendula. I-neuroleptics, ke ngoko, yabonakala inciphisa iipropathi ezinomvuzo ze-amphetamine kwaye ngaloo ndlela inciphisa ukuzilawula kwayo. Kuthatyathwe kunye, obu bungqina bucebisa ukuba i-dopamine ilamle iziphumo zokuqinisa i-amphetamine.

Nangona kunjalo, bekukho imida eliqela kwi-Wise's dopamine hypothesis yomvuzo. Okokuqala, i-dopamine ayifunyaniswanga iyimfuneko kulawulo lwazo zonke iziyobisi. I-Dopamine receptor antagonism ayizange ibangele ukunyuka kwembuyekezo exhomekeke kwidose kwi-heroin self-administration, ngelixa i-MOR (i-mu-opioid-receptor) inchaso kunye ne-naltrexone yenza, ecebisa ukuba ezona ziphumo ziphambili zokuqinisa i-heroin azizange zidityaniswe kukusayinwa kwe-dopamine, kodwa endaweni yokubonisa i-opiate.

Okwesibini, bekungenzeki ukwahlula iindlela zokufuna kunye nokuthanda ngexesha le-ICSS kunye novavanyo lokuzilawula, okwenza ukuba kungabikho sigqibo sokuba i-dopamine ilamle yonke imiba yomvuzo. Izifundo ezilandelayo zikwazile ukwahlula iindlela zokufuna ukuthanda ukutya kwiimpuku. Abantu abasandul' ukuzalwa kunye neempuku zenza iimpawu ezichaphazelayo kwincasa eswiti kunye nekrakrayo: Iimpendulo ezikhuthazayo kwizivuseleli eziswiti ziquka ukukhothwa kwamanqina kunye nokuphuma kolwimi, ngelixa ukusabela okungalunganga kwincasa ekrakra kubandakanya ii-gas kunye nokungcangcazela kwentloko. La manyathelo e-orofacial asetyenziswe ngokubanzi ukufunda i-neurocircuitry elawula ukuthanda imbuyekezo yokutya. U-Pecina et al wanika iigundane i-pimozide, i-dopamine receptor antagonist, kwaye yafumanisa ukuba iigundane azibonisi utshintsho kwiimpendulo ze-orofacial ekutyeni okunencasa. Oku kucebise ukuba i-dopamine ayilawuli ixabiso le-hedonic lomvuzo wokutya. Endaweni yoko, ukubonakaliswa kwe-opiate kubonakala kudlala indima, njengoko kungqinwa yinto yokuba i-MOR agonism iphucula ukusabela kwe-orofacial ekutyeni okunencasa kwiimpuku. Nangona kunjalo, kubalulekile ukuqaphela ukuba ukuphendulwa kwe-orofacial kubonakaliswa kwiintsana ezisanda kuzalwa ezingenazo i-cortex kunye nezilwanyana ezihlanjululweyo. Ke ngoko, ezi datha zodwa azinakusetyenziselwa ukwenza izigqibo malunga nolonwabo oluzimeleyo ebantwini njengoko ezi ziphathamandla zingathembeli kwimisebenzi ephezulu yokuqonda.

Ebantwini, ukufuna kunye nokuthanda kunokwahlulwa kusetyenziswa iingxelo ezizimeleyo. Umzekelo, i-L-Dopa lichiza, elonyusa amanqanaba e-dopamine engqondweni, kodwa, izigulana ezingabantu ezinikwe i-L-Dopa ukunyanga isifo sika-Parkinson azixeli ngokwazo ukonyuka kolonwabo. Oku kubonisa ukuba i-dopamine ayisoloko inxulunyaniswe nomvuzo, icela umngeni kumandla obudlelwane phakathi kwe-dopamine kunye nomvuzo, owazama ukusekwa nguBulumko.

Iimbono zangoku zomjikelezo womvuzo wabantu abadala

Okunye okufunyenweyo kwizigulana ezingabantu kuncede ukubumba imbono yethu yangoku yenkqubo yokuvuza abantu abadala. Okubalulekileyo, izigulana ezinengxaki yokusetyenziswa kweziyobisi zihlala zichaza ukufuna kakhulu iziyobisi ngaphandle kweemvakalelo zolonwabo, ebonisa ukuhlukana okucacileyo phakathi kweenkqubo zokukhuthaza kunye ne-hedonic.

Iinkqubo zenkuthazo kubantu abadala

I-Dopamine ayibonakali ibandakanyeka kwimiba eyonwabisayo yomvuzo, kodwa eneneni inokubethelela ubungangamsha kunye nexabiso lenkuthazo elibalelwa kwimivuzo kunye neempawu zokuqikelela umvuzo. Ubungqina obubonakalayo buxhasa indima ye-dopamine kwiinkqubo zenkuthazo.

Okokuqala, i-ICSS ngoku icingelwa njengomlinganiselo wokomeleza. Ukonyuka kwe-extracellular dopamine kwi-NaC ebangelwa yi-ICSS kubonakala ngathi isonyusa i-lever, eyomeleza ukucinezelwa kwe-lever. Iigundane zabantu abadala ke ngoko zonyusa amazinga azo okuphendula ngenxa yokunyuka komnqweno wokucinezela i-lever ngokuchasene nolonwabo olwandisiweyo ekwenzeni oko.

Kukho nobungqina obubambekayo bokuba i-dopamine mediates iinkqubo zenkuthazo kubantu abadala. Ukuvuselela ingqondo enzulu kwizigulane ezinoxinzelelo kwiindawo ezifana ne-NaC kwandisa umnqweno wabo wokuthatha imisebenzi ethile. Ngaphezu koko, xa izigulana ezinesifo sikaParkinson ziphathwa nge-dopamine agonists, uninzi lubonisa ukuba lufumana isiphumo seminqweno enzulu, ebandakanya ukufuna iziyobisi, ukugembula kunye nesondo.

Okwesibini, iinkqubo zenkuthazo zinokuthi zingenelele ngokufunwa kosulelo lwe-dopaminergic ngaphakathi kwendlela ye-nigrostriatal. I-Difeliceantonio kunye ne-Berridge baqeqeshe iigundane ukuba baphendule i-sucrose phantsi kweshedyuli yesibini yokuqinisa, apho abaqinisekisi abahambelana nomvuzo bagcina i-sucrose befuna ixesha lokulibaziseka ngaphambi kokufikelela kwi-sucrose. Ezinye iimpuku zibonakalise ukufuna ukuziphatha ngokubhekiselele kwi-conditioned stimulus (CS)-lever ngelixa ezinye zibonise ukuziphatha okufunwayo malunga nesitya sokujolisa. Ezi mpuku zibizwa ngokuba ngabalandeleli bomqondiso kunye nabalandeleli beenjongo, ngokulandelelanayo. Iinaliti ze-Amphetamine kwi-dorsolateral striatum (DLS) yeempuku zonyuse umkhondo wophawu kubakhangeli beempawu kunye nokulandela umkhondo kwiitraki zenjongo. Baye bafumanisa ukuba abalandeleli beempawu baya kusebenza ukufumana ukufikelela kwiintetho ze-CS-lever kwaye baya kulandela i-lever kwiindawo ezintsha ngexesha lovavanyo. Oku kubonisa ukuba i-dopamine kwi-DLS yonyusa ubungangamsha beendlela zokuqikelela umvuzo ukunyusa indlela enemeko. Nangona kunjalo, ababhali bagqibe kwelokuba okongeziweyo kumtsalane we-cue kubonwe kungenxa yokuziphatha okunamandla okujolise ekujoliseni kwaye hayi imikhwa eyomeleleyo. Obu bungqina abubonisi ukuba; endaweni yoko, isixelela ukuba i-lever ngokwayo iye yaba yi-conditioner reinforcer. Ukuvavanya ukuba i-dopamine kwi-DLS izisa ukuziphatha okuqhelekileyo, imifuniselo yokuthotywa kwexabiso, apho isiphumo senjongo sithotyiwe, siyafuneka. Ukuba izimilo beziqhelekile ngokwenene, bezinokuxhathisa ekuthotyweni kwenjongo njengoko imikhwa ilawulwa lunxulumano lwempendulo yovuselelo.

Ngokubanzi, iimvavanyo zibonise ukuba iinkqubo zenkuthazo, ezilawula inqanaba lomnqweno wokuziphatha okukhuthazwayo, zilamlwa ngokuyintloko ngokuhanjiswa kwe-dopamine kwindlela ye-mesolimbic. Ekubeni ukunyuka kwe-dopaminergic ekufuneni imbuyekezo kunokwenzeka ngaphandle kotshintsho kuqikelelo lwe-hedonic, njengoko ngamanye amaxesha kubonwa kwisifo sika-Parkinson kunye nokukhotyokiswa kweziyobisi kwabantu abadala, kubonakala kukho ukwahlukana phakathi kwenkqubo yenkuthazo kunye ne-hedonic. Kodwa yintoni elawula ezi nkqubo ze-hedonic?

Iinkqubo ze-Hedonic kubantu abadala

I-endogenous opiates ibonakala idlala indima ebalulekileyo kwiinkqubo ze-hedonic. Izitofu ze-MOR kunye ne-DOR (i-delta-opioid-receptor) i-agonists kwi-rostrodorsal quadrant ye-NaC medial ye-shell yokuphucula ukusabela kwe-orofacial kwincasa emnandi kwiimpuku, ngelixa i-KOR (i-kappa-opioid-receptor) i-agonism kwingingqi efanayo ibangela ukucaphuka. Ukongeza, i-MOR agonism ngaphakathi kweempuku 'posterior ventral pallidum (VP), ulwakhiwo oluphambili lwemveliso ye-NaC, ivimba ukonyuka okuqhelekileyo okubonwa ekuthandeni i-sucrose kumazwe alambileyo. Ithatyathwe kunye, ezi datha zibonisa ukuba i-rostrodorsal quadrant ye-NaC medial shell kunye ne-VP yangasemva zi-hedonic hotspots kunye nokuba i-opioid neurotransmission ngaphakathi kwezi ndawo zibandakanya ukuthanda ukutya.

Kukho iindawo ezimbini ze-hedonic ngaphakathi kwengqondo. I-NaC medial hotspot yeqokobhe, malunga ne-millimeter enye yetyhubhu ngevolumu kwiimpuku, ibekwe kwiquadrant yerostrodorsal yeqokobhe. I-hotspot yesibini ikwi-posterior ventral pallidum. I-MOR kunye ne-DOR kunye nomqondiso phakathi kwezi ndawo zishushu kwandisa ukuthanda ngelixa ukuvuselela kwe-KOR kuvelisa ukucaphuka. Ngokuchasene noko, kukho iindawo ezibandayo ze-hedonic; Ukubonisa i-MOR kunye ne-DOR ngaphakathi kwezi ndawo zibandayo zicinezela ukuthanda. Iindawo ezibandayo zibekwe ngaphakathi kweqokobhe le-NaC le-caudal kunye ne-ventral pallidum yangaphambili. Iindawo ezishushu kwi-VP kunye ne-NaC zixhunyiwe; ukuba ukubonakaliswa kwe-opiate kuvaliwe kwindawo enye ngoko ukunyuka kokuthanda akukwazi ukuveliswa. I-Opiate neurotransmission kuyo yonke i-NaC kunye ne-VP mhlawumbi yongeza okanye icinezela ukuthanda ngokuxhomekeke apho uvuselelo lwenzeka khona; ngale ndlela ikhibhodi echaphazelekayo iveliswa kuzo zonke ezi sayithi. Ngaphaya koko, isekethe ye-glutamatergic esuka kwi-lateral hypothalamus (LH) ukuya kwi-VTA imodareyithwa yi-orexin. I-Orexin esuka kwi-LH isebenza apha ukunyusa ukuthanda ngokuzimeleyo ngexesha lendlala.

Iziphumo ezidibanisa i-opiates kwiinkqubo ze-hedonic ziye zaphinda ziphindwe kwizifundo zabantu. U-Ziauddeen et al wanika abatya kakhulu abaneminyaka eyi-18-60 MOR umchasi we-GSK1521498. Xa kuthelekiswa nolawulo, abatya kakhulu kwichiza babonise ukwehla okukhulu kwiingxelo zabo zokusabela kwe-hedonic ekutyeni okuswiti.

Kuthatyathwe kunye, kukho ubungqina bokwahlukana phakathi kwenkqubo yenkuthazo kunye ne-hedonic, kunye ne-dopamine elawula yangaphambili kunye ne-opiates yokugqibela (Umzobo 1). Nangona kunjalo, oku akuchazi ukuba kutheni abasebenzisi be-cocaine bahlala bexela iimvakalelo eziphezulu kunye ne-euphoria xa isenzo esiphambili se-cocaine kukunyusa amanqanaba e-dopamine e-extracellular. Ke ngoko, ukujongwa ngakumbi kolu qhawulo-mtshato kuyafuneka.

Ifayile yangaphandle enomfanekiso, umzobo, njl.njl. Igama lento ngu SAR-10-33-g0001.jpg

Ukwahlukana phakathi kweenkqubo zokukhuthaza kunye ne-hedonic. Iinkqubo zenkuthazo zilawula inqanaba lomnqweno "lokufuna" lokuziphatha okukhuthazwayo. Kuyavunywa ngokubanzi ukuba iinkqubo zenkuthazo ziphakathi kokubonakaliswa kwe-dopaminergic. Ngakolunye uhlangothi, iinkqubo ze-hedonic zilawula isigaba sokugqibela sokuziphatha okukhuthazwayo. Balawula ukuthanda imbuyekezo kwaye bacingelwa ukuba balamlwa ngokubonakaliswa kwe-opioid.

Ukwahlukana kwaphonononga ngakumbi

Kuvavanyo olusondeleyo, ukwahlukana phakathi kwendima yee-opiates kunye nendima ye-dopamine kwinkuthazo kunye neenkqubo ze-hedonic kubonakala kulula kakhulu. Kukho ama-nuances afihlakeleyo kwaye angekho ngqiqweni.

Iinuances ezifihlakeleyo

Okokuqala, ubungqina bubonisa ukuba ii-nuances ezifihlakeleyo zikhona kwiinkqubo ze-hedonic ezilawula ukuqiniswa kweziyobisi ze-psychostimulant. Kubonakala ngathi iziphumo zokuqinisa iziyobisi ze-psychostimulant zilamlwa ubuncinci ngokuyinxenye ngokusayinwa kwe-dopamine kwaye hayi ukubonakaliswa kwe-opiate. Oku kubonisa imeko ekhethekileyo apho kubonakala ngathi i-dopamine idlala indima kwiinkqubo ze-hedonic. UGiuliano et al baqeqeshe iimpuku ukuba bazilawule ngokwakho icocaine okanye iheroin. Abachasi be-MOR GSK1521498 okanye i-naltrexone (NTX) banikwa. I-GSK1521498 ineprofayile yomchasi egcwele ngakumbi ngelixa i-NTX kuye kwaxelwa ukuba inomsebenzi we-agonist oyinxalenye ye-MORs. Ngaphantsi kweshedyuli eqhubekayo yokomeleza, akukho siyobisi siphembelele ukuzilawula kwe-cocaine; nangona kunjalo, iidosi zazo zombini ichiza zonyuse ulawulo lwe-heroin-self (iimpuku zonyuse ukuphendula kwazo ukoyisa inkcaso). Isibakala sokuba abachasi be-MOR babengenasiphumo kulawulo lwe-cocaine sibonisa ukuba ukuvuselela kwe-MOR akulamleli ezona ziphumo zokuqinisa i-cocaine. Iziyobisi ezivuselelayo, ezinje ngecocaine, zikhokelela ekonyukeni kwamanqanaba e-dopamine engaphandle kwe-NaC. Uphononongo lokucinga lubonise ukuba olu lwando lunxulunyaniswa nolonwabo oluzixelayo. Obu bungqina, budibene nobungqina obuvela kuGiuliano et al, bongeza ubunzima kwithiyori yokuba i-dopamine idibanisa ukuthanda iziyobisi ezikhuthazayo.

Nangona kunjalo, i-dopamine-receptor antagonism ebantwini ayinciphisi ngokuthe gqolo ukuphakama okunxulumene neziyobisi ezivuselelayo. Ngokomzekelo, i-pimozide, i-dopamine-receptor antagonist, ayithinteli i-amphetamine-induced euphoria ebantwini. Enye ingcaciso ebangela oku kukuba amachiza avuselelayo aphinda afune inkqubo ye-opioid engapheliyo kwi-NaC, ekhokelela kwisizukulwana solonwabo njengesiphumo sesibini. Nangona kunjalo, oku kuqesha kuhlala kuthotywa ngokuthatha iziyobisi ngokuqhubekayo kwaye ke akunakuchaza ukuba kutheni abantu abakhobokileyo bezixela ngokwazo euphoria xa bethatha iziyobisi zengqondo. Endaweni yoko, kusenokwenzeka ukuba ukufuna ngamandla, okuveliswe kukwanda kwe-dopamine, kuphinda kuqwalaselwe kwakhona njengolonwabo ebantwini. Ngoko ke, ukwahlula ukuthanda nokufuna kuyinkqubo enzima. Oku kuthetha ukuba kukho i-subjective overlap phakathi kwenkqubo yenkuthazo kunye ne-hedonic xa kuziwa kumachiza e-psychostimulant. Oku kuneempembelelo ezibalulekileyo xa kuqwalaselwa unyango lwamayeza kubantu abadala abangamakhoboka eziyobisi njengoko mhlawumbi amachiza asebenza kuzo zombini ezi nkqubo afuneka.

Iinuances ezingaqhelekanga

Umqondiso weDopamine okwangoku ulawula izikhokelo zethiyori kwiinkqubo zenkuthazo. Nangona kunjalo, iqela elikhulayo lomsebenzi libonisa ukuba ukubonakaliswa kwe-opiate kudlala indima. Ngaphantsi kweshedyuli yesibini yokuqinisa, iigundane ezinikwe i-MOR antagonist GSK1521498 zanciphisa kakhulu ukuziphatha kwazo kokufuna ukutya ngaphambi kokubonisa ukutya. Iishedyuli ze-second-order of reinforcement ziyimilinganiselo yokufuna okulawulwa yi-cue. Indlela yokuziphatha elawulwa yiCue icingelwa ukuba ilawulwa yi-dopamine neurotransmission kodwa kolu vavanyo lwe-GSK1521498 lukwazile ukunciphisa le ndlela yokuziphatha. Oku kubonisa ukuba i-opiates idlala indima kwiindlela ezilindelekileyo. Ukwehliswa kokufuna ukuziphatha kunokuziswa yisenzo se-GSK1521498 kwi-MORs kwi-GABAergic interneurons kwi-VTA okanye utshintsho kwimpembelelo ethi i-condition-stimuli ibe nayo ekuphenduleni kwesixhobo.

Umsebenzi we-Opioid kwi-MORs kwi-GABAergic interneurons kwi-VTA ngokungathanga ngqo ikhokelela ekonyukeni kokukhutshwa kwe-dopamine kwi-NaC ekhokelela ekonyukeni kwenkuthazo. Ii-opiates zithintela i-GABAergic interneurons, ethintela i-VTA dopamine neurons. Ii-opiates zikwasebenza ngokuthe ngqo kwi-MORs kwi-Neuron ye-NaC nakweminye imimandla emininzi. I-opiate receptors kunye ne-dopamine receptors kwi-NaC neurons isignali nge-Gi; ngoko, umqondiso uyongezwa.

I-GSK1521498 ngoko isebenza ngokuthintela isenzo esingathanga ngqo kunye nesithe ngqo se-opiates kwi-MORs kule ndlela. Nangona kunjalo, kukho enye ingcaciso yokunciphisa ukufuna ukuziphatha okuziswa yi-GSK1521498. Ii-MOR kwi-BLA ziyafuneka kwi-incentive learning., Ukufunda ngenkuthazo yinkqubo apho iziphumo ezilungileyo zomvuzo zifakwe kwiikhowudi njengexabiso lenkuthazo ukukhokela indlela yokuziphatha yokufuna umvuzo kwixesha elizayo. Ke ngoko, ukuchasana kwi-BLA kunokwenza buthathaka ukufakwa kweekhowudi kwimibutho yezixhobo ekhokelela ekunciphiseni ukufuna ukuziphatha. Uphononongo oluthelekisa iziphumo zesenzo somchasi we-MOR wasekhaya kunye nesistim kuya kunceda ukucazulula ngcono iziphumo ze-opiates ekufuneni ukuziphatha.

Kukho ezinye iisayithi apho i-opioid neurotransmission inokulamla iinkqubo zenkuthazo. Okokuqala, ubungqina buxhasa indima ye-opiates kwiinkqubo zenkuthazo kwi-DLS. Kuvavanyo lwe-autoshaping apho i-agonist ye-MOR i-DAMGO yafakwa kwi-DLS yeempuku, ukufuna ukuziphatha kwafunyaniswa ukuba kuthe ngqo kwimpuku nganye. Ezinye iimpuku zasilela kwisitya sokujolisa ngokulindela umvuzo ngelixa ezinye zisilele kwi-CS lever. Iinaliti ze-DAMGO zandise indlela elawulwa yi-cue kuzo zombini iindidi zeempuku. Oku kubonisa ukuba i-MOR agonism ngaphakathi kwe-DLS idlala indima kwiinkqubo zokukhathazeka. Ukongeza, i-Agonism ye-MOR kumbindi wenucleus ye-amygdala (CeN) ikwafunyaniswe ukuba yongeza inkuthazo ye-cues-paired cues kunye nokwandisa ukufuna ukuziphatha kwiimpuku.

Ebantwini, kwenziwa ukuguqulwa kwenkqubo kuphela. UCambridge et al wanika i-GSK1521498 kwizigulana ezinokuziphatha okuphakathi kokutya. Xa kuthelekiswa nolawulo, izigulana ezifumana iyeza zibonise umzamo oncitshisiweyo wokugcina imifanekiso yokutya okunencasa kwizikrini zabo usebenzisa i-grip force transducer. Oku kubonisa ukuba iyeza linciphise ukuvuma ukusebenzela isivuseleli esivuzayo kwaye libonisa ukuba ichiza kwaye ngenxa yoko ii-opiates zidlala indima kwiindlela zenkuthazo. Nangona kunjalo, indima ye-opiates ibonakala iyinkimbinkimbi, njengoko u-Ziauddeen et al wachaza ukuba i-GSK1521498 ayizange ihluke kwi-placebo kwimiphumo yayo kubunzima, ubunzima be-fat mass and binge-eating scores of the binge. Ke, abachasi be-MOR baye baxuba ukusebenza ngendlela ekhuthazayo ekuziphatheni.

Isishwankathelo, ubungqina bucebisa ukuba zombini i-opiates kunye ne-dopamine mediate ngokufuna kunye nothando kwiimeko ezithile. Ubungqina buphinda bucebise ukuba ukuthanda luvavanyo lwethu lokuqonda zombini iinkqubo zokukhuthaza kunye ne-hedonic. Ke ngoko, kukho ukudibana phakathi kwenkqubo yenkuthazo kunye ne-hedonic. Oku kutyhoboza kumjikelezo womvuzo wabantu abadala kunokuba neziphumo ezibalulekileyo zokuhlalutya ithiyori malunga nomjikelezo womvuzo wokufikisa.

Ukusetyenzwa komvuzo ebusheni: ithiyori yeenkqubo ezimbini

Ngexesha lokufikisa, ukufuna imvakalelo kunye neempawu zokungxama zilandela iindlela ezahlukeneyo zokukhula. Ngexesha lokufikisa, ukufuna imvakalelo kunye nokungxama zombini ziphezulu. Ukufuna imvakalelo kunobudlelwane be-curvilinear kunye nobudala kuyo yonke iminyaka yokufikisa. Oku kucingelwa ukuba kubonakalisa ukungasebenzi kakuhle kokujikeleza komvuzo okuziswa kukuvuthwa okukhawulezayo kwe-striatum xa kuthelekiswa nePFC. Impulsivity inonxulumano olubi lomgca kunye nobudala kuyo yonke iminyaka yokufikisa. Oku kucatshangelwa ukuba kubonakalisa ukonyuka kolawulo lwengqiqo njengoko i-PFC ikhula. Oku kwenza isiseko sethiyori yenkqubo-mbini, ethi ukufuna imvakalelo kunye nokungxamiseka kuyanda, ekuqaleni, ngexesha lokufikisa ngenxa yokungalingani phakathi kwenkqubo yomvuzo esele ikhulile kunye nenkqubo yokulawula ingqondo engekakhuli kwi-PFC. Amacandelo alandelayo ajonga ngakumbi iindlela zemivuzo ngexesha lokufikisa kunye neenkcazo ezimfutshane zotshintsho lwengqondo oluye lwenzeka ngexesha lokufikisa, ngokubhekiselele kwizifundo zokufikisa.

Uphuhliso lwe-neurocircuitry elawula ukufuna imvakalelo ebusheni

Ukonyuka kokusebenza kwe-incentive circuitry ngexesha lokufikisa

Kubonakala ngathi ukunyuka kokufuna imvakalelo kuyanda ekufikiseni ngenxa ye-hyperactivity yesekethe elamla iinkqubo zenkuthazo. UBurton et al uthelekise ukufunyanwa kwempendulo enemeko kulutsha kunye neempuku zabantu abadala. Okokuqala, iigundane ezifikisayo kunye nabantu abadala bafunda ukudibanisa ukuhanjiswa kwe-sucrose kunye ne-light-tone-CS. Ukuphendula kwi-lever ehambisa i-CS kwaye yalinganiswa ukuvavanya ukuba i-CS iye yaba ngumxhasi onemeko. Emva kweshedyuli yoqeqesho olungabanzi (i-420 pairings ngaphezulu kweentsuku ze-14), iigundane ezifikisayo zifumene ukuphendula kwi-lever ngelixa iigundane zabantu abadala zingazange zikwenze oko, zibonisa ukuba ngoqeqesho oluncinci iigundane ezifikisayo zinokufumana impendulo kumxhasi onemeko. Oku kuphakamisa ukuba iinkqubo zenkuthazo zinokuphuculwa kulutsha xa kuthelekiswa nabantu abadala. Ababhali baphinde banika iigundane ezifikisayo i-dopamine kunye ne-opioid receptor antagonists kwaye balinganisa iziphumo ekuphenduleni okusemgangathweni, zombini iindlela zobuchule zanciphisa ukuphendula kwi-CS-predicting lever. Oku kubonisa ukuba kulutsha, zombini ii-opiates kunye ne-dopamine zidlala indima ekulamleni iinkqubo zenkuthazo. I-Dopamine iphucula iinkqubo zenkuthazo ngokunika umqondiso kwindlela ye-mesolimbic kunye nee-opiates zongeza iinkqubo zenkuthazo nokuba kungesenzo se-MORs kwi-GABAergic interneurons kwi-VTA okanye isenzo kwi-MORs kwi-BLA.

Ubungqina obuvela ebantwini bukwabonisa ukuba iinkqubo zenkuthazo ziyaphuculwa xa umntu efikisa. Uhlalutyo lwe-meta lwezifundo ze-fMRI ezenziwa kubantu abadala kunye nabakwishumi elivisayo bachaze ukusebenza okuphezulu kwe-NaC kulutsha olufikisayo xa kuthelekiswa nabantu abadala ngexesha lokusetyenzwa kwemivuzo. Ukongezelela, u-Urošević et al wafumanisa ukuba ngexesha lokufikisa ukunyuswa kokunyuka kobuntununtunu kwizinto ezisingqongileyo kubonakaliswe ngokunyuka kwevolumu ye-NaC. Zithathiwe kunye, ubungqina obuvela kwezi zilwanyana kunye nezifundo zabantu bucebisa ukuba, ngenxa yokwanda komsebenzi kwi-NaC, ulutsha lufumana amandla amakhulu okuvuselela amandla. Oku kunceda ukucacisa ukuba kutheni ukufuna imvakalelo kuyanda ekufikiseni.

Amandla acacisayo okwanda komsebenzi we-NaC ekuziphatheni kwabafikisayo omelezwa ngakumbi bubungqina obuchaza umahluko ngokwesini obonwa ekufuneni imvakalelo. Amakhwenkwe afikisayo adla ngokubonisa umdla ngakumbi kunamantombazana afikisayo. U-Alarcón et al wathelekisa umsebenzi wobuchopho bamakhwenkwe kunye namantombazana ngexesha leWheel of Fortune. Amakhwenkwe ayenomsebenzi we-NaC ophezulu xa kuthelekiswa namantombazana, ekwanxulunyaniswa nokwanda kwezigqibo ezinobungozi ngexesha lomsebenzi kunye nokwanda kwenkuthazo yenkuthazo yabaxhasi bomsebenzi. Kubalulekile ukuqaphela ukuba iiyantlukwano zesini azizange zihlanganiswe ngumahluko kumanqanaba eehomoni zesini. Oku ke ngoko kubonisa ukuba umsebenzi we-NaC ophezulu udlala indima ebalulekileyo ekufuneni imvakalelo ngexesha lokufikisa ngokwandisa amandla okuvuselela amandla. Ukuthatha kubungqina kwizifundo zeempuku, lo msebenzi we-NaC ophezulu ubonakala udityaniswa ngokudibanisa phakathi komsebenzi we-neurobiological substrates ezibandakanyekayo kwiinkqubo zenkuthazo kunye ne-hedonic; zombini ukuhanjiswa kwe-dopaminergic kunye nokuhanjiswa kwe-opiate kubalulekile apha.

Enye ingcaciso yokufumanisa ukuba ulutsha lunokusebenza okuphezulu kwe-NaC xa kuthelekiswa nabantu abadala ngexesha lokusetyenzwa kwemivuzo. kukuba ubuchopho babo bunophawu lokufunda lwe-phasic dopamine ngokuchasene nokonyuka kobuchule bokuvuselela okuvuzayo. UCohen et al wafumanisa ukuba, kwi-fMRI, imiqondiso yempazamo yokuqikelela i-dopaminergic kwi-striatum yayiphezulu kulutsha xa ithelekiswa nabantu abadala. Oku kuphakamisa ukuba umqondiso wokufunda onxulunyaniswa nokuvuselela okuvuzayo uyatshintshwa ebusheni. Isiginali yempazamo yokuxela kwangaphambili i-dopaminergic inokuchaza ukusebenza okuphezulu okubonwayo ngaphakathi kwe-NaC kwaye inokuba negalelo ekunyukeni kokuziphatha okufunwayo okubonwa ekufikiseni.

Le ithiyori yomelezwa ngakumbi bubungqina obuvela kwizifundo ze-fMRI ezibonisa ukuba abantu abafikisayo babonisa ukuncipha komsebenzi wokubetha ngexesha lesigaba sokulindela umvuzo xa kuthelekiswa nabantu abadala; nangona kunjalo, babonisa ukwanda komsebenzi wokubetha ngexesha lesaziso / isiphumo sesigaba somvuzo. Ezi ziphumo zikwaluphawu lokukhotyokiswa kwabantu abadala. U-Luijten et al wafumanisa ukuba abantu abadala abanengxaki yokusetyenziswa kweziyobisi baye banciphisa ukusebenza kwe-fMRI ngexesha lokulindela umvuzo kodwa bandise umsebenzi we-ventral striatum ngexesha lesigaba somvuzo. Ingcaciso yeziphumo ezibonwa kulutsha kunye nokuphazamiseka kokusetyenziswa kweziyobisi kwabantu abadala yintsilelo yokufunda ngomvuzo. Ngexesha leenkqubo zokufunda zomvuzo oqhelekileyo, ukwanda komsebenzi kwimimandla yokubetha kwenzeka ngokuphendula imivuzo engalindelekanga (isigaba sesiphumo). Le miqondiso imele imiqondiso yempazamo yoqikelelo. Ngexesha lenkqubo yokufunda, le miqondiso iye idityaniswe nezinto ezixela kwangaphambili umvuzo (inqanaba lokulindela). Umsebenzi oncitshisiweyo wokubulala obonwe ngexesha lokufikisa kunye nokuphazamiseka kokusetyenziswa kweziyobisi kwabantu abadala kunokubonisa intsilelo yokufunda apho kukho impazamo kuqikelelo lwemivuzo. Oku kuya kukhokelela kwiimpazamo eziqhubekayo zoqikelelo njengoko imivuzo yexesha elizayo ibinokungalindelwanga. Oku kuchaza umsebenzi ophezulu wokubetha kwinqanaba lesaziso / lesiphumo sokuvuza njengoko zimele iimpazamo ezichanekileyo kwimivuzo "engalindelekanga". Kobu bungqina bungasentla kubonakala ngathi kubomi bokufikisa kunye nokuphazamiseka kokusetyenziswa kweziyobisi kwabantu abadala kukho inkqubo yokufunda yomvuzo ombi. Ulutsha olubonisa oku kwandiswa komsebenzi we-NaC kwisigaba sesiphumo somvuzo / ukukhubazeka kokufunda umvuzo kunokuba semngciphekweni omkhulu wokuba likhoboka kamva ebomini ukuba baqala ukusebenzisa iziyobisi ngexesha lokufikisa njengoko ingqondo yabo sele iziphatha ngendlela efanayo kumntu omdala osebenzisa iziyobisi. ukuphazamiseka.

Ukunciphisa ulawulo lwengqondo

Ukuncipha kolawulo lwengqondo ngexesha lokufikisa kubonakala kukongeza ekwandeni kokufuna imvakalelo okubonwa ngeli xesha. Ngokuqhelekileyo uphuhliso lwePFC luthatha ixesha elide, luphela ekupheleni kokufikisa. Njengoko i-PFC ikhula, imisebenzi yolawulo efana nokuthintela kunye nocwangciso iyaphuculwa. Oku kunceda ukucacisa ukuba kutheni ukufuna imvakalelo kuncipha kwindlela yokukhula.

Ukuphuhliswa kwe-neurocircuitry elawula impulsivity ebusheni

Uhlobo lwesibini lokuziphatha olunokwandiswa ngexesha lokufikisa kukungxama. Ukungabinamdla kukucinga ngeziphumo zexesha elide kwaye ekuqaleni iphezulu ngexesha lokufikisa. Oku kucingelwa ukuba kungenxa yokuncipha kolawulo lwengqondo, oluziswa kukungakhuli kwi-PFC. Impulsivity kamva iyehla ukusuka kwishumi elivisayo ukuya ekubeni mdala njengoko iPFC ikhula.

Iindlela zolawulo kwi-NaC

Indima edlalwa yi-PFC kulawulo olusuka phezulu-phantsi lokunyanzeliswa luvunywa ngokubanzi. Nangona kunjalo, kukho izinto ezibonisa ukuba i-NaC inokuba negalelo ngendlela esezantsi ukuya phezulu. Okokuqala, i-NaC-core ibonakala ibalulekile kulawulo lwe-impulsivity. Kwinqanaba lokukhetha ukungalawuleki, iigundane ezikwishumi elivisayo ezithintelwe ngokutya zanikwa ukhetho phakathi kwelever ehambisa iipellets ezi-4 zokutya emva kokulibaziseka kunye nelever ethe yazisa kwangoko i-pellet enye encinci yokutya. Izilonda ze-Excitotoxic ze-NaC-core ziphazamisa amandla eempuku ekukhetheni umvuzo olityazisiweyo omkhulu. Ezi datha zibonisa ukuba i-NaC-core idlala indima ekulawuleni ukungxamiseka.

Uphononongo olongezelelweyo lubonise ukuba ukuhanjiswa kwe-dopaminergic kubandakanyeka kwezi ndlela zokulawula. UBesson et al wasebenzisa in-situ hybridization ukulinganisa intetho ye-dopamine D2-amanqanaba e-receptor kwingqondo ye-high-impulsivity kunye ne-low-impulsivity rats. Amagundane anamandla aphezulu ayenamanqanaba asezantsi e-dopamine D2-i-receptor mRNA kwindlela ye-mesolimbic kuneegundane eziphantsi. Ababhali bafunde oku ngokusondeleyo ngakumbi xa babenika iimpuku ezinoxinzelelo oluphezulu lwe-D2/D3-i-receptor antagonist kwi-NaC-core okanye igobolondo kunye nokulinganisa impulsivity kwi-5-choice serial reaction time task. I-NaC-core infusions yanciphisa kakhulu i-impulivity ngelixa i-NaC-shell infusions inyusa amandla. Ngokudibeneyo, ezi ziphumo zibandakanya i-accumbal dopamine kulawulo lokungashukumi.

Ukongeza kuthumelo lwe-dopaminergic, usasazo lwe-opioidergic ngaphakathi kwe-NaC lunokudlala indima ekulawuleni ukungangxami. U-Olmstead et al uqeqeshelwe abantu abadala i-MOR kunye ne-DOR yokunkqonkqoza iimpuku kumsebenzi wokuxhoma impumlo olinganisa ukutsalwa kwemoto. EZINYE iimpuku zokunkqonkqoza zibonise ukuncipha kokutsalwa kwemoto ngelixa iimpuku ze-DOR zokunkqonkqoza zazingxamisekile kunolawulo. Ezi datha zibonisa ukuba umqondiso we-MOR usebenza ekwandiseni ukungxamiseka kunye nokubonisa i-DOR kunceda ukuthoba. Kuba i-NaC-core ityebile kwii-MORs, kusenokwenzeka ukuba usulelo lwe-opioidergic apha luzisa iziphumo ezibonwe kolu phononongo. Izifundo zokulawula i-MOR-antagonists ngaphakathi kwe-NaC-core okanye iqokobhe kunye nokulinganisa impulsivity kwiimpuku kuya kunceda ukuqinisekisa isenzo se-opiates apha. Nangona kunjalo, ubungqina obukhoyo busacebisa ukudityaniswa kwemisebenzi ye-substrates elamla iinkqubo zenkuthazo kunye ne-hedonic.

Ukugqithelana kumsebenzi wesubstrates mediating incentive incentive kunye ne-hedonic substrates ke ngoko kunegalelo kukokubini imvakalelo eyonyukileyo yokufuna kunye nokunyuka kokungalawuleki okubonwa ekufikiseni. Ukongezelela, ukuxhatshazwa kweendlela ngaphakathi kwe-NaC ukungalingani yinkqubo yokulawula ingqondo engakhulanga kwi-PFC. Ke ngoko, ithiyori yeenkqubo ezimbini ibonakala inika ingxelo ehambelanayo yokufuna imvakalelo kunye nokungxama okubonwa ekufikiseni. Nangona kunjalo, kubalulekile ukuqaphela ukuba kukho ukungafani phakathi komntu ngamnye kumanqanaba ezi mpawu ngexesha lokufikisa. Olunye ulutsha lufumana utshintsho olukhawulezayo kumanqanaba alo okufuna imvakalelo kunye nokungxama njengoko ludlula ebutsheni ngelixa abanye begcina amanqanaba azinzileyo ezi mpawu ngokuya ngeminyaka. Oku kubalulekile njengoko ezi mpawu ziyi-endophenotypes eqikelelwayo kumlutha weziyobisi wabantu abadala. Amakhonkco phakathi kweprofayili yomvuzo kumlutha weziyobisi wabantu abadala kunye nobukho bezi mpawu ebusheni bunokucacisa ukuba kutheni iminyaka yobudala yeyona nto ingumngcipheko omkhulu kuphuhliso lokulutha.

Iinkqubo ezikhuthaza ukuba likhoboka ukusuka kwangethuba (ubufikisa)

Nangona uninzi lwabakwishumi elivisayo ludlula kwishumi elivisayo lungenazo naziphi na iingxaki ezihlala ixesha elide, umlinganiselo omkhulu usemngciphekweni wokuba likhoboka leziyobisi kamva. Ulutsha oluqalisa ukusebenzisa iziyobisi phambi kokuba lube neminyaka eyi-14 ngabona basengozini enkulu yokuxhomekeka kwiziyobisi. Ke ngoko, ukufikisa kubonisa ixesha elibuthathaka ekukhuleni apho ukuqaliswa kokusetyenziswa kweziyobisi kunokubeka umntu emngciphekweni omkhulu wokuba likhoboka leziyobisi kamva.

Ukukhotyokiswa kweziyobisi kwabantu abadala kuchazwa njengokuthatha iziyobisi okunyanzelekileyo okuqhubeka nokuba kukho iziphumo ezibi. Ukuphulukana nolawulo luphawu olungundoqo lwesidubedube njengoko ukuziphatha kuqala kujongwe kodwa emva koko kuqhubele phambili ekubeni sisiqhelo kunye nokunyanzeliswa kwendalo. Ukuba likhoboka leziyobisi kubantu abadala kunokubonakaliswa ngeempawu ezintathu eziphambili; uvakalelo lwenkuthazo, ukwandiswa kokwakheka kwemikhwa kunye nokuncipha kolawulo lwengqondo. Okokuqala, ukubonakaliswa okuphindaphindiweyo kwiziyobisi ezikhobokisayo kubangela uvakalelo lweenkqubo zenkuthazo. I-NaC yongeza impendulo yayo kumachiza kunye neempawu ezidityaniswe neziyobisi ezibangela inkuthazo egwenxa yokuthatha iziyobisi. Ngokuhamba kwexesha, i-hedonic allostasis nayo iyenzeka. Ngenxa yoku, abasebenzisi beziyobisi bayaqhubeka nokuthatha iziyobisi ukuthomalalisa iimeko ezimbi ezithi zivele. Kukwakho notshintsho ukusuka ekuziphatheni okujoliswe kuko ukuya kwindlela yokuziphatha ngokwesiqhelo ngokuhamba kwexesha kunye nokuziphatha ngokungxama nako kuyanda ngeli xesha. Okokugqibela, iinkqubo ezigwenxa zenkuthazo kunye nokwanda kokulawulwa kokuziphatha kukhokelela kwimikhwa yenkuthazo. Le mikhwa yenkuthazo ilamla ukufuna ichiza elisisinyanzelo elibonwa kubantu abadala abangamakhoboka eziyobisi.

Eli candelo lilandelayo lijolise ekuxoxeni amakhonkco phakathi kweempawu ezintathu eziphambili zokukhotyokiswa kwabantu abadala eziphawulwe ngasentla kunye neempawu zokuziphatha ezibonwa ekufikiseni. Ngokwenza njalo, sinethemba lokucacisa indlela enokwenzeka yokwanda komngcipheko wokukhula komlutha onxulumene nokuqala ukusetyenziswa kweziyobisi okufikisayo.

Ukonyuka kovakalelo lwenkuthazo

Uvakalelo luchaza inkqubo apho ulawulo oluphinda-phindayo lwe-stimuli luphucula impendulo kweso sivuseleli. Ubungqina bucebisa ukuba iziyobisi zikhuthaza inkqubo ye-mesolimbic dopamine kumlutha weziyobisi wabantu abadala. Umzekelo, kwiimpuku, iidosi ezizisiweyo zovavanyo lwe-amphetamine zonyusa iipatheni zokudubula ze-neurons kwizakhiwo ze-mesolimbic. Ezi ziphumo ziphinde zaphindwa ebantwini apho iidosi eziphindaphindiweyo ze-amphetamine zikhuthaza ukukhutshwa kwe-dopamine kwi-NaC. Kunyaka omnye kamva, umngeni weziyobisi nge-amphetamine usavelisa ukukhutshwa kwe-dopamine ephuculweyo. Oku kubonisa ukuba iimpembelelo zokuvuselela zithatha ixesha elide. I-NaC, eyinxalenye yenkqubo ye-mesolimbic dopamine, iyafuneka kwi-pavlovian stimuli ukulawula ukuphendula kwesixhobo. Ngaphantsi kweshedyuli yesibini yokomeleza, uvakaliso lokukhutshwa kwe-dopamine kucingelwa ukuba kulamle ukufuna iziyobisi ezilawulwa yicue. Kwiimpuku, abachasi be-dopamine receptor banciphisa ukufuna i-cocaine elawulwa yi-cue. Ke ngoko, i-hypersensitivity ye-dopaminergic neurons kwi-NaC ibonakala inoxanduva lokuchazwa okugwenxa kweziyobisi kunye neempawu ezidityaniswe neziyobisi ezikhokelela ekufuneni iziyobisi. Le yinkcazo-bungcali yenkuthazo yabantu abadala abangamakhoboka eziyobisi.

Ukufuna kakhulu iziyobisi kubantu abadala abakhotyokiswa ziziyobisi kufana nokufuna imbuyekezo ebonwa kolunye ulutsha olufikisayo. Ukuqonda iziyobisi akusayi kwenzeka ngexesha lokufikisa kodwa, njengoko kujongwe ngaphambili, inkqubo efanayo iyasebenza kakhulu. Kwixesha lokufikisa, ukusebenza ngokugqithiseleyo kwale nkqubo kulamla ukufuna imvakalelo, nto leyo ebonisa ukuqaliswa kokusetyenziswa kweziyobisi. Ulutsha olufikisayo olubonakalisa amanqanaba aphezulu olu phawu ngoko ke lusengozini enkulu yokuqalisa ukusebenzisa iziyobisi. Kusenokwenzeka ukuba abantu abafikisayo abafuna imvakalelo ephezulu banokuqalisa ukusetyenziswa kweziyobisi kuba i-hyperactive salience circuitry yongeza iinkqubo zenkuthazo kwaye yenza imivuzo emihle ibe nomtsalane kakhulu.

Kubalulekile ukuqaphela ukuba nangona ukufuna imvakalelo kuqikelela ukuqaliswa kokusetyenziswa kweziyobisi, oko akubeki mngcipheko wokuba likhoboka leziyobisi lilodwa kamva. Ubungqina bubonisa ukuba phantsi kweemeko ezithile ukufuna imvakalelo kunokuba yinto ekhuselayo. Kodwa yintoni elamla oku? Ukufuna uvakalelo kulinganiswa ebantwini kusetyenziswa isikali sokufuna imvakalelo (SSS-V). Amava okufuna amava kunye nokukruquka-kukuchaphazeleka kokufuna imvakalelo yinguqulelo yeentlobo ezahlukeneyo zokukhetha into entsha kwiimpuku, uphawu oluqikelela uphuhliso lokunyanzeliswa kokuthatha iziyobisi kwiimpuku ezivunyelweyo ukuba zizenzele ngokwakho icocaine. I-subscales efuna imincili kunye ne-disinhibition yokufuna imvakalelo inxulumene kuphela neempawu ezifuna imvakalelo, uphawu olubanzi oluxela ukuqaliswa kokusetyenziswa kweziyobisi. Ukwahlula ke ngoko kunokubonwa ngaphakathi kolwakhiwo olufuna imvakalelo apho umngcipheko wokuthatha ichiza elinyanzelekileyo lixhomekeke ekubeni yeyiphi i-subscales adolescents amanqaku aphezulu.

Ukunyuka kokwakheka komkhwa

Olunye uphawu lokukhotyokiswa ziziyobisi ngabantu abadala kukukhula kokuqhelana nemikhwa. Kwingxaki yokusetyenziswa kweziyobisi yabantu abadala, indlela yokuziphatha yokukhangela iziyobisi ngokuthe ngcembe iyatshintsha ukusuka ekubeni ijolise ekubeni sisiqhelo. Oku kungqinwa yinto yokuba i-cocaine kunye nokuziphatha kokufuna utywala kuqala kunovakalelo ekuthotyweni kweziphumo kwiimpuku; nangona ixesha elongezelelekileyo, indlela yokuziphatha iba luvuselelo olubotshelelweyo kwaye luxhathise ukuhla., Usulelo lwe-Dopamine ngaphakathi kwe-DLS lunoxanduva loluvuselelo lubophelelekile ekuphenduleni amachiza. U-Everitt et al uxele ukuba emva kokuvezwa ixesha elide kwi-cocaine, ukukhutshwa kwe-dopamine kunyuke kuphela kwi-dorsal striatum ngexesha lokufuna i-cocaine elawulwa yi-cue.

I-DLS ifumana ulawulo lokuziphatha kokufuna iziyobisi ngokusebenza kwe-striato-nigro-striatal loops ekhoyo phakathi kwe-ventral striatum, midbrain kunye ne-dorsal striatum, engqinwe bubungqina obuvela eBelin & Everitt ngo-2008. Iimpuku zanikwa izilonda ezicalanye zondoqo we-NaC kunye nokufakwa kwe-dopamine antagonist kwi-contralateral DLS ukuphazamisa unxibelelwano lwe-striato-nigro-striatal ngokubini. Ubuqhophololo buye banciphisa indlela yokuziphatha elawulwa kukufunwa kweziyobisi kwiimpuku. Oku kubonisa ukuba i-striato-nigro-striatal loops igcina isimilo esilawulwa yicue kwaye oku kukuziphatha kulamlwa kukuhanjiswa kwe-dopaminergic kwi-DLS.

Kumntu omdala okhotyokiswe ziziyobisi, indlela yokuziphatha yokukhangela iziyobisi ekugqibeleni iba sisinyanzelo. Impulsivity yi-endophenotype eqikelelwayo kuphuhliso lokufuna i-cocaine kunye nokuxhomekeka. Oku kubeka ulutsha olukwishumi elivisayo oluphezulu kolu phawu kumngcipheko owongeziweyo wokuphuhlisa indlela yokuziphatha enyanzelekileyo yokufuna iziyobisi.

Okubangel 'umdla kukuba, ukonyuka komngcipheko wokuphuhlisa ukuthathwa kweziyobisi okunyanzelekileyo okunxulunyaniswa nokufuna amava kunye nokudinwa-ukuchaphazeleka kwe-subscales yokufuna imvakalelo kunokuziswa lunxulumano lwezi nqanaba kunye nokungxama. U-Molander et al wavavanya iigundane zokunyanzeliswa okuphezulu kwi-novelty reactivity kunye nokukhetha. Iigundane ezinochuku oluphezulu zibonise ukhetho lweemeko zenoveli kwaye zazikhawuleza ukuqalisa indlela yokuziphatha ephononongayo kwiisetingi zenoveli, ngelixa iimpuku eziphantsi kwempembelelo zidla ngokuchitha ixesha elininzi kwindawo eqhelekileyo yesixhobo. Oku kuphakamisa ukuba iimpuku ezinochuku oluphezulu zikwaphezulu ekufuneni amava kunye nokuba sesichengeni sokukruquka. Ke ngoko, imilinganiselo ephezulu kwizikali ezifuna imvakalelo ezinxibelelana nokungxama zinokucacisa ukuba kutheni ukufuna imvakalelo ayisoloko ingumba okhuselayo.

Ngamafutshane, ama-subscales okufuna imvakalelo; ukuba sisithukuthezi sesichengeni kunye nokufuna amava anxulumene nophuhliso lwamva lokuthatha amachiza okunyanzelekileyo. Impulsivity ikwanxulunyaniswa ngokuzimeleyo nophuhliso lwamva lokuthatha ichiza elinyanzelekileyo. Nangona kunjalo, okubangel 'umdla kukuba ezi zicandelwana zikhankanywe ngasentla zokufuna ukuva nokungxama zikwanxulumene. Oku kuthetha ukuba ezi mpawu zokuziphatha azicacanga kangako. Ukufiphala phakathi kwenkqubo yenkuthazo kunye ne-hedonic ebonwa nge-neurobiologically , ebusheni ikwabonwa ngokuziphatha njengoko kukho ukufiphala kwemida phakathi kweempawu zokuziphatha ezifuna imvakalelo kunye nokungxama. Kunokucingelwa ukuba ulutsha olufumana amanqaku aphezulu kweli qela leempawu ezimnyama lunokuba semngciphekweni omkhulu wokuba likhoboka kamva ebomini (Umzobo 2).

Ifayile yangaphandle enomfanekiso, umzobo, njl.njl. Igama lento ngu SAR-10-33-g0002.jpg

Ukwahlukana okungacacanga phakathi kwenkqubo yenkuthazo kunye ne-hedonic. Ukufiphala phakathi kwenkqubo yenkuthazo kunye ne-hedonic ebonwa nge-neurobiologically ebusheni ikwabonwa ngokuziphatha njengoko kukho ukufiphala kwemida phakathi kweempawu zokuziphatha zokufuna imvakalelo (SS) kunye nokungxama (I). Kunokucingelwa ukuba ulutsha olufumana amanqaku aphezulu kweli qela leempawu ezimfiliba lunokuba semngciphekweni omkhulu wokuba likhoboka kamva ebomini.

Ukunciphisa ulawulo lwengqondo

Uphawu lokugqibela lokuba likhoboka leziyobisi kubantu abadala kukuncipha kolawulo lwengqondo. I-PFC ithobela ukusebenza kwesigqeba. Izinto ezingaqhelekanga kumsebenzi we-PFC zidlala indima ekuphuhliseni ukuthathwa kweziyobisi okunyanzelekileyo. UGoldstein et al uxele ukuba ukuncitshiswa koxinzelelo lwe-PFC grey kunye nobukhulu kumakhoboka eziyobisi anxulunyaniswa nokunyuka kobunzima kunye namaxesha amade okuphazamiseka kokusetyenziswa kotywala kunye nemisebenzi embi kakhulu. Iziphumo zabonwa ukuya kutsho kwiminyaka emithandathu emva kokuba uyekile. Ezi datha zibonisa ukuba umonakalo owenziwa ngamachiza kwi-PFC unegalelo ekuququzeleleni nasekugcineni umlutha kamva ebomini. Nangona kunjalo, imo ehlala ixesha elide yeziphumo ikwacebisa ukuba ukungahambi kakuhle kwesakhiwo kwi-PFC yoxinzelelo lwegrey inokuba sesichengeni sokulahla kwangaphambili phambi kokuthatha iziyobisi.

Kwixesha lokufikisa, ukusebenza kwePFC kukwayinto encinci. Uphuhliso lwePFC luthatha ixesha elide kude kube mdala; ngoko ke, ulawulo lwengqondo luyancipha ngexesha lokufikisa. Olu lawulo luncitshisiweyo lwengqondo lunokwenza lula ukonyuka kokungxama kunye nokufuna imvakalelo phakathi kokufikisa. Ulutsha olufikisayo olunamanqanaba aphezulu azo zombini ezi mpawu lunokuba kowona mngcipheko mkhulu wokuba likhoboka leziyobisi kamva ebomini.

Mhlawumbi ukukhuthaza ulawulo lokuqonda kulutsha olusemngciphekweni ekufikeleleni ebudaleni kunokunciphisa umngcipheko wokuba likhoboka labantu abadala? Ubungqina obuthembisayo buvela kulingo lwenkqubo ye-HOPE yabophuli-mthetho abaselugcinweni, uninzi lwabo ngabantu abadala abanengxaki yokusebenzisa iziyobisi. Abantu abakule nkqubo kufuneka bafowunele iziko yonke imihla ukubona ukuba banyanzelekile na ukuba beze kuvavanyo lweziyobisi olungacwangciswanga. Oku kukhuthaza ukusebenza kwesigqeba kunye nolawulo lokuqonda njengoko abantu kufuneka babeke iliso kwindlela abaziphethe ngayo kwaye bafowunele kwiziko yonke imihla. Inkqubo ye-HOPE yalandelwa kangangonyaka nge-asaynmenti engacwangciswanga. I-13% yamalungu e-HOPE aluphumelelanga iimvavanyo zawo zamachiza xa kuthelekiswa nama-46% olawulo. Ezi datha zithembisa njengoko zibonisa amandla okwandisa ulawulo lwengqondo kunokuba neziphumo.

Obunye ubungqina obuxhasa oku buvela kulingo lolawulo olungacwangciswanga lwabantwana besikolo samabanga aphakamileyo abangama-732 eLondon. Abathathi-nxaxheba abafumene amanqaku aphezulu kwi-impulsive, ukufuna imvakalelo kunye neminye imingcipheko yobuntu bokusetyenziswa kakubi kweziyobisi babelwa kwiqela lolawulo okanye iqela lokungenelela kwizakhono zokumelana. Ungenelelo lwezakhono zokuhlangabezana lujolise ekufundiseni ukumisela iinjongo, ukuqonda ngokuziphatha kunye ne-CBT elula. Iqela lokulawula lalinamazinga aphezulu okusetyenziswa kweziyobisi kunye neziyobisi ezininzi ezisetyenzisiweyo ukuba iqela lokungenelela kwithuba leminyaka emibini yokulandelelana xa kuthelekiswa neqela lokungenelela. Oku kuxhasa uluvo lokuba ukuphucula ulawulo lwengqondo kulutsha olukwishumi elivisayo olusemngciphekweni kunokuthintela ukuqala kokuphazamiseka kokusetyenziswa kweziyobisi kamva ezantsi emgceni. Uphononongo olude kufuneka kwakhona luqhutywe ukuvavanya amazinga okusetyenziswa kweziyobisi ixesha elide kulutsha olufikisayo kolu hlobo lwenkqubo.

Izigqibo kunye nophando lwexesha elizayo

Uphando oluneenkcukacha lweendlela ezilawula umvuzo ekufikiseni kwenze ukuba kubekho ukudibana phakathi kwemisebenzi ye-neurobiological substrates elamla inkuthazo kunye neenkqubo ze-hedonic ukuze zibonwe. Ukonyuka kokusebenza kokujikeleza kwenkuthazo, efunyenwe ixhomekeke kuzo zombini iinkqubo ze-dopaminergic kunye ne-opioidergic, inegalelo ekonyukeni kokufuna imvakalelo kunye nokungxama okubonwa ngexesha lokufikisa. Ezi mpawu zikwayi-endophenotypes eqikelelwayo kuphuhliso lweziyobisi kamva ebomini; ulutsha olufikisayo oluphezulu kuzo zombini ezi mpawu ke ngoko lusemngciphekweni omkhulu wokuba likhoboka leziyobisi kamva. Ukuhlalutya amakhonkco phakathi kwezi mpawu ziqikelelwayo kunye neprofayili yokukhotyokiswa kweziyobisi kwabantu abadala kuqaqambise iinkalo ezithile eziphambili ekufuneka kugxilwe kuzo uphando lwexesha elizayo.

Okokuqala, kuba ukufuna imvakalelo kunye nokungxama zombini zilawulwa kukusebenza kwe-salience circuitry, unyango lunokujoliswa apha kubo bobabini abantu abadala kunye nabafikisayo. Ukudibana phakathi kwendima ye-opiates kunye ne-dopamine kuthetha ukuba mhlawumbi unyango lweziyobisi kufuneka lugxile kunyango olubini olusebenza kuzo zombini iindlela.

Okwesibini, ukufunyaniswa kweempawu zokuziphatha ebusheni ezixela kwangaphambili ukukhula kokukhotyokiswa ziziyobisi kamva ebomini kuvula amathuba eenkqubo zothintelo ekujoliswe kuzo ezijolise kulutsha olusemngciphekweni omkhulu. Njengoko kungqinwa yi-HOPE kunye nenkqubo yezakhono zokumelana, ungenelelo olomeleza ulawulo lwengqondo lunokusetyenziswa njengezixhobo zonyango ebusheni ukunciphisa amanqanaba okufuna imvakalelo kunye nokungxama kwabo basengozini. Iziphumo zangoku zonyango kumakhoboka eziyobisi zimbi. Uhlolo lwangaphandle olwenzeka kumaziko okubuyisela kwisimo sangaphambili aluthinteli ukuphinda uthabathe iziyobisi xa umntu ebuyela kuluntu. Ukongezelela, iziyobisi ezifana ne-GSK1521498, ezinciphisa ukufuna ukuziphatha, azisebenzi kakuhle ekusebenzeni ukunciphisa ukutya okanye ukusetyenziswa kotywala. Ukunika ulawulo kunye ne-arhente ukubuyisela iziyobisi ngundoqo ngokucacileyo. Iindlela zokulawula ukukhotyokiswa ziziyobisi kubantu abadala kufuneka zithathelwe ingqalelo; kufuneka benze abantu bakwazi ukusebenzisana neziyobisi kodwa bazilawule.

Uphando lwexesha elizayo kwezi ndawo lusenokungapheleli ekuveliseni iindlela zonyango ezineziqhamo zokukhotyokiswa kweziyobisi ngabantu abadala, kodwa olu phando luya kwandisa isiseko solwazi kwaye lusisondeze kwizisombululo ezisebenzayo.

Imibulelo

Sithanda ukubulela uGqr David Belin ngenkxaso kunye nesikhokelo kulo lonke.

Igalelo lababhali

I-FK, i-OO kunye ne-RM zibandakanyeka ekuqulunqweni, ukuyila, ukuyila, ukubhala kunye nokuvunywa kokugqibela kwenqaku. Bonke ababhali bayavuma ukuba baphendule kuzo zonke iinkalo zokuchaneka kunye nokuthembeka komsebenzi.

ukuxela

Ababhali babika ingxabano yomdla kulo msebenzi.

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