Indima ye-cortex ye-orbitofrontal kwi-drug addiction: ukuphononongwa kwezifundo zengqungquthela (2008)

Biol Psychiatry. I-2008 ngoFebruwari 1; 63(3): 256-262. Ipapashwe kwi-intanethi ye-2007 Agasti 23. ikhonkco:  I-10.1016 / j.biopsych.2007.06.003

Abstract

Izifundo ezisebenzisa iindlela zokucinga ngengqondo zibonise ukuba umsebenzi we-neuronal kwi-cortex ye-orbitof, indawo yengqondo ecinga ukukhuthaza amandla okulawula indlela yokuziphatha ngokubhekisele kwiziphumo okanye kwiziphumo ezinokubakho. Ezi zinto zikhangelekayo zokucinga zabantu zikhokelele ku-hypothesis yokuba amanqaku aphambili okulutha njengokusebenzisa iziyobisi ngokunyanzelekileyo kunye nokubuyela kweziyobisi zixakwe yinxalenye yeenguqu ezenziwa zeziyobisi ekusebenzeni kwe-orbitof Pambal. Apha, sixoxa ngeziphumo ezivela kwizifundo zaselabhoratri kusetyenziswa iigundane kunye neenkawu kwiziphumo zokuvezwa kweziyobisi kwimisebenzi yokufunda ejikeleza ecaleni kunye nesakhiwo se-neuronal kunye nomsebenzi okwenzeka kwi-cortex ye-orbitof. Sikwaxoxa ngeziphumo ezivela kwizifundo ngendima ye-orbitofadal cortex kulawulo lweziyobisi kunye nokubuyela umva. Isiphelo sethu esiphambili kukuba ngelixa kukho ubungqina obucacileyo bokuba ukubonakaliswa kweziyobisi kuyayonakalisa imisebenzi yokufunda exhomekeke kwicala le-orbitofrontal, indima echanekileyo yokuba olu tshintsho idlale ekusebenziseni iziyobisi ngokunyanzelekileyo iphinde ibuye.

intshayelelo

Ukusetyenziswa kweziyobisi gwenxa kuphawulwa ngokunyanzelwa kokufumana iziyobisi kunye nokuxhaphaka okuphezulu kokubuyela ekusebenziseni iziyobisi i-1-3. Kumashumi eminyaka, uphando olusisiseko kwikhoboka leziyobisi linikezelwe ikakhulu ekuqondeni iindlela eziphantsi kwemiphumo yokufumana iziyobisi kwi-4. Olu phando lubonisa ukuba inkqubo ye-dopamine ye-mesolimbic kunye nokunxibelelana okusebenzayo kunye nokuhambelana kwayo yi-neural substrate kwiziphumo ezivuzayo zeziyobisi zokuxhaphaza i-4-7. Kwiminyaka yakutshanje, nangona kunjalo, kuye kwacaca ukuba iziphumo ezincomekayo zamachiza azinakho ukubalasela ngezinto eziphambili zokulutha, kubandakanya ukubuyela ekusetyenzisweni kweziyobisi emva kokuyeka ixesha elide i-8-10 kunye notshintsho olusuka ekusetyenzisweni kwamachiza okulawulwayo ukuya kusebenzisa kakhulu iziyobisi. I-11-14.

Ngokusekwe kwimigca emininzi yobungqina, kuye kwaqinisekiswa ukuba ukufuna iziyobisi ngokunyanzelekileyo kunye nokubuyela kweziyobisi kulungelelaniswe ngokwenxalenye ngotshintsho olwenziwe ngamachiza kwi-orbitofrontal cortex (OFC) 14-18. Umsebenzi we-Hypermetabolic kwi-OFC uye wanyanzeliswa kwi-etiology yezifo zokunyanzeliswa okungapheliyo (i-OCD) i-19-22, kwaye kukho ubungqina bokuba imeko ye-OCD kubaphengululi iziyobisi ingaphezulu kwenqanaba kuluntu ngokubanzi i-23-25. Izifundo zokulinganisa kwi-cocaine 26; I-27, i-methamphetamine 28; I-29 kunye ne-heroin i-15 abasebenzisi baveza i-metabolism eguqulweyo kwi-OFC kunye nokunyusa ukusebenza kwe-neuronal ekuphenduleni i-cues enxulumene neziyobisi i-15; 30. Nangona kunzima ukwazi ukuba ngaba utshintsho lwe-metabolic lubonisa ukuphuculwa okanye ukuphazamiseka komsebenzi we-neural, ukuguqulwa kwe-neuronal signaling kokubini kwizigulana ze-OCD kunye neziyobisi ezinokubakho ngokudibanisa okungaqhelekanga ngokufakwayo kokungeniswa kwiindawo ezinobudlelwane. Ngokuhambelana nolu qikelelo, iziyobisi, njengezigulana ezinomonakalo we-XCUMX, ziyasilela ukuphendula ngokufanelekileyo kwiiyantlukwano ezahlukeneyo zomsebenzi 'wokungcakaza' i-31-32. Le ntsebenzo intle ihamba kunye nokusebenza ngokungaqhelekanga kwe-OFC 34. Iziphumo ezivela kwezi zifundo zeklinikhi zibonisa ukuba umsebenzi we-OFC ubetheleleke kumakhoboka eziyobisi, kodwa okubaluleke kakhulu, ezi datha azinako ukwahlula ukuba utshintsho kwi-OFC yomsebenzi lubangelwa kukuvezwa iziyobisi okanye libonisa imeko yangaphambili ebeka umntu othile ukuba likhoboka leziyobisi. Lo mbandela unokuqwalaselwa kwizifundo kusetyenziswa iimodeli zezilwanyana.

Kolu hlaziyo, kuqala sixoxa ngomsebenzi we-OFC wokukhokela kwindlela yokuziphatha. Emva koko sixoxa ngobungqina obuvela kwizifundo zaselabhoratri kwifuthe lokuchazwa kweziyobisi kwihambo ye-OFC ehleliweyo kunye nakwisakhiwo se-neuronal kunye nomsebenzi kwi-OFC. Emva koko sixoxa ngoncwadi olulinganiselweyo kwindima ye-OFC kulawulo lweziyobisi nasekubuyeleni kweziyobisi kwiimodeli zezilwanyana. Sigqiba kwelokuba ngelixa kukho ubungqina obucacileyo bokuba ukubonakaliswa kweziyobisi kubangela iinguqu ezingapheliyo kwisakhiwo se-neuronal kunye nomsebenzi kwi-OFC kunye neendlela zokuziphatha ezixhomekeke ku -C, indima echanekileyo le nguqu idlala ekusebenziseni ngokunyanzelekileyo ukusebenzisa iziyobisi kunye nokubuyela umva ingekasungulwa. Itheyibhile 1 ibonelela uluhlu lwamagama asetyenziswe kuphononongo lwethu (oonobumba abangoonobumba kwisicatshulwa).

Umsebenzi we-OFC ekukhokeleni kwindlela yokuziphatha

Ngokubanzi, indlela yokuziphatha inokulawulwa ngumnqweno wokufumana isiphumo esithile, esibandakanya ukumelwa okusebenzayo kwexabiso lesiphumo, okanye imikhwa, eyalela impendulo ethile kwimeko ethile ngaphandle kokujonga okanye ukubaluleka (okanye ukungafunekiyo) yesiphumo. Ubungqina be-Ample ngoku bubonisa ukuba isekethe ebandakanya i-OFC ibaluleke kakhulu ekukhuthazeni isimilo ngokusekwe kumelo olusebenzayo lwexabiso lesiphumo esilindelekileyo se36. Lo msebenzi ubonakala kumandla ezilwanyana ukulungisa ngokukhawuleza iimpendulo xa kuqikelelwa iziphumo kwi-37-39. Kwigundane kunye neenkawu, obu buchule buhlala buvavanywa kwimisebenzi yokufunda eguqukayo apho intlekelelo yomvuzo luqikelelwe ngokungaxhamliyo (okanye ukohlwaywa) kwaye ikamva lixelwe kwangaphambili komvuzo. Izifundo zokulinganisa zibeka i-OFC ekufundeni okuguqukayo ebantwini 40-42, kunye iigundane kunye ne-primates ngomonakalo we-OFC zichaphazeleka ekubuyiseleni ekufundeni nokuba kufundwa izixhobo zantlandlolo kuyinto eyi-38; I-43-51. Oku kusilela kuboniswa kwiigundane kuMzobo 1A. Izilonda ze-OFC zinokuphazamisa umsebenzi ofanayo kwimisebenzi 'yokungcakaza' apho izifundo ezinzulu zifunda ukuguqula ukuphendula kwabo kwi-cue eveze kwangaphambili ixabiso elikhulu, kodwa kamva liza kuqikelela ingozi enkulu yokulahleka kwe-31. Nangona okwangoku kuyimpikiswano ngesihloko se-cositive neuroscience, kukho ubungqina bokuba indima ye-OFC kwimisebenzi yokungcakaza iboniswa ikakhulu yimfuno yokubuyela umva kokufunda eyindalo kuyilo lwemisebenzi yokungcakaza eyi-51.
Umzobo 1
Umzobo 1
Ukuvezwa kwecocoaine kuzisa i-OFC yokuxhomekeka ekuguqukeni kwimfundo yokufunda eyimilinganiselo efanayo yokuphambuka kokufunda okubangelwa zizilonda ze-OFC

Ukubandakanyeka kwe-OFC ekumeleni ixabiso lezi ziphumo ezichaziweyo kungabekwa wedwa kwimisebenzi yokuqinisa amandla, apho ixabiso lesiphumo lisetyenzisiwe ngokuthe ngqo ngokuhamba ngokugula okanye kukhetho lwe-52. Kwezi zicwangciso, izilwanyana eziqhelekileyo ziya kuphendula kancinane kwimikhwa yokuqikelela emva kwesiphumo sesiphumo. Iigundane kunye neepropati ezingezizozomntu ezinomonakalo kwi-OFC ziyasilela ukubonisa lo mphumela wesiphumo sokudalwa kwe37; I-38; 53. Olu phononongo libonisa intsilelo kubuchule bezilwanyana ezi-OFC ezikhuselweyo ukuba zisebenzise umfuziselo wexabiso lesiphumo sokukhokela indlela abaziphethe ngayo, ngakumbi xa kujongwa imeko ezinemeko. Ngenxa yoko, isimilo esikhutshwe ziimpawu ziba ngaphantsi ngokuxhomekeke kwixabiso lesiphumo esilindelekileyo kwaye, ngokungagqibekanga, njengokuthanda kakhulu. Nangona ezi zifundo zenziwe kwizilwanyana zaselabhoratri, izifundo zophando zibonakalise ukuba iimpendulo ezivela-kwi-BOLD kwi-OFC zijongise kakhulu kuzinzo lokutya abakuqhelileyoI-54. Apha ngezantsi, sixoxa ngobungqina bokuba ukubonakaliswa iziyobisi okuphindaphindiweyo kuphembelela utshintsho kwi-neuronal kunye neempawu zemolekyuli yokusebenza ye-OFC; ezi nguqu zinokulamla ukonakaliswa okubonakalayo kwindlela yokuziphatha e-OFC-yokulamla kwizilwanyana ezinamava kwelebhu. Ezo nguqu zinokukhokelela, ngokuyinxalenye, kwindlela yokuphendula efana nokubakho ekuziphatheni kweziyobisi nakwizilwanyana ezinolwazi ngamachiza.

Iziphumo zokuvezwa kweziyobisi kwi-OFC

Ihlala ingumbuzo ovulekileyo zeziphi iindawo zobuchopho kunye neenguqu eziphakathi zokungakwazi ukwenza iziyobisi ukulawula indlela yokuziphatha. Enye indlela yokuphendula lo mbuzo kukujonga ukuba ngaba indlela yokuziphatha eqhelekileyo, exhomekeke kwimimandla ethile yobuchopho okanye imijikelezo, iyachaphazeleka ekuvezweni kweziyobisi, kunye nokunxibelelana notshintsho ekufundeni okuqhelekileyo kunye nokuziphatha okufuna iziyobisi kwimodeli yezilwanyana efanelekileyo. Ukuba ilahleko yokulawula ukukhangela iziyobisi ibonisa utshintsho olwenziwe iziyobisi ngokukodwa kwimijikelezo yobuchopho, impembelelo yolu tshintsho kufuneka ibonakale kwindlela yokuziphatha exhomekeke kwezo zangqa. Kule meko, ukubonakaliswa kweziyobisi kubonakalisiwe kuchaphazela iindlela zokuziphatha ezifundiweyo eziphakathi kwimimandla yangaphambili, i-amygdala, kunye ne-striatum kwiirati 55-58. Ukuvezwa kweziyobisi kukwaguqula indlela inkqubo ye-neurons yokufunda ulwazi kwezi ndawo zobuchopho i-59; 60. Phakathi kwezi zifundo, ngoku kukho ubungqina bokuba ukubonakaliswa kwe-cocaine kuphazamisa ukusebenza okukhokelwa kwisiphumo okuxhomekeka kwi-OFC. Umzekelo, iigundane ezazivezwe ngaphambili kwi-cocaine kwiintsuku ze-14 (30 mg / kg / day, ip) yehlulekile ukulungisa imeko ekuphendulwa kuyo emva kokuqiniswa kwe-1 inyanga emva kokurhoxiswa kwe57. Iigundane ezinamava e-cocoaine nazo ziphendula ngokukhawuleza xa ubungakanani bomvuzo kunye nexesha lokuvuza lilawulwa kwimisebenzi ekhethiweyo kwiinyanga ezininzi emva kokurhoxiswa kwe61; 62. Ezi ntsilelo ziyafana nezo zibangelwa zi-OFC lesion 37; 63.

Ukubuyela umva kufundiswa kuphazamiseka emva kokuvezwa kwecocaine. Oku kuboniswe okokuqala nguJentsch kunye noTaylor 64 kwiinkawu ezinikwe ixesha elide ukubonakaliswa kwe-cocaine kwiintsuku ze-14 (2 okanye 4 mg / kg / day, ip). Ezi nyani bezihamba kancinci ukufumana ukubuyiselwa kokucalulwa kwento xa kuvavanywa i-9 kunye neentsuku ze-30 emva kokurhoxa kwi-cocaine. Ngokufanayo, sifumene ukuba iigundane ezazivezwe ngaphambili kwi-cocaine (i-30 mg / kg / usuku ip ngeentsuku ze-14) zibonisa ukuphazamiseka ukusebenza okungalunganga malunga ne-1 inyanga emva kokurhoxa kwichiza i-65. Njengoko kubonisiwe Kumzobo 1B, le ntsilelo ekufundeni okuguqukayo ifana nqwa neeresi ezinesilonda esise-50; I-65; 66.

Le ntsilelo yokubuyela umva inxulunyaniswa nokusilela kwee-neuron ze-OFC ukuveza iziphumo ezilindelekileyo kwi59. I-Neurons zarekhodwa zivela kwi-OFC kumsebenzi ofanayo nalowo usetyenziswe ngentla ukubonisa ukuphambuka kwemeko yokufunda; Imihla ngemihla iigundwane zifunda inoveli yokuhamba, ukungabikho kocalucalulo, ekuphenduleni kuyo ivumba lokufumana i-sucrose kunye nokuthintela i-quinine. I-neuron ye-OFC, erekhodwe kwiigundane ezivezwe kwi-cocaine ngaphezulu kwenyanga ngaphambili, yadubula ngokuqhelekileyo kwiziphumo ze-sucrose kunye ne-quinine, kodwa yahluleka ukuvelisa iimpendulo ezikhethiweyo emva kokufunda. Ngamanye amagama, ii-neurons ezikwii-cocaine eziphathweyo ngecocaine azizange zibonise ziziphumo xa kusenziwa isampulu, xa olo lwazi lunokusetyenziselwa ukukhokela impendulo. Ukuphulukana nalo mqondiso kwakubonakala ngakumbi ngexesha lokubonakaliswa kwe-cue eveze iziphumo zokuphinda zibuyele kwi-quinine kwaye zinxulunyaniswa notshintsho olungaqhelekanga ekuphenduleni kokuphindaphindiweyo kwezi zilingo zinxaxhileyo. Ngapha koko, emva kokurhoxa kwemibutho enesiphumo se-cue, ii-neuron ze-OFC ezikwi-cocaine eziphathwe ngecocaine ezinokuphinda zibuyele umva ziyasilela ukubuyisela umva ukukhetha kwazo. Ezi ziphumo ziyahambelana ne-hypothesis ethi i-cocaine-induction neuroadaptations iphazamise isiphumo esiqhelekileyo sokusayina umsebenzi we-OFC, apho ke kutshintsha amandla esilwanyana ukwenza iinkqubo eziguqukayo zokwenza izigqibo ezixhomekeke kulo msebenzi we-14; 67. Ezi ziphumo zikwacebisa ukuba umsebenzi we-OFC ongekho mthethweni oqwalaselwe kwizichazi ezinokubakho unakho ukutshintsha kweempembelelo ezibangelwa zezi ziyobisi okanye ukongeza ekungasebenzi kakuhle kwe-OFC.

Ewe kunjalo, kukho iingozi ezinzulu ekusebenziseni iziphumo zezifundo zangaphantsi kwesifo ukufumana ulwazi lokuba zeziphi iindawo ezichaphazelekayo kukuvezwa kweziyobisi. Iziphumo zokuvezwa kweziyobisi ngokucacileyo azilingani nesilonda, kunye neziphumo zangaphakathi kwezinye izakhiwo zinokulinganisa kakuhle iimpembelelo zezilonda. Ukanti ukusebenza kwizilwanyana zaselabhoratri kubonisa ukuba ukuvezwa kwengqondo yengqondo kubangela utshintsho kwiimpawu zomsebenzi we-OFC. Umzekelo, iigundane eziqeqeshelwe ukuzilawula ngokwazo i-amphetamine zibonisa ukwehla okungapheliyo kwi-OFC dendritic density 68. Ukongeza, iigundane ezinamava ze-amphetamine zibonisa ubuncinci beplastiki kwimimandla yazo ye-dendritic kwi-OFC emva koqeqesho lwezixhobo xa kuthelekiswa nolawulo lwe68. Ngokukodwa, ezi ziphumo zimi ngokuchaseneyo noko kufunyanweyo kwezinye iindawo zobuchopho ezifundwe, kubandakanywa namanye amacandelo e-cortex yangaphambili, apho ukubonakaliswa kwe-psychostimulant kuvame ukukhulisa ukuxinana komgogodla we-dendritic, okunokwenzeka kubonakalise ukwanda kwe-neuronal plastikiity 69-71. Ezi ziphumo zichaza i-OFC njengommandla obonisa ukwehla okungapheliyo kwipulasitiki- okanye amandla okufaka ulwazi olutsha - ngenxa yokufumana i-psychostimulants. Ngokuhambelana noku, i-cocaine yeziyobisi zibonise ukunciphisa umxholo wegrey kwi-OFC 72.

Kukho imiba eliqela ekufuneka iqwalaselwe malunga nokuhambelana kweziphumo zezifundo zokuziphatha eziphononongiweyo apha ngasentla kwimeko yomntu. Umcimbi omnye kukuba kuzo zonke izifundo eziphononongiweyo apha ngasentla, iziyobisi zanikwa ngaphandle kokuphikisana, zisebenzisa iirejimeni zokubonisa ezikhokelela kunyamezelo lwe-psychomotor sensitization 73; 74. Izifundo ezininzi zibonise umohluko obonakalayo kwimpembelelo yokuboniswa kwesiyobisi ngokuchaseneyo nokungazibandakanyi kwimisebenzi yobuchopho kunye nokuziphatha 75-78. Ukongeza, abukho ubungqina obuncinci bokuba ubonakalisi be-psychomotor bubonakaliswa kwi-cocaine yeziyobisi ezingapheliyo okanye kwiinkawu ezinembali ebanzi ye-cocaine ye-self-management 79. Ke ngoko, kubalulekile ukuba kufunyanwe intsilelo kwimisebenzi exhomekeke kwi-OFC elawulwa emva kwerejimeni yokuvezwa kwecocaine engalawulekiyo iyaqwalaselwa nakwiimodeli zokusetyenziswa kweziyobisi ezibandakanya ukusetyenziswa kweziyobisi ezinesiyobisi (oko kukuthi, ukuzilawula kwamachiza). Ngokuhambelana, kutshanje saxela ukuba iigundane eziqeqeshelwe ukuzilawula i-cocaine ye-14 d ye-3 h / d (i-0.75 mg / kg / infusion) ibonise ukubuyela umva kwimeko yokufika kwiinyanga ezintathu emva kokurhoxa kwichiza i-80. Njengoko kubonisiwe kumzobo 1C, le ntsingiselo iphindaphindayo yayifana kubukhulu obuqaphelekayo emva kokubhenca i-cocaine kwi-65 okanye emva kwezilonda ze-OFC ze-50.

Omnye umba ekufuneka uqwalaselwe kukuba kuzo zonke ezi zifundo, intsilelo ye-OFC yaboniswa kwizilwanyana zaselebhu ezazvinjelwe ixesha elithile. Ngenxa yoko, ikhosi yexesha kunye nobude besiphumo sokuvezwa kweziyobisi kwi-OFC yokusebenza ayaziwa kakhulu. Olunye ukhetho luphando olwenziwa nguKantak noogxa bakhe i-81 apho baye bavavanya isiphumo sokubonakala kwe-cocaine kwi-OFC exhomekeke kwi-odolo ehambelana nephulo lokuhanjiswa kwe-winC. Aba babhali baxele ukuba indlela yokuziphatha kulo msebenzi ibiphazamisana necocaine kodwa engeyiyo eyomdibano kwiigundane eziye zavavanywa kwangoko emva kweeseshini zokuzilawula. Esi siphumo sibonisa ukuba ukubonakaliswa kwe-cocaine kunokuba nefuthe kwangoko kwimisebenzi exhomekeke kwi-OFC. Into enomdla kukuba ukusilela ekuvezeni i-cocaine engadibaniyo nokuziphatha ngokuphakathi kwe-OFC kolu phononongo kuthelekiswa neengxelo eziqwalaselwe apha ngasentla zibonisa ukuba ifuthe lokuvezwa kweziyobisi emsebenzini we-OFC linganyuka emva kokurhoxa kwichiza.

Ukuqukumbela, ukubonakaliswa kwe-cocaine (nokuba kuyimpikiswano okanye ukungangqinelani) kukhokelela kusilelo olusisigxina lweendlela zokuziphatha ezixhomekeka kwi-OFC ezifanayo ngobukhulu kwezo zibonwe emva kwezilonda ze-OFC. Ukuvezwa kwe-cocaine engahambelaniyo nako kukhokelela kutshintsho olwakhiwo kwii-neuron ze-OFC, okunokwenzeka kubonakalise ukuncipha kwe-plastiki kwezi ntsholongwane, kunye nokufakwa ngendlela okungaqhelekanga kwe-neuronal kwi-OFC. Okulandelayo, sichaza iziphumo ezivela kwizifundo eziphonononge indima ye-OFC kumvuzo wamachiza kunye nokubuyela umva, njengoko kulinganiswa kulawulo lwe-83 yeziyobisi kunye nokubuyisela kwimodeli ye-84.

Indima ye-OFC kulawulo lweziyobisi nokubuyela kwimeko yesiqhelo

Idatha ehlaziywe apha ngasentla ibonisa ukuba umsebenzi we-OFC utshintshwa ngokuchazwa kwesiyobisi rhoqo. Umbuzo osusela kule datha yeyiphi indima edlalwa yi-OFC ekuchaseni indlela yokuziphatha kweziyobisi kwiimodeli zezilwanyana. Okothusayo bambalwa amaphepha avavanye lo mbuzo ngqo. Kwisifundo sokuqala, Phillips et al. I-85 inike ingxelo yokuba i-rhesus ezine zeenkawu zisebenza ngokuzimela zisebenza ngokwazo i-amphetamine (10-6 M) kwi-OFC. Okothusayo kukuba, ezo nyani azizange zizenzele ngokwazo i-amphetamine kwi-nucleus accumbens, indawo eyaziwayo ukubandakanyeka kwiziphumo ezivuzayo ze-amphetamine kumagundane 86. U-Hutcheson kunye no-Everitt 87 kunye noFuchs et al. I-88 inike ingxelo yokuba izilonda ze-neuroto ze-OFC azizange ziphazamise ukufunyanwa kwe-cocaine ye-self-management phantsi kweshedyuli yokuqinisa i-1 ishedyuli yokuqinisa kumagundane. U-Hutcheson kunye no-Everitt 87 baye baxela ukuba izilonda ze-OFC azichaphazeli ijika lokuphendula le-cocaine (i-0.01 ukuya kwi-1.5 mg / kg). Nangona kunzima ukuthelekisa iireyithi kunye nezifundo zeenkawu ngenxa yomahluko kusetyenziso lweziyobisi kunye neendlela zokuphatha, kunye nokwenzeka kweentlobo ezahlukeneyo kwi-OFC anatomy 89, iziphumo zezifundo zekreyithi zibonisa ukuba ye-OFC ayibalulekanga kwiziphumo ezizuzisayo zokuzenzela -ukusetyenziswa kwe-cocaine ye-intravenous. Oku kuqaphela kuyafana neziphumo kwizifundo eziqhelekileyo zokufunda, ezibonisa ukuba izilonda ze-OFC ngokwesiqhelo azinampembelelo yokufunda ukuphendula ngembuyekezo engezizo iziyobisi kwiimeko ezahlukeneyo ze-37; I-50; 90.

Ngokwahlukileyo, uHutcheson kunye no-Everitt 87 bafumanisa ukuba i-OFC yayifuneka kwimeko yokuqiniswa kwemeko yokudibana necocaine, njengoko ilinganiselwa kwishedyuli yoku-odola yesibini yenqubo yokuqinisa i-91; 92. Baye baxela ukuba izilonda ze-neuroto OFC ziye zaphazamisa amandla e-cocaine ye-Pavlovian coca ukugcina impendulo. Ngokufanayo, uFuchs et al. I-88 inike ingxelo yokuba i-inactivation e-inaltivation ye-lateral (kodwa ingeyiyo medial) ye-OFC ngomxube we-agonists ye-GABAa + GABAb (muscimol + baclofen) ichaphazele imeko yokuqiniswa kwe-cocaine cuesine, njengoko ilinganiswa kwinkqubo yokubuyisela kwi-cueine. Obunye ubungqina obunokubakho kwindima ye-OFC ekufuneni i-cocaine-in ccaine kukuba ukubonakaliswa kwi-cocaine eyakhe yaqhutywa ngaphambili kunye nokuzilawula kwe-cocaine kukonyusa ukubonakaliswa kohlobo lwangaphambili lwe-Zif268 (uphawu lwento yokwenza i-neuronal activation) kule ngingqi ye93. Ngokudibeneyo ezi datha zibonisa ukuba i-OFC idlala indima ebalulekileyo ekulamleni amandla athile ahambelana neziyobisi ukukhuthaza indlela yokufuna iziyobisi. Indima enjalo inokubonakalisa indima ye-OFC echazwe ngaphambili ekufumaneni nasekusetyenzisweni kwemibutho yeziphumo zomthombo we-37; I-38; 53. Ewe, izilonda ze-OFC zithintela ukuphendula kokuqiniswa kwimeko engeyiyo yeziyobisi i-94-96 kwaye kuye kwaxelwa ukuba kuchaphazela ukuhanjiswa kwe-Pavlovian-to-instrumental 90, ebonisa ukuba i-OFC ixhasa amandla eendlela zase-Pavlovia ukukhokela ekuphenduleni ngesixhobo.

Okubangela umdla kukuba uFuchs et al. I-88 ichaze ipatheni eyahlukileyo yeziphumo xa besenza izilonda zecalal ye-oral okanye ye-medic ngaphambi koqeqesho. Bafumanise ukuba ezo zilonda zangaphambi koqeqesho azinampembelelo ekubuyiselweni komdla ekufumaneni i-cocaine. Ngenxa yokuba ezi zilonda zazenziwe ngaphambi koqeqesho lokuzilawula, i-OFC yayingafumaneki ukuba ithathe inxaxheba ekufumaneni imibutho ye-cue-cocaine. Ngenxa yoko, iigundane ezikhutshiwe zisenokuba zifunde ukuxhomekeka ngakumbi kwezinye iindawo zobuchopho ezibandakanyekileyo kwi-cocaine ye-cocaine eyenzelwe i-97.

Okokugqibela, i-OFC ikwabonakala ibalulekile ekubuyiselweni kokuphindayo ekufumaneni iziyobisi. Izifundo zangaphambili zisebenzisa inkqubo yokubuyiselwa kwe10; I-98 ibonakalise ukuba ukuvezwa koxinzelelo lwe-footshock elenzayo kubuyisela amandla eziyobisi emva koqeqesho lokuzilawula ngokwamachiza kunye nokupheliswa okulandelayo kwempendulo ye-99 yokuqinisa iziyobisi; 100. Kutshanje, iCapriles et al. I-101 ithelekise indima ye-OFC ekuvuseleleni ngoxinzelelo kunye nokubuyiswa kwakhona okwenziwe ngenaliti ye-cocaine priming. Bafumanise ukuba inactivation eguqukayo ye-OFC ene-tetrodotoxin inciphise uxinzelelo lwe-footshock- kodwa ayibuyiswanga ekuvuseleleni kwe-cocaine. Baphinde baxela ukuba inaliti ye-D1-efana ne-receptor antagonist SCH 23390 kodwa ayisiyi-D2-efana ne-receptor antagonist raclopride kwi-OFC evaliweyo yokubuyisela uxinzelelo.

Ukuqukumbela, uncwadi olulinganiselweyo oluhlolisiswe apha ngasentla licebisa ukuba i-OFC inokwenzeka ukuba ingayichaphazeli imiphumo ebabazekayo yokusebenzisa i-cocaine, kodwa ibandakanyeka kumandla we-cocaine cessine kunye noxinzelelo lokukhuthaza ukufuna iziyobisi. Ukongeza, ii-receptors ze-D1-ezifana ne-dopamine receptors kwi-OFC zibandakanyeka kukubuyela koxinzelelo ekuvuseleleni nasekufuneni i-cocaine.

Iziphelo kunye nolawulo lwekamva

Iziphumo zezifundo ezisebenzisa ukuzilawula kunye neenkqubo zokubuyiselwa emsebenzini zicebisa indima eyinkimbinkimbi ye-OFC kumvuzo weziyobisi kunye nokubuyela umva. Siza kufikelela kwisigqibo esithile esibambekayo kwezi zifundo zangaphambi kliniki. Okokuqala, i-OFC ayibonakali ngathi idlala indima ebalulekileyo kwisiphumo sokuvuza kwe-cocaine okanye ekuvuseleleni oko ekubonakaliseni ichiza. Esi siphumo sihambelana nedatha ebonisa ukuba i-OFC inqabile ukuba izilwanyana zifunde ukuphendula ngomvuzo, ngenxa yokusebenza kweenkqubo ezahlukeneyo zokufunda ezi-37; I-50; 90.

Okwesibini, i-OFC ibonakala idlala indima ebalulekileyo kubuchule bezinto ezinxulumene neziyobisi ukukhuthaza ukufuna icocaine. Ezi zinto zifunyanisiweyo ziyavumelana nesiphumo esivela kwizifundo ezibonakalayo ezibonakalisa ukwenziwa kwamandla kwe-OFC yimikhwa enxulumene neziyobisi i-15. Izilonda okanye ukuphinda kuguqulwe kwi-OFC kunokunciphisa ukufunwa kweziyobisi, ngenxa yokusilela ukwenza ngokwenyani ulwazi malunga nexabiso elilindelweyo lesiyobisi i-36. Umbuzo omnye wophando lwexesha elizayo likhondo lexesha lokutshintsha kweziyobisi e-OFC kunye nokuba i-OFC iyabandakanyeka ekunyukeni okuxhomekeka kwixesha lokufuna icocaine emva kokurhoxa i-102-104, into ebizwa ngokuba kukuzibandakanya kokufuna.

Okwesithathu, i-OFC ikwabonakala ibalulekile ekubuyiselweni koxinzelelo lokufuna icocaine. Kuxelwe ukuba ifuthe loxinzelelo lwe-footshock ekubuyiselweni kokufuna i-cocaine kuxhomekeke kubukho be-discrete ithoni-ukukhanya kwe-105. Ke ngoko, indima ye-OFC ekubuyiseleni uxinzelelo-oluxhonywe ngaphakathi inokuba sesibini kwisiphumo soxinzelelo kuxinzelelo ekuphenduleni okulawulwayo kwendaba.

Kubalulekile ukugxininisa ukuba izigqibo zethu malunga nendima ye-OFC kulawulo lweziyobisi kunye nokubuyela kwimeko yesiqalo ethile inikwe ulwazi olulinganiselweyo. Umcimbi omnye ekufuneka uqwalaselwe kukuba igalelo le-OFC kwiindlela zokuziphatha ezifuna iziyobisi linokubonakalisa utshintsho kwi-OFC ebangelwa kukuvezwa ichiza kwangaphambili. Ngenxa yoku kuthathelwa ingqalelo, ukutolika iimpembelelo zezilonda okanye ezinye izixhobo zepilisi ze-OFC ekufumaneni iziyobisi ngokuqhutywa zii-cises okanye uxinzelelo kumagundane anembali yokuzilawula iziyobisi kufuneka wenziwe ngononophelo.

Umcimbi wesibini kwaye mhlawumbi ophambili ekufuneka uqwalaselwe kukuba imifuziselo yezilwanyana yangoku yokulawula iziyobisi nokubuyela umva isenokungakulungeli ukuvavanya ukuba yeyiphi indima ye-OFC yokudlala iziyobisi. Ukongeza kwindima yakhe ngokubanzi yokulamla kwindlela yokuziphatha ekhokelwa ziziphumo, i-OFC ibonakala ibaluleke kakhulu ekuboneni nasekuphenduleni utshintsho kwiziphumo ezilindelekileyo 38; I-43; 50. Oku kubonakala ngakumbi xa iziphumo zitshintsha ukusuka kokulungileyo ukuya kokubi okanye xa zithe zacothiswa okanye zavela i-37; I-50; I-63; I-106-108. Apha siphonononge ubungqina bokuba lo msebenzi we-OFC uphazamiseka ngokufumana iziyobisi ezingamakhoboka, zikhokelela kwisigqibo esingesiso sokuthatha isigqibo se57; I-58; I-61; I-62; I-64; I-65; 80. Ngenxa yokuba indlela yokuziphatha yokufuna iziyobisi ebantwini kusenokwenzeka ukuba sisiphumo sokulingana phakathi komnqweno okwethutyana wechiza kunye nokuvavanywa kwesiqhelo esixhaphakileyo sokuxhaphaka kwaye sihlala silibazisa iziphumo zokufuna iziyobisi kwi-109-111, iziphumo zamachiza kubukho be-OFC ukuya Iziphumo ezichaziweyo zokulibaziseka okanye iziphumo ezinokubakho zingaphantsi kokungakwazi ukwenza iziyobisi ukuyeka ixesha elifutshane kunye nokuzanelisa kwangoko kokusebenzisa iziyobisi. Nangona kunjalo iimpembelelo ezinjalo azizukubonakala kuninzi lweemodeli zokusetyenziswa kwesiyobisi nokubuyela umva, ezingaxelisi ukungqubana komlutha phakathi kweziphumo ezikhawulezayo kunye zokulibaziseka.

Nangona izifundo zangaphambili zazibandakanya iinkqubo zesohlwayo zokuvavanya ukuqiniswa kwesiyobisi i-112; I-113, kutsha nje sele kuphinde kwabakho abaphandi abaliqela kweziyobisi. Aba baphandi banike ingxelo yokuba ezinye iigundane ezinembali ebanzi yokuchazwa iziyobisi ziya kuqhubeka nokuzibandakanya ekuziphatheni iziyobisi xa ujongene nesohlwayo okanye imiphumo emibi eqhelekileyo yokucinezela iziyobisi- okanye ukutya kuthatha ukuphendula i-114-116. Ukohlwaywa- okanye iinkqubo ezisekwe kungquzulwano nazo ziye zaziswa kutshanje ukuvavanya ukunyusa iziyobisi- kunye nokubuyela kwi-cue-kwaye ngenxa yokubuyela kumachiza afuna i-117. Ezi nkqubo zinokulungelwa ngokufanelekileyo ukwahlula indima ye-OFC kumakhoboka eziyobisi, kuba zisondelisa ngakumbi iindima ezaziwayo ze-OFC yokuziphatha kunye nokuziphatha komntu olikhoboka leziyobisi. Ke, ukuvavanya indima ye-OFC kwisohlwayo okanye imodeli yongquzulwano kubalulekile kwindawo yophando oluzayo. Kule meko, ngokusekwe kwiziphumo zokufumana ukuphambuka kokufunda okuguqukayo emva kokuvezwa kwecocaine, siqikelela ukuba utshintsho olwenziwe nge-cocaine ekusebenzeni kwe-OFC luyakunxulumana nokukwazi ukuncipha ukuphendula phambi kweziphumo ezibi.

Izinto ezongezelelweyo
01
Cofa apha ukujonga. (27K, doc)
Yiya e:
Imibulelo

Ukubhalwa kolu phononongo kwaxhaswa yi-R01-DA015718 (GS) kunye neNkqubo yoPhando lwe-Intramural yeZiko likaZwelonke ngokuSetyenziswa gwenxa kweziyobisi (YS).
Yiya e:
Imihlathi

Ukuvezwa kwemali: Drs. I-Schoenbaum kunye ne-Shaham azinangxabano yemali yomdla yokuveza.

Iphepha elichazayo ukuba awusenanto oyipapashileyo: Le yifayile yePDF yemibhalo ebhaliweyo engamiswanga eyamkelweyo ukuba ipapashwe. Njengenkonzo kubathengi bethu sinikezela ngolu hlobo lwengqangi. Umbhalo obhaliweyo uza kukopishwa, ukuhlelwa kweesetingi kunye nokuphononongwa kobungqina obunokubakho ngaphambi kokuba upapashwe kwifom yokugqibela. Nceda uqaphele ukuba ngexesha lokuveliswa kwempazamo kunokufunyanwa iimpazamo ezinokuchaphazela umxholo, kunye nazo zonke izinto ezisemthethweni ezichazayo ezisebenza kwijenali leyo.

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