I-Prefrontal / i-accumbal system ye-catecholamine isebenza ngobuchule obukhulu bokukhuthaza (2012)

Front Behav Neurosci. I-2012; 6: 31. I-Epub 2012 Jun 27.

Internet: inkuthazo, imvakalelo, isidima, i-norepinephrine, i-dopamine, imvelaphi yangaphambili, oonobumba

Inkuthazo yenkuthazo kunye ne-mesoaccumbens

Kule minyaka mashumi mabini idlulileyo ithiyori ithiybhile yokufezekisa okubaluleke kakhulu kwisayikholoji kunye ne-neuroscience. Ithiyori yenkuthazo yenkuthazo ibiyindlela ebalulekileyo kwindlela ekhokelela kuphuhliso olubaluleke kangaka. Iingcamango zokhuthazo lokukhuthaza ukunyuka kwii-1960s xa ukwaziwa okutsha malunga nengqondo kunye nokhuthazo kukhokelele uninzi lweengcali zengqondo kunye nokuziphatha kwe-neuroscientist ukuba yenqabe ukuqhuba okulula kunye neethiyori zokunciphisa. Iithiyori ezichaseneyo ezithile zaqulunqwa ngohlobo lwethiyori zezikhuthazo (iiBolles, 1972; Bindra, 1978; Iifestile, 1986, 1994; I-Panksepp, 1998; IBerridge, 2001). Iingcali zebhayoloji ezintathu zenza igalelo elikhulu ekukhuleni kwalo. Iibhola (1972) iphakamise ukuba abantu abathile bachukunyiswe kukulindelwa okukhuthazayo, kungekuko ukuqhuba okanye ukuncitshiswa kwe drive. Ukulindelwa okukhuthazayo, iiBolles ezibizwa ngokuba yi-S-S^* Imibutho, eyafundisWe ngokulindelweyo komvuzo we-hedon, engaqondakali kuqikelelo lwengqondo. Ngokuhambelana, isivuseleli sokungathathi hlangothi (S), njengokukhanya okanye isandi, siye sanxulunyaniswa nokubhanqa okuphindaphindiweyo ngomvuzo we-hedonic owalandelayo (S^*), njengokutya okuthandekayo. I-S ibangele ukulindeleka kwe-S^*. I-S yayi, ngokweenkqubo zokufunda zePavlovian, inkuthazo enomgangatho (CS okanye CS +), kunye ne-S^* isikhuthazo esingavunyelwanga (UCS).

Bindra (1974, 1978) yamkelwe into yokuba ulindelo lungabalulekile kwiqhinga lokuqonda lokufumana umvuzo, kodwa yacebisa ukuba i-CS yomvuzo inyusa imeko ekhuthazayo efanayo ebangelwa ngumvuzo ngokwawo, njengesiphumo sobume bohlobo. Unxibelelwano olufundileyo alubangeli ulindelo lomvuzo. Ikwabangela umntu ngamnye ukuba azibone i-CS njengomvuzo we-hedonic, kwaye ivumela i-CS ukuba ichukumise inkuthazo kanye njengoko bekuya kuba ngumvuzo wokuqala we-hedonic. Oko kuthetha ukuba i-CS ithatha iipropathi zentshukumo ezithile eziqhele ukuba zezesi-S^* ngokwayo, kwaye ezi zinto zisishukumisayo zizakhiwo ezikhuthazayo. Qaphela ukuba oku kuyinyani ayisiyomvuzo S kuphela^*, kodwa kunye nentlungu S^* ukukhuthaza, oko kuya kusekelwa kukoyiko okanye kuzohlwayo zepropathi. Iifestile (1986) Ihlengahlengise iimbono zeBolles-Bindra iphakamisa ukuba imeko yokuphela komzimba inokuphucula ixabiso lokukhuthaza iinjongo zabo. Oku kukhokelela kukunxibelelana okuphindaphindayo phakathi kwentsilelo yomzimba kunye nenkuthazo yangaphandle, ethe yagqiba ixabiso lenkuthazo. Nangona kunjalo, imiqondiso yokusilela komzimba ayiqhubeki nokuziphatha okukhuthazayo ngokuthe ngqo, kodwa bayakwazi ukukhulisa ifuthe le-hedonic kunye nexabiso lenkuthazo yomvuzo uqobo (S^*), kunye nexabiso le-hedonic / inkuthazo yenkuthazo yomvuzo (ii-CSs). Ngokujikeleze i-1990 imodeli yesikhuthazo yesasense yacetywayo (iBerridge et al., 1989; IBerridge kunye neValenstein, 1991) elandela iBindra-Toate imigaqo yemeko yenkuthazo kodwa ichonga amacandelo engqondo ahlukanisayo “ukuthanda” umvuzo othelekiswa “nokufuna” umvuzo ofanayo. "Ukuthanda" ngokuyimpembelelo ye-hedonic-intshukumo yengqondo eqhutywa kukuzonwabisa okwenziwa ngokukhawuleza kukufumana umvuzo, umzekelo, incasa emnandi (engathandekiyo "engathandekiyo").

"Ukufuna," okanye ukukhuthaza isidenge, lixabiso lokukhuthaza lomvuzo ofanayo (iBerridge neRobinson, 1998), ixabiso lesishukumiso senkuthazo, hayi impembelelo ye-hedonic. Inqaku elibalulekileyo kukuba "ukuthanda" kunye "nokufuna" zihlala zihamba kunye, kodwa zinokwahlulahlulwa phantsi kweemeko ezithile, ngakumbi ngokusetyenziswa kwengqondo okuthile. Ukuthanda "ngaphandle" kokufuna "kunokuveliswa, kwaye ngoku" kufuna "ngaphandle kokuthanda.

Inkuthazo inokuthi ichazwe ngokwenyani njengenkqubela phambili apho isikhuthazi sinokuqinisa okanye ukohlwaya iimpendulo kolunye untshukumo. Ngokuziphatha kakuhle, isikhuthazo esomeleza ukubizwa ngokuba ngumvuzo kunye nezohlwayo ezinxaxhileyo (Isikhumba, 1953). Umvuzo kunye nokuphambuka kuchaza ifuthe lesinyanzelo esinaso ekuziphatheni, kunye nokubonelela ngeempawu ezisishukumisayo, ngoko ke sinakho ukubonakalisa uphawu lokunganyanzeleki.

Imodeli yokhuthazo lwesisweli igxininisile kwindima ephambili yokusebenza kwe-dopamine (DA) njengendlela yokusebenza kwengqondo yeenkqubo ezishukumisayo. Ngokwenyani uxinzelelo lwe-DA lushiya umntu phantse ngaphandle kwesizathu sayo nayiphi na into ekhuthazayo: ukutya, isondo, iziyobisi, njl. Njl. (Ikemoto kunye nePanksepp, 1999; UNaranjo et al., 2001; IBerridge, 2004; USalamone et al., 2005). Ke ngoko, ukuphazamiseka kwenkqubo ye-mesolimbic ye-DA ngokuhamba kwezilonda zendlela ye-DA ethi iiprojekthi ziye kwi-nucleus accumbens (NAc) okanye ngokuthintela iziyobisi, kunciphisa ngokubabazekayo okanye "ukufuna" ukutya umvuzo omnandi, kodwa ayinciphisi imbonakalo yobuso "ukuthanda" umvuzo ofanayo (Pecina et al., 1997; IBerridge kunye neRobinson, 1998).

I-DA inendima ebaluleke kakhulu kulawulo lwentshukumisa. Olunye uhlobo lwe-neuron ye-encodos ye-DA yokuxabiseka, inomdla kwimicimbi enomvuzo kwaye ithintelwe zizigantsontso okanye izigameko ezixinzelelweyo (Bromberg-Martin et al., 2010; ICabib nePuglisi-Allegra, 2012, yoqwalaselo). Ezi zi-neurons zixhasa iinkqubo zobuchopho zokukhangela iinjongo, ukuvavanya iziphumo, kunye nexabiso lokufunda. Ewe, uninzi lwee-neuron ze-DA zenziwa zangumvuzo wokuxela umvuzo kunye neempazamo zekhowudi yokuxela umvuzo (okt, ngcono kunokuba kulindelwe / kubi kakhulu kunokuba kulindelwe) ebantwini, iinkawu, kunye neempuku (Ikemoto kunye nePanksepp, 1999; Ikemoto, 2007; Schultz, 2007). Nangona ivuselela inxaxhileyo efana nokuphefumla komoya, iswekile yehypertonic, kunye nothuselo lombane ukwenza iimpendulo kwinani elincinci lee-neurons ze-DA kwizilwanyana ezipholileyo (iGuarraci neKapp, 1999; UJoshua et al., 2008; Matsumoto kunye neHikosaka, 2009), uninzi lwee-neurons ze-DA zixinezelekile ngenxa yokuthandabuza (Ungless et al., 2004; UJou et al., 2009). Le yantlukwano yokuphendula ibonisa ukuba iiseli ezirekhodiweyo ziyinxalenye yezijikelezo ezahlukeneyo, ezizimeleyo (iMargolis et al., 2006; Ikemoto, 2007; UBromberg-Martin et al., 2010). Uhlobo lwesibini lwe-neuron ye-encode ye-DA eyashukumisayo, eyonwabisayo yeziganeko ezonwabisayo nezihlaziyayo (Bromberg-Martin et al., 2010).

Ubungqina bucebisa ukuba amaqela ahlukeneyo e-neuron ye-DA adlulisela imiqondiso ekhuthazayo ngeendlela ezizimeleyo (iMatsumoto neHikosaka, 2009) kunye ne-mesocorticolimbic ye-DA inkqubo inokuqulathwa ngemijikelezo eyahlukileyo, nganye iguqulwe ngamanqaku aqinisekileyo okuqhubela phambili, ngokubhekisele kwingqikelelo ye-DA kwi-NAc medial shell mediation stimuli entle, kuqikelelo lwe-DA ukuya mpFC echatshazelwa kukuthandabuza, Igobolondo elichukunyiswe kukuvuyisa kunye nokukhuthaza ukuvuselela, ukubonakalisa ubuntu (uLammel et al., 2011). Ibonisiwe indlela i-VTA DA neurons enokuthi isebenzise ngayo isicwangciso sokuguqula ikhowudi yokuguqula amava afanelekileyo kunye nokubi, ukudibanisa ngokusondeleyo kunye nemikhwa kunye nemeko yokusingqongileyo (uWang noTsien, 2011).

Inkqubo ye-mesolimbic dopaminergic system, yokuba iiprojekthi ezivela kwindawo ye-ventral tegmental ndawo (VTA) imizimba yeeseli zemithambo ye-nerost ukuya kwi-NAc, ikhonkco eliphambili kwindlela yomvuzo (Isilumko, 1996, 2004). Nangona kunjalo, ukukhutshwa kwe-DA akuyimfuneko kuzo zonke iindlela zokufunda ngembuyekezo kwaye akunakuhlala "kuthandwa" ngombono wokwenza ulonwabo, kodwa kubalulekile ukwenza ukuba iinjongo zibe "zifunwa" ngombono wokuqhubela phambili amanyathelo okuzifezekisa ( URobinson kunye neBerridge, 1993, 2003; IBerridge kunye neRobinson, 1998; I-Palmiter, 2008).

Umgca wobungqina obuxhasa indima ye-DA kwizinto ezisishukumisayo zokuvela kweshukumiso esivela endaweni yomgaqo wokubekwa endaweni (Mucha no-Iversen, 1984; van der Kooy, 1987; UCarr et al., 1989). Le paradigm inyanga ukonyuka kwexesha elichithwe kwindawo edibene ne-UCS (nokuba ziziyobisi okanye yokomeleza kwendalo) njengesalathiso sepropathi yomvuzo wokukhuthaza. Ngokwahlukileyo, ukuba izilwanyana zivezwa ngokuphindaphindiweyo kwindawo ebhangqwe ngamandla avuselelayo baya kuyiphepha imeko-bume. Kwimeko yokuqala sithetha ngokukhetha indawo ekhethiweyo (CPP), kwindawo yesibini yokumisa indawo (CPA). Abachasi be-DA babephethwe ngaphambi kweseshoni nganye yemeko yokuma kunye ne-amphetamine block amphetamine-ekhethiweyo kwindawo ekhethiweyo (Nader et al., 1997 uphononongo). Ezi ziphumo azinakho ukutolikwa ngokubhekisele kwintsilelo yokufunda ngokubanzi kuba izilwanyana zibonisiwe ukuba zikwazi ukwakha imibutho ye-CS-US eqhelekileyo kwimeko enomndilili nezinye i-US (Shippenberg neHerz, 1988). Ezi ziphumo zibonisa ukuba ukuhanjiswa okuqhelekileyo kwe-DA kuyimfuneko ukuze izakhiwo ezinomvuzo zenzeke.

Ukuba indlela yedopaminergic esuka kwiVTA iye kwi-NAc ikhonkco eliphambili kumendo ohamba ngeendlela zokuhambisa izinto ezishukumisayo (Tsai et al., 2009; I-Adamantidis et al., 2011), imizekelo yomvuzo ozimeleyo we-DA kufuneka ungabikho. Kukho inani lemizekelo, nangona kunjalo, yenkuthazo eneempawu zokuqinisa ezizimeleyo ze-DA. Ke ngoko, uvavanyo lokuziphatha kwezonyango lubonisa ukuba nangona usasazo lwe-mesolimbic lwe-DIV lidlala indima ebalulekileyo ekuqiniseni izinto ezihlukumezayo, kukho neenkqubo ezizimeleyo ze-DA ezinegalelo elibonakalayo kwiziphumo zokuqinisa kwezi khompawundi (uJoseph et al., 2003; UPierce noKumaresan, 2006 uphononongo). Umzekelo, ukuchasana kwe-DA okanye intsholongwane ye-6-OHDA kwi-NAc kuye kwathiwa akunampembelelo kwi-morphine okanye kulawulo lwe-heroin (Ettenberg et al., 1982; UPettit et al., 1984; UDworkin et al., 1988), nakwi-ethanol yolawulo lomlomo (Rassnick et al., 1993). Ukusilela kokuzibandakanya kwe-dopaminergic kukukhetha indawo ye-cocaine (Spyraki et al., 1982; IMackey kunye van van Kooy, 1985) kuchazwe ukuba kulandele inkqubo yenkqubo yolawulo okanye yokuqokelelwa kwe-intra (i-Koob kunye ne Bloom, 1988; Hemby et al., 1992; I-Caine kunye neKoob, 1993). Ngaphantsi kwemeko ezithile, ukhetho lwendawo yokuzimela ye-opiate ye-DA ibonakalisiwe (iMackey kunye ne van der Kooy, 1985; Bechara et al., 1992; UNader et al., 1994). Ngapha koko, iimpuku ezingalunganga ze-DA zibonisa indawo ekhethiweyo yendawo ethanda imomphine kwiimeko ezithile zovavanyo (Hnasko et al., 2005), kwaye i-DA ayibandakanyekanga kwi-opiate naive state (Laviolette et al., 2004; Vargas-Perez et al., 2009). Inkqubo yokufumana umvuzo ozimeleyo ye-DA ibonakalisiwe (Sturgess et al., 2010).

I-Dopamine D2 receptor changeout mutation kwi-C57BL / 6 iimpuku ziye zahluleka ukuthintela indawo ekhethiweyo ethanol kwindawo yokuxhomekeka kwe-ethanol kunye neempuku eziyekisiweyo (iTing-A-Kee et al., 2009). Kwimeko “yendalo” esebenzayo yokwenza imeko yophawu lwe-chemo-yamadoda kwiimpuku zowesifazane azichaphazelekanga yi-D1 okanye i-D2 receptor antagonists (Agustin-Pavon et al., 2007). Kubalulekile ukuba uqaphele ukuba i-VTA-mediated kodwa ukuqiniswa okuzimeleyo kwe-DA kubonisiwe (Fields et al., 2007).

Le mizekelo yokuziphatha ye-DA ezimeleyo nenokuthandabuza i-DA eyandulelayo yacebisa ukuba i-DA yindlela yokugqibela yokugqibela kwiinkqubo zokulamla.

Inkqubo yecatecholamine ephambili

Malunga neshumi leminyaka eyadlulayo, uphando lubonakalise kummiselo wokuqala we-catecholamine (CA) wokuhambisa ngogqithiso lwe-DA ngokuphendula okumnandi okanye ukuvuselela inkanuko (Le Moal noSimon, 1991). Ngokukodwa, ukuhanjiswa kwe-DA kwizakhiwo eziphantsi, ezinjenge-NAc, kubonakala ngathi kumodareyithwe yinkqubo ye-micocortical ye-DA ngendlela ye-inhibitory (Ventura et al., 2004, uphononongo), oko ke kucacisa ukuba impendulo ye -accaccumbens ye-DA inxulumene ngokungenampendulo kwimpendulo ye-DA e-mesocortical.

Ukuhanjiswa kwe-Mesoaccumbens ye-DA kuye kwacetyiswa ukuba kulawulwe ngogqithiso ngaphambi kwexesha ngokusebenzisa ubukho be-glutamatergic (Carr kunye neSesack, 2000,, uphononongo), ngokuvula ulangazelelo lwezinto eziphucukileyo zophando-ntliziyo kwiVTA (Sesack nePetel, 1990), kunye / okanye ngokuvula i-corticoaccumbens glutamatergic proion (Taber kunye neFibiger, 1995). Ke ngoko, ngaphandle kwesekethe ejongene ngqo ne-cortico-accumbal yesekethe, i-cortico- (VTA) - uthungelwano lwe-DA olubandakanya iindawo ezahlukeneyo zobuchopho, ezinjenge-amygdala (iJackson neMoghaddam, 2001; Mahler kunye neBerridge, 2011), kucetywe ukuba nendima ebalulekileyo kutshintsho lwe-DA olwenzekileyo.

Kwiminyaka yamashumi asithoba, isifundo sesiFrentshi (Darracq et al., 1998) ibonakalise ukuba i-nortpinephrine yangaphambili (i-cortical norepinephrine (NE) ibinendima ebaluleke kakhulu ekwenziweni kokukhululwa kwe-DA okwenziwa ngu-amphetamine wolawulo. Ukuza kuthi ga kulo mzuzu, inkqubo yengqondo ye-noradrenergic ukubandakanyeka kulawulo lokuziphatha yayijolise ikakhulu kwimisebenzi ye-Locus Coeruleus (LC) (Aston-Jones et al., 1999) okanye kulawulo lweememori zokomoya 2006). Umsebenzi wobuvulindlela waseDarracq kunye nabantu osebenza nabo, ucebise ngokungagungqiyo ukuba ukuhanjiswa kwe-DA kwi-NAc kungalawulwa kwaye kuhambelana ngokuthe ngqo ne-NE kwi-medial prefrontal cortex (mpFC). Olu luvo, kunye nendima esekwe ye-DA yangaphambili kwimisebenzi yedopaminergic kwii-accumbens, yacebisa inyathelo elinokuthi lichasane neendawo ezimbini ze-amine ekwi-cortex yangaphambi kokuhanjiswa kwe-DA.

Ubungqina bovavanyo oluvela kwelebhu yethu kwiigundane zeC57BL / 6 (C57) kunye ne-DBA / 2 (DBA) iintlobo zobunzima obuxhaswe yile hypothesis. Izifundo ezithelekisayo zomsebenzi we-neurotransmitter kunye nokuziphatha kwimvelaphi eyahlukeneyo yemfuza zenza ukuba kubekho isicwangciso esikhulu sokuphanda ngesiseko se-neural sempembelelo yeziyobisi ezinxulumene nokungafani komntu. Amagundane emvelaphi ye-DBA aboniswe ukuba angaphenduli kakuhle ekunyuseni ngaphandle kwe-DA ebangelwa yi-psychostimulant kwi-NAc (iqokobhe) kunye nefuthe lokuvuselela / lokuqinisa i-amphetamine, exhomekeke kukonyuka kokukhutshwa kwe-DA. Ukuphambuka kwenzeka kwiimpuku kwimvelaphi yeC57, eboniswe ukuba iphendula kakhulu ekuvuseleleni / ekuqiniseni iimpembelelo ze-amphetamine, njengoko kuboniswe ngokwanda komsebenzi we-locomotor okanye i-amphetamine-indened CPP (Zocchi et al., 1998; UCabib et al., 2000). Kwi-C57, i-Amphetanine ivelisa i-mpFC DA ephantsi kunye ne-DA ephezulu kwi-NAc, ngokuchaseneyo kwenzeka kwiimpuku ze-DBA ezibonisa umsebenzi ophantsi we-locomotor kune-C57and ngaphandle kwe-CPP okanye i-CPA. Ngaphaya koko, xa ukhetha i-DA ukuphelelwa amandla kwi mpFC yeempuku ze-DBA kwenza ukuba ubunzima bufane nempendulo ye-C57 yeempuku ezikhokelela ekuphumeni kwe-DA ephezulu kwi-NAc nakwi-hypom locomotion. Nangona kunjalo, akukho mahluko kwisakhiwo okanye kwimbonakalo ye-DA transporter kwi-NAc phakathi kweC57 kunye ne-DBA strains sele ixeliwe (Womer et al., 1994). Ezi ziphumo zibonise ukuba iziphumo ezahlukileyo ze-amphetamine ekuvekeni kwe-DA kwimbonakalo ezimbini zangaphambili azixhomekanga kuhluko kwiindlela ezinxulumene ne-DAT. Nangona kunjalo, uvavanyo lwe-microdialysis lubonise ukuba i-amphetamine yanda i-NE kunye ne-DA yokuphuma kwi-mpFC ye-C57 kunye neempuku ze-DBA ngendlela eyahlukileyo. Ngelixa i-C57 ibonise ukunyuka okuphezulu kwe-NE kune-DA, iimpuku ze-DBA zibonisa enye indlela, nto leyo ebonisa ukuba umda we-NE / DA obangelwa yi-amphetamine ungaphezulu kwi-C57 xa kuthelekiswa ne-DBA. Kuba iDA inhibitory kwiDA NAc, ngelixa i-NE yacetyiswa ukuba yenziwe (Darracq et al., 1998), sibonisa ukuba i-NE / DA yokungalingani kwi-mpFC ilawulwa yi-DA kwi-NAc kunye neziphumo zokuziphatha ezinxulumene noko, yenza ukuba ubunzima beC57 baphendule ngakumbi kune-DBA. I-hypothesis enjalo yaqinisekiswa kuvavanyo olwalandelayo olwalubonisa ukuba ukukhetha kwangaphambili kwe-cortical NE depletion kwazitshitshisa iziphumo ze-amphetamine kwi-DA kwii-accumbens kunye ne-CPP kwiimpuku ze-C57 (Ventura et al., 2003), ngelixa ukukhetha kwangaphambili ukudinwa kwe-DA (okonga i-NE) kukhokelele ekuveleni kwe-DA kwi-NAc kunye neziphumo zokuziphatha kwizimpuku ze-DBA ngokufanayo nezo zeC57 (Ventura et al., 2004, 2005).

Ezi datha ziphakamise ngamandla ukuba iDA kwi-NAc ilawulwa yi-cortical NE ye-cortical ye-pre-preal. Ngaphaya koko, idatha yethu ibonise ukuba ukuhanjiswa kwe-NE yokuqala kubaluleke kakhulu ukuze kubonakaliswe sisifo sokunyanzelwa, njengoko kubonakalisiwe kukhubazeka kwe-amphetamine-indenti ye-CPP kwi-mpFC NE yeempuku ze-C57 (Ventura et al., 2003).

Nangona kunjalo, ubungqina kuncwadi (uVentura et al., 2002 yokujonga kwakhona) kunye neziphumo zoxinzelelo olufunyenwe elebhu yethu kwi-C57 kunye neempuku zeDBA zibonisile ukuba kuyinyani nakumava okuphinda-phindwayo (ukuthintela, ukubhukuqa), ubuncinci njengolawulo lwe-DA phambili kwi-DA kwi-NAc yayichaphazelekayo. Ewe, sifumanise ukuba uxinzelelo loxinzelelo lwe-inhibhibitbens yokukhutshwa kwe-DA ehamba kunye nokusebenza ngokukhawuleza kunye nokuqina kwe-mesocortical DA metabolism kwi-C57 iimpuku, kunye nokuchasene neempuku ze-DBA, kubonisa ulawulo lwofuzo malunga nokulingana phakathi kwe-mesocortical kunye ne-mesoaccumbens. I-DA iphendula ngoxinzelelo (Ventura et al., 2001). Ngaphaya koko, iimpuku ze-C57 kodwa azikho iimpuku zovavanyo lwe-DBA zibonisa inqanaba eliphezulu lokungakwazi ukusebenza kumava abo okuqala ngovavanyo lokuqubha olunyanzelekileyo (FST) kunye nokusebenza kwangoko nangokuqinileyo kwemetabolism ye-micocortical ye-DA kunye nokuthintelwa kwemetabolism ye-DA kunye nokukhululwa. Ukongeza, indlela yokuziphatha kunye nokuphendula kwe -accaccabbens kwi-FST kwi-C57 iimpuku zancitshiswa kwaye zitshintshwa, ngokulandelelana, ngokukhetha i-dopamine DA depletion kwi-mpFC (Ventura et al., 2002).

Ukuhanjiswa kwangaphambili kwe-NE kwakusaziwa ukudlala indima ebalulekileyo ekulawuleni imisebenzi emininzi ye-cortical, kubandakanya ukuvusa inkanuko, ukuhoya, ukukhuthaza, ukufunda, inkumbulo kunye nokuziphatha ngokuguquguqukayo (uSara kunye neSegal, 1991; Tassin, 1998; Feenstra et al., 1999; Arnsten, 2000; Iibhothi, 2000; UBouret noSara, 2004; UDalley et al., 2004; UMingote et al., 2004; UTronel et al., 2004; UAston-Jones noCohen, 2005; URossetti noCarboni, 2005; ILapiz neMorilak, 2006; van der Meulen et al., 2007; IiRobbins kunye neArnsten, 2009). Ngapha koko, zombini ukuvuza / ukuqinisa kunye nokukhuthaza okunomdla kubonakalisiwe ukukhulisa ukukhutshwa kwe-NE kwi-pFC (Finlay et al., 1995; UDalley et al., 1996; UGoldstein et al., 1996; UJedema et al., 1999; Kawahara et al., 1999; McQuade et al., 1999; Feenstra et al., 2000; Iphepha kunye noLucki, 2002; UMorilak et al., 2005; Feenstra, 2007). Obu bungqina bucacisa ukuba ukuhanjiswa kwangaphambili kwe-CA kungalawula i-DA kwii-accumbens nako kwiimeko zoxinzelelo, isicatshulwa esifanelekileyo sokuba sihlolwe. Oku kwenziwa ziilebhu ezimbini ezizimeleyo kwaye zapapashwa kwi-2007. Olu phononongo lubonise ukuba amava einovelwano axinzelelekileyo akhuthaza ukukhutshwa kwe-DA kwi-NAc ngokunyanzeliswa kwangaphambili kwe-alpha-1 adrenergic receptors (i-ARs) ngamanqanaba aphezulu e-NE (Nicniocaill and Gratton, 2007; UPascucci et al., 2007). Ewe, amava ane-noxinzelelo lwenoveli akhuthaza ukonyuka ngokukhawuleza, okukhulu, kunye nokunyuka okwethutyana kokukhutshwa kwe-NE ngaphakathi kwe-mpFC ehambelana nokuphuculwa kokukhutshwa kwe-DAaccaccbens DA (Pascucci et al., 2007). Ukupheliswa okukhethiweyo kokhetho lwangaphambili lwe-cortical NE kuthintela zombini impendulo ye-cortical NE kunye nokunyuka kwe-DA yengozi, ishiya ukuphucula uxinzelelo lokukhululwa kwe-cortical DA ukukhutshwa kunye namanqanaba e-CAs basal angakhuselekanga (Pascucci et al., 2007). Ngaphaya koko, ukusetyenziswa kwe-alpha-1 AR ekhethiweyo yokuchasa benoxathian kwi-mpFC kuthintela ukukhutshwa koxinzelelo lwe-DA olukhutshwayo kwidosi ye-NAc ngokuxhomekeka (iNicniocaill naseGratton, 2007). UPascucci et al. (2007) ikwaqinisekisile ukuba uxinzelelo oluphuculweyo lwe-NAc DA luyakunyanzeliswa ukusebenza kwe-mpFC DA. Ewe, nokuba kukudaniswa kwe-DA (UDeutch et al., 1990; UDherty noGratton, 1996; King et al., 1997; UPascucci et al., 2007) okanye ukuvalwa kwe-receptors ye-D1 ngokunyanzeliswa komchasi okhethiweyo kwi-mpFC (Doherty naseGranton, 1996) yonyusa ukukhutshwa koxinzelelo oluphuma kwi-DA kwi-NAc. Kuyaziwa ukuba i-DA kwi-mpFC inefuthe elinamandla lokukhutshwa kwe-DA kwi-NAc kunye nokupheliswa kwe-mesocortical ye-DA exhasa ukunyanzeliswa okunyanzeliswa kokukhutshwa kwe-DA okukhutshiweyo (uDeutch et al., 1990; UDherty noGratton, 1996; King et al., 1997). Nangona kunjalo, iziphumo zethu zibonise ukuba ngexesha leenoveli zoxinzelelo amava mppC imisela impenduloaccumbens ye-DA ngempembelelo echasayo ye-NE kunye ne-DA. Idatha yethu inokuchaza ukuba kutheni uxinzelelo lungabandakanyeka kwiimeko ezahlukeneyo ze-pathological. Ewe inyathelo lokulinganisa kwezi CAs zimbini kwi-mpFC inokufuneka ukuze kulungiswe impilo, ngelixa isenzo esingenakulinganiswa sinokuphakamisa ukunyanzeliswa kwe hyper- okanye hypo-impendulo ye -accaccumbens ye-DA, ekhokelela kuphazamiso olwahlukileyo kunye nokuchaseneyo kokuziphatha.

Impembelelo echaseneyo eboniswe yi-mpFC NE kunye ne-DA kuthumelo lwe-DA kwi-NAc ngexesha loxinzelelo lwamava oxinzelelo ekunokwenzeka ukuba kumodareyithwe kwicala langaphambili le-cortical glutamate (GLU) zii-CAs ezimbini. Ukusukela kwibhlokhi ye-mpFC alpha-1 ARs okanye i-D1 receptors ineziphumo ezichaseneyo noxinzelelo olwenziwe kwi-GLU (uLupinsky et al., 2010), kunokwenzeka ukuba i-cortical NE kunye ne-DA yangaphambili ikhuphe iziphumo ezichaseneyo kwimveliso ye-mpFC, ngokunokwenzeka kukhuthazo lobuhle be-GABA interneurons kwi-mpFC (Del Arco neMoz, 1999; I-Homayoun neMoghaddam, 2007).

Ukubandakanyeka kwe-alpha1-ARs kulawulo lwangaphambili lwe-NE lokukhululwa kwe-DA kwi-NAc ngexesha loxinzelelo kuyahambelana nobungqina bokuba ukunyuka okuzinzileyo kokukora kwe-cortical ye-cortical (njengalowo uchukunyiswe luxinzelelo) kuyakwazi ukwenza le misebenzi iphantsi yama-receptors aphantsi. ngelixa ukunyuka okuncinci kunakho ukwenza kusebenze i-alpha2 ephezulu- okanye i-beta1- ARs (iRamos neArnsten, 2007). Nangona kunjalo, indima ephambili ye-alpha1-ARs kwi-activaccumbens ye-activation ye-DA ngoxinzelelo okanye yi-amphetamine (Darracq et al., 1998; UVentura et al., 2003; INicniocaill kunye neGranton, 2007), kunye nendima ebaluleke kakhulu ye-NE ephambili kwi-NE kwisichazi sentshukumo yokunyusa amandla okuhambelana ne-amphetamine, njengoko kubonisiwe kufundwe nge-CPP kwimouse (Ventura et al., 2003), khomba kwindima ephambili yezi receptors kukuziphatha okuchukumisayo kunye nokujongana. I-mpFC kunye ne-NAc zifumana ii-arhente ze-DA ezivela kubantu abahlukeneyo kwiiseli zeVTA kwaye ezi zilawulwa ziisekethe ezahlukeneyo (uJoel noWeiner, 1997; UCarr no-Sesack, 2000; U-Lewis no-O'Donnell, 2000; UMargolis et al., 2006; U-Lammel et al., 2008; UTierney et al., 2008). I-VTA ikwafumana ii-afferents kwi-nucleus ese-amygdala (CeA); ukuthintelwa kwe-CeA, kwaye ngenxa yoko igalelo layo kuthintelo kwi-VTA, kukhokelela ekwandeni kwe-NAc DA (Ahn nasePhillips, 2003; Phillips et al., 2003a), ephakamisa ukuba okokufaka kuyinxalenye yendlela yesibini yokuthintela (i-Fudge kunye ne-Haber, 2000; Ahn noPhillips, 2002; UFloresco et al., 2003; UFudge no-Emiliano, 2003). Ii -othandizira kwi-mpFC zivela kwiqela elincinci leeseli ze-LC (i-Aston-Jones et al., 1999; UValentino noVan Bockstaele, 2001; IBerridge kunye naManzi, 2003). I-LC ifumana uqikelelo oluguquliweyo oluvela kwi-orbito-frontal kunye ne-cingex cortex, eye yacetyiswa ukuba iqhube utshintsho phakathi kweephasic kunye neethoni kwiindlela ze-NE neurons ukuze zilungele imeko yokuziphatha / yokuqonda kunye neemeko zokusingqongileyo (i-Aston-Jones neCohen, 2005). Umsebenzi we-LC nawo umodareyitha nguCeA (uCurtis et al., 2002) ngokwenziwa kwengingqi yommandla we-pericoerulear (iBerridge ne-Waterhouse, 2003) nangokusebenzisa i-corticotropin ekhulula iihomoni (uVan Bockstaele et al., 2001; UBouret et al., 2003; UJedema noGrace, 2004). I-NE ineempembelelo ezahlukeneyo kwiindawo ezijolise kuyo ye-cortical ngokuxhomekeke kugxinzelelo lwayo kunye nokusabalalisa kwe-alpha1 kunye ne-alpha2 receptors (iBriand et al., 2007; Arnsten, 2009). Ewe kunjalo, amanqanaba ahlukeneyo okukhutshwa kwetonomodulator yetoni ichaphazela ii-receptors ezibekwe ngokwahlukileyo phakathi konwebu ye-cortical, ukuze i-neuromodulator ichaphazele ngendlela eyahlukileyo ukujolisa kwayo ekujoliseni ngokuxhomekeke kwii-receptors zayo.

Ubungqina obuqwalaselweyo ukuza kuthi ga ngoku bubonisa ukuba inkqubo yangaphambili ye-CA ilawula ukukhutshwa kwe-DA kwi-NAc, indawo ephantsi kwecortical eyaziwa ngokuba nenxaxheba kuyo yonke indlela yokuziphatha, ngokuzimeleyo kukhuthazo okanye amava. Ke ngoko, umgaqo ofanayo wokuqala ophambili-wokungeniswa ubonisiwe ukuba unike umvuzo (amphetamine) okanye unversive (uxinzelelo) lokukhuthaza. Izifundo ezongeziweyo zibonelela ngenkxaso ebonakalayo kolu luvo, kusetyenziswa ubungqina bovavanyo lwangaphambili lwe-cortical NE lubalulekile kwiziphumo zamachiza amnye, ngokutya okuthandekayo, kunye nokukhuthaza ukuthengiswa kukhemesti okanye komzimba. Ngaphaya koko, babonisa ukuba i-NE yangaphambili ngenxa yentshukumo yayo kwi-NAc DA ibalulekile ekwenziweni kokunyanzeleka kwiimeko ezithile, njengoko kuya kuboniswa kumhlathi olandelayo.

Inguqulelo yokuqala ye-NE -umbumbulu ye-DA kwimpawu zentshukumo yokunyuswa kokubini kukutya kunye- nokukhuthaza okunxulumene nokushukuma.

Amanye amachiza alikhoboka, ukongeza kwi-amphetamine, ekonyusa ukukhutshwa kwe-DA kwi-NAc ngokusebenzisa i-NE yangaphambili, njengoko kubonisiwe kuhlolo olusekwe kubuchwephesha be-intracerebral kwimouse kunye nokukhetha kwe-NE ukuncipha kwi-mpFC. Ukhetho lokudakumba lwe-NE lwenziwa yi-neurotoxin 6-hydroxydopamine kunye nonyango lwangaphambili kunye ne-DA ye-transporter blocker ye-GBR-12909 eye yavelisa malunga ne-90% NE intshabalalo ehambelanayo. Ukuthintela utshintsho olukhulu kumgaqo we-receptor, uvavanyo lwe-neurochemical kunye nokuziphatha lwenziwa kwiveki enye ukusuka kotyando. Morphine (Ventura et al., 2005), Cocaine (Ventura et al., 2007), i-ethanol (Ventura et al., 2006,, kulungiselelo) kubonisiwe ukubangela ukunyusa kokuxhomekeka kwethamo le-NE kwi-mpFC kunye nokunyuka okufanayo kwe-DA kwi-NAc. Ukunyanzelwa kokupheliswa kokukhethwa kwe-NE kuphelise ukunyusa ukuphuma kwe-NE kunye ne-DA kwi-NAc, kungoko kuqinisekisa indima ebaluleke kakhulu ye-NE kump mp kwi-activation ye-DA eqhutywa ziindidi ezahlukeneyo zamachiza okuphathwa gadalala. Kubalulekile ukuqaphela ukuba onke amachiza avavanyiweyo ayonyusa ukuphuma kwe-DA kwi-mpFC, engachaphazelekanga ngenxa yokuphelelwa lithemba. Nangona kunjalo, omnye unokucinga ukuba, ngokusekelwe kwindima eyaziwayo ye-DA yangaphambili yokukhululwa kwe-DA kwi-NAc egcinwe kwizilwanyana ezifumana iziyobisi (umzekelo, amphetamine) okanye uxinzelelo, ukusilela kokonyuka kwe-DA kwi-NAc ye-NE mpFC kwizifundo ezifunyenweyo ezifumana amachiza. ibangelwa sisenzo esivakalayo sothintelo lwe-DA yaphambi kokungabikho kwe-NE. Umbono onjalo, ungangqina indima ebaluleke kakhulu "yokwazisa" ye-NE yokuqala ye-NE yokwenzakala kwi-DA, ekhomba, kodwa kwindima edibeneyo ye-DA eMpFC eya kuthi inike indima yokuzibophelela ekhokelela ku "kucaba" we-DA ophucukileyo xa i-cortical NE iphelisiwe. Oku kungenzeka kulawulwa ziinzame ezihlangeneyo ezibonisa ukuba ukudodobala okufanayo kwe-NE kunye ne-DA kwi-mpFC akukutshintshi ukukhululwa okukhubazekileyo kwe-DA ukukhutshwa kwiimpuku ezifumana i-AMPH xa kuthelekiswa nezilwanyana ezanyelwayo kwiNe depletion. Umzimba wobungqina ucebisa ukuba i-DA kwindawo yokuqala yangaphambi kokukhululwa (cortex) ikhutshwe kunye ne-NE kwi-termadals ye-Noradrenergic (uDevoto et al., 2001, 2002). Ngaphaya koko, kuye kwanikelwa ingxelo yokuba i-DA kule ndawo yobuchopho ihlala icocwa yi-NE transporter (Tanda et al., 1997; UMoron et al., 2002). Iseti eyahlukileyo yedatha efunyenwe kuzo zombini iimpuku kunye neempuku, ibonakalisa ukungabikho kweziphumo zokudodobala kwe-NE kwi-basal extracellular DA, icebisa ukuba ukuncitshiswa okungenzeka kwe-DA ekhutshiweyo kwisiphelo sendawo yokuchitha yase-Noradrenergic kubuyekezwa ngokufumaneka kwe-DA ngenxa yokuncipha kwayo ezi terminals (uVentura et al., 2005; UPascucci et al., 2007). Nangona kunjalo, iimpuku ezingasasebenziyo ze-NE zibonise ukonyuka kokukhululwa kwe-morphine-in-DA efanayo naleyo iboniswe zizilwanyana ezi-Sham, ngoko ke iphakamisa ukuba iingqikelelo zangaphambili ze-noradrenergic kunye ne-dopaminergic azisebenzi. Ukuvumelana nolu phononongo, ukukhethwa kokuqala kwe-NE yokudodobala kwinqanaba lamagundane akuchaphazeli ukukhutshwa koxinzelelo kukhetho lwe-DA kunye nokukhethwa kwe-DA depletion akuchaphazelekanga ukukhutshwa koxinzelelo lwe-NE. Ithathiwe kunye, ezi datha zibonisa ukuba, kuzo zombini ukuqiniswa (inaliti ye-morphine) kunye neemeko zokuphambukela (imeko yoxinzelelo), ukukhutshwa kwe-NE kunye ne-DA kwi-mpFC kuzimele.

Obu bungqina bucebisa ukuba i-NE yinto eqhelekileyo yokulawula ephendula kudidi olwahlukileyo lokuvuselela i-DA kwi-NAc, nokuba yeyiphi na imeko yezonyango okanye eyomzimba. Izinto ezinokwenzeka zothungelwano sele zikhankanyiwe ngaphambili kwaye ziya kuphinda ziqwalaselwe. Apha, kufanelekile ukwalatha ukuba udidi olwahlukileyo lweemeko ezimnandi kunye namava aguqukayo woxinzelelo olunokwenzeka ukuba kusebenze uthungelwano oluqhelekileyo lwangaphambili lwe-cortical-subcortical.

Indima yenkqubo ye-mesoccumbens ye-DA kwisisongelo isekwe kakuhle. Nangona kunjalo, nokuba ngaba inkqubo, ebandakanya i-NE yangaphambili kunye ne-accumbal DA, inendima, ifuna inkxaso yokuvavanywa. Ukufundisisa inkuthazo yokufunda kunye nokukhuthaza, imeko yendawo ixhaphake kakhulu kumagundane kunye neempuku, kodwa kuhlobo lokugqibela oluxhaphakileyo kuba iinkqubo zokusetyenziswa ezisetyenziswa kakhulu ekufundeni ukuzilawula kweziyobisi kwiigundane, ukubala ubunzima beempuku. Ngapha koko, le ndlela ivumela ukubonakaliswa kobunyanzeleko bokukhuthazeka okunxibelelene nokuba kumnandi (ukubanomdla) okanye intshukumo ethambekisayo (US). Kwizibini zokuqala ukudibanisa phakathi kokukhuthazwayo kunye nokusingqongileyo (CS) kukhokelela kwindawo ekhethiweyo (CPP), ngelixa kwimveliso yesibini ithintela indawo (CPA). Inkqubo yokuchazwa kwesisithukuthezi sokunyusa amandla ilinganiswa kukhetho (okanye inxaxhi) ebonisiweyo xa isifundo kufuneka sikhethe phakathi kobume bendawo ngaphambili kunye ne-US kunye nendawo yokungathathi cala (Tzschentke, 1998; UMueller noStewart, 2000). Le ndlela ikwaluncedo ukuvavanya ukuphinda ubuye kukhetho lwangaphambili (okanye ukuthanda) emva kokushabalala, kwaye yindlela ekhethiweyo yokumisela umlutha (Lu et al., 2003; UShaham et al., 2003). Ewe, uphando olukhankanyiweyo ngaphambili lubonakalisile ukuba ukunyanzelwa kokuthotyelwa kwe-cortical ye-cortical NE ngaphandle kokuthomalalisa ukukhula kwe-amphetamine-induction ye-DA kwanda i-NAc, i-CPP engalunganga ebangelwa ngumvuseleli. Ezi ziphumo bezingabangelwa kukusilela kwemoto, okanye ukuphazamiseka kokufunda, kuba izilwanyana eziphelelisiweyo zazingafani nolawulo lwe-sham ekuziphatheni kweemoto, kwaye, okona kubaluleke kakhulu, zazikwazi ukufunda ngokudibeneyo njengoko kubonisiwe kuvavanyo lokuphepha (Ventura et al., 2003).

Ngaphaya koko, ezi ziphumo zibonakalisa ukuba i-cortical ye-cortical ye-intactal iyimfuneko kwi-CPP ebangelwa yi-morphine, icocaine, okanye i-ethanol kunye nokubuyiselwa (ukuphinda ubuyiselwe) kokucinywa kwe-morphine-indEP, kunye nokufakwa kwe-ethanol kuvavanyo olukhethiweyo. Ke ngoko, babonisa ukuba i-NE yangaphambili ibalulekile ukukhutshwa kwe-DA kwi-NAc ebangelwa ziziyobisi ezikhobokisayo kwaye ichaza izizathu zoloyiko lokuvuselela amandla okuhambelana neziyobisi.

Nangona kunjalo, iziphumo ezinxulumene namava aguqukayo zibonisa ukuba ulawulo lwe-noradrenergic lwento yokwenza i-DA isebenze ngokubonakalayo kunye noxinzelelo, licebisa ukuba inethiwekhi eqhelekileyo ebandakanyekayo ekuqhubeni kakuhle kunye nokuvuyisa. Ukuvavanya le hypothesis sicwangcise iimvavanyo ezimbini. Kwincwadi yokuqala siphawule ukuba intsholongwane ebangela ukuba ikhemesti inikwe amandla kwi-cholester chloride elawulwa ngokulandelelana kwimigundane, inyanzelise ukwanda okucacileyo kwe-NE kwi-mpFC kunye ne-DA kwimisebenzi ebekhutshiwe. Ngaphaya koko, i-lithium yanyanzela i-CPA ukuba itshitshiswe kukudangala okwandulelayo kwe-NE, kungoko iqinisekisa ukuba i-NE ephambili ibalulekile ukuze ichaze izizathu zoko kushukumiseka okunxibelelene namava angaguqukiyo (Ventura et al., 2007).

Inqanaba elilandelayo lacetyiswa ziziphumo zokuqala ezifunyenwe xa sagqiba ukuvavanya indima yenkqubo yangaphambili ye-CA yokomelela kokunyanzeliswa kwesimo esishukumisayo kwindalo engeyiyo eyokwelapha. Idatha yangaphambili kuncwadi evunyelweyo ukuba ibangele ukuba iphinde iphinde ibambe umdla wokutya okanye umdla wokubuka ongemva kokuba uvelise uvavanyo olwenziwayo lokuhanjiswa kwangaphambili kwe-noradrenergic, ke ngoko ukuphambuka ngakumbi kukhuthaza ngakumbi ukukhutshwa kwe-NE kwangaphambili kuya kuba (Feenstra et al., 2000; UVentura et al., 2008 uphononongo). Ukuba bekunjalo, ukungakhutshwa kuqala kwe-NE kungathathelwa ingqalelo njengesalathiso sokuqina kwesizathu. Ukuqhubekeka nenkxaso yokuba inkqubo yangaphambili ye-NE-accumbal ye-DA ibalulekile ukuze ibonise ukuba sisiseko esishukumisayo kunye nesikhuthazo esasisisebenzisa njengamava angaguqukiyo e-pharmacological uxinzelelo (izibane eziphakathi) ezinokuhlelwa ukuze zibonelele ngeziphumo ezifanayo nezo zilungileyo ( onomvuzo) Inkuthazo njengokutya okumnandi ngaphambi kokuchazwa. Kwiimvavanyo zokuqala zokwenza imeko, apho kuthelekiswa nezo zoxinzelelo zimbini siye saphawula ukuba zahlukile kwimeko ezinokuphinda zenzeke, izibane ezihamba kancinci zinokuphambuka ngakumbi kunombane ongasukiyo. Esi siphumo safanekisa isiphumo seemeko ezimbini eziphikisayo kukukhutshwa kwangaphambili kwe-cortical NE. Zombini iimeko zokukhanyisa zonyuse ukukhutshwa kwangaphambili kwe-NE, kodwa ukukhanya kwesibane kuvelise ukwanda okubhengeziweyo kunombane ongatshiyo. Ngaphaya koko, impendulo ye-noradrenergic kwi-mpFC yafaniswa nokunyuswa komgangatho kwe-DA kwi-NAc (Ventura et al., Ngokulungiselela).

Emva koko, sivavanye ukuba umdla wokungabinamdla wokwenziwa kwezamayeza, osetyenziswa njenge-US kwindawo yokubeka imeko, efunekayo ukusebenza kwangaphambili kwe-NE-accumbal ye-DA yokusebenza ngenjongo yokubonisa amandla okunyusa amandla. Siqaphele ukuba iigundane zikhetha itshokholethi emhlophe (WCh) ukuya kubisi (MCh) -chocolate kuhlobo lwesigqibo sokuzikhethela, ukhetho olukhe lwaqinisekiswa kwiparadigm ye-CPP apho iigundane zikhethe indalo esihamba nge-WCh ngokuthelekiswa ne-MCh-chocolate. . Ngokuthe rhoqo, i-microsalysis ye-intracerebral ibonise ukuba ukubonakaliswa kwe-WCh intake kuvelisa ukukhutshwa okuphezulu kwe-NE kwi-mpFC kune-MCh (Ventura et al., 2008, ngolungiselelo) ehamba kunye nokuphuma kwe-DA okuqhubekayo kwi-NAc. Ezi ziphumo zibonisa ukuba i-NE yangaphambili kunye ne-DA eyonakeleyo isabela kwizikhuthazo ezahlukeneyo ezithandekayo, nokuba zilungile okanye zinxaxhile, ngendlela ekumgangatho.

Ithiyori yenkuthazo yenkuthazo ikhombe kwindima ephambili yenqanaba lokukhuthaza umzimba (ulambile, unxaniwe, udiniwe, ulumkisiwe njl.njl.) Xa ujongene neshukumisa okanye amava. Uxinzelelo lufumene uqwalaselo olukhulu kwizifundo ezinxulumene nokukhuthaza, ngakumbi ezo ziphathelele kwiimodeli zokulutha, kuba i-neuro-adaptation iyakwazi ukuvelisa kwiinkqubo zobuchopho ezibandakanyekileyo ekuphenduleni kokunyanga iziyobisi, iinkqubo zokukhuthaza ukufunda, kunye nokuphinda ubuye. Sibuze ukuba ukuvezwa kwangaphambili kwamava oxinzelelo kunokuchaphazela "ukuqonda" ukuthambeka kokunyuswa kunye nokuphendula kwenkqubo ye-CA yangaphambili, kwaye ukuba olo tshintsho lungachaphazela ukubonakaliswa kokunyanzelwa kokukhuthala kwiimeko zethu zovavanyo. Sisebenzise irejimeni yokuthintelwa kokutya njengoxinzelelo olungapheliyo olwaboniswa ukuba lutshintshe indlela yokuphendula kwi-amphetamine kwaye ichaphazele inkcaso yesifo sokuhamba kweempuku (kwiCabib et al., 2000; UGuarnieri et al., 2011). Ukuthintelwa kokutya (i-FR) kukhokelele ukukhutshwa okuphezulu kwe-NE kwi-mpFC kunye nokukhutshwa kwe-DA ephezulu kwi-NAc ngokuthelekiswa neempuku zokulawula. Olu nyuso lwalufana nolwaboniswa ziimpuku-ezingafunekiyo (ezingekho-FR) ezivezwe kwi-WCh, ngaloo ndlela zibonisa ukuba imeko yento ephilayo, njengoko kulindelekile, iphembelele ekuphenduleni okonwabisayo. Esi siphumo sinokuchazwa ngokucacileyo ekubandezelweni kokutya okuya kwenza ukuba kube lula ngakumbi kuwe. Nangona kunjalo, idatha yethu ibonisa ukuba irejimeni ye-FR yimeko yokusingqongileyo echaphazela ukungasebenzi kwindawo, ngokuzimela kumatshini onxulumene nokutya. Ewe, siphawule ukuba u-FR wenza iimpembelelo ezibangelwa kukucinezeleka okungathathi ntweni (ukukhanya kwexeshana) kufana neempembelelo eziveliswa kwiimpuku ezingezizo ezikaFR ngokucinezeleka okungathethekiyo (ukudonsa ukukhanya kwexesha). Oku kuthetha ukuba i-FR iyakwazi ukonyusa ubumbeko kuzo zombini ezi zinto zimnandi (ezinomvuzo; zokutya) kunye neziphindaphindiweyo (ukukhanya koxinzelelo) isikhuthazo, ngaphandle kwendlela ezinxulumene nendlala. Qaphela ukuba kwiimvavanyo ezongeziweyo i-Sham kunye ne-NE yeempuku eziphelileyo ezingafakwanga kukutya okunxulumene nokuxakeka okungapheliyo (ukubekwa ecaleni ngokwasentlalweni) kubonise iziphumo ezifanayo kwizilwanyana ze-FR, ngaloo ndlela kubonakalisa ukuba isiphumo sokudangala okwenziwe ngaphambili kwe-NE kwi-MP-eyenziweyo ye-CPP ayinakuba ichazwe njengempendulo ye-homeostatic kuthintelo kokutya (Ventura et al., 2008). Ukuthintelwa kokutya kunokuthathwa njengokukhokelela kwisiphumo sokuqhuba ngokubanzi (Niv et al., 2006; Phillips et al., 2007) ukuba "yenze amandla" enkuthazo. Lo matshini ubonakala uxhomekeka kumhlaba wokuhluthwa. Iziphumo zethu, nangona kunjalo, zibonisa ukuba isiphumo esiqhelekileyo sokuqhuba esiveliswa yimiqobo yokuthintelwa kokutya ngaphambi kokuchaphazeleka kwishukumisa esithile asichaphazeli kuphela umdla weememary kodwa sinomdla osisiphelo. Ngapha koko, iimpembelelo zokuphindaphinda ukukhanya okuphakathi zinamandla kukutya okuthintelwe kunokutya kweempuku ezondlekileyo. Ke ngoko, isiphumo esiqhutywa ngokubanzi sokuqhutywa kwemoto kufuneka sibandakanye neendlela eziqhelekileyo zokusebenza zokulawula ukonwaba kunye namava okuphindaphindiweyo.

Ithathiwe kunye, ezi ziphumo zibonisa ukuba impendulo yangaphambili ye-CA sisalathiso sempembelelo / yovuselelo yempembelelo yesisusa ezahlukileyo ngokuxhomekeka kwiimpawu zesikhuthazo okanye kwimeko yento ephilayo. Impendulo yomgangatho wokuqala we-NE yayivisisana neziphumo zangaphambili kwaye yacebisa kuthi ukuba siqiniseke ngendima yenkqubo yangaphambili ye-CA ekubalulekeni kokunganyamezeli okunxulumene nenkuthazo eyahlukileyo. Sisebenzisa ubuchule bokuvavanya kwezinye izifundo kwizihloko ezifanayo, sivavanye iziphumo zokunyanzelwa kokuthotyelwa kwe-NE yokuqala kwimpendulo ye-CA kunye nokuchazwa kwendlela yokunyuswa komzimba olinganiswe ngemeko yendawo. Okothusayo kukuba sabona ukuba i-NE yokuphelisa amandla inyanzelisa ukwanda kokukhululwa kwe-cortical NE ye-Cortical kunye ne-DA ye-accumbal, ngokuqhubekayo kwiimvavanyo zangaphambili. Nangona kunjalo, yathintela indawo ekhethiweyo (i-CPP) kwizilwanyana ezivezwe kwi-WCh nakwizilwanyana ezithintelwe ukutya (i-FR) ezivezwe itshokholethi yobisi (i-MCh; zombini iimeko zonyawo oluphezulu) kodwa ingezizo izilwanyana ezinga-F (zine-free-feed) ezivezwe I-MCh (isisele esisezantsi). Ngapha koko, yayithintela indawo yokuthintela (i-CPA) kwizilwanyana ezivezwa kukukhanya kokwexeshana kokukhanya (i-IPL) nakwizilwanyana ezi-FR ezichazwe kukukhanya kwexeshana (i-IL; i-salience ephezulu) kodwa ingezizo izilwanyana ezingezizo ii-FR ezichazwe kwi-IL (indawo ephantsi; Isazobe11).

 

Umzobo 1

Iziphumo zokupheliswa kohambo lwangaphambili lwe-coreical coreical norepinephrine kukhetho lwendawo ekhethiweyo (CPP) ebangelwa yitshokholethi (itshokholethi yobisi kulawulo, i-MCh; itshokholethi yobisi kwindawo yokutya ethintelwe i-MCh + FR; itshokolethi emhlophe kulawulo, i-WCh) kunye nokuthintela indawo elungileyo. ...

Ezi ziphumo zibonisa ukuba loo pFC NE depletion ichaphazela ukubonakaliswa kokunyanzeliswa kuphela xa i-UCS iphakamile ngokwaneleyo ukuba ibangele ukuba kusebenze CA, nto leyo ke ebonisa ukuba inkqubo yangaphambili ye-CA ibandakanyeka ekuqhubekekiseni inkcaso ekhuthazayo xa kufuneka yenziwe. Ubungqingqwa kubhekisa kubunamandla bokubangela ukuvusa (Horvitz, 2000). Inkuthazo ebukhali ebangela ukuba uhlengahlengiso ngokutsha lwezixhobo ezikhoyo zokuqonda ukuze zivelise ingqalelo okanye indlela yokuziphatha (Zink et al., 2006). Okukhona unyanyekayo ukhuthazo, kokukhona kuya kukhokelela ekunakekeleni ingqalelo okanye ekutshintsheni kokuziphatha. Iingxelo zamva nje zabantu zibonise ukuba i-striatum inendima enkulu ekushukumiseni ukwabiwa ngokutsha kwezixhobo kwizikhuthazo ezibambekayo (Zink et al., 2003, 2006). Nangona kunjalo i-cortex yangaphambili, ngenxa yemisebenzi yayo "yokujonga", inendima engathandabuzekiyo yendawo ekuqwalaseleni nasekuqhubekeni kwesizathu sokuvuselela umdla.

Ngaphaya koko, idatha ibonakalisa ukuba i-ventral striatum (okanye i-NAc) kunye ne-cortex yangaphambili zenza umlinganiso oqhelekileyo wokucwangcisa kunye nokuvuselela umdla (iBerridge neRobinson, 1998; UDarracq et al., 1998; Becerra et al., 2001; UJensen et al., 2003; I-Kensinger kunye ne-Schacter, 2006; Borsook et al., 2007), kunye nezifundo ze-neuroimaging ebantwini zibonisa ukuba iindawo ezahlukeneyo zecortex yangaphambili (O'Doherty et al., 2001; Encinci et al., 2001; UKillgore et al., 2003; U-Wang et al., 2004) kunye ne-striatum (uJensen et al., 2003; UZink et al., 2006; Borsook et al., 2007) zenziwa zasebenza ngendlela elungileyo okanye ezingathandekiyo. Ngaphaya koko, ngaphambili sibonisile ukuba ukuhanjiswa kwangaphambili kwe-NE kuyimfuneko ekuqinisekiseni isisusa sentsingiselo kuzo zombini indalo (kwizilwanyana ezithintelwe ukutya) kunye nefemeli yohambiso lwekhemestiiks kunye nokuvuselelwa kunzamezo lwezonyango ngokuguqukela kwi-DA kwi-NAc (Ventura et al. , 2007). Ke ngoko, kunokwenzeka ukuba iziphumo zokuphelelwa ngamandla kwe-NE ngaphambili kwi-CPP kunye ne-CPA kwizilwanyana ezivezwa kukukhuthala okuqinisekileyo kuxhomekeke kwinkqubo engafanelekanga yenkqubo ye-CA yangaphambili, ukusebenza kwayo ngokunganiki mdla kunye nokuvuselela inkanuko enkulu engummangaliso. ukuthamba. Nangona kunjalo, ezinye iindawo zobuchopho kunye ne-neurotransmitters zinokwenzeka ukuba zibandakanyeke. Ke, ekubeni i-amygdala ibandakanyeka kwimeko ye-pavlovia yeempendulo zemozulu kwaye idlala indima ethile ekumodeni inkumbulo yamava ovusayo (i-Balleine, 2005; IBalleine neKillcross, 2006; McGaugh, 2006), kwaye unikezwe unxibelelwano oluyindalo kunye nokusebenza oluluqilima phakathi kwale ndawo yengqondo kunye ne-cortex yangaphambili (Cardinal et al., 2002; IHolland neGallagher, 2004; Roozendaal et al., 2004) indima ye-preortal ye-cortex-amygdala yenkqubo kwiziphumo zesizathu esiphambili esichazwe apha kufuneka siqwalaselwe (I-Belova et al., 2007).

izigqibo

Ukuchaphazeleka kwesishukumisi sokunyusa inxulumene nokuthambeka kwe-UCS (Dallman et al., 2003; UPecina et al., 2006). Ke ngoko, ukuba i-UCS ethembekileyo ngakumbi iya kukhuthaza ngakumbi ukungangqinelani (ukuba kwimeko-yokuba kwimeko) iya kunxulunyaniswa nayo ngokusebenzisa inkcazo yobunyanzelekileyo bokunyaniseka. Amava angaphambili sisigqibo esikhulu sokuchaphazeleka kwempembelelo yanoma yimuphi umfutho onikiweyo (Borsook et al., 2007) kunye novuselelo ngokwasemphefumlweni olwenziwe kukuvuselelwa kwesishukumiso sonyusa ingqwalaselo enikwe kwisishukumisi sokuphembelela kokubini ukufakwa kwe-perceptual encoding kunye nenkqubo yokudibanisa (Anderson et al., 2006; McGaugh, 2006). Sibonelele ubungqina bokuba ukuhanjiswa kwe-CA yangaphambili kuyimfuneko ukuze isisusa sibonisa amandla omvuzo kunye nokuvuselela okunxulumene nokuthathelwa ingqalelo phantsi kweemeko ezinokubangela ukonyuka okuthe kratya kokuphuma kwe-CA ekuphenduleni isikhuthazo sendalo esingagungqiyo, ngaphandle kokungagungqiyo.

Ke ngoko, ukukhetha kwangaphambili kwe-NE yokupheliswa kuyitshitshisile imeko ebangelwa kukuvuselelwa kwesibindi (okt, i-WCh kunye ne-IPL) kwizilwanyana ezilawulayo nangokubamba ngokuzithemba (okt, i-MCh kunye ne-IL) kumaqela acinezelweyo, kodwa akabanga naziphumo zibalulekileyo kulawulo lwezilwanyana ezibonisiweyo kukukhuthaza ngobumnene. Ezi ziphumo zibonisa ukuba ukuhanjiswa kwe-CA yangaphambili kuyimfuneko ukuze kufunyanwe iipropathi ezinemeko ekhuthazwayo enezinto ezinomtsalane wendalo okanye imijikelezo yokuphambukela kwinkqubo yokubekwa endaweni. Izinto ezininzi ezahlukeneyo zinendima ephambili yokulawula kwindlela yokuziphatha eqhubayo, kubandakanya izinto eziguquguqukayo zangaphakathi (oko kukuthi, imeko ekhuthazayo, ukuphendula ngoxinzelelo) kunye neempawu zokuvuselela (okt, ukuphakama okanye ubukhulu), zombini ezo zinto zichaphazela iinkqubo zokunikezela ubungqina (Berridge and Robinson) , 1998; URichard noBerridge, 2011). Kutshanje kucetyiswa ukuba iinkqubo zokutya kunye nezobuchwephesha zibambe ongezantsi "zenze ngendlela" kwiinkqubo ezinobuthathaka bokuqina (ukungasebenzi) kodwa kungenjalo valence "(Belova et al., 2007), ngaloo ndlela kucebisa ukuba inkqubo eqhelekileyo ye-neural ingabandakanyeka ekusombululeni ubumbeko lwesifo, ngaphandle kobuhlanga. Ngaphaya koko, kuvusa umtsalane omnandi okanye ophikisayo othi ubangele iimpendulo ezichaziweyo kucacisiwe ukonyusa ingqalelo kunye nokwenziwa kwememori ngendlela eqhelekileyo, engavakaliyo engahambelaniyo (i-Belova et al., 2007) kunye ne-cortex yangaphambili ibandakanyekile ekuqhubeni phambili imbuyekezo kunye nokukhuthaza ukuthanda (iRoll, 2000; O'Doherty et al., 2001; UKillgore et al., 2003; UVentura et al., 2007).

Ukuhanjiswa kwe-Dopaminergic ngaphakathi kwe-NAc kuthathwa njengokuthethelela impembelelo ye-hedonic yomvuzo okanye ezinye iinkalo zokufunda komvuzo (i-Everitt neRobbins, 2005 uphononongo). Iziphumo zethu, ngokuvumelana ngombono owahlukileyo (iBerridge kunye neRobinson, 1998), bonisa ukuba ukuhanjiswa kwe-DA kwi-NAc kudlala indima kukuziphatha kakuhle nangokuzithemba; okona kubaluleke kakhulu, nangona kunjalo, babonisa ukuba le nkqubo yenkuthazo ilawulwa yi-cortical NE ye-cortical ye-cortical.

I-Norepinephrine kwi-mpFC inokwenza ukuba kusebenze ngakumbi kwii-DA ezikhululweyo ngohlobo olucokisekileyo lwentelekelelo ye-cortical cortical to seli ze-VTA DA (Sesack nePetel, 1992; Shi et al., 2000) kunye / okanye ngokuqikelelwa kwe-corticoaccumbal glutamatergic (Darracq et al., 2001). Ngaphaya koko, indima yokuqikelelwa kwe-mpFC kwi-LC ekubonakaliseni ifuthe lokuchwayitisa kungacingelwa ngenxa yokuba le nyukliya ibonakalisiwe ukuba ivuse i-VTA DA neurons (Grenhoff et al., 1993; UJodo et al., 1998; I-Liprando et al., 2004), enokuthi ikhokelele ekunyuseni ukuphuma kwe-DA kwi-NAc. Nangona kunjalo, kuba i-amygdala ibandakanyeka kwimeko yePavlovian yeempendulo zemozulu kwaye idlala indima ethile ekuguquleni inkumbulo yamava ovusayo (iBalleine neKillcross, 2006; McGaugh, 2006), kwaye unikezwe unxibelelwano oluyindalo kunye nokusebenza oluluqilima phakathi kwale ndawo yengqondo kunye ne-cortex yangaphambili (Cardinal et al., 2002; Roozendaal et al., 2004), indima yenkqubo yangaphambili ye-cortex-amygdala kwimpembelelo yesizathu esiphambili esichazwe apha kufuneka siqwalaselwe (I-Belova et al., 2007; Mahler kunye neBerridge, 2011).

Qaphela ukuba i-NAc kunye nokuhanjiswa kwedopaminergic kuthathwa njengeyona ndima idlala indima enkulu kwiinkqubo zokuqhubela phambili ngaphandle kwendima edlalwa yi-DA kwezinye iinkalo zesishukumisi kunye nokufunda kwesixhobo (i-Salamone et al., 2005). Ewe, ngokusekwe kumbono othandabuzayo ukuba uhlanganisa iDA yenza umsebenzi omnye, ubungqina obuqinisekileyo buxhasa umbono wokuba iDA ibandakanyeka ekuzimiseleni okanye ekuthathweni kwezigqibo. (Salamone et al., 2007; Bardgett et al., 2009), engahambelani nokuzibandakanya kwale nkqubo ekufundeni ngesixhobo, ukukhuthaza inkuthazo, okanye ukudluliselwa kwesixhobo se-pavlovian. Izifundo zezilwanyana kunye nezabantu zibonakala ngathi ziyaguquka kuba, kunye nezifundo zezilwanyana ezijolise kwimisebenzi enxulumene nomzamo we-DA yezothutho, iziphumo zeklinikhi ziyahambelana kunye ne-hypothesis yokuba iinkqubo ze-DA zibandakanyeka ekusebenzeni kokuziphatha, zibonisa ukufana okukhoyo phakathi kweenkqubo zobuchopho ezigxininiswe iinkqubo ezinxulumene nomzamo kwizilwanyana kunye nezo zibandakanyekayo kukungasebenzi kwamandla ebantwini (uSalamone et al., 2007). Ngokwolu luvo ukusebenza kwe-NAc kufuneka kuthathelwe ingqalelo, kunye ne-cortex yangaphambili kunye ne-amygdala, njengecandelo lokujikeleza kobuchopho kulawula imisebenzi ehambelana nomzamo. Kule nkqubo-sikhokelo, inkqubo yangaphambili ye-CA eyandulelayo siyicinge ukuba inokuba yinxalenye yothungelwano oluntsonkothileyo olubandakanya iindawo zengqondo kunye neengqondo ezibandakanyekileyo kubandakanyo lwemisebenzi ezinxulumene nomzamo ukulawula iziphumo zentshukumo, kunye nokunxibelelanisa ubungqindeka bokubaluleka kokuqina. Ngokoluvo lwethu ifuthe lokunyanzelwa kwesisusa kubalulekile kwiinkqubo ezikhokelela ekuchazeni amandla okunyanzeleka, ngenxa yesisele esibonakalayo. Oko kuthetha ukuba impembelelo yesishukumiso ukuvelisa impendulo engokweemvakalelo edibanisa iinkqubo zoncedo ezikhokelela kwisiphumo sesishukumisi, ngaloo ndlela sibonisa indima esisiseko yeemvakalelo zesithukuthezi njengoko umntu etyhilekile kwi-UCS. Inkqubo yangaphambili / yengozi esicebisa ukuba ilawule iinkqubo zokuhambisa isidenge ngokuxhomekeke kubumbeko bokuqina kufuneka ithathelwe ingqalelo kufakwe kuthungelwano oluntsonkothileyo lokulawula iimvakalelo ezaziwayo (Phillips et al., 2003b). Umbono weemvakalelo, ngokweengcinga ze-Appraisal (uArnold, 1960; Lazaro, 1991) kucetyiswe ukuba kuqhume kwiinkqubo ezintathu: ukwaziwa kweyona nto ibalulekileyo yovuselelo, imveliso yelizwe elinempendulo ukuphendula ukhuthazo, kunye nommiselo welizwe elichaphazelekayo. Njengoko kuboniswe ngoncwadi lomntu kunye nolwezilwanyana (Phillips et al., 2003b yokujonga kwakhona), ezi nkqubo zixhomekeke kwiinkqubo ezahlukeneyo zeemvakalelo zobuchopho ezibandakanya iindawo zengqondo kubandakanya ne-mesencephalic, i-cortical, kunye ne-subcortical efana ne-amygdala, i-insula, i-ventral striatum, i-ventral, kunye ne-dorsal anterior cingate gyrus, inkqubo ye-septo-hippocampus, i-cortex yangaphambili. Zonke zibonakaliswa bubuhlobo obusebenzayo bobuhlobo (Salzman noFusi, 2010). Inkqubo ye-septo-hippocampus ithathelwe ingqalelo njengomthelekisi weenjongo ngokubanzi, nendima ephambili ekumiseleni ubungakanani bengxabano phakathi kokuziphatha okujolise ngqo kwiinjongo (uGrey noMcNaughton, 2000). I-Amygdala inendima eyaziwayo kwimvakalelo nakwinkqubo zokuhlanganisa inkumbulo ngokuxhomekeka kwimvakalelo evuselelayo. Mva nje indima yale ndawo ekuthathweni kwezigqibo ibonakalisiwe. Ngokwenyani, i-amygdala ingavusa iimpendulo ezinemeko ekwaziyo ukwenza isiphumo esikhulu ekukhetheni, kwaye ibonwa ngamaxabiso emvakalelo kwimeko yePavlovian isetyenziswa ngeendlela zokufunda (ezisekelezelwe kunye nasekolweni) i-cortex eyandulelayo (iSeymour neDolan, 2008).

Kuyaphawuleka ukuba "amaxabiso" achaphazeleka sisenzo soxinzelelo lwehomoni, ezinje ngeglucocorticoids, kwi-amygdala, kwaye ezi ziphumo zilawula ukuqiniswa kwememori zibonisa ikhonkco phakathi kwendlela evakalayo kunye namandla eenkumbulo (Roozendaal, 2000; Ukuseta et al., 2000; McGaugh, 2005). Ngapha koko i-glucocorticoids ibonakalisiwe ukuba ibe lungelelwaniso lwebhayoloji yomvuzo (i-Piazza kunye neLe Moal, 1997) Ubungqina obucacileyo bubonisa ukuba badlala indima ekuguqulweni kwamanqanaba omdla kunye nemvakalelo yokubuyela umva ebonisa ukuba ukumanyanisa kokufunda kunye nokufunda okungafunekiyo kokufunda kungasetwa ngumatshini oqhelekileyo (iZorawski and Killcross, 2002).

Sinike ubungqina bokuba inkqubo yangaphambili ye-CA eyandulelayo iyabandakanyeka ekusombululeni amandla enkangeleko yesimo sokukhetha xa kuqhutyekekwa ngenkcaso enkulu, ngaloo ndlela sibonisa inkqubo yecala lokwahluka nelibandakanyekayo ekubonakalisweni kwesidengelo esishukumisayo esihambelana nokuvuselela ngobunono. Iziphumo zethu ziyahambelana nezo zazibonise ukuhanjiswa kwe-DA akusoloko kubandakanywa inkuthazo (Nader et al., 1997, uphononongo). Ngokuchasene ne-hypothesis ye-DA esekwe kwimodeli yenkqubo enye yomvuzo, imodeli engasingeliyo / ehluthwayo iye yacetyiswa kwisithuba sokugqibela esithi amabango amabini ahlukeneyo enkqubo yembuyekezo ye-neurobiological angakwazi ukwahlulwa kabini, nganye nganye yenza Igalelo elibalulekileyo kwindlela yokuziphatha exhasayo kuxhomekeka kwimeko yokuhlwexwa. Qaphela ukuba imodeli ixhaswe kuvavanyo apho izilwanyana ezingenamthi zithathwa njengeziyimfuneko kukutya-okt (okt, engahluthwanga), ngokwahlukileyo kwizilwanyana ezixhomekeke kwiziyobisi ekurhoxiseni okanye izilwanyana ezithintele ukutya ezithathwa njengezisweleyo (Nader et al., 1997; ULaviolette et al., 2004). Imodeli ineempembelelo ezimbini ezibalulekileyo. Okokuqala, ubudlelwane phakathi kwezi nkqubo zimbini zibonakala zikhethekile. Isimo sokuncitshiswa kuthintela inkqubo engathathi ntweni [ebandakanya i-peduncolo-pontine nucleus (TPP)]. Ke, ukusebenza okwahlukileyo kwezi nkqubo zimbini kumiselwe ngokukodwa ukuba izilwanyana, umzekelo, zikwimeko yokurhoxa okanye hayi (uNader et al., 1997). Intsingiselo yesibini kukuba ilizwe lokuncitshiswa libeka inkqubo yesibini yempembelelo ekhuthazayo, eyinxalenye yayo yi-DA.

Umbuzo ocacileyo ophakamayo kule modeli ngowokuba ngaba zonke iindlela zokuziphatha ezixhasayo zinokujongwa njengezinezinto ezingafunekiyo nezilahliweyo. Njengoko yabuzwa ngabaxhasi (uNader et al., 1997, uphononongo): "Ngaba izinto ezikhuthazayo zisebenza kuphela kwenye yezi nkqubo?" Nangona le ngxoxo ingekho kwinjongo zomsebenzi wethu wangoku, asinakukunceda ukuqaphela ukufana phakathi kweziphumo zethu kwinkqubo ye-CA yangaphambi kokuqokelelwa kwenkqubo kunye nenkqubo engabanjwanga / yokuhluthwa, ekubeni inkqubo yethu ibalulekile ekunikezelweni kwesibindi xa i-salience ye-stimuli iphezulu kwaye ibonakaliswe yimpembelelo ephezulu yemvakalelo (nokuba yeyokulungileyo okanye embi). Kule meko, enye inkqubo ebandakanyeka kulungiso olusezantsi lokuthintela ukungasebenzi ithintelwe okanye "ayisebenzi," kwaye le nkqubo ikwi-intanethi xa kusenziwa ulwazelelelo oluphantsi (kwaye besingekacingeli okwangoku), iyafana nenkqubo engabanjwanga, ibonakaliswa yimpembelelo yeemvakalelo eziphantsi. Iziphumo zethu zikwacebisa ngamandla ukuba, njengokuphakanyiswa kwemodeli engabanjwanga / yokuhluthwa, inkqubo yokulungisa isisitya esiphezulu (inkqubo ye-CA yangaphambili) kunye nomntu obandakanyekayo kubuchwephesha obuphantsi. Ngokumalunga namandla e-neural abandakanyekayo kukhetho kunye nokuzibandakanya okukhethekileyo kwezi nkqubo, sinokubonisa ukuba ukunyuka okuhleliweyo kokuphuma kwe-NE kwi-mpFC kuxhomekeke kubunzulu obuphantsi okanye obuphezulu besikhuthazo, kunokubandakanya ii-subtypes ezahlukeneyo ze-AR, zona ezo , Kuxhomekeke kwinqanaba lokunikezelwa kwe-NE ekhutshiweyo, iya kuthi ibandakanye imijikelezo eyahlukeneyo, kwaye kwimeko yesibindi, kubandakanya ne-DA kwi-NAc. Le yinjongo yovavanyo oluqhubekayo olunokuthi lucacise lo mbuzo ubalulekileyo.

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