Biol Psychiatry. Zolemba zolemba; ilipo mu PMC 2014 May 1.
Lofalitsidwa mu mawonekedwe omaliza omaliza monga:
Biol Psychiatry. 2013 May 1; 73 (9): 819-826.
Idasindikizidwa pa intaneti 2012 Oct 5. do: 10.1016 / j.biopsych.2012.09.001
PMCID: PMC3548035
NIHMSID: NIHMS407698
Kudalirika
Funso loti (kapena kuti ndi mlingo wotani) kunenepa kwambiri kumasonyeza kusokonezeka kwa zakudya zapamwamba zowonjezera nthawi zambiri kumaphatikizapo kufunsa ngati kudya mopitirira muyeso kwa zakudya zimenezi kumayambitsa matenda omwe amatenga nthawi yayitali monga momwe amadziwira ndi mapeto a kuledzera. Mwa chidwi chofanana kapena mwinamwake chachikulu ndi funso lakuti kaya njira zamagulu zofanana zimagwirizanirana ndi kupeza ndi chitukuko cha chizolowezi chodya ndi kumwa mankhwala. Umboni woyambirira pa funsoli ndi wochokera m'maphunziro oyambirira a ubongo wopatsa mphotho. Kutsitsimutsa kwa magetsi kosokoneza bongo kungakhale kulimbikitsana muzinthu zina ndipo kungalimbikitse kudyetsa ena. Kulimbikitsana kumeneku kwa dera lomwelo kumayenera kulimbikitsa komanso kuyendetsa galimoto ndizovuta; Nchifukwa chiyani nyama imayenera kugwira ntchito ngati momwe amachitira ndi njala monga njala? Izi zimadziwika kuti "mphotho ya mphotho." Kudziwa mu magawo a mphotho yopereka mphoto kumapereka yankho la funso lovutitsa ngati dopamine dongosolo - dongosolo "lotsika" kuchokera ku zowonjezera za hyperhalamus-ndilo zambiri zokhudzana ndi "kufuna" kapena "kukonda" madalitso osiyanasiyana kuphatikizapo zakudya ndi mankhwala osokoneza bongo. Kuti ubongo womwewo umakhudzidwa ndi cholinga cholimbikitsidwa ndi zakudya komanso mankhwala osokoneza bongo kumapangitsa kuti pakhale mgwirizano wodabwitsa womwe umayambitsa kudya mopitirira muyeso komanso kumangokhalira kumwa mankhwala osokoneza bongo.
M'zaka zaposachedwapa, zokambirana za kuledzera zakhala zikuyang'ana pazigawo zake, ngati kubwereza kwa mankhwala mobwerezabwereza kwasintha ubongo m'njira zomwe zingakhoze kuwerengedwa ndi biologist zamagetsi, electrophysiologists, ndi zinthu zamagetsi. M'zaka zoyambirira, chidwi chinali pa chizoloŵezi chopanga mankhwala osokoneza bongo; kodi mankhwala osokoneza bongo amatha bwanji kugwiritsa ntchito njira za ubongo zolimbikitsira ndi mphotho? Funso la kukhala wonenepa kwambiri zotsatira kuchokera Kuledzera kwa zakudya kumatibweretsera ku funso loyambirira la zomwe njira za ubongo zimayendera pa chitukuko chokakamiza zakudya ndi mankhwala osokoneza bongo, ndipo izi, zimatibweretsanso ku vuto la kuyesa zopereka zofunafuna mphotho ndi reinforcement (1).
Mbali yaikulu, umboni womwe umasonyeza kuti chinthu chofala kwambiri cha kunenepa ndi kusokoneza ubongo ndi umboni wosonyeza ubongo wa dopamine mu chizoloŵezi chopanga zotsatira za chakudya (2) komanso mankhwala osokoneza bongo (3). Pamene dongosolo la dopamine likuyambitsidwa ndi chakudya (4) ndi mankhwala osokoneza bongo ambiri (5), kukangana kumakhalabebe ngati ntchito ya dopamine imathandizira kwambiri kuonjezera zotsatira za zakudya ndi mankhwala kapena zomwe zimawathandiza kukhala nazo (6-8); muzithunzithunzi, ndi dopamine ofunika kwambiri ku "kukhumba" kwa mphotho kapena "kufuna" kwa mphotho (9)? Mzere wa umboni wovomerezeka womwe sunawonedwe mochulukirapo m'zaka zaposachedwapa ndi umboni wakuti chinthu chodabwitsa chimatchedwa "mphotho yotsatsa galimoto." Apa ine ndikufotokoza chododometsa ndikuchifotokozera ndi umboni wakuti dopamine ali ndi maudindo ofanana pakufunafuna chakudya ndi kukakamiza mankhwala osokoneza bongo- kufuna ndikufunsanso kuti ndiwotani chifukwa cha maudindo kapena ntchito zowonjezera-zimadalira dongosolo la dopamine.
Kupititsa patsogolo magetsi kumagetsi
Mu 1950s, lateral hypothalamus inalembedwa malo osangalatsa ndi ena (10) ndi malo a njala ndi ena (11). Kulimbikitsa magetsi a dera lino kunali kopindulitsa; Mphindi zochepa, kukakamiza kotereku kungayambitse kusokoneza chiwindi pamapikisano ochulukitsa zikwi zingapo pa ola limodzi (12). Zomwe zinapangitsa kuti zochitika zoterezi zikhazikitsidwe zinakhazikitsanso chidwi choyandikira chiwombankhanga, ndipo izi zikhoza kukhala zokwanira kuthana ndi kupweteka kovuta (12). Kotero kusangalatsa uku kunakhala ngati kulimbikitsana kosavomerezeka, "kudumpha" muzochita zowonongeka komanso mabungwe ogwira mtima omwe anayambitsa chiwindi choyankhira ngati chikhalidwe cholimbikitsana chomwe chinapangitsa kuti anthu aziyandikira ndi kugwiritsira ntchito. Kuchokera pa maphunziro oyambirira izo zinatsimikiziridwa kuti makoswe ankakonda kukondweretsa ndipo kuti kukonda izo kunapangitsa kuti iwo azifuna zambiri (10); Kafukufuku wokhuza anthu odwala amatsimikizira kuti kukondweretsa koteroko kunali kosangalatsa (13).
Kulimbikitsidwa kwa dera lino kungalimbikitsenso khalidwe. Ntchito yoyamba ya Hess inavumbulutsa kuti kugwiritsira ntchito magetsi kungachititse kuti munthu adye chakudya chokwanira, chomwe chimatchedwa "bulimia" (14). Pambuyo kupezeka kwa ubongo kukakamiza mphotho (15), posakhalitsa anapeza kuti kukondowetsa m'mbuyo mwa hypothalamus kungapangitse chakudya chotero komanso mphotho (16). Zoonadi, kulimbikitsa malo opindulitsa kungapangitse mitundu yambiri ya zamoyo-zowoneka, zamoyo zamakono monga kudya, kumwa, kusokoneza, ndi kugwirana (17). M'njira zambiri, zotsatira za zokopa zimayenderana ndi zotsatira za madera oyendetsa magetsi (18), ndipo zotsatira za kukhumudwa ndi kuwonongedwa kwa chakudya zimadziwika kuti zimatsutsana (19). Ichi, ndiye, chinali mphotho yopereka mphoto (20); chifukwa chiyani makoswe ayenera kuyimitsa chiwindi kuti apange dziko ngati njala?
Zida zamagetsi zogwirira ntchito
Poyamba, funso loyambitsidwa ndi mphotho yopereka mphotho linali ngati zofanana kapena zosiyana zowonjezera zimaphatikizapo zotsatira ziwiri zokopa. Izi sizinali zophweka kuti zitheke chifukwa kutengeka kwa magetsi kumayambitsa machitidwe osiyanasiyana a mphuno m'malo mopanda tsankho. Malo ogwira ntchito okondweretsa ndi mwinamwake mamitamita awiri (21, 22) ndipo mkati mwa malo awa zokopa zimapangitsa kuti zitsulo zilizonse zikuzungulira chida cha electrode. Komabe, ma fiber a kukula kosiyana ndi kusinkhasinkha ali ndi makhalidwe osiyana siyana, ndipo zokopa zomwe zimagwiritsidwa ntchito pazinthu ziwirizo zinali zosiyana (23, 24). Ngakhale kuti chinali bedi la bwalo la lateral hypothalamus lomwe poyamba linkayesa kuti ndilo gwero lalikulu la njala ndi mphotho, zowonjezereka za ndime zimakhala ndi zochepetsetsa zochepa kwambiri kuposa za maselo, ndipo pedi la bedi la lateral hypothalamus likudutsa Zida za 50 zomwe zimapangidwa ndi mthunzi wamkati (25, 26). Choyambirira, zolinga zam'tsogolo, ndi njira yokhala ndi ubongo wa njira yopititsa patsogolo ubongo (mphotho) ndi kupititsa patsogolo-kupititsa patsogolo kudyetsa kumakhala kosadziwikiratu, koma zigawo za ndime zikuphatikizidwa momveka bwino ndipo zingapo za makhalidwe awo zatsimikiziridwa. Zomwe zimagwiritsidwa ntchito moyendetsa galimoto komanso zotsatira zake zowonjezera zowonongeka zimakhala ndi makhalidwe ofanana.
Choyamba, mapu a mapangidwe amodzi awonetsa kuti gawo lotsatira la hypothalamic gawo lopangitsa ubongo kulimbikitsa mphotho ndi chakudya cholimbikitsana chokhala ndi zolaula chomwe chili ndi malire ofanana kwambiri omwe amatha kupitilirapo ndipo amakhala osagwirizana pakati pa malire (27, 28). Kuwonjezera apo, pamene gawo lokhalitsa lokhalokha la mthunzi wam'mbuyo wam'mbuyo umayamba kudziwika ndi kudyetsa ndi kupatsa mphotho, kulimbikitsidwa kwa ziwonetsero zochuluka za mtolo, mu ventral tegmental dera, zingakhalenso zopindulitsa (29-31) ndikupangitsa kudya (32-34). M'dera la ventral tegmental, malire a masewera olimbitsa thupi otetezera masewera pafupi ndi malire a magulu a dopamine omwe amapanga mesocorticolimbic ndi nigrostriatal machitidwe a dopamine (30). Kulimbikitsana kwa cerebellar peduncle (nthambi yowonjezereka kwambiri ya mthunzi wamkati) ingathandizenso kudzikweza ndi kudyetsa (35, 36). Choncho, ngati magawo osiyana akugwirizana ndi makhalidwe awiri, magawo amenewa ali ndi njira zofanana ndi zina zomwe zimagwiritsidwa ntchito mofanana.
Ngakhale kuti salola kuti kusiyana kwa matenda a ubongo, njira za psychophysical-kuwonetsa zotsatira za khalidwe la kusintha kwa kayendedwe kowonjezera-kulola kusiyana kwakukulu pakati pa zizindikiro za axonal. Njirazi sizikukambidwa mozama muzoledzera kapena kudyetsa zilembo.
Choyamba, kulimbikitsa "kuthamanga kwapakati" kumagwiritsidwa ntchito poyerekeza nthawi zomwe zimapangidwira nthawi ndi maulendo a "siteji yoyamba" zowonjezera (zomwe zimapatsidwa mphoto ndi zowonjezera zomwe zimagwiritsidwa ntchito pamagetsi ). Njira yokonzekera nthawi yowonongeka-nthawi yoyenera kuti nembanemba ikhale yothandizira pakatha kukhumudwa kwa ntchito yomwe ingatheke-imagwiritsa ntchito njira yomwe amagwiritsira ntchito electrophysiologist akuphunzira za neurons imodzi. Ngakhale kuti pali zinthu zina zosavuta kuganiziridwa mozama, njirayi ndi yosavuta kwambiri. Pamene mukuwerenga single neurons, imodzi imangoyambitsa neuron kawiri, kusiyanitsa nthawi pakati pa yoyamba ndi yachiwiri kukakamiza kuti kupeza nthawi yochepa yomwe imalola selo kuthana ndi kachiwiri kukondoweza. Ngati kukakamiza kwachiwiri kukutsatira mofulumira kwambiri, neuron sichidzapulumutsidwa kuchokera ku zotsatira za yoyamba mu nthawi kuti ayankhe yachiwiri. Ngati kachilombo kawiri kadzafika mochedwa, neuron idzapulumuka mokwanira kuchokera ku kuwombera kumene koyamba kuyaka moto potsatira kachiwiri. Nthawi yochepa yomwe imakhalapo pakati pa mapulaneti pofuna kupeza mayankho ku mapulumu onse awiri imatanthawuza "nthawi yotsutsa" ya axon yomwe yasokonezeka.
Kuti tipeze mayankho a machitidwe kumagulu olimbitsa magetsi, zowonjezera zowonjezera ziyenera kukhala zolimbikitsa ndipo zopitilira zowonjezereka zimayenera kuperekedwa; Mapangidwe apamwamba amachititsa kuti afike kumagetsi ambiri kuzungulira electrode, ndipo "kuphunzitsa" kutengeka mobwerezabwereza kumafunika kuti mutsegulire maulendo angapo. Mwa kudzikweza komweko amaphunzira masewera olimbikitsa a masekondi a 0.5 amaperekedwa mwachizolowezi; mu zopititsa patsogolo zopatsa chidwi zophunzitsa zokopa za 20 kapena masekondi 30 amapatsidwa. Aliyense amalowa mkati mwa sitimayo amatha kukhala ndi 0.1 msec yekha: motalika kuti atsegule ma neuroni apamtima kamodzi koma osakwanira kuti abwezeretsenso kachiwiri nthawi yomweyo. Mipira imaperekedwa pafupipafupi a 25-100 Hz, kotero kuti ngakhale mu sitima yachiwiri yokondweretsa sitimayi pali maulendo ambirimbiri obwerezabwereza. Maphunziro a zokopa zosavuta ndi zojambula Chithunzi 1A.
Kuti mudziwe nthawi yotsatila yoyamba, ma sitima a ophatikizidwa mapulusa (Fanizo la 1B), m'malo mophunzitsa sitima zamodzi (Fanizo la 1A), amapatsidwa. Kupsa koyamba muwiri pawiri kumatchedwa "C" kapena "conditioning" pulse; Chikondi chachiwiri muwiri lirilonse chimatchedwa "T" kapena "kuyesa" pulse (Fanizo la 1C). Ngati mapulaneti a C akutsatiridwa kwambiri ndi ma T-pulsi awo, mapulaneti a T sangathe kugwira ntchito ndipo nyamayo idzayankha ngati idavomerezedwa ndi C-pulses. Ngati mpata pakati pa C-ndi T-pulses ukukwanika mokwanira, T-pulse idzagwira ntchito ndipo nyama, kulandira mphoto zambiri, idzayankha mwamphamvu kwambiri. Chifukwa chakuti anthu omwe ali ndi gawo loyamba la neuroni ali ndi nthawi zosiyana siyana, zomwe zimayambitsa chikhalidwe zimayambira pamene nthawi ya CT imatha kufika nthawi yotsalira kwambiri, ndipo nthawi zonse zimakhala zowonjezereka mpaka zitapitirira nthawi yotsutsa Mitambo yochepa kwambiri (Fanizo la 1D). Potero njirayi imatipatsa nthawi yowonetsera zizindikiro za anthu kapena anthu omwe ali ndi magawo oyambirira a neuroni chifukwa cha khalidwe lomwe liripo.
Monga momwe zisonyezedwera ndi njira zoterezi, nthawi zowonongeka zogwiritsira ntchito ulusi wothandizana ndi ubongo wa mphotho zimaperekedwa kuchokera ku 0.4 kufika pa 1.2 msec (37-40). Nthawi zowonongeka zowonongeka-zomwe zimapangidwira kudya zimakhalanso muzinthu izi (38, 40). Sizinthu zokhazokha zokhazokha; magawo awiriwa ali ndi vuto lofanana: Pazifukwa zonse, samasonyeza kusintha kwa khalidwe pamene nthawi ya CT ikuwonjezeka pakati pa 0.6 ndi 0.7 msec (39, 40). Izi zikutanthauza kuti pali magulu awiri omwe amawathandiza aliyense khalidwe: kachigawo kakang'ono ka ma fiber kwambiri (nthawi zosokoneza kuyambira 0.4 mpaka 0.6 msec) ndi chiwerengero chachikulu cha ziboda zochepa (nthawi zosokoneza kuyambira 0.7 mpaka 1.2 msec kapena mwina pang'ono). Zimakhala zovuta kulingalira kuti anthu osiyanasiyana amatsutsana ndi zopindulitsa komanso zotsatira za kuyendetsa galimoto pamene mafilimu omwe amatsutsa nthawi ndi ofanana, aliwonse omwe ali ndi pakati pa 0.6 ndi 0.7 msec.
Umboni wowonjezereka kwa gawo lodziwika kuti zotsatira zowonongeka ndi mphotho zowonongeka ndizokuti kukakamiza pa malo kwinakwake pampando wam'mbuyo wam'mbuyo kungathandizenso onse kudyetsa (32-34, 40, 41) ndi mphotho (29, 42-44). Kupatula nthawi yopereka malipiro ndi mphotho yopititsa patsogolo chakudya ndi chimodzimodzi ngati magetsi oyambitsa mphamvu ali pa ventral tegmental kapena msinkhu wothandizira wothandizana nawo (foregrain bundle)40). Izi zikutanthauza kuti anthu awiri omwe ali ndi magulu awiriwa ali ndi udindo pa zikhalidwe zonse.
Kuwonjezera apo, pokhapokha ngati kugwiritsidwa ntchito kwa nsalu zomwe zimayambitsanso zokhudzana ndi zokopa zimatchulidwa, mbali yapamwamba yoyendetsa mapangidwe a zigawo ziwiri zingathe kudziwika ndi kuyerekezedwa (43). Njira yowonetsera kayendetsedwe ka kayendedwe kameneka ndi yofanana ndi yoyerekeza nthawi yowonongeka, koma pakadali pano ma C-pulses amaperekedwa pa malo amodzi otsekemera pamtunda (mwachitsanzo, pang'onopang'ono hypothalamus) ndipo T-pulses amaperekedwa kwa wina (mwachitsanzo, gawo la ventral tegmental). Izi zimafuna makina osokoneza mazira omwe akugwirizana kuti asokoneze miyeso yomweyo pambali ziwiri (kutalika kwake)45). Pamene ma electrode amapezeka kuti akugwiritsidwa ntchito bwino kwambiri pamtunda kuti apereke mphotho, amakhalanso ogwirizana kwambiri pamagetsi kuti azidyetsa (33). Apa, pamene mapepala apakati amaperekedwa, nthawi yayitali pakati pa mapulaneti a C ndi ma T-pulsi ayenera kuloledwa kuti T-impulse isagwire ntchito. Izi zili choncho chifukwa, pokhapokha nthawi yowonongeka kuchokera ku refractoriness, nthawi imayenera kuloledwa kuti ipange zomwe zingatheke kuchokera kumtundu umodzi wa electrode kupita kumzake (43, 45). Pochotsa nthawi yosokoneza (yotsimikiziridwa ndi mphamvu imodzi ya electrode) kuchokera ku nthawi yovuta ya CT yomwe imaperekedwa ku magetsi osiyanasiyana, tikhoza kulingalira nthawi zosiyanasiyana zomwe zimapangidwira nthawi ndipo timapeza maulendo ambiri omwe amachititsa anthu omwe ali ndi mapepala oyambirira. Kafukufuku wogwiritsa ntchito njirayi asonyeza kuti nsonga za mphotho zomwe zimapangidwira zimakhala ndi maulendo ofanana ndi ofanana ndi omwe amachititsa kuti maulendo apitirize kukhala odyetserako (33). Momwemonso mphotho ya mphotho imakhala yosasinthika mosavuta malinga ndi malire, nthawi zosokoneza, maulendo othandizira, kapena njira yoperekera magawo kuti apindulitse ndi zotsatira zoyendetsa galimoto zowonongeka zamagetsi; M'malo mwake, zikuwoneka kuti kayendedwe kabwino ka galimoto kameneka kakuyambitsa kusonkhezera mthunzi kumakhala kofanana kapena kofanana kwambiri ndi njira yowonjezeramo zotsatira zolimbikitsa.
Umboni wa zachipatala umatanthauzanso gawo limodzi lopangitsa ubongo kukondweretsa mphotho ndi kupititsa patsogolo-kudyetsa kudya; Umboni uwu umasonyeza kuti anthu ambiri amachita nawo dopamine neurons, ma neurons omwe alibe nthawi yowonongeka ndi machitidwe oyendetsa matayala oyambirira a mthunzi wamkati wamkati koma mwachiwonekere gawo lachitatu kapena gawo lachitatu pamtundu wochepa kuchokera pansi pa zitsulo zokhazikika. Choyamba, kudyetsa-kumapangitsa kuti kudyetsa ndi kusakanikirana kosavuta kumagwiritsa ntchito ubongo umapindula ndi otsutsa a dopamine (46-51). Kuwonjezera apo, aliyense amathandizidwa ndi jekeseni la ventral tegmental ya morphine (52, 53) komanso mu-delta opioid agonists (54, 55) zomwe zimayambitsa dongosolo la dopamine (56). Mofananamo, zonsezi zimatsogoleredwa ndi delta-9 tetrahydrocannabinol (57-59). Ngakhale amphetamine ndi mankhwala osokoneza bongo, ngakhale izo zimapangitsa mbali zina za kudyetsa-kudyetsedwa kudya (60) komanso ubongo wolimbikitsa mphoto (61), makamaka pamene tizilombo toyambitsa matenda tizilombo toyambitsa matenda (microyjected) mu khunyu accumbens (62, 63).
Kuyanjana ndi dongosolo la dopamine
Kodi mapepala oyambirira a ubongo wopindulitsa amaphatikizana bwanji ndi dongosolo la dopamine? Kafukufuku wina wopanga magetsi awiri akusonyeza kuti polojekiti yoyamba yamagetsi imachokera kumalo ozungulira kumalo ozungulira, kumbali kapena kudera la dopamine kumene kumayambira. Kulimbikitsanso kumagwiritsidwanso ntchito pogwiritsa ntchito makina awiri a electrode omwe amachititsa kuti azigwiritsira ntchito makina omwewo pamtundu wosiyana, koma pakali pano imodzi ya electrodes imagwiritsidwa ntchito ngati mankhwala (kujecting cations zabwino amagwiritsidwa ntchito monga anode (kusonkhanitsa cations) kuti awonetsere mankhwala omwewo mosiyana ndi kutalika kwake. Chifukwa chakuti chikoka cha mitsempha chimaphatikizapo kuyenda pansi pa axon of zone of depolarization, phokoso limalephera ngati ilo lilowa m'dera la hyperpolarization. Pamene kutengeka kwakukulu kumalepheretsa zotsatira za khalidwe la kukondweretsa kwa cathodal kumatanthauza kuti anode ndi pakati pa cathode ndi mitsempha ya mitsempha. Pogwiritsa ntchito zokopa za cathodal ndi blockade yodutsa pakati pa malo awiri a electrode ndikudziwitsanso kuti kukonzekera kumakhala kotani, tingathe kudziwa momwe tingayendetsere mafayilo oyambirira. Chiyesochi chimasonyeza kuti kuchuluka kwa makina opangidwe kumapereka mauthenga a mphoto mu njira ya rostral-caudal, kumalo a ventral tegmental (64). Ngakhale kuti chiyambi kapena chiyambi cha dongosololi chikhalebe chotsimikiziridwa, lingaliro limodzi ndi lakuti kutsika kwa mapepala oyambirira-sitepe kumathera kumalo a ventral tegmental, synapsing pa maselo a dopaminergic kumeneko (65); lingaliro lina ndilo kuti magawo oyambirira a masitepe amadutsa m'dera la ventral tegmental ndipo amathera mu phokoso la pedunculopontine tegmental, lomwe limabwereranso ku maselo a dopamine (66). Njira iliyonse, umboni wochuluka umasonyeza kuti zofanana kapena zofanana kwambiri za medial forebrain katundu wa fiber (67) zimapindulitsa kwambiri komanso zimapangitsa kuti phokoso likhale lopangitsa kuti pakhale njira yowonongeka yomwe imapangitsa kuti phokoso likhale labwino kwambiri.
Kudyetsa mankhwala ndi mankhwala
Mphoto yotsatsa galimoto sizongopeka pa maphunziro a khalidwe omwe amachititsa chidwi cha magetsi; Chitsanzo china chimaphatikizapo khalidwe lopangidwa ndi microinjections za mankhwala osokoneza bongo. Mwachitsanzo, makoswe amatha kuthamanga-phokoso kapena mphuno kuti apereke mankhwala ochepa a morphine (68, 69), kapena otalikira mu opioid endomorphin (70) mu gawo la ventral tegmental; Amaphunziranso kudzipereka kuti azigwiritsa ntchito ma opioids mu dera ndi delta DAMGO ndi DPDPE m'dera lino la ubongo (71). Mankhwalawa ndi opindulitsa pokhapokha ngati ali ndi luso loyambitsa dongosolo la dopamine; mu ma opioids ndi nthawi zoposa 100 zogwira ntchito kuposa delta opioids poyambitsa dopamine system (56), komanso, nthawi zoposa 100 zimapindula kwambiri monga mphoto (71). Momwemonso m'magazi a opioid ndi am'tawuni amapindulitsa kwambiri chifukwa cha kuchitidwa (kapena, mwinamwake, kuteteza [72]) chiyambi cha mesocorticolimbic dopamine dongosolo. Majekeseni enieni a opioids mu ventral tegmental m'deralo amachititsanso kuti azidyetsa makoswe komanso kuti azikhala ndi njala. Kudyetsa kumayambitsidwa ndi jekeseni la ventral tegmental ya morphine (73-75) kapena mu olasioids kapena mu delta (76, 77). Monga momwe zilili ndi zotsatira zake zopindulitsa, mu opioid DAMGO ndi 100 kapena nthawi zambiri zedi kuposa DPDPD ya delta opioid polimbikitsa kudya (77). Momwemonso, mphotho ndi chakudya zingachititse aliyense kugwiritsidwa ntchito pogwiritsa ntchito malo omwe amagwiritsa ntchito ubongo, pogwiritsa ntchito mankhwalawa, omwe amakhala osankhidwa kwambiri kuposa mphamvu zamagetsi zothandizira zinthu zina zamkati.
Chitsanzo china chimaphatikizapo agonist kwa GABA wa neurotransmitter. Microinjections wa GABA kapena GABAA agonist muscimol mu caudal koma osati gawo lokhazikika la ventral tegmental dera limapangitsa kudyetsa zinyama (78). Mofanana ndi jekeseni wa muscimol mu caudal koma osati rostral ventral tegmental m'derali ndipindulitsa (79). GABAA otsutsa ndipindulitsa (80), ndipo amachititsa nucleus accumbens dopamine kukwera (81); Pachifukwa ichi malo ogwiritsira ntchito jekeseni ndi otero rostral osati osati caudal gawo lachitukuko, kutanthauza kutsutsana ndi machitidwe a GABAergic. Kudyetsa sikunayambe kuyesedwa ndi antchito a GABA-A m'madera awa.
Pomaliza njira zamagetsi (82) ndipo amatha kuyambitsa tizilombo toyambitsa matenda m'kati mwa dera la ventral tegmental (83) akulimbikitsanso okhaokha komanso njira zowonongeka zomwe zimayambitsa matendawa zimathandizanso kuti zakudya zowonjezera zamagetsi zisawonongeke (84). Apanso, timapeza jekeseni zomwe zimapindulitsa komanso zimalimbikitsa kudya. Apanso, ma mesocorticolimbic system dopamine amawonekera; Pachifukwa ichi, mankhwalawa amathandiza kwambiri (monga mphoto) m'dera la ventral tegmental, kumene amagwirizana ndi njira zopangira dopamine ndipo amachititsa kuti asinthe (85, 86).
Maphunziro omwe adawonekeratu pamwambapa akuwoneka kuti akutsitsa dongosolo mu njira ya medial forebrain mtolo mu yin ndi yang ya chilimbikitso: cholimbikitsani kuchitapo kanthu mwa lonjezano la mphotho zisanapangidwe ndi kukhazikitsidwa kwa mayankho atsopano ndi makampani otsitsimula ndi kukalandira kwa nthawi yake mphotho, yomwe yapeza. Njirayi imayendetsedwa kuchokera ku lateral hypothalamus kupita ku dopamine system-mosakayika ikuphatikizapo pa izo kapena zomwe zimapangitsa-zomwe zimakhala zofunikira, (mwina mwina osati zofunikira (87, 88)), zitha kuwonetsa zochitika zonsezi (46) ndikulimbikitsanso (50).
Lingaliro
Kodi dongosolo la dopamine, dongosolo lomwe limakhudzidwa ndi zotsatira za chizoloŵezi cha zakudya zopangira mankhwala osokoneza bongo, zimathandiziranso momwe zilili zotsutsa kuti zipeze madalitso awa? Chowoneka bwino kwambiri ndi chakuti njira zosiyanasiyana za dopamine zikhoza kusunga ntchito zosiyanasiyanazi. Zomwe zingagwire ntchito zosiyanasiyana zimatchulidwa, choyamba, ndi kusiyana kwa mtundu wa nigrostriatal, mesolimbic, ndi mesocortical systems ndi machitidwe omwe ali mkati mwawo. Mchitidwe wa nigrostriatal umagwirizanitsidwa ndi kuyambitsa kayendetsedwe ka thupi, pamene masolimbic dongosolo limagwirizana ndi mphotho (89, 90) ndi zolimbikitsa (91) gwiritsani ntchito (koma onani [92]). Maselo a mesocortical akuphatikizidwanso mu mphoto ntchito (93-95). Zokwanira (shell), ventrolateral (core) ndi dorsal striatum-yaikulu dopamine mapulaneti masamba-amasiyana mosiyana ndi mitundu yosiyanasiyana ya mphotho ndi mphoto zovomerezeka (96-101). Mapulogalamu osiyanawa angathe kugwira ntchito zosiyanasiyana zimatchulidwa kuti pali magulu awiri a dopamine receptor (D1 ndi D2) komanso njira ziwiri zomwe zimatuluka mwachindunji. Chinthu chinanso chodabwitsa, ndi chakuti dopamine neurons yomweyi ikhoza kusunga mayiko osiyanasiyana pogwiritsa ntchito njira zosiyana zowonetsera. Mwina kusiyana kwakukulu kwambiri kwa chidwi ndi kusiyana pakati pa machitidwe awiri a dopamine neurons: chikhalidwe chosangalatsa cha pacemaker ndi chiwonongeko cha phasic (102).
Ndiwo kupweteka kwapopopang'ono kwa dopamine neurons yomwe ili ndi chikhulupiliro cha nthawi kuti chiwonetsere kubwera kwa mphotho kapena mphoto zowonetsera (103). Dopamine neurons imakhala ndifupikitsa pang'ono pamene mphotho kapena zowonetsera mphoto zimapezeka. Chifukwa chakuti dopamine neurons amavomereza kuti adzalandire mphotho yokha pokhapokha ngati sakuyembekezera, kusinthira yankho lawo pazinthu zowonongeka monga momwe maulosi amakhazikitsira, zakhala zikuchitika nthawi zambiri kuti ziwononge mphotho ndi kulongosola mphotho zochitidwa ngati zochitika zodziimira (103). Njira yina ndiyokuti kulandira mphotho, kupyolera mu Pavlovian conditioning, imakhala yokonzedweratu ndi chigawo chimodzi chokhala ndi mphoto (104): ndithudi, kuti iyo imakhala kutsogolo kwa mphoto (105, 106). Ndi chizoloŵezi-kupanga zotsatira za mphotho-kaya ziri zopanda malire kapena mphotho zapadera (zowonetsera mphoto) -kusowa kuperewera-latency, phasic,-response-contingent delivery. Mphoto imaperekedwa mwamsanga atayankhidwa bwino kwambiri kuposa mphoto yomwe imaperekedwa ngakhale kamphindi kamodzi kanthawi; Mphoto ya kuwonongeka kwapadera monga ntchito ya kuchedwa pambuyo poyankha atalandira (107). Kugwiritsa ntchito phasic kachitidwe ka dopamine kumadziwika kuti kunayambitsidwa ndi zifukwa ziwiri zosangalatsa: glutamate (108) ndi acetylcholine (109). Zonsezi zimakhala ndi zotsatirapo zabwino za cocaine: glutamatergic ndi cholinergic pulogalamu ya dopamine dongosolo aliyense amayamba ndi mwayi wa cocaine mphotho, ndipo chilichonse mwa zotsatirazi zimapangitsa zotsatira zabwino za cocaine palokha (110, 111).
Kumbali ina, kusintha kwapang'onopang'ono kwa kuwombera kwa tonic pacemaker kuwombera dopamine neurons ndi kusintha kwa dopamine yambiri yomwe imayendera limodzi ndi iwo omwe angakhale okhudzidwa ndi kusintha kwa dziko lolimbikitsa lomwe likugwirizana ndi zolakalaka za zakudya kapena mankhwala. Mosiyana ndi zolimbikitsana, zolimbikitsana sizidalira kanthawi kochepa chabe komanso nthawi yotsutsana. Zotsitsimula zikhoza kumanga pang'onopang'ono ndipo zimatha kukhalapo kwa nthawi yayitali, ndipo zikhalidwezi zimatha kusonyeza kusintha kwapang'onopang'ono pamtundu wa kupopera kwa pacemaker wa dopamine neurons ndi kusintha kochepa m'magulu a extraplular dopamine. Zotsatira zolimbikitsa za kukweza ma dopamine (112) mwina mwatsatanetsatane kwambiri mu mapulogalamu obwezeretsa kubwezeretsa chakudya ndi mankhwala omwe amadzipangira okha (113), kumene zinyama zomwe zatha kuwonongedwa zimatha kukwiyidwa ndi nkhawa zosautsa, chakudya kapena mankhwala osokoneza bongo, kapena chakudya-kapena mankhwala okhudzana ndi mankhwala osokoneza bongo. Zonsezi zimatipweteka-kupsinjika maganizo (114), chakudya (115) kapena mankhwala (116) Kupatsa, ndi chakudya- (97) kapena mankhwala- (110, 111, 116) zokhudzana ndi cues-elevates extracellular levels dopamine mphindi kapena makumi khumi. Kotero kusintha kwa kuwombera kwa pacemaker ya dopaminergic neurons ndiko kugwirizana kwa zomwe zimayambitsa kuyambitsa mayankho okhudzana ndi chakudya kapena mankhwala osokoneza bongo.
Pamene kufotokozera za mphotho-mphotho zotsutsana sizingakhale zotsimikiziridwa, maphunziro omwe tawunikiridwa pamwambapa amasonyeza kuti kuyendetsa galimoto ndi mphotho kumayimira pakati pa njira zowonetsera zowonongeka zogwirira ntchito zomwe, mwachindunji kapena mwachindunji, zimayambitsa machitidwe apakatikati a dopamine. Lingaliro losavuta ndilokuti dopamine imagwira ntchito yodzikweza yomwe ili yofunika kuti onse ayendetse ndi kuyimitsa. Izi zikugwirizana ndi mfundo yakuti extracellular dopamine ndi yofunikira pa khalidwe lonse, monga kutsimikiziridwa ndi akinesia wa zinyama zomwe ziri pafupi-kwathunthu dopamine kutaya (117). Kuwonjezereka kwachangu kumaphatikizapo kuchulukitsa kwa dopamine (zomwe zikugwirizana ndi kuwonjezereka koopsa kwa dopamine system) chifukwa cha kuwonjezeka kwa ntchito zowonongeka, mwinamwake pokhapokha kuwonjezera mphamvu za buku ndi zolimbikitsa zomwe zimapangitsa kufufuza kwa Pavlovian ndikuphunzira mayankho a zida (118-120). Malingaliro awa, kuwonjezeka kwa minofu ya dopamine yomwe imaphatikizidwa ndi chakudya-kapena mankhwala osokoneza bongo ndizogwirizanitsa kawirikawiri zokhumba zofuna kapena "kufuna." Kuyankha kumawonjezeka mu kamphindi kakang'ono ka dopamine kamene kamagwirizanitsidwa ndi kuponyedwa kwa phasic ya dopamine dongosolo pamtundu ndi mayankho ogwira ntchito, mwinamwake mwa kulimbikitsa kukhazikika kwa njira yomwe ikuchitikabe yomwe imagwirizanitsa kukumbukira kwa kanthawi kochepa kwa mayanjano awa (121, 122). Ngakhale malingaliro ameneŵa akusonyeza kuti kusintha kwapadera kwa dopamine kumayendetsa kayendetsedwe kake ndi kayendetsedwe ka mphamvu, kumatsimikizira kuti zotsatira zowonjezera ndizofunikira; Pambuyo pakuwona chakudya kapena kansalu kamene kamakhudzana ndi kuonjezera chakudya kapena mankhwala osokoneza bongo kuti chakudya kapena chiwindi chimakhala cholimbikitsana cholimbikitsa chomwe chimatha kukhala ndi chilakolako chofuna kukonda. Chotsutsana apa ndi chakuti kulimbikitsanso zotsatira za chakudya kapena mankhwala ena omwe amachititsa chidwi cha lero cha chakudya kapena mankhwala.
Ndemanga zomaliza
Sikuti kudya mopitirira muyeso kwa zakudya zamphamvu kumakhala kovuta ndipo kumakhalabe ndi mavuto omwe amasonyeza kuti kudya kwambiri kumatenga katundu. Zimakhala zovuta kulingalira momwe kusankhidwa kwa chilengedwe kukanachititsa kuti pakhale njira yosiyana ya mankhwala osokoneza bongo pamene zipangizo zamakono zowonjezera komanso kukwanitsa kusuta kapena kuzizira muzitali zapamwamba ndizochitika posachedwa m'mbiri yathu. Kugwiritsa ntchito mankhwala ndi chakudya chodyera kumafuna kayendedwe kamodzi komweko ndipo motero njira zawo zimagwiritsira ntchito njira yomaliza. Onsewa ali ndi zofuna zawo ndipo amatha kukhala osangalala. Zina zimaphatikizapo maulendo oyendayenda omwe amathandiza kwambiri pakulimbikitsana ndi kulimbikitsa, kuyendetsa magulu olimbitsa mtima pokonza zizoloŵezi zowonongeka (12, 123-125). Ngakhale zili ndi chidwi kwambiri pa zomwe tingaphunzire za kunenepa kwambiri kuchokera ku maphunziro oledzera (126), zidzakhalanso zokondweretsa kuona zomwe tingaphunzire za kuledzera kuchokera ku maphunziro a kunenepa kwambiri ndi kudya. Mwachitsanzo, hypothalamic orexin / neconsin hypocretin agwira ntchito pakudyetsa (127) ndi mphotho (128) ndipo amadziwika kuti ubongo zosangalatsa mphotho (129), monga chakudya mphotho (130) akhoza kusinthidwa ndi mthupi la satiety hormone leptin. Njira zatsopano za optogenetic (131) zimapangitsa kuti anthu ambiri azitha kugwiritsira ntchito njira zolimbikitsira zamagetsi kusiyana ndi magetsi, ndipo tikuyembekeza kuti njira izi zikhoza kupititsa kumvetsetsa kwathu kwa kugwiritsira ntchito mankhwala osokoneza bongo komanso kumangokhalira kudya mopitirira muyeso komanso kuthetsa vutoli.
Kuvomereza
Kukonzekera kwa zolembedwerazi kunathandizidwa kudzera mwa malipiro a Intramural Research Program, National Insititute on Drug Abuse, National Institutes of Health.
Mawu a M'munsi
Kulengeza zachuma
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