Mukofot tizimi - Reward system

The mukofotlash tizimi (mezokortikolimbik zanjir) - bu mas'ul bo'lgan asabiy tuzilmalar guruhidir rag'batlantirish (ya'ni, motivatsiya va "xohlash"; mukofotga intilish yoki orzu qilish), assotsiativ o'rganish (birinchi navbatda ijobiy mustahkamlash va klassik konditsioner ) va ijobiy valentli hissiyotlar, xususan, o'z ichiga olganlar zavq asosiy komponent sifatida (masalan, quvonch, eyforiya va xursandchilik ).[1][2] Mukofot - bu ishtahani qo'zg'atadigan, shuningdek, ma'lum bo'lgan stimulning jozibali va motivatsion xususiyati yondashuv yoki iste'mol qiluvchi xulq-atvor.[1] Muvaffaqiyatli rag'batlantirish (ya'ni "mukofot") "deb ta'riflanganbizga yaqinlashishimiz va uni iste'mol qilishimizga imkon beradigan har qanday rag'batlantirish, ob'ekt, voqea, faoliyat yoki vaziyat - bu ta'rifga ko'ra mukofot".[1] Yilda operatsion konditsionerligi, mukofotlovchi rag'batlantirish funktsiyalari ijobiy mustahkamlovchilar;[3] ammo, teskari bayonot ham o'z kuchini yo'qotmaydi: ijobiy kuchaytiruvchilar mukofotlashadi.[3]

Birlamchi mukofotlarning namunalari.[3] Yuqoridan soat yo'nalishi bo'yicha: suv, oziq-ovqat, ota-ona g'amxo'rligi va jinsiy aloqa.
Giyohvandlik va qaramlikka oid lug'at[4][5][6][7]
  • giyohvandlik - a biopsixososyal jiddiy zarar va salbiy oqibatlarga qaramay, giyohvand moddalarni (shu jumladan spirtli ichimliklarni) doimiy ravishda ishlatish bilan tavsiflangan tartibsizlik
  • qo'shadi xulq - ham foydali, ham mustahkamlovchi xatti-harakatlar
  • qo'shadi giyohvandlik - ham foydali, ham quvvat beruvchi dori
  • qaramlik - stimulga takroran ta'sir qilish to'xtatilganda (masalan, giyohvand moddalarni iste'mol qilish) to'xtash sindromi bilan bog'liq bo'lgan adaptiv holat
  • giyohvandlik sezgirligi yoki teskari bag'rikenglik - ma'lum dozada takroriy qo'llanilishidan kelib chiqadigan dori ta'sirining kuchayishi
  • giyohvand moddalarni olib tashlash - takroriy giyohvand moddalarni iste'mol qilishni to'xtatganda paydo bo'ladigan alomatlar
  • jismoniy qaramlik - doimiy jismoniy ta'sirga bog'liqlik -badandagi tortib olish alomatlari (masalan, charchoq va deliryum tremens )
  • psixologik qaramlik - emotsional-motivatsion chekinish alomatlarini o'z ichiga olgan qaramlik (masalan, disforiya va anhedoniya )
  • mustahkamlovchi ogohlantiruvchi vositalar - ular bilan bog'langan xatti-harakatlarni takrorlash ehtimolini oshiradigan stimullar
  • foydali ogohlantiruvchi vositalar - miya ichki ijobiy va kerakli yoki yaqinlashadigan narsa sifatida talqin etadigan stimullar
  • sezgirlik - stimulga takroran ta'sir qilish natijasida kelib chiqadigan kuchaytirilgan javob
  • moddani ishlatish buzilishi - moddalardan foydalanish klinik va funktsional jihatdan muhim buzilish yoki bezovtalikka olib keladigan holat
  • bag'rikenglik - ma'lum bir dozada takroriy qo'llanilishidan kelib chiqadigan preparatning pasayishi ta'siri

Mukofotlash tizimi hayvonlarni ogohlantiruvchi vositalarga yaqinlashishga yoki jismoniy tayyorgarlikni oshiradigan xatti-harakatlarga undaydi (jinsiy aloqa, energetikaga boy ovqatlar va hk) Hayvonlarning aksariyat turlari uchun tirik qolish foydali stimullar bilan aloqani maksimal darajaga ko'tarish va zararli ogohlantirishlar bilan aloqani minimallashtirishga bog'liq. Mukofotlash bilimlari assotsiativ o'rganishni keltirib chiqarish, yondashuv va iste'molchi xulq-atvorni keltirib chiqarish va tetiklash orqali tirik qolish va ko'payish ehtimolini oshirishga xizmat qiladi. ijobiy valentli hissiyotlar.[3] Shunday qilib, mukofot - bu hayvonlarning adaptiv tayyorgarligini oshirishda yordam beradigan mexanizm.[8] Giyohvandlikda giyohvandlik, ba'zi moddalar mukofot sxemasini haddan tashqari faollashtiradi, bu esa konturdagi sinaptik plastisit natijasida moddani izlashga majbur qiluvchi xatti-harakatga olib keladi.[9]

Birlamchi mukofotlar - bu engillashtiradigan foydali stimullar sinfidir o'z-o'zidan va avloddan omon qolish va gomeostatikani o'z ichiga oladi (masalan, mazali taom ) va reproduktiv (masalan, jinsiy aloqa va ota-ona sarmoyasi ) mukofotlar.[1][10] Ichki mukofotlar - bu jozibali va xulq-atvorni qo'zg'atadigan shartsiz mukofotlar, chunki ular tabiatan yoqimli.[1] Tashqi mukofotlar (masalan, pul yoki sevimli sport jamoasining o'yinda g'alaba qozonishini ko'rish) jozibali va xulq-atvorga turtki beradigan shartli mukofotlar, ammo tabiatan yoqimli emas.[1][11] Tashqi mukofotlar o'zlarining motivatsion qiymatini a assotsiatsiyani o'rgandi ichki mukofotlar bilan (ya'ni, konditsionerlik).[1] Tashqi mukofotlar, shuningdek, zavqni keltirib chiqarishi mumkin (masalan, lotereyada juda ko'p pul yutib olishdan eyforiya) klassik shartli ichki mukofotlar bilan.[1]

Ta'rif

Neyrologiyada mukofotlash tizimi - bu mukofot bilan bog'liq bilish uchun javobgar bo'lgan miya tuzilmalari va asab yo'llarining to'plami, shu jumladan assotsiativ o'rganish (birinchi navbatda klassik konditsioner va operativ mustahkamlash ), rag'batlantirish (ya'ni, motivatsiya va "istash", istak yoki mukofotga intilish) va ijobiy valentli hissiyotlar, xususan, o'z ichiga olgan hissiyotlar zavq (ya'ni, hedonik "yoqtirish").[3][2]

Odatda mukofotning "xohlash" yoki xohlash komponenti bilan bog'liq xatti-harakatni tavsiflash uchun ishlatiladigan atamalarga quyidagilar kiradi tuyadi harakati, yondashuv harakati, tayyorgarlik xatti-harakatlari, instrumental xatti-harakatlar, taxminiy xatti-harakatlar va izlash.[12] Odatda mukofotning "yoqtirish" yoki zavqlanish komponenti bilan bog'liq xatti-harakatni tavsiflash uchun ishlatiladigan atamalarga quyidagilar kiradi iste'mol qilish harakati va o'zini tutish.[12]

Mukofotlarning uchta asosiy vazifalari:

  1. mahsulot assotsiativ o'rganish (ya'ni, klassik konditsioner va operativ mustahkamlash );[3]
  2. qarorlarni qabul qilishga ta'sir qiladi va yondashuv xatti-harakatlarini keltirib chiqaradi (tayinlash orqali motivatsion keskinlik foydali stimullarga);[3]
  3. aniqlang ijobiy valentli his-tuyg'ular, ayniqsa zavq.[3]

Neyroanatomiya

Umumiy nuqtai

Mukofot tizimini tuzadigan miya tuzilmalari asosan ichida joylashgan kortiko-bazal ganglion-talamo-kortikal halqa;[13] The bazal ganglionlar loopning bir qismi mukofot tizimidagi faoliyatni boshqaradi.[13] Mukofot tizimidagi tuzilmalarni birlashtiradigan yo'llarning aksariyati glutamaterjik internironlar, GABAerjik o'rta tikanli neyronlar (MSN) va dopaminerjik proektsion neyronlar,[13][14] boshqa turdagi proektsion neyronlarning hissasi bo'lsa ham (masalan, orexinergik proektsion neyronlar). Mukofotlash tizimiga quyidagilar kiradi ventral tegmental maydon, ventral striatum (ya'ni akkumulyator yadrosi va xushbo'y naycha ), dorsal striatum (ya'ni kaudat yadrosi va putamen ), substantia nigra (ya'ni pars kompakt va pars reticulata ), prefrontal korteks, oldingi singulat korteksi, ichki korteks, gipokampus, gipotalamus (xususan, orexinergik yadrosi lateral gipotalamus ), talamus (bir nechta yadro), subtalamik yadro, globus pallidus (ikkalasi ham tashqi va ichki ), ventral pallidum, parabrachial yadro, amigdala va qolgan qismi kengaytirilgan amigdala.[2][13][15][16][17] The dorsal raphe yadrosi va serebellum mukofot bilan bog'liq bo'lgan idrokning ba'zi shakllarini modulyatsiya qiladigan ko'rinadi (ya'ni, assotsiativ o'rganish, motivatsion keskinlik va ijobiy his-tuyg'ular ) va xatti-harakatlar ham.[18][19][20] The laterodorsal tegmental yadro (LTD), pedunklopontin yadrosi (PPTg) va lateral habenula (LHb) (to'g'ridan-to'g'ri va bilvosita orqali rostromedial tegmental yadro ) induktsiyalashga qodir jirkanch tirishqoqlik va rag'batlantirish ventral tegmental hududga (VTA) o'zlarining proektsiyalari orqali.[21] LDT va PPTg ikkalasi ham VTAga dopaminerjik neyronlarda sinapsga uchraydigan glutaminerjik proektsiyalarni yuboradilar, ikkalasi ham rag'batlantiruvchi shov-shuvga olib kelishi mumkin. LHb glutaminerjik proektsiyalarni yuboradi, ularning aksariyati GABAerjik RMTg neyronlarida sinaps bo'lib, bu o'z navbatida dopaminerjik VTA neyronlarining inhibisyonini keltirib chiqaradi, ammo ba'zi LHb proektsiyalari VTA internironlarida tugaydi. Ushbu LHb proektsiyalari aversiv stimullar bilan ham, kutilgan mukofotning yo'qligi bilan ham faollashadi va LHb qo'zg'alishi nafratni keltirib chiqarishi mumkin.[22][23][24]

Ko'pchilik dopamin yo'llari (ya'ni, ishlatadigan neyronlar neyrotransmitter dopamin ventral tegmental zonadan tashqariga chiqadigan mukofot tizimining bir qismi bo'lgan boshqa neyronlar bilan aloqa qilish;[13] ushbu yo'llarda dofamin ta'sir qiladi D1 o'xshash retseptorlari yoki D2 o'xshash retseptorlari ishlab chiqarishni rag'batlantirish (D1 o'xshash) yoki inhibisyon (D2 o'xshash) lager.[25] The GABAerjik o'rta tikanli neyronlar ning striatum mukofot tizimining tarkibiy qismlari hamdir.[13] Subtalamik yadro, prefrontal korteks, gipokampus, talamus va amigdaladagi glutamaterjik proektsion yadrolar mukofot tizimining boshqa qismlari bilan glutamat yo'llari orqali bog'lanadi.[13] The medial old miya to'plami, bu vositachilik qiladigan ko'plab asabiy yo'llarning to'plamidir miya stimulyatsiyasi mukofoti (ya'ni to'g'ridan-to'g'ri elektrokimyoviy stimulyatsiya natijasida olingan mukofot lateral gipotalamus ), shuningdek, mukofot tizimining tarkibiy qismidir.[26]

Ikkita nazariya mavjud akumbenslar faoliyati va avlodni yoqtirish va xohlashi. Tormozlanish (yoki giperpolarizatsiya) gipotezasi, akumbens yadrosi ventral pallidum, gipotalamus yoki ventral tegmental maydon kabi quyi oqim tuzilmalariga tonik inhibitiv ta'sir ko'rsatadi va inhibe qilishda MSNlar accumbens yadrosida (NAcc) ushbu tuzilmalar hayajonlanib, mukofot bilan bog'liq xatti-harakatlarni "ozod qiladi". Esa GABA retseptorlari agonistlar akumbens yadrosidagi "yoqtirish" va "istash" reaktsiyalarini, glutaminerjik kirishlarni keltirib chiqarishi mumkin. bazolateral amigdala, ventral hipokampus va medial prefrontal korteks rag'batlantirish qobiliyatini kuchaytirishi mumkin. Bundan tashqari, ko'pgina tadqiqotlar NAcc neyronlari mukofotga javoban otishni kamaytiradi deb topsa-da, bir qator tadqiqotlar qarama-qarshi javobni topadi. Bu qo'zg'alish yoki NAcc neyronlari yoki hech bo'lmaganda ba'zi bir kichik guruhlar mukofot bilan bog'liq xatti-harakatlarni keltirib chiqaradi deb taxmin qiladigan disinhibitsiya (yoki depolarizatsiya) gipotezasining taklifiga olib keldi.[2][27][28]

Miyani stimulyatsiya qilish bo'yicha mukofot bo'yicha qariyb 50 yillik tadqiqotlardan so'ng mutaxassislar miyadagi o'nlab saytlarni saqlab qolishlarini tasdiqladilar intrakranial o'z-o'zini stimulyatsiya qilish. Hududlarga lateral gipotalamus va medial oldingi miya to'plamlari kiradi, bu ayniqsa samarali. U erda stimulyatsiya ko'tarilgan yo'llarni hosil qiluvchi tolalarni faollashtiradi; ko'tarilgan yo'llarga quyidagilar kiradi mezolimbik dopamin yo'li, qaysi ventral tegmental hududidan to akkumulyator yadrosi. Mezolimbik dopamin yo'li nega mukofotni vositachilik qiladigan davrlar uchun markaziy ekanligi haqida bir nechta tushuntirishlar mavjud. Birinchidan, hayvonlar intrakranial o'z-o'zini stimulyatsiya qilganda mezolimbik yo'ldan dopamin ajralishining sezilarli darajada ko'payishi kuzatiladi.[8] Ikkinchidan, tajribalar shuni ko'rsatadiki, miya stimulyatsiyasi mukofoti odatda faollashtirilgan yo'llarni kuchaytirishni rag'batlantiradi tabiiy mukofotlar va dori mukofoti yoki intrakranial o'z-o'zini stimulyatsiya qilish markaziy mukofotlash mexanizmlarini yanada kuchliroq faollashtirishi mumkin, chunki ular mukofot markazini to'g'ridan-to'g'ri faollashtiradilar periferik nervlar.[8][29][30] Uchinchidan, hayvonlar o'ziga qaram bo'lgan giyohvand moddalarni iste'mol qilganda yoki oziqlantirish yoki jinsiy faoliyat kabi tabiiy ravishda foydali xatti-harakatlar bilan shug'ullanganda, akumbens yadrosi ichida dopaminning sezilarli darajada chiqarilishi mavjud.[8] Biroq, dopamin miyadagi yagona mukofot birikmasi emas.

Kalit yo'l

Mezokortikolimbik ("mukofot") sxemasining ba'zi asosiy tarkibiy qismlarini aks ettiruvchi diagramma.

Ventral tegmental hudud

  • VTA mukofot mavjudligini ko'rsatuvchi ogohlantirishlarga va ogohlantirishlarga javob berishda muhim ahamiyatga ega. Maqbul mukofotlar (va barcha qo'shadi dorilar) VTA ni to'g'ridan-to'g'ri yoki bilvosita akumbens yadrosiga dopamin signallarini chiqarishga undash orqali harakat qiladi.[31] VTA ikkita muhim yo'lga ega: mezolimbik yo'l limbik (striatal) hududlarni loyihalashtirish va motivatsion xatti-harakatlar va jarayonlarni qo'llab-quvvatlash va mezokortikal yo'l prefrontal korteksga proektsiyalash, tashqi funktsiyalarni o'rganish kabi kognitiv funktsiyalarni qo'llab-quvvatlash. [32]
  • Ushbu mintaqadagi dopaminerjik neyronlar aminokislotani o'zgartiradi tirozin ferment yordamida DOPA tarkibiga kiradi tirozin gidroksilaza, so'ngra ferment yordamida dopaminga aylanadi dopa-dekarboksilaza.[33]

Striatum (Nucleus Accumbens)

  • Striatum keng ma'noda foydali ma'lumotlarga javoban o'rganilgan xatti-harakatlarni sotib olish va ularni shakllantirishga jalb qilingan. VTA striatumni loyihalashtiradi va ventral (Nucleus Accumbens) va dorsal striatum ichidagi D1 va D2 retseptorlari orqali GABA-ergic Medium Spiny Neurons-ni faollashtiradi. [34]
  • The Ventral Striatum (Nucleus Accumbens) VTA tomonidan oziqlanganida xatti-harakatlarni qabul qilishda va PFC tomonidan oziqlanganida xatti-harakatlarda ishtirok etadi. NAc qobig'i pallidum va VTA-ga chiqib, limbik va vegetativ funktsiyalarni tartibga soladi. Bu rag'batlantiruvchi xususiyatlarni va mukofotning qisqa muddatli tomonlarini o'zgartiradi. NAc Core nigra asosidagi loyihalarni amalga oshiradi va mukofot talab qiladigan xatti-harakatlarning rivojlanishi va uning ifodalanishida ishtirok etadi. U mekansal o'rganish, shartli javob berish va impulsiv tanlov bilan shug'ullanadi; mukofotning uzoq muddatli elementlari.[35]
  • Dorsal Striatum o'rganish bilan shug'ullanadi, Dorsal Medial Striatum maqsadli o'rganishda va Dorsal lateral striatum Pavlovning javobiga asoslangan stimul-javobni o'rganishda.[36] Rag'batlantiruvchi vositalar tomonidan takroriy faollashganda, Nucleus Accumbens Dorsal Striatumni intrastriatal tsikl orqali faollashtirishi mumkin. Signallarning NAc dan DS ga o'tishi, mukofot bilan bog'liq signallarni DS-ni mukofot mavjud bo'lmasdan faollashtirishga imkon beradi. Bu ishtiyoqni va mukofotni qidiradigan xatti-harakatlarni faollashtirishi mumkin (va giyohvandlikdan voz kechish paytida relapsni keltirib chiqarish uchun javobgardir).[37]

Prefrontal korteks

  • VTA dopaminerjik neyronlari PFCga prognoz qiladi, boshqa ko'plab mintaqalarga, shu jumladan Dorsal Striatum va NAc ga prognoz qilinadigan glutaminerjik neyronlarni faollashtiradi va natijada PFC stimullarga javoban keskinlik va shartli xatti-harakatlarda vositachilik qilishga imkon beradi.[38]
  • Shunisi e'tiborga loyiqki, giyohvand moddalarni iste'mol qilishdan voz kechish PFCni faollashtiradi, NAc ga glutamaterjik proektsiyani kuchaytiradi, bu kuchli istaklarga olib keladi va abstentsiyadan kelib chiqadigan giyohvandlik xatti-harakatlarini tiklashni modulyatsiya qiladi. PFK shuningdek VTA bilan mezokortikal yo'l orqali o'zaro ta'sir qiladi va atrof-muhitga oid ogohlantirishlarni mukofot bilan bog'lashga yordam beradi. [39]

Gipokampus

  • Gippokampus bir nechta funktsiyalarga ega, shu jumladan xotiralarni yaratish va saqlashda. Mukofot pallasida u kontekstual xotiralar va tegishli belgilarga xizmat qiladi. Bu oxir-oqibat signallar va kontekstli ogohlantirishlar orqali mukofotni qidirish xatti-harakatlarini tiklashga yordam beradi. [40]

Amigdala

  • AMY VTA-dan ma'lumot oladi va NAc-ga chiqadi. Amigdala kuchli hissiyotlarni yaratishda muhim ahamiyatga ega lampochka xotiralari va, ehtimol, kuchli belgilar bilan bog'liq bo'lgan xotiralarni yaratishga yordam beradi.[41] Shuningdek, bu giyohvand moddalarni iste'mol qilishdan voz kechish va giyohvand moddalarni iste'mol qilishning tashvishlanishiga ta'sir qilishda muhim ahamiyatga ega.[42]

Lazzatlanish markazlari

Zavq mukofotning tarkibiy qismidir, ammo barcha mukofotlar yoqimli emas (masalan, agar bu javob shartlanmagan bo'lsa, pul zavq keltirmaydi).[1] Tabiatan yoqimli va shuning uchun jozibali bo'lgan stimullar quyidagicha tanilgan ichki mukofotlar, ammo jozibali va yondashuvni rag'batlantiradigan, ammo o'ziga xos yoqimli bo'lmagan stimullar deyiladi tashqi mukofotlar.[1] Tashqi mukofotlar (masalan, pul) a natijasida foydali bo'ladi assotsiatsiyani o'rgandi ichki mukofot bilan.[1] Boshqacha qilib aytadigan bo'lsak, tashqi mukofotlar motivatsiya magnitlari sifatida ishlaydi, ammo ular "yoqtirish" reaktsiyalariga ega bo'lmaydilar.[1]

Mukofotlash tizimi o'z ichiga oladi zavq markazlari yoki hedonik issiq nuqtalar - ya'ni, ichki mukofotlardan lazzatlanish yoki reaktsiyalarni "yoqtirish" vositachisi bo'lgan miya tuzilmalari. 2017 yil oktyabr oyidan boshlab, ichidagi kichik bo'limlarda hedonik issiq nuqtalar aniqlangan accumbens yadrosi, ventral pallidum, parabrachial yadro, orbitofrontal korteks (OFC) va ichki korteks.[2][17][43] Yadro qobig'i ichidagi issiq nuqta medial qobiqning rostrodorsal kvadrantida, gidonik sovuq nuqta esa ko'proq orqa mintaqada joylashgan. Orqa ventral pallidumda hedonik issiq nuqta, oldingi ventral pallidumda esa hedonik sovuq nuqta mavjud. Microinjections opioidlar, endokannabinoidlar va orexin ushbu qaynoq nuqtalarda yoqtirishni kuchaytirishi mumkin.[2] Old OFC va posterior insulada joylashgan hedonik issiq nuqtalar, oldingi insula va orqa OFCda bir-birining ustiga tushgan gemonik sovuq nuqta kabi, orexin va opioidlarga ta'sir ko'rsatishi isbotlangan.[43] Boshqa tomondan, parabrachial yadroli issiq nuqta faqat benzodiazepin retseptorlari agonistlariga javob berish uchun namoyish etildi.[2]

Gedonik nuqtalar funktsional jihatdan bir-biriga bog'langan bo'lib, bitta faol nuqtaning faollashishi boshqalarni jalb qilishga olib keladi, chunki induksiya qilingan ifoda ning c-Fos, an darhol erta gen. Bundan tashqari, bitta faol nuqtani taqiqlash boshqa faol nuqtani faollashtirish ta'sirining xiralashishiga olib keladi.[2][43] Shu sababli, mukofot tizimidagi har bir hedonik issiq nuqtani bir vaqtning o'zida faollashishi kuchli hissiyotlarni yaratish uchun zarur deb hisoblanadi. eyforiya.[44]

Istash va yoqtirish

Asosiy maqola: Rag'batlantiruvchi e'tibor
Yadro qobig'idagi tuyadi va himoya reaktsiyalarini sozlash. (Yuqorida) AMPA blokadasi valentligidan qat'i nazar, motivatsion xatti-harakatlarni yaratish uchun D1 funktsiyasini va mudofaa xatti-harakatlarini ishlab chiqarish uchun D2 funktsiyasini talab qiladi. Boshqa tomondan, GABA agonizmi dopamin retseptorlari funktsiyasini talab qilmaydi. (Quyida) stress ostida mudofaa xatti-harakatlarini keltirib chiqaradigan anatomik mintaqalarning kengayishi va AMPA antagonizmi tomonidan ishlab chiqarilgan uy sharoitida ishtaha xatti-harakatlari. Ushbu moslashuvchanlik GABA agonizmi bilan kamroq namoyon bo'ladi.[27]

Rag'batlantiruvchi e'tibor motivatsion komponentni o'z ichiga olgan "xohlash" yoki "xohish" xususiyati bo'lib, u tomonidan foydali rag'batlantiruvchi tomonidan tayinlangan accumbens yadrosi (NAcc qobig'i).[1][45][46] Dopamin nörotransmisyon darajasi NAcc qobig'iga mezolimbik yo'l mukofotlantiruvchi stimullar uchun rag'batlantiruvchi g'ayratning kattaligi bilan juda bog'liq.[45]

Akumbens yadrosining dorsorostral mintaqasini faollashishi istakning ko'payishi bilan o'zaro bog'liq bo'lib, yoqtirishning bir vaqtning o'zida ko'payishi mumkin emas.[47] Shu bilan birga, akumbens yadrosi dopaminerjik nörotransmisyonu nafaqat tuyadi uchun javobgardir motivatsion keskinlik (ya'ni, rag'batlantiruvchi keskinlik) mukofotlantiruvchi stimullarga nisbatan, shuningdek xatti-harakatni istalmagan stimullardan uzoqlashtiradigan aversiv motivatsion keskinlik uchun.[12][48][49] Dorsal striatumda MSNni ifodalovchi D1 ning faollashishi tuyadi rag'batlantiruvchi ta'sirchanlikni keltirib chiqaradi, DNni ekspresatsiyalashgan MSN esa nafratni keltirib chiqaradi. NAcc-da bunday dixotomiya unchalik aniq emas va motivatsiyani kuchaytirish uchun D1 va D2 MSNlarning faollashishi etarli,[50][51] ehtimol ventral pallidumni inhibe qilish orqali VTAni zararsizlantirish orqali.[52][53]

Robinson va Berrijning 1993 yildagi rag'batlantirish-sensitizatsiya nazariyasi shuni taklif qildi sovrin ajraladigan psixologik komponentlarni o'z ichiga oladi: xohlash (rag'batlantirish) va yoqtirish (zavq). Shokolad kabi ma'lum bir ogohlantiruvchi bilan aloqani kuchaytirishni tushuntirish uchun ishda ikkita mustaqil omil mavjud - bizning shokoladga ega bo'lish istagi (istash) va shokoladning lazzatlanish ta'siri (yoqtirish). Robinzon va Berrijning fikriga ko'ra, istash va yoqtirish bir jarayonning ikki jihati, shuning uchun mukofotlar odatda bir xil darajada talab qilinadi va yoqadi. Biroq, istash va yoqtirish ham muayyan sharoitlarda mustaqil ravishda o'zgaradi. Masalan, dofamin qabul qilgandan keyin ovqat yemaydigan kalamushlar (ovqatga bo'lgan ishtiyoq yo'qoladi) xuddi o'zlariga ovqatni yoqtirgandek harakat qilishadi. Boshqa bir misolda, kalamushlarning lateral gipotalamusidagi faollashtirilgan o'z-o'zini stimulyatsiya qiluvchi elektrodlar ishtahani oshiradi, shuningdek, shakar va tuz kabi ta'mga ko'proq salbiy ta'sir ko'rsatadi; aftidan, rag'batlantirish istakni oshiradi, lekin yoqtirmaydi. Bunday natijalar shuni ko'rsatadiki, kalamushlarni mukofotlash tizimi mustaqil istak va yoqtirish jarayonlarini o'z ichiga oladi. Istagan komponent tomonidan boshqariladi deb o'ylashadi dopaminerjik yo'llar, yoqtirish komponenti opiat-benzodiazepin tizimlari tomonidan boshqariladi deb o'ylashadi.[8]

Mukofotga qarshi tizim

Koobs & LeMoal mukofotni ta'qib qilish xatti-harakatlarini susaytirishi uchun mas'ul bo'lgan alohida sxema mavjudligini taklif qildi va ular mukofotlarga qarshi davri deb atashdi. Ushbu komponent mukofot pallasida tormoz vazifasini bajaradi, shu bilan oziq-ovqat, jinsiy aloqa va hokazolarni ko'proq qidirishni oldini oladi. Ushbu sxemada amigdalaning ko'p qismi (stria terminalisning yotoq yadrosi, markaziy yadro), yadro aksumbensi va signal mavjud. molekulalar, jumladan noradrenalin, kortikotropinni ajratuvchi omil va dinorfin.[54] Ushbu sxema, shuningdek, stressning yoqimsiz tarkibiy qismlarini vositachilik qilish uchun faraz qilingan va shuning uchun giyohvandlik va voz kechish bilan bog'liq deb o'ylashadi. Mukofot davri, giyohvandlikning rivojlanishida ishtirok etadigan dastlabki ijobiy mustahkamlashga vositachilik qilsa-da, keyinchalik salbiy kuchaytirish orqali ustun keladigan anti-mukofot davri, bu foydali stimullarni izlashga undaydi.[55]

O'rganish

Qo'shimcha ma'lumotlar: Assotsiativ o'rganish

Rag'batlantiruvchi stimullar haydovchi bo'lishi mumkin o'rganish shaklida ham klassik konditsioner (Pavlov konditsioneri) va operatsion konditsioner (instrumental konditsionerlik). Klassik konditsionerda mukofot shartsiz rag'batlantiruvchi rol o'ynashi mumkin, bu esa shartli stimul bilan bog'liq holda, shartli stimulni ham mushak-skelet tizimini (oddiy yondashuv va qochish xatti-harakatlari shaklida), ham vegetativ javoblarni keltirib chiqaradi. Operant konditsionerligida mukofot quyidagicha harakat qilishi mumkin mustahkamlovchi u o'ziga olib keladigan harakatlarni kuchaytiradi yoki qo'llab-quvvatlaydi.[3] O'rganilgan xatti-harakatlar, ular olib keladigan natijalarning qiymatiga sezgir bo'lishi mumkin yoki bo'lmasligi mumkin; harakatning bajarilishidagi natija kutilmaganligiga, shuningdek natija qiymatiga sezgir bo'lgan xatti-harakatlar maqsadga yo'naltirilgan, kutilmagan holatga yoki qiymatga befarq bo'lgan aniqlangan harakatlar deyiladi odatlar.[56] Ushbu farq ta'limning ikkita shaklini aks ettirgan deb o'ylashadi, bepul va modelga asoslangan model. Modelni bepul o'rganish oddiy keshlashni va qadriyatlarni yangilashni o'z ichiga oladi. Aksincha, modelga asoslangan ta'lim xulosalar va moslashuvchan bashorat qilishga imkon beradigan hodisalarning ichki modelini saqlash va qurishni o'z ichiga oladi. Garchi pavlovian konditsioneri odatda modelsiz deb qabul qilingan bo'lsa-da, shartli stimulga berilgan rag'batlantiruvchi choralar ichki motivatsion holatlarning o'zgarishiga nisbatan moslashuvchan.[57]

Alohida asab tizimlari stimullar va natijalar, harakatlar va natijalar, stimullar va javoblar o'rtasidagi assotsiatsiyalar uchun javobgardir. Klassik konditsioner mukofotlash tizimi bilan cheklanmagan bo'lsa-da, stimulyatorlar yordamida instrumental ishlashni kuchaytirish (ya'ni, Pavlovian-instrumental transfer ) akumbens yadrosini talab qiladi. Odatiy va maqsadga yo'naltirilgan instrumental o'rganish lateralga bog'liq striatum navbati bilan medial striatum.[56]

Instrumental o'rganish paytida, nisbati o'zgarishiga qarshi AMPA ga NMDA retseptorlari va fosforillangan ERK sodir bo'ladi D.1 - turi va D.2 -ni tashkil etuvchi MSN turlari to'g'ridan-to'g'ri va bilvosita yo'llar navbati bilan.[58][59] Sinaptik plastiklikdagi bu o'zgarishlar va unga qo'shilgan ta'lim striatal D1 va NMDA retseptorlarining faollashuviga bog'liq. D1 retseptorlari tomonidan faollashtirilgan hujayra ichidagi kaskad ishga qabul qilishni o'z ichiga oladi oqsil kinazasi A va natijada hosil bo'lgan fosforillanish orqali DARPP-32, ERKni o'chiradigan fosfatazalarning inhibatsiyasi. NMDA retseptorlari ERK ni boshqacha, lekin o'zaro bog'liqligi orqali faollashtiradi Ras-Raf-MEK-ERK yo'li. ERK ning NMDA vositachiligidagi yakka o'zi faollashuvi o'z-o'zidan cheklangan, chunki NMDA aktivatsiyasi, shuningdek, PKK vositasida ERK deaktivatsiyalovchi fosfatazalarning inhibatsiyasini inhibe qiladi. Shu bilan birga, D1 va NMDA kaskadlari birgalikda faollashtirilganda, ular sinergik tarzda ishlaydi va natijada ERK ning faollashishi sinaptik plastisitni orqa miya restrukturizatsiyasi, AMPA retseptorlari transporti, regulyatsiya shaklida tartibga soladi. CREB va inhibisyon orqali uyali qo'zg'aluvchanlikni oshirish Kv4.2[60][61][62]

Buzilishlar

Giyohvandlik

Asosiy maqola: Giyohvandlik

OsFosB (DeltaFosB) - a gen transkripsiyasi omili – haddan tashqari ifoda ichida D1 turi o'rta tikanli neyronlar ning akkumulyator yadrosi bo'ladi hal qiluvchi Giyohvandlikning deyarli barcha shakllari orasida umumiy omil (ya'ni, xulq-atvorga bog'liqlik va giyohvandlik ) giyohvandlik bilan bog'liq xatti-harakatlarni keltirib chiqaradi va asab plastisiyasi.[5][63][64][65] Xususan, ΔFosB targ'ib qiladi o'z-o'zini boshqarish, mukofotni sensibilizatsiya qilish va o'ziga xos qo'shadi giyohvand moddalar va xatti-harakatlar o'rtasida o'zaro sezgirlik ta'sirini mukofotlash.[5][63][64][66][67] Aniq epigenetik modifikatsiyalari histon miyaning ma'lum mintaqalaridagi oqsil dumlari (ya'ni giston modifikatsiyalari) ham molekulyar asosda hal qiluvchi rol o'ynashi ma'lum giyohvandlik.[65][68][69][70]

Qo'shadi giyohvand moddalar va xatti-harakatlar foydali va mustahkamlovchi (ya'ni, bor qo'shadi) ta'siriga qarab dopamin mukofotlash yo'li.[16][71]

The lateral gipotalamus va medial old miya to'plami miya stimulyatsiyasi mukofotiga, xususan, giyohvand moddalarning miya stimulyatsiyasi mukofotiga ta'sirini o'rganishda eng ko'p o'rganilgan miya stimulyatsiyasi.[72] Giyohvand moddalarni iste'mol qilish odatini shakllantirish harakatlari bilan aniq aniqlangan nörotransmitter tizimi bu mezolimbik dopamin tizimidir. efferent akumbens yadrosidagi maqsadlar va uning mahalliy GABAerjik afferentslar. Amfetamin va kokainning mukofotga oid harakatlari yadro akumbenslarining dopaminerjik sinapslarida va ehtimol medial prefrontal korteks. Sichqonlar, shuningdek, medial prefrontal korteksga kokain in'ektsiyasi uchun qo'lni bosishni o'rganadilar, bu esa akumbens yadrosidagi dopamin aylanishini oshirish orqali ishlaydi.[73][74] To'g'ridan-to'g'ri akumbens yadrosiga kiritilgan nikotin, shuningdek, ushbu mintaqaning dopaminerjik terminallariga presinaptik ta'sir ko'rsatishi bilan mahalliy dopaminning tarqalishini kuchaytiradi. Dopaminerjik hujayralar tanasiga joylashtirilgan nikotinik retseptorlari va mahalliy nikotin in'ektsiyalari nikotinik mukofot uchun juda muhim bo'lgan dopaminerjik hujayralarni otishni kuchaytiradi.[75][76] Ba'zi odat tusiga kiradigan qo'shimcha dorilar ham ishlab chiqarishni kamaytirishi mumkin o'rta tikanli neyronlar Natijada, dopaminerjik proektsiyalarni faollashtirishga qaramay. Afyunlar uchun mukofot effektlari uchun eng past darajadagi sayt GABAergik neyronlarda harakatlarni o'z ichiga oladi ventral tegmental maydon, akumbens yadrosining o'rtacha tikanli neyronlari bo'yicha opiat-mukofotlash harakatlarining ikkilamchi joyi. Shunday qilib, quyidagilar hozirgi vaqtda tavsiflangan dori-darmonlarning sxemasini tashkil etadi; GABAerjik afferentslar mezolimbik dopamin neyronlariga (afyut mukofotining asosiy substratiga), mezolimbik dopamin neyronlarining o'ziga (psixomotor stimulyator mukofotining asosiy substratiga) va mezolimbik dopamin neyronlariga GABAerjik efferentsga (afyun mukofotining ikkilamchi joyiga).[72]

Motivatsiya

Asosiy maqola: Motivatsion keskinlik

Disfunktsional motivatsion keskinlik bir qator psixiatrik alomatlar va kasalliklarda namoyon bo'ladi. Anhedoniya An'anaviy ravishda zavqni his qilish qobiliyatini pasayishi deb ta'riflangan, ko'ngilni rag'batlantiruvchi g'ayratni aks ettiruvchi sifatida qayta ko'rib chiqildi, chunki aksariyat anhedonik populyatsiyalar buzilmagan "yoqtirish" ni namoyish etadi.[77][78] Spektrning boshqa uchida, o'ziga xos ogohlantirishlar uchun toraytirilgan rag'batlantiruvchi keskinlik xulq-atvor va giyohvandlikka xosdir. Qo'rquv yoki paranoyada disfunktsiya ko'tarilishi mumkin jirkanch tirishqoqlik.[79]

Anhedoniya bilan bog'liq tashxislar bo'yicha neyroimaging tadqiqotlari OFK va ventral striatumdagi faollikning pasayishi haqida xabar berdi.[80] Bir meta-tahlilda anhedoniya kaudat yadrosi, putamen, yadro akumbenslari va medial prefrontal korteks (mPFC) da kutishni mukofotlash uchun asabiy reaktsiyani kamaytirish bilan bog'liq.[81]

Kayfiyatning buzilishi

Depressiyaning ayrim turlari motivatsiya pasayishi bilan bog'liq bo'lib, mukofot uchun kuch sarflashga tayyorligi bilan baholanadi. Ushbu anormalliklarning taxminiy ravishda striatum sohasidagi faoliyatning pasayishi bilan bog'liqligi va dopaminerjik anormalliklarning rol o'ynashi taxmin qilingan bo'lsa-da, depressiyada dopamin funktsiyasini tekshiradigan ko'pgina tadqiqotlar bir-biriga mos kelmaydigan natijalar haqida xabar bergan.[82][83] Postmortem va neyroimaging tadqiqotlari mukofot tizimining ko'plab mintaqalarida anormalliklarni aniqlagan bo'lsa-da, ozgina topilmalar doimiy ravishda takrorlanadi. Ba'zi tadkikotlar NAcc, hipokampus, medial prefrontal korteks (mPFC) va orbitofrontal korteks (OFC) faolligining pasayishi hamda ko'tarilganligi haqida xabar bergan bazolateral amigdala va subgenual singulat korteksi (sgACC) mukofot yoki ijobiy rag'batlantirish bilan bog'liq vazifalar paytida faoliyat. Ushbu neyroimaging anormalliklari o'limdan keyingi kichik tadqiqotlar bilan to'ldiriladi, ammo ozgina tadqiqotlar mPFCda qo'zg'atuvchi sinapslarni kamaytirishni taklif qiladi.[84] Mukofot bilan bog'liq vazifalar davomida mPFC kamaytirilgan faoliyati ko'proq dorsal mintaqalarda mahalliylashtirilgan ko'rinadi (ya'ni. tug'ma singulat korteksi ), ko'proq ventral sgACC esa depressiyada giperaktivdir.[85]

Hayvonlarning modellarida yotgan asab tizimlarini o'rganishga urinishlar ham qarama-qarshi natijalarga olib keldi. Ikkita paradigma odatda depressiya, surunkali ijtimoiy mag'lubiyat (CSDS) va surunkali engil stressni (CMS) simulyatsiya qilish uchun ishlatiladi, garchi ularning ko'pchiligi mavjud. CSDS sukroz uchun imtiyozlarni kamaytiradi, ijtimoiy o'zaro ta'sirlarni kamaytiradi va majburiy suzish testida harakatsizlikni oshiradi. CMS xuddi shu tarzda sukrozni afzal ko'radi va xatti-harakatlarning umidsizligini quyruqni to'xtatib turish va majburiy suzish sinovlari bilan baholaydi. CSDSga sezgir bo'lgan hayvonlar VTA-ning fazali otilishini kuchaytiradi va VTA-NAcc proektsiyalarining inhibatsiyasi CSDS tomonidan kelib chiqadigan xulq-atvor etishmovchiligini susaytiradi.[86] Biroq, VTA- ning inhibatsiyasimPFC prognozlar ijtimoiy chekinishni kuchaytiradi. Boshqa tomondan, saxaroza afzalligi va harakatsizligi bilan bog'liq bo'lgan CMS kamayishi navbati bilan VTA qo'zg'alishi va inhibatsiyasi bilan susaytirildi va kuchaytirildi.[87][88] Ushbu farqlar turli xil stimulyatsiya protokollari yoki yomon tarjima paradigmalariga tegishli bo'lishi mumkin bo'lsa-da, o'zgaruvchan natijalar, shuningdek, mukofot bilan bog'liq mintaqalarning heterojen funktsionalligida bo'lishi mumkin.[89]

Optogenetik mPFCni umuman stimulyatsiya qilish antidepressant ta'sirini keltirib chiqaradi. Ushbu ta'sir pgACC (prelimbik korteks) ning kemiruvchilar gomologida lokalizatsiya qilingan ko'rinadi, chunki sgACC (infralimbik korteks) ning kemiruvchilar gomologiyasini stimulyatsiya qilish hech qanday xulq-atvor ta'sirini keltirib chiqarmaydi. Bundan tashqari, inhibitiv ta'sirga ega deb hisoblanadigan infralimbik korteksdagi miyani chuqur stimulyatsiyasi antidepressant ta'sirini ham keltirib chiqaradi. Ushbu topilma infralimbik korteksning farmakologik inhibatsiyasi depressiv xatti-harakatlarni susaytirishi haqidagi kuzatuvga mos keladi.[89]

Shizofreniya

Shizofreniya kabi boshqa salbiy alomatlar ostida guruhlangan motivatsiya etishmovchiligi bilan bog'liq o'z-o'zidan nutqni qisqartirish. "Yoqtirish" tajribasi ko'pincha buzilmaganligi haqida xabar beriladi,[90] ham xulq-atvori, ham asabiy jihatdan, ammo natijalar pul mukofotlari kabi ba'zi bir ogohlantirishlarga xos bo'lishi mumkin.[91] Bundan tashqari, shizofreniyada yashirin o'rganish va mukofot bilan bog'liq oddiy vazifalar ham buzilmaydi.[92] Aksincha, mukofot tizimidagi kamchiliklar kognitiv jihatdan murakkab bo'lgan mukofot bilan bog'liq vazifalar paytida aniq ko'rinadi. Ushbu defitsitlar g'ayritabiiy striatal va OFC faolligi bilan, shuningdek, kognitiv funktsiyalar bilan bog'liq mintaqalardagi anormalliklar bilan bog'liq. dorsolateral prefrontal korteks (DLPFC).[93]

Tarix

Skinner qutisi

Miyada mukofot tizimining borligi to'g'risida birinchi maslahat 1954 yilda Jeyms Olds va Piter Milner tomonidan baxtsiz hodisalar kashf etilishi bilan paydo bo'ldi. Ular kalamushlar barni bosish kabi xatti-harakatlarni amalga oshirishini aniqladilar. ularning miyasidagi saytlar. Ushbu hodisa deyiladi intrakranial o'z-o'zini stimulyatsiya qilish yoki miya stimulyatsiyasi mukofoti. Odatda, kalamushlar bu miyaning stimulyatsiyasini olish uchun soatiga yuzlab yoki minglab marta qo'lni bosib, faqat charchaganlarida to'xtaydi. Sichqonlarga muammolarni qanday hal qilishni va labirintlarni qanday ishlatishni o'rgatishda, stimulyatsiya topilgan miyaning ayrim hududlarini stimulyatsiya qilish hayvonlarga zavq bag'ishlaganga o'xshaydi. Ular odamlar bilan xuddi shu narsani sinab ko'rishdi va natijalar o'xshash edi. Hayvonlarning nima uchun o'zlari yoki ularning turlari uchun omon qolish uchun hech qanday ahamiyatga ega bo'lmagan xatti-harakatlarni qilishining izohi shundaki, miya stimulyatsiyasi asosiy mukofot tizimini faollashtirmoqda.[94]

1954 yilda o'tkazilgan fundamental kashfiyotda tadqiqotchilar Jeyms Olds va Piter Milner, kalamush miyasining ayrim mintaqalarini past kuchlanishli elektr stimulyatsiyasi hayvonlarga labirintlarni ishlashga va muammolarni hal qilishga o'rgatishda mukofot vazifasini o'tashini aniqladilar.[95][96] Miyaning bu qismlarini stimulyatsiya qilish hayvonlarga zavq bag'ishlaganday tuyuldi,[95] va keyingi ishlarda odamlar bunday stimulyatsiyadan yoqimli hissiyotlar haqida xabar berishdi. Sichqonlar sinovdan o'tkazilganda Skinner qutilari ular qo'lni bosib, mukofot tizimini rag'batlantirishi mumkin bo'lgan joyda, kalamushlar soatlab siqib qo'yilgan.[96] Keyingi yigirma yillik tadqiqotlar shuni aniqladi dopamin ushbu mintaqalarda asab signalizatsiyasiga yordam beradigan asosiy kimyoviy moddalardan biri bo'lib, dofamin miyaning "lazzatlanish kimyoviy moddasi" ekanligi taxmin qilingan.[97]

Ivan Pavlov o'qish uchun mukofotlash tizimidan foydalangan psixolog edi klassik konditsioner. Pavlov qo'ng'iroq yoki boshqa stimulni eshitgandan keyin itlarni ovqat bilan mukofotlash orqali mukofotlash tizimidan foydalandi. Pavlov itlarga mukofot berar edi, shuning uchun itlar oziq-ovqat, mukofotni qo'ng'iroq, stimul bilan bog'lashdi.[98]Edvard L. Thorndayk operatsion konditsionerligini o'rganish uchun mukofot tizimidan foydalangan. U mushuklarni jumboq qutisiga solib, mushuk qochib ketishi uchun qutining tashqarisiga oziq-ovqat mahsulotlarini qo'yishdan boshladi. Mushuklar ovqatga etib borish uchun jumboq qutisidan chiqish uchun ishladilar. Mushuklar qutidan qochib qutulganlaridan keyin ovqatni yeyishgan bo'lsa-da, Torndayk mushuklar qutichadan ovqat mukofotisiz qochib qutulmoqchi bo'lganligini bilib oldi. Thorndike mushuklarni mukofotlash tizimini rag'batlantirish uchun oziq-ovqat va erkinlik mukofotlaridan foydalangan. Torndayk bundan mushuklar qutidan qanday qochishni o'rganganliklarini bilish uchun foydalangan.[99]

Boshqa turlar

Hayvonlar tezda afyun in'ektsiyasini olish uchun barni bosishni o'rganadilar o'rta miya tegmentum yoki akkumulyator yadrosi. Dopaminerjik neyronlari bo'lsa, xuddi shu hayvonlar opiat olish uchun ishlamaydi mezolimbik yo'l inaktiv qilingan. Shu nuqtai nazardan, hayvonlar, odamlar kabi, dopamin chiqarilishini ko'paytiradigan xatti-harakatlar bilan shug'ullanadilar.

Kent Berrij, tadqiqotchi affektiv nevrologiya, shirin ekanligini aniqladi (yoqdi ) va achchiq (yoqmadi ) ta'mi aniq ishlab chiqarilgan orofatsional iboralar va bu iboralarni xuddi yangi tug'ilgan chaqaloqlar, orangutanlar va kalamushlar ko'rsatgan. Bu lazzatlanishning dalili edi (xususan, yoqtirish) ob'ektiv xususiyatlarga ega va asosan turli xil hayvon turlari bo'yicha bir xil bo'lgan. Ko'pgina nevrologiya tadqiqotlari shuni ko'rsatdiki, mukofot qancha ko'p chiqarilsa, mukofot shunchalik samarali bo'ladi. Bu mukofot uchun harakat va mukofotning o'zi tomonidan o'zgartirilishi mumkin bo'lgan hedonik ta'sir deb ataladi. Berrij dopamin tizimlarini blokirovka qilish shirin narsaga (yuz ifodasi bilan o'lchanadigan) ijobiy reaktsiyani o'zgartira olmasligini aniqladi. Boshqacha qilib aytganda, hedonik ta'sir shakar miqdoriga qarab o'zgarmadi. Bu dopamin zavqni vositachilik qiladi degan odatiy taxminni bekor qildi. Dopaminning yanada kuchli o'zgarishi bilan ham, ma'lumotlar doimiy bo'lib tuyuldi.[100] Biroq, 2019 yil yanvar oyidan boshlab dopamin prekursorining ta'sirini baholagan klinik tadqiqotlar (levodopa ), antagonist (risperidon ) va musiqa uchun javob beradigan javoblar bo'yicha platsebo - shu bilan birga zavqlanish darajasi musiqiy sovuqlar, o'zgarishi bilan o'lchangan elektrodermal faollik shuningdek sub'ektiv reytinglar - dopamin nörotransmisyonu manipulyatsiyasi zavq idrokini ikki tomonlama tartibga soladi (xususan, musiqaning hedonik ta'siri ) inson sub'ektlarida.[101][102] Ushbu tadqiqot shuni ko'rsatdiki, ko'paygan dopamin nörotransmisyonu a sine qua non odamlarda musiqaga yoqimli gidonik reaktsiyalarning sharti.[101][102]

Berrij ishlab chiqardi rag'batlantirish ga tegishli gipoteza xohlamoq mukofotlarning jihati. Unda giyohvandlar giyohvand moddalar eyforiya hosil qilmayotgan bo'lsa ham, ularni majburiy ravishda ishlatishi va shaxs o'zini olib tashlaganidan keyin ham o'zgacha bo'lgan istaklari tushuntiriladi. Ba'zi giyohvandlar giyohvand moddalar tomonidan kelib chiqadigan asabiy o'zgarishlar bilan bog'liq ba'zi ogohlantirishlarga javob berishadi. Miyadagi bu sezuvchanlik dofamin ta'siriga o'xshaydi, chunki xohlamoq va yoqtirish reaktsiyalar paydo bo'ladi. Inson va hayvonlar miyasi va xatti-harakatlari mukofot tizimlarida shunga o'xshash o'zgarishlarni boshdan kechirmoqda, chunki bu tizimlar juda mashhur.[100]

Shuningdek qarang

Adabiyotlar

  1. ^ a b v d e f g h men j k l m Schultz, Wolfram (2015 yil iyul). "Neyron mukofotlash va qaror signallari: nazariyalardan ma'lumotlargacha". Fiziologik sharhlar. 95 (3): 853–951. doi:10.1152 / physrev.00023.2014. PMC  4491543. PMID  26109341.
  2. ^ a b v d e f g h Berrij KC, Kringelbax ML (may, 2015). "Miyadagi zavq tizimlari". Neyron. 86 (3): 646–664. doi:10.1016 / j.neuron.2015.02.018. PMC  4425246. PMID  25950633. Prefrontal korteksda so'nggi dalillar shuni ko'rsatadiki, [orbitofrontal korteks] OFC va insula kortekslari o'zlarining qo'shimcha issiq joylarini o'z ichiga olishi mumkin (D.C. Castro va boshq., Soc. Neurosci., Mavhum). In specific subregions of each area, either opioid-stimulating or orexin-stimulating microinjections appear to enhance the number of yoqtirish reactions elicited by sweetness, similar to the [nucleus accumbens] NAc and [ventral pallidum] VP hot spots. Successful confirmation of hedonic hot spots in the OFC or insula would be important and possibly relevant to the orbitofrontal mid-anterior site mentioned earlier that especially tracks the subjective pleasure of foods in humans (Georgiadis et al., 2012; Kringelbach, 2005; Kringelbach et al., 2003; Small et al., 2001; Veldhuizen et al., 2010). Finally, in the brainstem, a hindbrain site near the parabrachial nucleus of dorsal pons also appears able to contribute to hedonic gains of function (Söderpalm and Berridge, 2000). A brainstem mechanism for pleasure may seem more surprising than forebrain hot spots to anyone who views the brainstem as merely reflexive, but the pontine parabrachial nucleus contributes to taste, pain, and many visceral sensations from the body and has also been suggested to play an important role in motivation (Wu et al., 2012) and in human emotion (especially related to the somatic marker hypothesis) (Damasio, 2010).
  3. ^ a b v d e f g h men Schultz V (2015). "Neyronal mukofot va qaror signallari: nazariyalardan ma'lumotlargacha". Fiziologik sharhlar. 95 (3): 853–951. doi:10.1152 / physrev.00023.2014. PMC  4491543. PMID  26109341. Rewards in operant conditioning are positive reinforcers. ... Operant behavior gives a good definition for rewards. Anything that makes an individual come back for more is a positive reinforcer and therefore a reward. Although it provides a good definition, positive reinforcement is only one of several reward functions. ... Rewards are attractive. They are motivating and make us exert an effort. ... Rewards induce approach behavior, also called appetitive or preparatory behavior, sexual behavior, and consummatory behavior. ... Thus any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward. ... Rewarding stimuli, objects, events, situations, and activities consist of several major components. First, rewards have basic sensory components (visual, auditory, somatosensory, gustatory, and olfactory) ... Second, rewards are salient and thus elicit attention, which are manifested as orienting responses (FIGURE 1, middle). The salience of rewards derives from three principal factors, namely, their physical intensity and impact (physical salience), their novelty and surprise (novelty/surprise salience), and their general motivational impact shared with punishers (motivational salience). A separate form not included in this scheme, incentive salience, primarily addresses dopamine function in addiction and refers only to approach behavior (as opposed to learning) ... Third, rewards have a value component that determines the positively motivating effects of rewards and is not contained in, nor explained by, the sensory and attentional components (FIGURE 1, right). This component reflects behavioral preferences and thus is subjective and only partially determined by physical parameters. Only this component constitutes what we understand as a reward. It mediates the specific behavioral reinforcing, approach generating, and emotional effects of rewards that are crucial for the organism’s survival and reproduction, whereas all other components are only supportive of these functions. ... Rewards can also be intrinsic to behavior (31, 546, 547). They contrast with extrinsic rewards that provide motivation for behavior and constitute the essence of operant behavior in laboratory tests. Intrinsic rewards are activities that are pleasurable on their own and are undertaken for their own sake, without being the means for getting extrinsic rewards. ... Intrinsic rewards are genuine rewards in their own right, as they induce learning, approach, and pleasure, like perfectioning, playing, and enjoying the piano. Although they can serve to condition higher order rewards, they are not conditioned, higher order rewards, as attaining their reward properties does not require pairing with an unconditioned reward. ... These emotions are also called liking (for pleasure) and wanting (for desire) in addiction research (471) and strongly support the learning and approach generating functions of reward.
  4. ^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". Sydor A, Brown RY (tahr.). Molekulyar neyrofarmakologiya: Klinik nevrologiya uchun asos (2-nashr). Nyu-York: McGraw-Hill Medical. 364-375 betlar. ISBN  9780071481274.
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    Giyohvandlik: Preparatni iste'mol qilishni to'xtatish istagiga qaramay, majburiy dori qabul qilishda ko'rsatilgandek, o'z-o'zini nazorat qilishning sezilarli darajada yo'qolganligi sababli, moddani iste'mol qilish buzilishining eng og'ir, surunkali bosqichini ko'rsatish uchun ishlatiladigan atama. DSM-5-da, giyohvandlik atamasi moddani ishlatishning og'ir buzilishi tasnifi bilan sinonimdir.
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    Figure 3: Neural circuits underlying motivated 'wanting' and hedonic 'liking'.
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  43. ^ a b v Kastro, shahar; Berrij, KC (2017 yil 24-oktabr). "Sichqoncha orbitofrontal korteks va insula ichidagi opioid va oreksinli hedonik faol joylar". Amerika Qo'shma Shtatlari Milliy Fanlar Akademiyasi materiallari. 114 (43): E9125-E9134. doi:10.1073 / pnas.1705753114. PMC  5664503. PMID  29073109. Here, we show that opioid or orexin stimulations in orbitofrontal cortex and insula causally enhance hedonic “liking” reactions to sweetness and find a third cortical site where the same neurochemical stimulations reduce positive hedonic impact.
  44. ^ Kringelbax ML, Berrij KC (2012). "Quvnoq aql" (PDF). Ilmiy Amerika. 307 (2): 44–45. Bibcode:2012SciAm.307b..40K. doi:10.1038 / Scientificamerican0812-40. PMID  22844850. Olingan 17 yanvar 2017. Shunday qilib, miyadagi haqiqiy zavqlanish markazlari - yoqimli hissiyotlarni hosil qilish uchun bevosita mas'ul bo'lganlar - ilgari mukofot pallasida aniqlangan ba'zi tuzilmalar ichida joylashgan bo'lib chiqadi. Ushbu hedonik issiq nuqtalardan biri medial qobiq deb nomlangan yadro akumbensining subregionida joylashgan. Ikkinchisi ventral pallidum ichida joylashgan bo'lib, oldingi miyaning pastki qismiga yaqin chuqur joylashgan struktura bo'lib, u signallarning aksariyatini akumbens yadrosidan oladi. ...
    Boshqa tomondan, kuchli eyforiya har kungi zavqlarga qaraganda qiyinroq. Buning sababi shundaki, lazzatlanishni kuchli oshirish, masalan, laboratoriya hayvonlarida ishlab chiqarilgan kimyoviy ta'sir tufayli - butun tarmoqni birdaniga faollashtirishni talab qiladi. Har qanday komponentning defektsiyasi yuqori darajani susaytiradi.
    Lazzatlanish davri, xususan, ventral pallidum odamlarda xuddi shunday ishlayaptimi, aniq emas.
  45. ^ a b Berridge KC (April 2012). "From prediction error to incentive salience: mesolimbic computation of reward motivation". Yevro. J. Neurosci. 35 (7): 1124–1143. doi:10.1111/j.1460-9568.2012.07990.x. PMC  3325516. PMID  22487042. Here I discuss how mesocorticolimbic mechanisms generate the motivation component of incentive salience. Incentive salience takes Pavlovian learning and memory as one input and as an equally important input takes neurobiological state factors (e.g. drug states, appetite states, satiety states) that can vary independently of learning. Neurobiological state changes can produce unlearned fluctuations or even reversals in the ability of a previously learned reward cue to trigger motivation. Such fluctuations in cue-triggered motivation can dramatically depart from all previously learned values about the associated reward outcome. ... Associative learning and prediction are important contributors to motivation for rewards. Learning gives incentive value to arbitrary cues such as a Pavlovian conditioned stimulus (CS) that is associated with a reward (unconditioned stimulus or UCS). Learned cues for reward are often potent triggers of desires. For example, learned cues can trigger normal appetites in everyone, and can sometimes trigger compulsive urges and relapse in addicts.
    Cue-triggered 'wanting’ for the UCS
    A brief CS encounter (or brief UCS encounter) often primes a pulse of elevated motivation to obtain and consume more reward UCS. This is a signature feature of incentive salience.
    Cue as attractive motivational magnets
    When a Pavlovian CS+ is attributed with incentive salience it not only triggers 'wanting’ for its UCS, but often the cue itself becomes highly attractive – even to an irrational degree. This cue attraction is another signature feature of incentive salience ... Two recognizable features of incentive salience are often visible that can be used in neuroscience experiments: (i) UCS-directed 'wanting’ – CS-triggered pulses of intensified 'wanting’ for the UCS reward; and (ii) CS-directed 'wanting’ – motivated attraction to the Pavlovian cue, which makes the arbitrary CS stimulus into a motivational magnet.
  46. ^ Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY (tahrir). Molekulyar neyrofarmakologiya: Klinik nevrologiya uchun asos (2-nashr). Nyu-York: McGraw-Hill Medical. pp. 147–148, 367, 376. ISBN  978-0-07-148127-4. VTA DA neurons play a critical role in motivation, reward-related behavior (Chapter 15), attention, and multiple forms of memory. This organization of the DA system, wide projection from a limited number of cell bodies, permits coordinated responses to potent new rewards. Thus, acting in diverse terminal fields, dopamine confers motivational salience ("wanting") on the reward itself or associated cues (nucleus accumbens shell region), updates the value placed on different goals in light of this new experience (orbital prefrontal cortex), helps consolidate multiple forms of memory (amygdala and hippocampus), and encodes new motor programs that will facilitate obtaining this reward in the future (nucleus accumbens core region and dorsal striatum). In this example, dopamine modulates the processing of sensorimotor information in diverse neural circuits to maximize the ability of the organism to obtain future rewards. ...
    The brain reward circuitry that is targeted by addictive drugs normally mediates the pleasure and strengthening of behaviors associated with natural reinforcers, such as food, water, and sexual contact. Dopamine neurons in the VTA are activated by food and water, and dopamine release in the NAc is stimulated by the presence of natural reinforcers, such as food, water, or a sexual partner. ...
    The NAc and VTA are central components of the circuitry underlying reward and memory of reward. As previously mentioned, the activity of dopaminergic neurons in the VTA appears to be linked to reward prediction. The NAc is involved in learning associated with reinforcement and the modulation of motoric responses to stimuli that satisfy internal homeostatic needs. The shell of the NAc appears to be particularly important to initial drug actions within reward circuitry; addictive drugs appear to have a greater effect on dopamine release in the shell than in the core of the NAc.
  47. ^ Berridge KC, Kringelbach ML (1 June 2013). "Neuroscience of affect: brain mechanisms of pleasure and displeasure". Neyrobiologiyaning hozirgi fikri. 23 (3): 294–303. doi:10.1016/j.conb.2013.01.017. PMC  3644539. PMID  23375169. For instance, mesolimbic dopamine, probably the most popular brain neurotransmitter candidate for pleasure two decades ago, turns out not to cause pleasure or liking at all. Rather dopamine more selectively mediates a motivational process of incentive salience, which is a mechanism for wanting rewards but not for liking them .... Rather opioid stimulation has the special capacity to enhance liking only if the stimulation occurs within an anatomical hotspot
  48. ^ Calipari, Erin S.; Bagot, Rosemary C.; Purushothaman, Immanuel; Davidson, Thomas J.; Yorgason, Jordan T.; Peña, Catherine J.; Walker, Deena M.; Pirpinias, Stephen T.; Guise, Kevin G.; Ramakrishnan, Charu; Deisseroth, Karl; Nestler, Eric J. (8 March 2016). "In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward". Proceedings of the National Academy of Sciences. 113 (10): 2726–2731. Bibcode:2016PNAS..113.2726C. doi:10.1073/pnas.1521238113. PMC  4791010. PMID  26831103.
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  63. ^ a b Ruffle JK (2014 yil noyabr). "Giyohvandlikning molekulyar neyrobiologiyasi: FosB (f) nima haqida?". Am. J. Drug Alcohol Abuse. 40 (6): 428–437. doi:10.3109/00952990.2014.933840. PMID  25083822. S2CID  19157711.
    The strong correlation between chronic drug exposure and ΔFosB provides novel opportunities for targeted therapies in addiction (118), and suggests methods to analyze their efficacy (119). Over the past two decades, research has progressed from identifying ΔFosB induction to investigating its subsequent action (38). It is likely that ΔFosB research will now progress into a new era – the use of ΔFosB as a biomarker. ...
    Xulosa
    DFOSB giyohvandlikning takroriy ta'siridan keyin giyohvandlikning molekulyar va xulq-atvor yo'llarida muhim ahamiyatga ega bo'lgan transkripsiya omilidir. Ko'p sonli miya mintaqalarida DFB hosil bo'lishi va AP-1 komplekslarini hosil bo'lishiga olib keladigan molekulyar yo'l yaxshi tushuniladi. DFOSB uchun funktsional maqsadni belgilash GluR2 (87,88), Cdk5 (93) va NFkB (100) kabi effektorlarni o'z ichiga olgan uning molekulyar kaskadlarining ba'zi asosiy jihatlarini yanada aniqlashga imkon berdi. Bundan tashqari, aniqlangan ushbu molekulyar o'zgarishlarning aksariyati hozirda surunkali dori ta'siridan keyin kuzatilgan strukturaviy, fiziologik va xulq-atvor o'zgarishlari bilan bevosita bog'liqdir [60,95,97,102]. New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a molekulyar kalit (34). DFOSB-ni giyohvandlikda yaxshilagan tushunchamiz natijasida, hozirgi dori-darmonlarning o'ziga qaramlik potentsialini baholash mumkin [119], shuningdek uni terapevtik aralashuvlarning samaradorligini baholash uchun biomarker sifatida foydalanish mumkin [121,122,124]. Ushbu taklif qilingan tadbirlarning ba'zilari cheklovlarga ega (125) yoki boshlang'ich bosqichida [75]. Biroq, ushbu dastlabki topilmalarning ba'zilari giyohvandlikda juda zarur bo'lgan innovatsion davolanishga olib kelishi mumkin deb umid qilamiz.
  64. ^ a b Olsen CM (2011 yil dekabr). "Tabiiy mukofotlar, neyroplastiklik va giyohvandlikka qaram bo'lmaganlar". Neyrofarmakologiya. 61 (7): 1109–1122. doi:10.1016 / j.neuropharm.2011.03.010. PMC  3139704. PMID  21459101. Functional neuroimaging studies in humans have shown that gambling (Breiter et al, 2001), shopping (Knutson et al, 2007), orgasm (Komisaruk et al, 2004), playing video games (Koepp et al, 1998; Hoeft et al, 2008) and the sight of appetizing food (Wang et al, 2004a) activate many of the same brain regions (i.e., the mesocorticolimbic system and extended amygdala) as drugs of abuse (Volkow et al, 2004). ... Cross-sensitization is also bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA ... As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. Transkripsiya faktori delta FosB takroriy jinsiy xatti-harakatlardan so'ng NAc, PFC, dorsal striatum va VTA da ko'payadi (Wallace va boshq., 2008; Pitchers va boshq., 2010b). Delta FosBdagi tabiiy o'sish yoki NAc ichidagi delta FosB ning virusli haddan tashqari ekspressioni jinsiy ko'rsatkichlarni modulyatsiya qiladi va delta FosB ning NAc blokadasi bu xatti-harakatni susaytiradi (Hedges va boshq, 2009; Pitchers va boshq., 2010b). Bundan tashqari, delta FosB ning virusli haddan tashqari ekspressioni jinsiy tajriba bilan bog'langan muhit uchun shartli joy afzalligini oshiradi (Hedges va boshq., 2009). ... In some people, there is a transition from "normal" to compulsive engagement in natural rewards (such as food or sex), a condition that some have termed behavioral or non-drug addictions (Holden, 2001; Grant et al., 2006a). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. Ushbu sindrom, giyohvandlik, xarid qilish yoki jinsiy aloqa kabi giyohvand bo'lmagan mukofotlarda dori vositalarining ko'payishi (yoki majburiy) bilan tavsiflanadi (Evans va boshq, 2006; Aiken, 2007; Lader, 2008). "
    Table 1: Summary of plasticity observed following exposure to drug or natural reinforcers "
  65. ^ a b Biliński P, Voytila ​​A, Kapka-Skrzypcak L, Chvedorovich R, Kiranka M, Studzinskiy T (2012). "Epigenetic regulation in drug addiction". Ann. Agric. Atrof. Med. 19 (3): 491–496. PMID  23020045. For these reasons, ΔFosB is considered a primary and causative transcription factor in creating new neural connections in the reward centre, prefrontal cortex, and other regions of the limbic system. This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to relapse even after long periods of abstinence. These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken ... In this way, the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3. A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine. This depends on ΔFosB inhibiting G9a gene expression, i.e. H3K9me2 synthesis which in turn inhibits transcription factors for ΔFosB. For this reason, the observed hyper-expression of G9a, which ensures high levels of the dimethylated form of histone H3, eliminates the neuronal structural and plasticity effects caused by cocaine by means of this feedback which blocks ΔFosB transcription
  66. ^ Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM (2013 yil fevral). "Tabiiy va dori-darmon bilan mukofotlash asosiy mediator sifatida DFOSB bilan umumiy asabiy plastika mexanizmlariga ta'sir qiladi". Neuroscience jurnali. 33 (8): 3434–3442. doi:10.1523 / JNEUROSCI.4881-12.2013. PMC  3865508. PMID  23426671. Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. ... Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. ... Sexual behavior is highly rewarding (Tenk et al., 2009), and sexual experience causes sensitized drug-related behaviors, including cross-sensitization to amphetamine (Amph)-induced locomotor activity (Bradley and Meisel, 2001; Pitchers et al., 2010a) and enhanced Amph reward (Pitchers et al., 2010a). Moreover, sexual experience induces neural plasticity in the NAc similar to that induced by psychostimulant exposure, including increased dendritic spine density (Meisel and Mullins, 2006; Pitchers et al., 2010a), altered glutamate receptor trafficking, and decreased synaptic strength in prefrontal cortex-responding NAc shell neurons (Pitchers et al., 2012). Finally, periods of abstinence from sexual experience were found to be critical for enhanced Amph reward, NAc spinogenesis (Pitchers et al., 2010a), and glutamate receptor trafficking (Pitchers et al., 2012). These findings suggest that natural and drug reward experiences share common mechanisms of neural plasticity
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    Shakl 4: Gen ekspressionining dori regulyatsiyasining epigenetik asoslari
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  91. ^ Yosh 2018 yil, p. 215a, "Yaqinda o'tkazilgan bir nechta sharhlar (masalan, Koen va Minor, 2010 yil) shizofreniya bilan kasallangan shaxslar ta'sir ko'rsatuvchi stimullarga nisbatan ta'sirchan o'z-o'zidan xabar qilingan hissiy reaktsiyalarni va buzilmagan javobning boshqa ko'rsatkichlarini ko'rsatganligini aniqladilar ... Keyinchalik aralash rasm paydo bo'ldi miyaning shizofreniyada boshqa yoqimli turtki turlariga ta'sirini tekshiradigan funktsional neyroimaging tadqiqotlaridan (Paradiso va boshq., 2003) "
  92. ^ Yosh 2018 yil, p. 215b, "Shunday qilib, xulq-atvor tadqiqotlari shizofreniyada o'rganish nisbatan aniq bo'lsa, kuchaytirishni o'rganish buzilmasligini taxmin qilganligi ajablanarli (garchi Siegert va boshq., 2008-yilda ketma-ket reaksiya vaqti buzilganligini tasdiqlovchi dalillar uchun qarang), ammo ko'proq buzilgan bo'lsa rag'batlantiruvchi mukofot kutilmagan holatlarning aniq namoyandalariga ehtiyoj bor (Gold va boshq., 2008 ga qarang) .Bu naqsh shizofreniyada striatal vositachilik bilan bosqichma-bosqich mustahkamlashni o'rganish tizimi buzilmagan bo'lishi mumkin degan nazariyani keltirib chiqardi. vositachilik asosida o'qitish tizimlari buzilgan. "
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  101. ^ a b Ferreri L, Mas-Herrero E, Zatorre RJ, Ripolles P, Gomes-Andres A, Alicart H, Oliveé G, Marko-Pallarés J, Antonijoan RM, Valle M, Riba J, Rodriguez-Fornells A (2019 yil yanvar). "Dopamin musiqa natijasida olingan mukofot tajribalarini modulyatsiya qiladi". Amerika Qo'shma Shtatlari Milliy Fanlar Akademiyasi materiallari. 116 (9): 3793–3798. doi:10.1073 / pnas.1811878116. PMC  6397525. PMID  30670642. Xulosa – Nevrologiya yangiliklari (2019 yil 24-yanvar). Yoqimli musiqani tinglash ko'pincha goz gumbazlari yoki umurtqa pog'onasidan titragan kabi tanadagi reaktsiyalar bilan birga keladi, odatda "chill" yoki "frissons" deb nomlanadi. ... Umuman olganda, bizning natijalarimiz to'g'ridan-to'g'ri farmakologik aralashuvlar musiqa tomonidan olingan mukofot javoblarini ikki tomonlama modulyatsiya qilganligini aniqladi. Xususan, biz risperidon ishtirokchilarning musiqiy zavqlanish qobiliyatini buzganligini, levodopa esa uni kuchaytirganligini aniqladik. ... Bu erda, aksincha, odamlarning mavzularidagi mavhum mukofotlarga javoblarni o'rganish, biz dopaminerjik transmissiya bilan manipulyatsiya ham zavqga ta'sir qilishini (ya'ni, EDA bilan o'lchangan vaqtni bildiruvchi sovuqlik va hissiy qo'zg'alish) va musiqiy mukofotning motivatsion tarkibiy qismlariga ta'sir qilishini ko'rsatamiz. (sarflashga tayyor pul). Ushbu topilmalar shuni ko'rsatadiki, dopaminerjik signalizatsiya nafaqat motivatsion javoblar uchun, balki asosiy va ikkilamchi mukofotlar bilan ko'rsatilganidek, musiqaga bo'lgan hedonik reaktsiyalar uchun ham shartli shart emas. Ushbu natija, dopaminning boshqa mavhum mukofotlarning boshqa turlari tomonidan qabul qilingan yoqimli vositachilik qilishda vositachilik qilganligini ko'rsatadigan so'nggi topilmalarni qo'llab-quvvatlaydi [37] va hayvonot modellarida avvalgi topilmalarni, masalan, oziq-ovqat kabi [42, 43].
  102. ^ a b Gupil L, Aucouturier JJ (fevral, 2019). "Musiqiy zavq va musiqiy tuyg'ular". Amerika Qo'shma Shtatlari Milliy Fanlar Akademiyasi materiallari. 116 (9): 3364–3366. doi:10.1073 / pnas.1900369116. PMC  6397567. PMID  30770455. PNASda nashr etilgan farmakologik tadqiqotda Ferreri va boshq. (1) levodopa yoki risperidon yordamida dopamin signalizatsiyasini kuchaytirish yoki inhibe qilish musiqa tinglash paytida boshdan kechiradigan zavqni modulyatsiya qilishiga oid dalillar mavjud. ... Dopaminning nafaqat korrelyatsion, balki musiqiy zavqga sababchi ta'sirini aniqlash uchun yakuniy shov-shuvda mualliflar striatumdagi dopaminerjik signalizatsiyani to'g'ridan-to'g'ri manipulyatsiya qilishga o'tdilar, birinchi navbatda ularning ishtirokchilari ustidan qo'zg'atuvchi va inhibitor transkranial magnit stimulyatsiyani qo'lladilar. chap dorsolateral prefrontal korteks, striatal funktsiyani modulyatsiya qilish uchun ma'lum bo'lgan mintaqa (5) va nihoyat, ushbu tadqiqotda, dopamin sinaptik mavjudligini (1) o'zgartirishi mumkin bo'lgan farmatsevtik vositalarni boshqarish orqali, ikkalasi ham sezilgan zavq, uyg'otishning fiziologik choralari, va bashorat qilingan yo'nalishda musiqaga berilgan pul qiymati. ... Tuyg'ularni musiqiy ifoda etish masalasi uzoq tarixga ega bo'lsa-da, shu jumladan PNAS (6) va 1990-yillarning psixofiziologik tadqiqot yo'nalishi allaqachon musiqiy zavq avtonom nerv tizimini faollashtirishi mumkinligini aniqlagan (7), mualliflarning mukofot tizimining musiqiy his-tuyg'ularga ta'sirini namoyish etishi, bu bizning kundalik bilim, ijtimoiy va ta'sirchan funktsiyalarimizning neyrobiologiyasini xabardor qilish uchun to'liq qonuniylikka ega bo'lgan vertikal his-tuyg'ular ekanligining dastlabki isboti sifatida qabul qilindi [8]. Aytgancha, Ferreri va boshqalarning maqolasi bilan yakunlangan ushbu ish yo'nalishi. (1), musiqiy ilmlar sohasidagi tadqiqotlarni moliyalashtirishni jalb qilish uchun ushbu jamoadagilarga qaraganda ko'proq narsani amalga oshirdi. Ferreri va boshqalarning dalillari. (1) musiqiy zavq qadimgi mukofotlash / baholash tizimlarining (striatal-limbik-paralimbik) ko'proq filogenetik jihatdan ilg'or idrok etish / bashorat qilish tizimlari (temporofrontal) bilan o'zaro ta'siridan kelib chiqadigan jozibali neyrobiologik modelni so'nggi qo'llab-quvvatlaydi.
  • Yosh, Jared V.; Antitsevich, Alan; Barch, Deanna M. (2018). "Psixotik buzilishlarning kognitiv va motivatsion nevrologiyasi". Charneyda Dennis S.; Sklar, Pamela; Buxbaum, Jozef D .; Nestler, Erik J. (tahr.). Charney & Nestlerning ruhiy kasallik neyrobiologiyasi (5-nashr). Nyu-York: Oksford universiteti matbuoti. ISBN  9780190681425.

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