Intsu yeDrr yeCr. 2012;18(1):113-8.
Blum K, UGardner E, Oscar-Berman M, IGold M.
imvelaphi
ISebe lezeMpilo yeNgqondo kunye neMcK Night Brain Institute, iYunivesithi yaseFlorida, Gainesville, FL 32610, eMelika. [imeyile ikhuselwe]
Abstract
Kwinzame yokusombulula impikiswano ngokubhekisele kwigalelo leesistimimbic dopamine (DA) iinkqubo zokufumana umvuzo, sivavanya ezi zintathu ziphambili zokhuphiswano ezichazayo: "ukuthanda," "ukufunda," kunye "nokufuna" [1]. Oko kukuthi, i-DA inokulamla (a) impembelelo ye-hedonic yomvuzo (ukuthanda), (b) ifundo eqikelelweyo malunga neziphumo ezinomvuzo (ukufunda), okanye (c) ukulandela umvuzo ngokuchaza ukhuthazo lokuvuselela okunxulumene nomvuzo (ukufuna) . Sivavanya ezi hypotheses, ngakumbi njengoko zinxulumene ne-Reward Defence Syndrome (RDS), kwaye sifumanisa ukuba ukunyanzela okukhuthazayo okanye "ukufuna" hypothesis yomsebenzi we-DA kuxhaswa luninzi lobungqina. Izifundo ze-Neuroimaging zibonise ukuba iziyobisi zokuxhatshazwa, ukutya okuthandekayo, kunye nokuziphatha okulindelweyo okunjengokwabelana ngesondo kunye nokudlala kuchaphazela imimandla yobuchopho ebandakanya ukujikeleza komvuzo, kwaye akunakuba kukungafuneki. Iziyobisi zokuxhatshazwa zenza ukuba umqondiso we-DA ubonakale kwaye uvakale iindlela zemolimbic ezivele zibonisa ukuba kukhuthazekile kwimivuzo. Iziyobisi ezikhobokileyo ziye zafana ukuba zilawulwa ngokuzithandela, ziyaphucula (ngokuthe ngqo okanye ngokungathanga) umsebenzi we-dopaminergic synaptic kwi-nucleus accumbens, kwaye zivuselela ukusebenza kokujikeleza komvuzo wobuchopho (ukuvelisa "okuphezulu" okufunwa ngabasebenzisi beziyobisi). Nangona kwasekuqaleni bekukholelwa nje ukuba kufakwe encotsheni yeethoni ye-hedon, ezi zisekethe ngoku kukholelwa ekubeni zisebenza ngokuxineneyo, ziqwalasele ukutsala ingqalelo, ukulindelwa komvuzo, ukuqinisekiswa kokulindelwa komvuzo, kunye nokukhuthaza. Amanqanaba oxinzelelo oluphakanyisiweyo, kunye neepolymorphisms zentlobo zedopaminergic kunye nezinye iintlobo zemfuza ezinokubakho, zinokuba nefuthe elinobungozi bokuba semngciphekweni wokulutha. Imodeli ye-RDS ye-etiology ephethe kakuhle kakhulu kwiintlobo zamakhemikhali nakwindlela yokuziphatha.
I-Neurobiology ye-Reward Defence Syndrome
Igama elithi, Umvuzo Defence Syndrome (RDS) laqala ukwenziwa nguBlum okqhubekayo. [U2-3] kwaye ibhekisele kukunqongophala kwe iimvakalelo eziqhelekileyo zokwoneliseka. I-RDS isiphumo sokungasebenzi kakuhle "kumvuzo wobuchopho", unxibelelwano olunzima phakathi kwe-neurotransmitters (ngokuyintloko dopaminergic kunye ne-opiodergic). Abantu abanembali yosapho enotywala okanye ezinye iziyobisi banokuzalwa banesiphene kumandla okuvelisa okanye ukusebenzisa ezi neurotransmitters. Ukuchanaba ixesha elide loxinzelelo kunye notywala okanye ezinye izinto kunokukhokelela kwinkohliso yomsebenzi we-Cascade yembuyekezo. Ngayiphi na imeko, xa ii-neurotransmitters ziphantsi okanye zithintelwe ekufikeleleni kwii-receptors zobuchopho obucwangcisiweyo, abantu bavame ukuziva bengonwabanga okanye beva iintlungu. Iimpawu zokuziphatha ezibangelwa kukusilela kwenkqubo exhasa ukwaneliseka kubandakanya iziyobisi kunye nokusebenzisa kakubi utywala, ukuzonwabisa kakhulu, ukutshaya kakhulu, ukungcakaza nokungasebenzi kakuhle. Blum kunye noogxa2,3] zidibanise ezi ngxaki kunye nesiphene semfuza, ngakumbi ukungasebenzi kwe-dopamine receptors, iintlobo zemfuza ezibonakalisa iindlela ezininzi eziguqukayo.
I-Dopamine (DA) yengqondo enamandla ye-neurotransmitter elawula iimvakalelo zokuba sempilweni. Inxibelelana nezinye iikhemikhali ezinobuchopho obunamandla kunye nee-neurotransmitters (umzekelo, i-serotonin kunye neopioid), nganye nganye ibophelela kwizamkeli ezithile zisebenza imisebenzi ethile ye -ellellular kulawulo lweemvakalelo kunye neenkanuko. Ukubopha kwe-neurotransmitter kwii-receptors ze-neuronal kubangela isiphumo esiyinxalenye yomdlalo wecala. Ukuphazanyiswa kwezi khasethi zihamba phakathi kubangela ukungqubeki kwi-RDS, kubandakanya umlutha, ukunyanzeliswa, kunye nokuthatha ingozi enkulu. Ke, abantu abanesiphene kwi-DRD2 DA receptor gene, basilela inani elaneleyo le-receptors ye-DA kwiingqondo zabo ukuvelisa i-Cascade yomvuzo wobuchopho. Emva koko, oku kukhokelela kwi-RDS, kubandakanya iminqweno engaqhelekanga kunye nesiphumo sokungathandeki. I-RDS ngumqondo onzima odibanisa umvuzo ufuna umvuzo ochasene nemizila yemfuza kwimikhwa dopaminergic, kwaye imiba ebalulekileyo ilandelwe ngabaninzi ukusukela oko yaqalwa kwi1996.
I-RDS kunye nokuSebenzisa gwenxa iziyobisi
NgokukaGardner [4], iziyobisi zikhobokisa ukuba zinokuqhutywa ngokuzithandela zizilwanyana zaselabhoratri (zihlala zifuna njalo), kunye nokonyusa ukusebenza komjikelezo wengqondo (ukuvelisa 'okuphezulu' okufunwa ngumsebenzisi wesiyobisi). Umjikelezo womvuzo ophambili uqulathe isekethe yechungechunge elidibanisa indawo yecandelo le-ventral tegmental (VTA), i-nucleus accumbens (NAc) kunye ne-porral pallidum nge-bundle ye-medial forebrain. Nangona kwasekuqaleni bekukholelwa nje ukuba kufakwe encotsheni yeethoni ye-hedonic, eziisekethe ngoku kukholelwa ekubeni zisebenza kakhulu nangakumbi, zinika ingqalelo kwakhona, ulindelo lomvuzo, isiqinisekiso sokulindelwa komvuzo, kunye nokhuthazo lokukhuthaza. Kucingelwe ukuba ukudodobala kwe hedonic ngaphakathi kwezijikelezo kunokukhokelela kwikhobokisa [5]. Icandelo lesibini le-dopaminergic elikwinqanaba lomvuzo licandelo elinobuchule kakhulu lokuchaphazela iziyobisi. Zonke iziyobisi ezinamakhoboka nazo ziyafana ukuba ziyakhuthaza (ngokuthe ngqo okanye ngokungathanga ngqo okanye nkqu ne-transsynaptically) umsebenzi we-dopaminergic umvuzo we-synaptic kwi-NAc [6]. Amachiza amakhobokisayo (umzekelo, ii-opiates), ukunyamezeleka kwimiphumela ye-euphoric ikhula ngokusetyenziswa okungapheliyo. I-dysphoria yasemva kokusebenzisa iya kuthi ke ilawule ithoni yomjikelo we-hedonic, kwaye iziyobisi azisasebenzisi iziyobisi ukuze ziphakame, kodwa ngokubuyela nje kwesiqhelo (ukuze 'ungene ngqo'). Ngokubalulekileyo, imijikelezo yobuchopho ejongene neziphumo zokuzonwabisa zamachiza amakhoboka zi-anatomically, i-neurophysiologic, kunye ne-neurochemically eyahlukileyo kwezo kuxhomekeka ekuxhomekekeni komzimba, nakwabo banqwenela ngokubuyela umva. Kukho umahluko obalulekileyo wemfuzo kumngcipheko wokuchaphazeleka kwiziyobisi (umzekelo, umahluko kwi-gene encoding ye-dopamine D2 receptor - uhlobo lwe-DRD2 gene). Ngexesha elinye, izinto zokusingqongileyo ezifana noxinzelelo (uxinzelelo oluphezulu oluhlanganiswe neepolymorphisms kudidi lwedopaminergic, kunye nezinye iintlobo zemfuza), kunye nokwahlulwa kwentlalo nako kutshintsha iindlela zomvuzo wobuchopho ngendlela yokudlulisela ingozi yokuba likhoboka [7]. Ke, amanqanaba aphezulu oxinzelelo, kunye neepolymorphism zedopaminergic genes kunye nezinye iintlobo zemfuza ezinokubakho, zinokuba nefuthe elinobungozi bokuba semngciphekweni wokulutha [8]. Imodeli ye-bio-psycho-yentlalo ye-etiology ebambe kakuhle kakhulu ukuba ilikhoboka. NgokukaContner okqhubekayo. [U9], umlutha ubonakala ulungisa imeko yokungasebenzi kakuhle ye-hypodopaminergic ngaphakathi komjikelo wengqondo, uvelise ubuntu.
Izifundo ze-Neuroimaging ebantwini zongeza ukukholelwa kule hypothesis. Ubungqina obuqinisekileyo bukwanyanzelisa i-serotonergic, opioid, endocannabinoid, GABAergic, kunye neendlela ze-glutamatergic kwikhoboka lotywala njengoko kuchaziwe kumvuzo wobuchopho bembuyekezo yengqondo [10]. Ngokugwetyiweyo, ukulutha iziyobisi kuyaqhubekeka ukusuka ekusetyenzisweni kokuzonwabisa ukuya kuthi ga ngokusetyenziswa okukungxamisekileyo, ukuya ekusebenziseni okunyanzelekileyo. Oku kunxibelelana nokukhula ukusuka kumvuzo oqhutywa kukuziqhelanisa neziyobisi. Oku kuqhubela phambili kokuziphatha kuyahambelana nokunyuka okuqhubayo kwe-neuroanatomical ukusuka kwi-ventral striatal / NAc ukuya kulawulo lwe-dorsal striatal kulawulo lokufuna iziyobisi. Iiseti ezintathu zodidi lomnqweno wokubuyela ekuvuseleleni nasekuvuselelekeni kweziyobisi kukuphinda ubonakale kumachiza amakhoboka, uxinzelelo, kunye nokubekwa kwindawo yokuziphatha kwakhona (abantu, indawo, nezinto) ezazikudibene nokuziphatha ngaphambi kokuthatha iziyobisi. Ukubuyela umva kweziyobisi kubangela i-NAc kunye ne-neurotransmitter DA, ngakumbi imvakalelo yokuqaqanjelwa (receptors) kwe-DA [11]. Ukubuyela kwakhona koxinzelelo okubangelwa kukudakumba kubandakanya (a) isuntswana embindi ye-amygdala, i-nucleus yebhedi ye-stria terminalis, kunye ne-neurotransmitter corticotrophin-releasing factor, kunye (b) ne-lateral tegmental noradrenergic nuclei yesisu sobuchopho kunye ne-neurotransmitter norepinephrine. Ukubuyela umva kwe-cue-triggered kubandakanya i-basolateral nucleus ye-amygdala, hippocampus, kunye ne-neurotransmitter glutamate.
I-RDS kunye neOvereating
Isitya okqhubekayo. [U12-15] kunye nabanye [16-19Ifumene umahluko obonakalayo phakathi kokwenza ukuba kusebenze ukutya okuzinzileyo kunye nokufumana ukutya okuthandekayo. Ewe, ukuphendula okuthe gabalala kwenkqubo ye-mesocorticolimbic yokufumana itshokhole yobisi lwekokhethi eqikelelweyo lokufumana isisindo somzimba [12,13], ngelixa impendulo ephezulu yale mimandla isiya kwi-cue signing efumanekayo yokufika kwe-milkshake (ulindelo) ikwatsho ingqikelelo yesisindo esizayo [13]. Lo mahluko uphawulweyo ngumzekelo wokwahlula phakathi kwe-hedonic "ukuthanda" kunye nokungathandekiyo "kokufuna" iBerridge okqhubekayo. [U1,21-23] ibhalwe
Into enomdla kukuba, iingingqi zobuchopho ngaphakathi komjikelezo womvuzo ziphendule ngokungafaniyo kwi -ese-feta xa zithelekiswa ne-lean probands, iphakamisa iindlela ezinokubakho zokufumana ubunzima bomntu [12]. Ng okqhubekayo. [U15] ndafumanisa ukuba umntu otyebileyo ohambelana nabasetyhini ababhinqileyo ubonakalise ukwenziwa okukhulu ku-somatosensory (Rolandic operculum), gustatory (frontal operculum), kunye nomvuzo wemimandla yokuxabisa (i-amgydala, i-cortex ye-ventromedial yangaphambili) ngokuphendula kunye nolindelo olucingelweyo lwe-milkshake kuthelekiswa nesisombululo esingenambathiso. ubungqina bokutshintsha okuguqulweyo kwestiri. I-Obese ehambelana nabasetyhini ababhinqileyo ibonakalise ukwanda okukhulu kwi-Rolandic operculum, ngaphambili i-operculum, kunye ne-ventromedial preortal cortex ekuphenduleni i-isocaloric yobisi olubhalwe rhoqo ngokuchasene namafutha asezantsi. Ababhali bacebise ukuba ukujongana kwehyper ye-somatosensory, gustatory, kunye nokuxabisa ubuchopho loci kunokuhambelana nokutya kakhulu kwaye ukuqhubela phambili ukuthoba ifuthe lokufaka ikhowudi yembuyekezo, okunokuthi kube negalelo ngakumbi ekufumaneni ubunzima. Abaphandi abafanayo bapapashe ubungqina obukholisayo bokuba iipateni ezifanayo ze-neural activation zisebenza ngokuchasene nokuziphatha okufana nokutya kunye nokuxhomekeka kwezinto: ukunyanzeliswa okuphakanyisiweyo kumjikelezo womvuzo (i-dorsolateral preortal cortex kunye ne-caudate) ekuphenduleni iindlela zokutya kunye nokuncitshiswa kokusebenza kwemimandla enhibitory (lateral orbitof Pambal i-cortex) ukuphendula ukutya14].
IBerridge [20] Ucacise ukuba iisistimu zembuyekezo yobuchopho zivumelana nokufuna kunye ukuthanda ukuthanda iziyobisi. Kwinqaku lakutshanje malunga neendlela zobuchopho bokuthanda i-hedonic, yena kunye nabadibene naye bafumana ii-cubic-millimeter hedonic hotspots kwi-NAc kunye ne-ventral pallidum yolwazi lwe-opioid yolonwabo lweemvakalelo. Abaphandi baqwalasele ubuchopho "njengokufuna" okanye iinkqubo zokukhuthaza isidenge [21,22] kubalulekile ukuba unomdla wokutya, njengeenkqubo ze-mesolimbic ze-DA kunye neesekethe zentshukumo ye-opioid eyandisa ngaphaya kweendawo ezinobungozi. Baqwalasele iindlela ezinokwenzeka zokuthi ukuthanda nokuthanda kungangqubana nokutya kakhulu, becacisa ukuba ukuthanda umhlaba kunokubangela ukuba ubenomqolo owahlukileyo kunokufuna okungafunekiyo.
Pechiña okqhubekayo. [U23", ngokusebenzisa indlela yemfuza yokuguqula imeko yemvelo kuhlolwe iziphumo zokuphakama kwe-synaptic DA kwi: (a) ukutya okuzenzekelayo kunye nokuthatha amanzi, (b) inkuthazo yokufunda kunye nokufunda ukufumana umvuzo otyhafisayo kumsebenzi weembaleki, kunye (c) nokuphendula okuthandabuzekayo ukuphakanyiswa kukungcamla kwe-sucrose. Ukuguqulwa kwe-DA-transporter ye-mutdown yogcino egcina kuphela i-10% yokudluliselwa kwesiqhelo kwi-DA, kwaye ke oko kubangela ukuba iimpuku eziguqukayo zinama-70% amanqanaba aphezulu e-synaptic DA, yayisetyenziselwa ukuqaphela iziphumo ze-DA kukutya kunye nomvuzo. Bafumanise ukuba i-hyperdopaminergic DA-transporter knockdown mutant iimpuku zazinokutya okuphezulu kunye nokutya okunamanzi. Kumsebenzi webaleki, izilwanyana zibonakalise ukuphuculwa kokufunyanwa kunye nokusebenza ngakumbi kokukhuthaza kumvuzo omnandi. Iimpazamo ze-Hyperdopaminergic mutant zishiya ibhokisi yokuqalisa ngokukhawuleza ngakumbi kunokuba zilungiselelwe uhlobo lweempuku zasendle, zifuna iimvavanyo ezimbalwa, ukuba zihlale kancinci kwindawo yokubaleka, zaxhathisa ukuphazamiseka ngakumbi, zaza zaya ngqo kwinjongo. Olu phononongo licebise ukuba iimpuku ezihlangeneyo ezinesifo esine-hyperdopaminergic zibonisa ukuba kukhuthazekile (ukufuna) kumvuzo omnandi kuvavanyo lokubaleka. Kodwa incasa ye-sucrose ayiphumelelanga ukufumana iimpendulo eziphezulu ze-orofacial hedonic ukuthanda iimpendulo ezivela kwiimpuku eziguqukayo kuvavanyo lokuphinda lusebenze. Ezi ziphumo zibonakalise ukuba i-DA enganyanzelekanga yangaphandle ikhuthaza ukufunwa kunye nokufunda komsebenzi wokukhuthaza womvuzo omnandi, kodwa i-DA ephakanyisiweyo ayonyusanga mpembelelo yokuthanda iimpembelelo ezinobunono. Ngokuchasene noko, ukwanda kokuphendula kokuthile kubangelwe yimpawu ye-hypodopaminergic okanye intswelo enokubakho ibotshelelwa kwiimpawu zepolymorphic kubandakanya i-DRD2 A1 allele [24-26].
Ukunyanga i-RDS
Ukuqwalaselwa kwe-hypothesis ethi ukunyanga i-RDS (umzekelo, iziyobisi ezinje ngokuxhomekeka kwecocaine) kufuneka kubandakanya, ubuncinci inxenye, i-DA D2 i-agonist agonistic agonistic therapy, Peng okqhubekayo. [U27] kuvavanye ukuphucuka kokuthatha ixesha le-monoamine reuptake inhibitor 31,345, i-analog ye-trans-aminotetralin, kwiindidi ezahlukeneyo zezilwanyana ezinxulumene nomlutha. Iziphumo zabo ziphakamise ukuba i-31,345 yecocaine ye-cocaine ye-cocaine ene-cocaine enokuthatha kancinci njengonyango lwe-agonist lokulutha i-cocaine. Nangona kunjalo, ipateni yayo yenyathelo yabonakala yahluke kakhulu kuleyo ye-methadone esetyenziswe njengemeko yonyango ye-agonist opioid. Peng okqhubekayo. [U27] Ucebise ukuba indawo efanelekileyo ye-agonist endaweni ye-cocaine kufuneka ilingise ngokupheleleyo isenzo se-methadone, oko kukuthi, isenzo esisebenzayo sokuchaphazela isenzo se-cocaine ngelixa uthintela abathuthi be-monoamine kwi-augment synaptic DA.
Malunga nonyango lwe-agonist, kubalulekile ukuba uqonde ukuba inani elisisiseko le-receptors ze-DA linokuqikelelwa ngokweziphumo ezahlukeneyo zekliniki kwi-RDS. UChen okqhubekayo. [U28] ufunde izifundo ze-10 nge-allele kwi-Taq1A DRD2 gene, edibene ne-DA receptor concentration kunye nokunciphisa iimpendulo ze-neural kwimivuzo (izifundo ze-A1 +). Izifundo zahlaziywa kabini, kanye kwi-placebo kunye kube kanye kwi-cabergoline, i-agonist ye-D2 receptor agonist. Kuhambelana nobudlelwane obungenakuthintelwa phakathi ko-U phakathi kwe-DRD2 polymorphism kunye neziphumo zeziyobisi, ikabergoline yonyusa iimpendulo ze-neural kwi-medial orbitofrontal cortex, i-cingate cortex, kunye ne-striatum yezifundo ze-A1, kodwa yanciphisa iimpendulo zomvuzo kwezi ngingqi kwizifundo ze-A1−. Ngokwahlukileyo, i-cabergoline inciphise ukusebenza komsebenzi kunye nokudibana kwe-fronto-striatal kwizifundo ze-A1 + kodwa zinefuthe elifanayo kwizifundo ze-A1−. Ukubaluleka kokuba ne-DRD2 A1 allele kwikhoboka leziyobisi kwaye unyango lwayo luyavumelana nezinye izifundo nguLawford okqhubekayo. [29] nguBlum okqhubekayo. [U30].
I-Neuroimaging kunye ne-Neural Substrates kwii-RDS Behaviors
Ko okqhubekayo. [U31] ichonge iziqwenga zemidlalo ye-neural yokulutha ngokukhuselekileyo kwi-intanethi ngovavanyo lweendawo zobuchopho ezinxulunyaniswa nomnqweno wokudlala. Abathathi-nxaxheba abalishumi abaye bafumana iziyobisi kwimidlalo ye-Intanethi kunye nezifundo ze-10 zokulawula ngaphandle kokulutha kwi-intanethi. Baboniswa ngemifanekiso yokudlala kunye nemifanekiso eqwetyiweyo ngelixa kusenziwa umzobo ocacileyo we-magnetic resonance imaging (fMRI). Umahluko kwizibonakaliso zegazi zeoksijini-ezixhomekeke (BOLD) xa ujonga imifanekiso yemidlalo xa ujonge imifanekiso esetyenziswa ukuvavanya ukusebenza kwengqondo. Kwizilingo zabo, i-cortex yasekunene ye-orbitofortal, ekunene i-NAc, i-cortex yangaphakathi ye-bilateal, i-cortex yangaphakathi ye-dentalolor yangaphambili, i-cortex yase-dorsolateral yangaphambili, kunye ne-nucleus ye-caudate yasekunene yenziwa kwiqela lomlutha ngokuchaseneyo neqela lokulawula. Ukusebenza kwezi ndawo zingasentla kobuchopho kudityaniswe kakuhle nomdla wokuzixela wokukhumbula kunye nokukhumbula amava emidlalo aphenjelelwa yimifanekiso yemidlalo. Iziphumo zabonisa ukuba i-neural substrate yomdla wokudlala we-cue-oqhubayo / ukuthanda inkanuko yokudlala kwi-Intanethi kuyafana noko komnqweno wokufumana into uxhomekeko kwizinto ezinje [32,33]. Ababhali baqaphele into eqhelekileyo phakathi kwemimandla yobuchopho enegalelo kukunqwenela ukuxhomekeka kwinto kunye nabo babandakanyekayo kwimidlalo ye-Intanethi. Ke, umnqweno wokudlala / umnqweno wokuthengisa iziyobisi kwi-intanethi kunye nokunqwenela ukuxhomekeka kwinto unakho wabelana ngendlela efanayo ne-RDS.
Kwisifundo usebenzisa i-fMRI yokuvavanya ukusebenza kwengqondo kwenkqubo yembuyekezo ye-DA ngexesha lomsebenzi wokungcakaza, uCohen okqhubekayo. [U34] ngokubonakalayo kubonise ukuba umahluko ophakathi kokutshintsha okungaphaya kunye nobukho be-A1 alale kwi-DA D2 i-receptor gene exelwe ngobuninzi bento yokusebenza. Kwimvavanyo ezimbini ezahlukeneyo, abathathi-nxaxheba bafumana umvuzo ngokulandelelana emva kokuphendula kokuziphatha, okanye emva kwexesha lokulindela le-7.5. Nangona iimephu zokuqalisa kweqela zivelise ulindelo- kunye nokwenza umsebenzi okunxulumene nomvuzo kwinkqubo yomvuzo, umahluko ophakathi kokuguqulwa okungaphaya kunye nobukho beD2 Taq1A allele waxela kwangaphambili ukwahluka okuphakathi kwesihloko kubuninzi bokunxulumene nomvuzo, kodwa hayi ulwalamano olunxulumene. . Ababhali baqaphele ukuba iziphumo zabo zixhasa ikhonkco phakathi kofuzo, ubuntu, kunye nokusebenza kwengqondo.
Inkuthazo enxulumene neziyobisi inokubangela umnqweno kwizigulana ezinamakhoboka, iqhubele ekuziphatheni ngokufuna iziyobisi. Ukongeza, uphononongo lubonise izigulana ezingamakhoboka ukuba zingaqwalaseli ubumnandi obunomdla, obungenzi iziyobisi, ezibonisa ukusilela kwempendulo yesiqhelo ye-hedonic okanye i-anhedonia [24]. Zijlstra okqhubekayo. [U35] ifumanise ukuba i-VTA ibibandakanyeka ikakhulu kwi-opioid ye-opioid ehambelana nomtshutshisi ohambelana ne-heroin, ukongeza kokubandakanyeka kwe-mesomimbic kunye neendlela ze-mesocortical njengoko zichongiwe kuphando lwangaphambili. Uphononongo lwabo lubonelela ubungqina obongezelelweyo obuxhasa ubukho bokwehliswa kwengqondo okuncitshisiweyo kwizigulana ezixhomekeke kwi-heroin ukuphendula isikhuthazo esimnandi esinxibelelene neziyobisi, ngokusebenza ngakumbi kwimikhwa yeziyobisi.
Ithiyori yeSalience yeNkuthazo kunye neeNdlela zoMvuzo
Ukutyeba kakhulu kuphawulwa ngokusetyenziswa okungaphezulu kokutya okunika amandla / okunika umvuzo, kubonakalisa ukungalingani ngokubaluleka kokulinganiswa kweempawu ze-hedonic ngokuchaseneyo neempawu zasekhaya. I-hypothesis yokhuthiso lwesessence yomvuzo wokutya ayamkeli kuphela icandelo le-hedonic / ulonwabo (ukuthanda) kodwa kunye necandelo lesikhuthazo (ukufuna). Okubaluleke kakhulu, ukusebenza kwe-neurobiological yeendlela zomvuzo wobuchopho kukuba inkqubo ye-DA engqinisisi inkuthazo hayi kuphela kwimivuzo yendalo njengokutya kodwa kunye nemivuzo yokufakelwa njengeziyobisi. Le nkqubo ye -ulekaaccumbal ye-DA ifumana kwaye idibanise ulwazi malunga nokukhuthaza / ukuxabisa ixabiso lokutya ngolwazi malunga nemeko yemetabolism. Ngokuka-Egecioglu okqhubekayo. [U36], ingxaki yokutya ngokungaphaya okunokubakho ibonisa ukulingana okuguqukayo kulawulo olugqityiweyo kwimijikelezo yomvuzo kunye / okanye notshintsho olukhulu kwindawo yokujonga into yokutya. Aba baphandi bafanayo babonakalise ukuba i-ghrelin isebenzisa inkqubo ye-DA eyi -accaccal kwaye ukutyikitya kwe-ghrelin ephambili kuyafuneka kumvuzo kuzo zombini iziyobisi ezinomlutha (umzekelo, utywala) kunye nokutya okuthandekayo.
Ngelixa i-ghrelin yaqala yavela njenge-hormone ekhutshwa sisisu ebandakanyeka kumgangatho wamandla, indlala, kunye nokuqalisa kwesidlo ngokuthatha inyathelo kwiziphaluka zokutya ezinxulumene nendlala, ngoku kubonakala kucacile ukuba i-ghrelin ikwadlala indima kukuziphatha okuqhutywa ngumvuzo ngokwenza kusebenze indawo ebizwa ngokuba yi-cholinergic-dopaminergic37,38]. NgokukaDickson okqhubekayo. [U38], eli khonkco lomvuzo liquka ingqikelelo ye-DA ukusuka kwi-VTA ukuya kwi-NAc kunye negalelo le-cholinergic, evela ngokuyintloko kwindawo yendawo ye-laterodorsal tegmental (LDTg). Ngapha koko, ulawulo lwe-ghrelin kwi-VTA okanye kwi-LDTg lusebenzisa ikhonkco lomvuzo we-cholinergic-dopaminergic, licebisa ukuba i-ghrelin inokunyusa ixabiso lokukhuthaza lokuziphatha okuzinzileyo njengokufuna umvuzo (ukufuna okanye ukhuthazo). Ngokubalulekileyo, isitofu ngqo se-ghrelin kwii-ventricles zobuchopho okanye kwi-VTA yonyusa ukusetyenziswa kokutya okunomvuzo kunye notywala kwiigundane nakwiigundane. Izifundo kwiintonga zibonisa iziphumo eziyingenelo ze-ghrelin receptor (GHS-R1A) ezichasene nengcinezelo yokutya okungathandekiyo, ukunciphisa ukuthanda ukutya okune-caloric, ukucinezela umvuzo wokutya kunye nokuziphatha okukhuthazayo kukutya [39]. I-Ghrelin receptor (GHS-R1A) abachasi nabo baye babonakaliswa ukunciphisa ukusetyenziswa kotywala, ukucinezela umvuzo obangelwa butywala, icocaine, kunye neamphetamine. Ngapha koko, ukwahluka kwi-GHS-R1A kunye ne-pro-ghrelin genes kunxulunyaniswa notywala obuninzi, ukutshaya, kunye nokunyuka kwesisindo kubantu abaxhomekeke kotywala, kunye ne-bulimia amanosa kunye nokukhuluphala [40]. Sicebisa ukuba ezi zinto zifunyanisiweyo nabachasene ne ghrelin kunye neesini ezinxulumene nazo zichaphazela uninzi lwezinto eziziphetheyo njengoko kuxelwe kwingcinga yeRSS.
Umsebenzi we-bio-behaviour yokuziphatha sele uvele kwielebhu ezininzi. UDavis okqhubekayo. [U41] Ucebise ukuba uphando malunga nokukhuluphala kunesiphumo sokubandakanyeka okungaphezulu apho bonke abathathi-nxaxheba abanesalathiso sobunzima bomzimba ngaphaya kwexabiso elithile le-cutoff (umz. 30) zihlala zidityaniswa kwiqela elinye kwaye zithelekiswa nezo zinobunzima obuqhelekileyo. Baye bavavanya imbonakalo yemfuza kunye neyengqondo yokutya kwe-hedonic kubantu abadala abatyebileyo kunye nesifo sokutya kakhulu (BED). Uhlalutyo lwabo lugxile kwi-DA nakwiimpawu ze-opioid zemfuzo ngenxa yokudibana kwabo kunye nokusebenza kweendlela zomvuzo wobuchopho. I-polymorphisms ezintathu ezisebenzayo ezinxulumene ne-D2 receptor (DRD2), kunye nokusebenza kwe-A118G polymorphism ye-mu-opioid receptor (OPRM1) gene. Bafumanise ukuba ubukhulu becala ulawulo lokutyeba kakhulu lunokulahleka-kokusebenza kwe-A1 ye-Taq1A ngokuthelekiswa neqela labo le-BED, ngelixa inzuzo ye-function ye-alilele ye-A118G yenzeka rhoqo kwiqela le-BED. Umdibaniso obalulekileyo wenzala ye-gene-gene eyi-X2 uhlalutyo lwabonisa ukuba kwabo babathathi-nxaxheba kwinzuzo yokufumana inzuzo (i-G + kunye ne-A1), i-80% yayikwiqela le-BED ngelixa i-35% kuphela yayine-genotype yelahleko elahlekileyo (G− kunye ne-A1 +) kweli qela. Izifundo ze-BED zazinamanqaku aphezulu kumgangatho wokunikwa kwengxelo yokutya kwe-hedon. Iziphumo zabo banokucebisa ukuba i-BED luhlobo olusekelwe kwimvelo lokutyeba kakhulu okanye i-RDS, kwaye ukuba umntu othambekele ekutyeni kakhulu unokuphembelelwa kukuphinda-phinda ukusebenza kwakhona kwimpahla yokutya ye-hedonic - into ebekwa phambili ngokokutsho kukaDavis okqhubekayo. [U41] isetyenziswa lula kwimeko yethu yangoku ngokubonakalayo nokufumaneka ngokulula kokutya okumnandi nokunamafutha. Isigqibo sabo sokuba iDA yeyoku “funa” kunye nee-opioid ezenzelwe "ukuthanda" isenokuba lula kakhulu. Kubalulekile ukuba uqaphele ukuba isenzo se-neurotransmitter yinto eqhubekekayo yokuhlangana kweziganeko kwaye akukho mntu kunye ne-neurotransmitter eyodwa ebonelela ngeziphumo ezihlukileyo.
Ukubuyela kwakhona kunye ne-Super Super Sensitivity kwi-Receptors
Kwiphepha elingaphambi kokuphinda kunyuswe-ukuphuculwa kwamayeza (i-DART) [11], sibhengeze ukuba ukubuyela kwakhona kweziyobisi zokuxhatshazwa kunye nezinye iziyobisi kunokubangelwa yi-DA D2 receptor super-sensitivity. Ngokukodwa, nangona abathwali be-A1 / A2 genotype banokuthi banciphise amanani e-D2 receptors kodwa izixa eziqhelekileyo ze-presynaptic DA, xa bengcakaza (umsebenzi obandakanya ulindelo lomvuzo), banokufumana ukukhutshwa kakhulu kwe-DA. Into enomdla kukuba, iindlela ezahlukeneyo kunye / okanye izinto zinxulunyaniswe nezixa ezahlukeneyo zokukhutshwa kwe-NAc DA. Umzekelo, ukutya kubangele ukukhutshwa kwe-6% ye-DA, umculo ukhululwe nge-9%, kunye ne-cocaine eyi-22% yokukhutshwa [42]. Ukutya kuvelise impendulo etyabekayo yokutya kokutya okuthandekayo kwabasetyhini abaye bafumana ubunzima malunga nexesha elifutshane elihambelana nabasetyhini abazinzileyo [12]. Ukungcakaza okunxulunyaniswa ne-genetics ye-DA eqhubayo [43], ivelise impendulo egwenxa [44]. Siyavuma ukuba uxinzelelo olunxulumene nokungcakaza luvelisa ukwanda okumangalisayo kokukhutshwa kwe-DA kwi-synapse [45], kodwa ukutya kungaphumeleli ukuvelisa ezo nqanaba zokuzikhukula kwe-DA.
Blum okqhubekayo. [U11] uqaphele ukuba ubuntununtunu obukhulu bunokubakho nakwi-DRD2 A1 izifundo ezifanelekileyo ezincitshisiweyo (30-40%) D2 receptors. Olu luvo lubalaseleyo lunokubangelwa kukuncitshiswa-ukuphuculwa. Kuyaziwa ukuba amanani ancitshisiweyo ama-receptors e-D2 (ngokunokwenzeka nge-D2 polymorphisms okanye enye indlela), avelise uvakalelo oluphezulu lwe-receptors ye-D2 eseleyo [46]. Ukuxhasa lo mbono, uHarrison noLaHoste [46] ixele ukuba i-striatal receptors ye-DA iye yanyanzeleka xa igalelo le-dopaminergic lisuswa ngokusebenzisa ukubekwa emngciphekweni okanye ukuncipha kwecandelo lezonyango, okanye ngeendlela zepolymorphisms.
Xa i-dopaminergic igalelo kwi-striatum isuswa ngokunyanga okanye kwi-pharmacologic, ii-receptors ziba novakalelo kakhulu. Nangona iinguqu ezinje ngokunyuka kwe-receptor ye-D2 eyandayo kunye nokudibanisa i-receptor-G protein kuye kwachazwa kwi-super striatal izicubu, iindima zabo kumatshini weemvakalelo eziphezulu zihlala zingaqinisekanga. I-Ras Homolog Ence e-Striatum (iRhes) iyafana namalungu e-Ras-enje nge-GTP ebopha usapho lweprotein, kwaye ichazwa kwiindawo zobuchopho ezifumana igalelo dopaminergic. UHarrison noLaHoste [46] ndivavanye ukuba ingaba utshintsho kwi-Rhes expression kuhamba kunye nonyango olukhuthaza ubuntu kwi-receptor super-sensitivity in rats. Ukususwa kwegalelo le-DA kwisistriatum ngokubekwa kwe-6-hydroxydopamine kubangele ukwehla kwentetho ye-Rhes mRNA kuyo yonke i-striatum, njengoko ilinganiswa ngokobungakanani kwi-hybridization. Ukwehla kwafunyaniswa kwangoko kwiiveki ezimbini kwaye emva kweenyanga ezisixhenxe emva kotyando. Ngaphaya koko, ukwehla kwe-Rhes mRNA kwabonakala emva konyango oluphindaphindiweyo okanye olubuhlungu nge-reserpine (ye-depleator ye-DA). Ukugula okungapheliyo kwemihla ngemihla ngamagundwane kunye ne-D2 antagonist eticlopride, eyaziwa ngokuba yimeko yolawulo kwii-receptors ze-D2 ngaphandle kokwenza uvakalelo olukhulu lwe-receptor, ayitshintshanga intetho ye-Rhes mRNA kwi-striatum. Ke, iinguqu kwisenzi se-Rhes mRNA zazinxibelelana ngokungqongqo nemvakalelo ye-receptor super, mhlawumbi njengesiphumo sokususwa okuqhubekayo kwengxelo yedopaminergic, njengoko kunokuba njalo kwi-RDS eyenzelwe oko.46]. Ezi ziphumo zibonisa ukuba i-Rhes mRNA expression igcinwe yi-DA kwaye inokudlala indima ekumiseleni uvakalelo oluqhelekileyo lwe-receptor ye-DA. Lo ngomnye umzekelo wendlela u-receptor super sensitivity angabonakala ngayo. Ke ngoko, iziphumo ezibiweyo okanye eziphakamileyo ezivela kwizinto zengqondo (umzekelo, utywala, icocaine, i-heroin, inicotine, iswekile, njl njl) kunye nokuziphatha (ngokwesondo, ukungcakaza, njl. Njl.) Zibonakala zintsokothile kwaye zinokuhambelana kakuhle nokuhlangana kwe-molecule-receptor. isimilo. Sicinga ukuba zonke ezi mpembelelo zibonakala ngathi zahluka-hlukeneyo ziyaxhomekeka kwaye ziswele umvuzo. Uphando olongezelelweyo, ke, luyafuneka ukuze kutyhilwe iindlela ezilawula iindlela zokuziphatha zokuxhomekeka kumvuzo.
Ngaba Indima kaDopamine “Ngaba uyafuna,” “uyafunda” okanye “uyathanda”?
Ngelixa kunokubonakala kunzima ukwahlula indima ye-DA kwiinkqubo zembuyekezo yobuchopho, iqela labaphandi lizamile ukwenza njalo. Robinson okqhubekayo. [47] iphonononge ukuba ingaba i-DA ilawula ukuthanda, ukuthanda, kunye / okanye ukufunda ngembuyekezo ngexesha lokuziphatha oluya ngqo kwiinjongo. Abaphandi bavavanye i-genetological engineering dopamine-defence (DD) ukuze bafumane umsebenzi onomdla we-T-maze ngaphandle kokubonisa uphawu lwe-DA. Bafumanisa ukuba iimpuku ze-DD ziphathwe nge-L-dihydroxyphenylalanine (L-dopa) eyenziwa ngokufanayo kulawulo kwimisebenzi ye-T-maze eyenzelwe ukulinganisa ukuthanda, ukufuna, kunye nokufunda ngemivuzo. Nangona kunjalo, olunye uvavanyo, oluvavanya i-saline-, icafefeine, kunye neempazamo ze-D-Dopa ezikwi-T-maze, zahlukanisa izinto zokusebenza kwiinkqubo zengqondo, kwaye iziphumo zatyhila ukuba i-DA yayinganyanzelekanga ukuba iimpuku zithande okanye zifunde malunga imbuyekezo, kodwa kwakuyimfuneko ukuba iimpuku zifune (zifuna) imbuyekezo ngexesha lokuziphatha elijolise kwinjongo. Eyona nto ibalulekileyo, nguRobinson okqhubekayo. [47] ibonakalise ukuba ukufundwa komvuzo kunokuqhubeka ngokuqhelekileyo kubuchwephesha be-DD, nangona bebengekho iDA ngelo xesha lokufunda, ukuba iimpuku zinikwe icaffeine ngaphambi nje kokufunda. I-Caffeine yasebenza ngeempuku ze-DD yindlela engeyiyo eyedopaminergic, ivumela ukuba zifunde apho zifumana khona umvuzo wokutya kwindawo yokubaleka ye-T-maze. Umvuzo wabo-wokufunda-ngaphandle kwe-DA watyhilwa ngemini elandelayo yovavanyo, xa umsebenzi we-DA ubuyiselwe kulawulo lwe-L-dopa. Robinson okqhubekayo. [47] Iqukumbele ukuba i-DA yayingafuneki kwimfundo eqhelekileyo malunga nemivuzo, okanye ukuthanda imbuyekezo ngexesha lokufunda, kodwa ilungiselelwe icandelo lokufuna umvuzo. Ezi ziphumo ziyavumelana nokufunyenwe nguDavis [41] (njengoko bekutshiwo ngaphambili) iphakamisa ukuba iDA yeyoku "funa" kunye neeopioid ezenzelwe "ukuthanda".
Wilson okqhubekayo. [48] ukuphanda ngokucwangcisiweyo kwindima yee-neurotransmitter ku “Ukufuna” kunye “nokuthanda”. Baye bavavanya iigundane elandela ukukhohlakala, ukulawulwa kwenkqubo yeziyobisi ezonyusa i-serotonin kunye ne-noradrenaline (imipramine), i-DA (GBR 12909), kunye ne-opioid (morphine) kumsebenzi wokuziphatha owenzelwe ukulinganisa ukuthanda kunye nokuthanda. Imipramine ixhase imiphumo yokulibaziseka kunye nokungcamla kwimbuyekezo "yokufuna", i-GBR 12909 ichaze imiphumo yokulibaziseka kumvuzo "ofuna" kunye neempembelelo zokungcamla kumvuzo "ukuthanda," kunye ne-morphine inciphise isiphumo sokulibaziseka kwinqanaba lomvuzo " kuba morphine yehlulekile ukukuchaphazela umvuzo "ukuthanda," kodwa ngaphambili ibifunyenwe inyusa umvuzo "ukuthanda" kwiimvavanyo zokwenza umsebenzi kwakhona, kwaye ekubeni i-DA ibonakala ichaphazela zombini "ukufuna" kunye "ukuthanda", ezi datha zibalaselisa ubunzima lo mxholo, kunye nemfuno yophando olucacileyo.
Nangona kunjalo, bukhona ubungqina bokuba umsebenzi we-DA ayisiyeyo ekuphembeleleni ukonwaba ngese kodwa kunoko uyimfuneko ekuzonwabiseni. Iziphumo zeSchmidt okqhubekayo. [49] ayixhasanga i-anhedonia hypothesis yangaphakathi dopaminergic dysfunction njengoko kucetyiweyo abanye abaphandi [50-52]. Endaweni yoko, ukuthambeka okubambekayo kubonakaliswa yimvakalelo ye-receptor ye-DA kunokubangelwa kukungabikho kwempendulo ebonakalayo ngokubhekisele kumvuzo obonakalisa umvuzo. Ezi ziphumo zibonise ukuba izigulana ezinengxaki yokuphazamiseka emzimbeni (dopaminergic dysfunction) azikwazanga ukufumana ulonwabo, kodwa zinokuba zasilela ukukhuthazeka yimeko yokusingqongileyo yokufuna umvuzo. Ubume bendlela yeendlela zembuyekezo zibonakaliswa kwakhona ngumsebenzi kaMirenowicz noSchultz [53], ndicebisa ukuba ii-neurons ze-DA kwiinkawu zenziwa zangabinamdla wokutya okungafunekiyo njengokutya kunye nemivuzo engamanzi nangokubhengeza kwangaphambili komvuzo. Baye bafumanisa ukuba ngokwahlukileyo kwimicimbi yolangazelelo, umdla ophambili kunye nomgangatho onesimo esivumayo mhlawumbi asiphumelelanga ukwenza ii-neurons ze-DA okanye iimpendulo ezibuthathaka kunokubangela umdla. Ke, ii-neurons ze-DA zichaze kuqala ukonyuka kwendalo ngokunomdla kunokuba iphindisele ixabiso elixhasayo.
Qaphela, uluvo lokuba ivuselela inkanuko kunye nokuvuselela umdla kwiimpembelelo ezifanayo, yinto ebaluleke kakhulu kwimbono yokuba i-DA ityikitya isidenge. Nangona kunjalo, ayisiyi-DA kuphela eziphethe ngale ndlela. Iipeptides ezifana ne-corticotropin-ekhulula iihormoni nazo ziphendula ngokufanayo kuzo zombini ezi ntlobo zokhuthaza, nangona ubukhulu beenguqu azifani. Ekugqibeleni, uKob noVolkow [54] xa kuxoxwa malunga nokusetyenziswa gwenxa kweziyobisi, wagxininisa indima ekunyanzelisweni nasekunyanzelisweni okukhokelela kumjikelezo kathathu wokubandakanyeka okubandakanya amabakala amathathu: ukuluma / ukunxila, ukurhoxisa / ukungachaphazeli / ukungalunganga, kunye nokugxila / ukulangazelela (ukunqwenela). Ukunyanzelwa kunye nokunyanzelwa, kunye namanqanaba ahlukeneyo kumjikelezo, aboshwe kwiinkqubo ezithile zobuchopho. Ngokucacileyo, umfanekiso awuyonto ilula.
Iziphumo ezibanzi
Ngokophando lwesiNgesi olwenziwe nguSharot kunye nezinxulumene [55], ubuchwephesha bemichiza be-DA buchaphazela indlela abantu abazenza ngayo izigqibo ezilula nezintsonkothileyo, ukusuka kwinto yokwenza isidlo sangokuhlwa ukuya nokuba nabantwana. "Abantu benza izigqibo ezintsonkothileyo kunezinye izilwanyana - njengowuphi umsebenzi ekufuneka bawuthathe, ukuba bangaya phi eholideyini, nokuba banokuqala usapho- kwaye besifuna ukuqonda indima yedopamine ekwenzeni ezi ntlobo zezigqibo." Abaphandi babonise ukuba uL -Dopa iphucule umsebenzi wedopaminergic ngexesha lolwakhiwo lweengcinga ezintle zekamva lobomi, kamva iingqikelelo zokuphucula ulonwabo lwe-hedonic ("ukuthanda") eziza kuthathwa kwezi ziganeko ezifanayo. Ezi ziphumo zibonelele ubungqina obungathanga ngqo ngendima ye-DA kumanyumnyezelo wolindelo lwengqondo lwe-hedonic ebantwini.
izigqibo
I-hypothesis yokuqala ye-RDS iphakamise ukuba uxinzelelo okanye ukungasebenzi kwe-mesolimbic DA kubangela ukhuthazo lokufuna umvuzo osisiseko oyimpembelelo [2,3]. Emva kwexesha, ubungqina obuvakalayo bunyanzelekileyo babonisa ukuba amandla okuqhuba okusetyenziselwa iziyobisi 'ayakuthanda' hayi ngokufuna nje [51-52,56], kodwa obunye ubungqina bukwabonisa indima 'yokufunda' [23]. Ngokusekwe kunobungqina, sicebisa ukuba i-RDS kufuneka ichazwe ngokutsha ukuba ichaze indima eyodwa ye-DA "yokufuna," "ukufunda," okanye ukuthanda ". Nangona kunjalo, i-hypothesis ye-RDS iyaqhubeka ukubala ukuba ukusebenza kwe-hypodopaminergic kusongela umntu ukuba afune izinto zengqondo kunye nokuziphatha ukukhupha i-DA kwimijikelezo yomvuzo wobuchopho ukoyisa ukusilela kwe-DA. Nangona kwasekuqaleni bekukholelwa ukuba imane ibetela indawo yeethoni ye-hedonic, ezi zisekethe ze-DA okwangoku zikholelwa ukuba ziyasebenza kakhulu, zinika ingqalelo, ukukhangela umvuzo, ukungqinisisa ukulindelwa komvuzo, kunye nokhuthazo lokukhuthaza. Ukudakumba kweHedonic ngaphakathi kwezijikelezo kunokukhokelela kwikhobokisa [5]. Icandelo lesibini le-dopaminergic elikwinqanaba lomvuzo licandelo elinobuchule kakhulu lokuchaphazela iziyobisi. Zonke iziyobisi eziluthayo zinokubakho ngokufanayo ukuba ziphucula (ngokuthe ngqo okanye ngokungathanga ngqo okanye nkqu ne-transsynaptically) umsebenzi we-dopaminergic umvuzo we-synaptic kwi-NAc [6]. Ukulawulwa kweziyobisi kulawulwa ngamanqanaba e-NAc DA, kwaye kwenziwa ukugcina i-NAc DA ikwinqanaba elithile eliphakamileyo (ukugcina inqanaba le-hedonic elifunayo). Ngapha koko, kubalulekile ukukhumbula ukuba i-hypothesis ye-DA endala [57], Imodeli yenkqubo enye, eceliwe ukuba i-neurotransmitter DA idlale indima ebalulekileyo ekulamleni iipropathi ezinomvuzo zazo zonke iiklasi zesikhuthazo. Ngokwahlukileyo koko, bobabini abalinganiswa / abangathathwanga kunye neemodeli zobuchule bokungqinisisa bathi iinkqubo ezahlukeneyo zenza igalelo elizimeleyo lokufumana umvuzo. Indawo yangaphambili ichonga umda wengqondo ochazwa ziinkqubo zombini njengophakathi kwamazwe okungaxhamli (umz., Ukutya okwaneleyo) kunye nokuswela (umzekelo, indlala). Le yokugqibela ichonga umda phakathi kweendlela zokuthanda kunye nokufuna. Ngokwenza oko, ukuqonda okutsha nguBerridge nabanye [1,54] ayisihoyi eyona nto ibangela ukuba likhoboka eli njengoko kucetyiswa ingcinga ye-RDS. Ngokombono wethu indima yokusilela kweDA ihlala ingumba ophambili wokufuna indlela yokuziphatha Olunye uphando olwenziweyo kusetyenziswa izixhobo zokufanisa ziya kubonelela ngolwazi olufanelekileyo lokudibana oluyimfuneko ukubonisa indima ye-DA kumjikelezo womvuzo nakwimikhwa ye-RDS.
Imibulelo
UMarlene Oscar Berman, Ph.D. Ngumamkeli weenkxaso-mali kwi-NIAAA (R01 AA07112, K05 AA 00219) kwaye usuka kwiNkonzo yoPhando lwezoNyango kwiSebe leMicimbi yeVeterans yaseMelika.
Imihlathi
Ukugqubana kwemidla:
UKenneth Blum, i-PhD inesitokhwe eLifeGen, Inc., isasazi esikhethekileyo emhlabeni jikelele samalungelo obunikazi anxulumene nomvuzo Defence Syndrome (RDS).
Ucaphulo
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