Kudyetsa ndi mphotho: Zomwe zimayambira pa Mitengo itatu ya Binge kudya (2012)

Rebecca L Cowin,¹ Nicole M. Avena,^2,3 ndi Mary M. Boggiano⁴

Kafukufuku wagwira ntchito kumvetsetsa mmene kudya kwambiri kungakhudzire njira zothandizira ubongo ndi khalidwe lotsatirali, mwapang'onopang'ono komanso mu kafukufuku wamakono. Ntchitoyi ndi mbali yowonjezera kufunika kokhala ndi chidziwitso chodziwika bwino komanso njira zothandizira kuti mliriwu ukhale wonenepa kwambiri. Komabe, kudya mopitirira muyeso, kapena kosakhala homeostatic, kungatheke popanda kudzikweza. Kuthetsa kusinthana kwa kudya kwapadera chifukwa cha kulemera kwa thupi kumathandiza kwambiri, monga kudziwika bwino kuti kuwonjezeka kwa thupi kapena kunenepa kwambiri kungawononge zotsatira zake zokhumudwitsa pazithupi za thupi, ndondomeko zamtundu, ndi khalidwe. Phunziroli, timapereka deta kuchokera ku zinyama zitatu zosankhidwa zomwe zimakhala zovuta kwambiri zomwe sizinapangitse amayi kuti azidya zakudya zomwe zakhala zikuyendetsedwa ndi Bart Hoebel's 40 + -kuphunzira ntchito, kudyetsa, kulimbikitsa, ndi njira zowonjezera zomwe zimagwirizanitsa ntchito izi. Choyamba, chitsanzo cha shuga chophimba shuga chimatchulidwa (Avena / Hoebel), momwe nyama zomwe zimakhala ndifupipafupi, zowonjezereka njira yothetsera shuga zimakhala ndi makhalidwe ndi kusintha kwa ubongo zomwe zimakhala zofanana ndi mankhwala osokoneza bongo, monga chinyama choyamba za mankhwala osokoneza bongo. Chachiwiri, chitsanzo china chikufotokozedwa (Boggiano) momwe mbiri ya kudya ndi kupanikizika ikhoza kupititsa patsogolo kudya chakudya chokoma komanso chosasangalatsa. Kuwonjezera pamenepo, chitsanzo (Boggiano) chafotokozedwa chomwe chimalola nyama kuti zikhale ndi zovuta zotsatila ndi zovuta zowonongeka. Potsirizira pake, chitsanzo chochepa choyendetsera bwino chikufotokozedwa (Corwin) momwe makoswe omwe sali chakudya chokhala ndi chakudya chokhala ndi chakudya chokwanira chokhala ndi zakudya zamakono amayamba kukhala ndi makhalidwe obwereza. Zitsanzo zimenezi zimaganiziridwa potsatira zomwe zimachitika pazochitika za ubongo, kuphatikizapo dopamine, opioids, machitidwe opatsa mphamvu, serotonin, ndi GABA. Pamodzi, deta yomwe imagwiritsidwa ntchito pogwiritsira ntchito zitsanzozi zikuwonetsa kuti zotsatira za khalidwe ndi zotsatira za kudya chakudya chokoma, ngakhalenso kulemera kwake kwa thupi, n'zosiyana ndi zomwe zimangokhala kudya chakudya chokoma mwachabechabe njira. Zotsatirazi zingakhale zofunikira pomvetsa mmene kudya kwambiri kungakhudzire makhalidwe ndi ubongo.

Kuledzera shuga kumabweretsa zizolowezi zoledzera

Pakhala pali nkhani zosawerengeka zomwe anthu amadzinenera kuti "amadwala" zakudya zina, ndipo chizoloŵezi chimenechi chimasonyeza kuti amadya kwambiri, kumverera kwachisoni pamene chakudya chokoma sichipezeka, ndi kukhumba zakudya zina [9]. Zakudya zamakonozi zimakonda kuganizira zakudya zowonongeka, zowonjezera mphamvu, kapena kwa anthu ena, chakudya chamadzimadzi. Mofanana ndi munthu wogwiritsira ntchito mankhwala osokoneza bongo, iwo amene amamva kuti ali ndi vuto la zakudya zina zimakuvuta kuti asiye kudya, zomwe zingathe kupangitsa kuti anthu ena azilemera.

Ngakhale kuti mawu oti "chizoloŵezi cha zakudya" amagwiritsidwa ntchito mogwiritsidwa ntchito mosagwirizana, kufotokoza kwake kwasayansi kukungoyamba kumene, ndipo umboni ukuwonjezeka kuti zisonyeze kuti kudyetsa zakudya zowonjezereka pansi pa zochitika zenizeni kungathe kuchititsa makhalidwe ndi kusintha kwa ubongo zomwe zimafanana ndi chizolowezi choledzeretsa monga boma. Odzidzidzidwa omwe amadya zakudya zowonongeka amagwiritsira ntchito chakudya kudzipangira mankhwala; Amadya akamamva kutopa, oda nkhawa, ovutika maganizo kapena okhumudwa kuti apulumuke.9]. Pofuna kukhazikitsa ndondomeko yodziwitsa anthu oterowo, Yale Food Addiction Scale, idapangidwa. Chida ichi ndicho chiwerengero choyamba chokhazikitsidwa ndi maganizo okhudzana ndi kudyetsa chakudya, malinga ndi kusintha kwa DSM-IV zoyenera kuzidalira [10]. Kuphatikiza pa kukhazikitsidwa kwa zovomerezeka zomveka bwino, maphunziro a ubongo ndi ma genetics amathandizanso lingaliro lakuti kudya moyenera chakudya chokoma kumafanana ndi kuledzera. Zambiri pa Yale Food Addiction Scale zimagwirizanitsa kwambiri ndi kutsegulira kanyumba koyambirira, kapenanso amygdala, madera okhudzana ndi chikoka, poyang'anira kuyembekezera chakudya chokoma [11]. Kugwiritsa ntchito zakudya zomwe zimakhala zovuta kwambiri kungachititse kuti m'madera amenewa ubongo [11, 12], zomwe zingakhale zovuta kumvetsa zolakalaka chakudya. Komanso, PET imawonetsa kuti maphunziro ovuta kwambiri amasonyeza kuchepetsa D₂ kupezeka kwa phwando komwe kumakhudzana ndi kulemera kwa thupi la phunzirolo [13] ndipo ali ofanana mofanana ndi kuchepa kumene kunanenedwa ndi maphunziro osokoneza bongo [14]. Kuwonjezera pamenepo, kusintha kumeneku kumagwirizana kwambiri ndi khalidwe lodyera mowa kwambiri kusiyana ndi kulemera kwa thupi [15]. Ophunzira omwe amadya chakudya amasonyezanso kuti ali ndi "phindu la ntchito" ya jini ya mu-opioid receptor, yomwe imagwirizanitsa ndi zilembo zapamwamba pa chidziwitso chokha cha hedonic kudya [16]. Masamba ena angapo afotokozera zazing'ono zomwe zilipo pakati pa kugwiritsira ntchito mowa ndi kudya kwambiri [17].

Wina angafunse kuti chinthu choyipa ngati chakudya chokoma, chomwe anthu ambiri amadya nthawi zonse popanda zotsatira zovuta pa thanzi kapena moyo wabwino, zingakhale zofanana ndi mankhwala osokoneza bongo. M'gawo lino, tikukambirana zachitsanzo cha nyama chomwe chinapangidwa mu labotale ya Hoebel yomwe imasonyeza njira zomwe chakudya chokoma chingabweretse makhalidwe mu makoswe omwe ali ngati omwe amawonedwa ndi zinthu zozunza. Chitsanzo ichi, chomwe chinapangidwa ndikukonzedwanso pamapeto omaliza a ntchito ya Bart, ndi zotsatira za zotsatira za 20 + kuti mudziwe ngati chakudya chingakhale chosokoneza. Monga momwe tafotokozera mu mapepala ake oyambirira a microdialysis omwe zotsatira za zakudya zomwe amadya pa danga la extracellular dopamine (DA) mu nucleus accumbens (NAc) linanenedwa kuti: "Kudya kungakhale kovuta kwambiri mpaka momwe zimakhudzira cocaine." ([18], pg. 1711). Chitsanzo cha chizoloŵezi cha shuga chimasonyeza chidziwitso cha mawu amenewo.

Mu chitsanzochi, makoswe amasungidwa tsiku ndi tsiku kwa 12-h chakudya chosowa, kutsatiridwa ndi 12-h kufika ku 25% shuga kapena 10% sucrose solution ndi rodent chow [19, 20]. Chitsanzocho chafotokozedwa mwatsatanetsatane kale [20], ndi zofufuza pogwiritsa ntchito chitsanzochi zikufotokozedwa mu ndemanga zapitazo [19, 21]. Mwachidule, patapita masiku angapo patsikuli, makoswe amayamba kuwonjezereka kudya ndi kumwa mowa tsiku ndi tsiku, monga akuwonekera ndi kuwonjezeka kwa kudya kwa shuga pa ola loyamba la kupeza. Kuphatikiza pa kuledzera kumayambiriro kwa kupeza, chakudya cha tsiku ndi tsiku chimasintha kotero kuti makoswe amatenga zakudya zazikulu za shuga panthawi yopeza poyerekeza ndi zinyama zodyetsa zodyetsa shuga ad libitum. Pogwiritsidwa ntchito ndi antagonist ndixxone, zizindikiro zowonongeka, monga kunjenjemera kwa mano, kuponderezana kwapadera, ndi kugwedeza mutu kumachitika pakakhala makoswe omwe akhala akudya shuga [22]. Makoswe ophika shuga amasonyezanso khalidwe lodzidetsa nkhaŵa, poyerekeza ndi kuchepa kwa nthawi yomwe amachitikira pa mkono woonekera wazitali. Zizindikiro za kuchotsa opiate zimatuluka mwadzidzidzi (mwachitsanzo, popanda mankhwala a nayxone), pamene zakudya zonse zimachotsedwa kwa 24 h [19, 22]. Makoswe a shuga amasonyezeranso zizindikiro zowonjezera zowonjezera kupeza sucrose; mphutsi yamphongo inakakamiza 23% kwambiri shuga muyeso pambuyo pa 2 wks za kudziletsa kuposa momwe anachitira [23], pamene gulu lolamulira lomwe linayambira tsiku ndi tsiku 0.5-yowonjezera shuga lotsatiridwa ndi 2 wks za kudziletsa silinasonyeze zotsatira. Izi zikusonyeza kusintha kwa zotsatira za shuga zomwe zimapitirizabe nthawi yaitali yodziletsa, zomwe zimawathandiza kuti azidya bwino. Zotsatira zake zikuwonetseratu kuti kuchepa kwafupipafupi kwa shuga sikukwanira kuti munthu adye kudya, koma m'malo mwake, kuchepa kwachizolowezi chodyera tsiku ndi tsiku, kumafunika kuti pakhale zotsatira.

Kuonjezera apo, kafukufuku wina amasonyeza kuti makoswe oledzera shuga amasonyeza kuwonetsetsa kwambiri ndi mankhwala ena ozunguza bongo. Zimakhala zovuta kwambiri chifukwa cha kuchepa kwa amphetamine komwe kumakhala kochepa kapena kopanda mphamvu pa zinyama zonyansa, pamene makoswe amakhalabe pa nthawi yodyetsa shuga koma amapereka saline sizowonongeka, ngakhalenso makoswe omwe ali ndi magulu olamulira (mwachitsanzo, makoswe amaloledwa khalani pa chow kokha, kapena ndi ad libitum kupeza shuga ndi chow, kapena ad libitum kupeza chow) okha omwe anapatsidwa vuto la amphetamine [24]. Komanso, pamene makoswe akudya shuga ndipo amakakamizidwa kuti asiye, amasonyeza kuti amadya kwambiri 9% poyerekeza ndi magulu omwe analipo kale ad libitum sucrose ndi chow, ad libitum chow kapena kujinga chow yekha [25]. Izi zikusonyeza kuti kudya kochepa kwambiri kwa shuga kungakhale njira yopangira mowa. Pamodzi ndi zofufuza za m'magazi zomwe zafotokozedwa m'munsimu, zotsatira za chitsanzochi zimasonyeza kuti kusakaniza shuga kumakhudza mazira a DA ndi ma opioid, omwe amachititsa kuti zikhale zowonongeka.

Mphamvu yamtundu uwu ndikuti ndiyo njira yoyamba yodyera yomwe zida zowonjezereka zokhudzana ndi kuledzera zafotokozedwa pamene makoswe amadya chakudya chokoma. Choncho, zingapangitse chida chothandizira kuphunzira njira za ubongo zomwe zimagwirizanitsidwa ndi kubwereza mobwerezabwereza, ndipo mwina kuthandizira pa chitukuko cha pharmacotherapies cholinga choletsa kudya kudya, kapena "kuledzera," chakudya chokoma [26]. Mankhwala oterewa angakhale ofunika kwambiri pakati pa anthu ogwira ntchito zachipatala akufotokozera kugwiritsa ntchito mankhwala a comorbid ndi matenda oledzeretsa [5, 6]. Mphamvu ina ya chitsanzo ichi (ndipo, zowonjezereka, zina zotchulidwa mu ndemangayi) ndizoti, popeza makoswe oledzera sakhala olemera kwambiri, kudya mowa mwauchidakwa kungatheke. Izi ndizofunikira, monga zimadziwika kuti zotsatira za kunenepa kwambiri zingapangitse kusintha kwa ubongo komwe kumakhudza mphotho [27]. Choncho, polekanitsa kusinthasintha kwa zakudya zolimbitsa thupi chifukwa cha kuwonjezeka kwa thupi, zotsatira za chakudya chokoma chokwanira pa ubongo ndi khalidwe zimatha kudziwika.

Ma laboratories ena apeza zochitika zowonjezereka zomwe zimasonyeza kuti zizindikiro zowonongeka zimatha kuyamba kugwiritsa ntchito ndondomeko zina zowonjezereka za asprose. Kuthamanga kokwanira kwa sucrose-kukuthandizani ndi cocaine [28] ndipo amachititsa chidwi ku DA agonist quinpirole [29]. Ndiponso, khalidwe lodzidetsa nkhaŵa lakhala likudziwika mu makoswe omwe sangakwanitse kupeza chakudya chokwanira kwambiri cha sucrose [30]. Zosintha zina zakuthupi ndi zamakhalidwe zomwe zimasonyeza kuti vuto loipa lakhala likudziwika mu makoswe omwe amamwa shuga mosakaniza. Mwachitsanzo, kuchotsedwa kwa shuga kunachepetse kutentha kwa thupi [31] ndipo amachititsa zizindikiro za khalidwe laukali [32].

Mbiri ya kuchepetsa kudya + imayambitsa kudya

Mafilimu a HD + Stress akufotokozedwa mwatsatanetsatane kwinakwake [33, 34]. Chitsanzochi chimaphatikizapo zizindikiro zingapo za kuchipatala [35, 36] komanso amalimbikitsanso kudya makoswe kuti asamangoganizira zozizwitsa. Choncho, ndi bwino kuphunzira za bulimia nervosa, binge-purige anorexia nervosa, ndi BED, zonse zomwe zimawoneka ndi HD ndi nkhawa, ndipo zimadziwika ndi kudya chakudya [8, 37-40].

Magulu anayi a makoswe aang'ono amafananitsidwa: gulu loyendetsa bwino (noHD + ndi Stress), gulu la HD okha (HD + Stress), gulu lokhazika mtima pansi (noHD + Stress) ndi gulu loyesera lomwe limakonda kudya, HD + Magulu opanikizika. A HD imayimilira poika makoswe kuti azitha kudya zakudya ndi kubwezeretsa. Amapatsidwa 66% ya maulamuliro a masiku a 5 otsatiridwa ndi masiku 2 ad libitum Makolo a Oreo (monga chakudya chokoma) ndi ad libitum chow, ndiye masiku a 4 okha ad libitum chow. Kuyesera kumachitika pa 12^th tsiku lozungulira ndipo panthawiyi magulu a HD atulukira kulemera kwake ndipo amalemera mofanana ndi makoswe a NOH. Kupanikizika kumayendetsedwa ndi 3 mphindi ya 0.6 mA modzidzimutsa pasanathe kuyesedwa koyetsa. Makoswe ndi Stress chikhalidwe amathera nthawi yofanana m'chipinda chododometsa popanda mantha. Pakati pa kuyezetsa kudya, makoswe ali nawo ad libitum kuchuluka kwa makeke ndi chow m'nyumba zawo zosayenera. Pambuyo pazitsulo / chitetezo chachitatu ndi kupsinjika maganizo, ndipo mutatha kuzungulira pambuyo pake (mpaka kufika kwa 23 miyendo yalembedwa [41]), gulu la HD + Stress limadzisiyanitsa palokha podya chakudya chokwanira (kuchokera ku 30-100% peresenti ya chakudya chokoma ndi magulu ena atatu) mkati mwa 4 yoyamba h ya kuyezetsa kudya ngakhale kuti sanali chikhalidwe cha kusowa chakudya [33]. Mavalo amavala ma cookies, osati chow, mogwirizana ndi kudya kwa mphotho mosiyana ndi zosowa zamagetsi [33, 42], ndikutsimikizira kuti palibe vuto la caloric lokhazikika kuchoka ku chiletso / kubwezeretsa. Umboni wotsutsa kwambiri wakuti kudya mowa siko kumakhala kosavuta pokhapokha ngati makoswe akugwedezeka ndikuyesedwa pamene ali ndi njala (panthawi ya chigawo cha caloric). Nthata za HD zonse ndi popanda nkhawa zimadya chakudya chowonjezereka mwa kuwonjezera chakudya chawo chodziwika bwino, koma HD + Yopanikizika imagonjetsa kudya kotereku kosamalidwa ndi homeostatically komanso kudya chakudya chokoma kwambiri [43]. Kudya chakudya chokoma motsutsana ndi chow, ndi kufufuza kumeneku ndi mankhwala osokoneza bongo (omwe takambirana m'munsimu) amasonyeza kuti kudya mowa mwauchidakwa ndikopindulitsidwa. Kudya mphotho ndi zotsatira zowonongeka (ndi njala) ndizochita zowonongeka [44-48]. Ndizodabwitsa kuwonetsa kuti magulu onse olamulira nthawi zonse amadya chakudya chokoma kwambiri kuposa chow pansi pa mikhalidwe yochepa, zotsatira zowonongeka zomwe zimayendetsedwa ndi makutu akuluakulu. Komabe, kudya kwakukulu komwe kumachitika ndi HD + Makoswe opsinjika maganizo siwowoneka bwino, ndipo amaonongeka kuti akungotengera chitsanzo ichi. Magulu angapo amasintha chitsanzo cha HD + Stress, posintha kutalika kwa chigawo chilichonse cha kayendetsedwe ka zakudya, mtundu wa zakudya zolimbitsa thupi, mtundu wa nkhawa, komanso mitundu ya antchito yogwiritsidwa ntchito [60, 62, 91, 92, 182].

Ngakhale kuti kupanikizika ndi kofunika kwambiri, makoswe amafunika osati kukhala ndi nkhawa kapena chakudya chokoma pa nthawi yoyamba ya HD yopangira zakudya zodyera kuti zichitike [49]. Ngakhale kuti zinthu zitatu zonsezi ndizofunikira pamapeto pake kuti anthu adye chakudya chambiri, mbiri yakale yowonongeka kwa mphamvu ndizofunikira kwambiri poyambitsa makoswe kuti adye [33]. Kulongosola kwa sayansi kwa kugwirizana pakati pa kudya ndi mphotho kunali koyamba kuperekedwa ndi Bart Hoebel: kuchepa kwa chakudya kumachepetsa kwambiri ma CD DAC [50]. Anapezanso kuti makoswe amagwira ntchito mwakhama kuti athandize magetsi mumtundu wa lateral hypothalamus akakhala ndi njala [51] ndipo adawonetsa kuti kubwezeretsa kamodzi pa makoswe osowa chakudya kumapatsa DA levels mu shell ya NAc kuti iwononge nthawi yoperekera chakudya [52]. Ntchitoyi inathandiza kulimbitsa mgwirizano wa matenda pakati pa ziweto ndi mphotho ndikupatsanso njira yomwe HD ingawononge ubongo kuti idye. HD ikhoza kutulutsa anhedonia yomwe imasinthidwa ndi kuwonjezeka kwa DA komwe kumapatsidwa kudya. Inde, ntchito yotsatira kuchokera ku lab lab Boggiano inapeza kuti makoswe omwe ali ndi HD anayamba kusintha maganizo ndi kusintha kwa khalidwe mogwirizana ndi anhedonia ngakhale kuti sangakwanitse. Izi zinali zowona mosasamala kanthu zazochitikira kapena popanda nkhawa [53] ndipo ngati makoswe anali ndi pakatikati, tsiku ndi tsiku, kapena ayi poyerekeza ndi chakudya chokoma pa HD [53, 54]. Kutanthauzira kwa anthu, "zakudya zoletsedwa" (zomwe nthawi zambiri zimadya zakudya) zimadyedwa panthawi ya kumwa mowa [55, 56]. Kudyetsa kwa DA kumeneku kumapangitsa kuti zakudya zimenezi zikhale zolimbikitsana kwambiri kwa anthu omwe ali ndi mphamvu zowononga mphamvu (mwachitsanzo, kudya zakudya zochepa) kusiyana ndi anthu omwe amadya zakudya zomwezo m'mayiko osauka.

Kuphatikiza pa chikoka champhamvu chomwe HD imakhala nacho pakadyedwe kudya, umboni watsopano umasonyezanso kuti kudya zakudya kumachepetsa nkhawa. Kuwonjezera apo phindu lenileni lingapangitse kudya kwambiri kumakhala kovuta kwambiri kuzimitsa. Bart Hoebel adalosera kuti "kumasulidwa kwa DA kungawononge maulendo ku NAC ndi malo ena omwe akuyambitsa zokondweretsa ndi mayankho" ([57], pg. 182). Inde, kupsinjika ndi makamaka, corticosterone (CORT), yatsimikiziridwa kuti ikuwonjezera DA kumasulidwa ku NAc [58, 59]. Mahomoni angapo owonetsetsa, mafukufuku opangidwa mu labbi Boggiano komanso ena omwe amagwiritsa ntchito HD + Stress model anasonyeza kuti kukwera kwa plasma CORT kunasiyanitsa makoswe odyera ku magulu olamulira (kuphatikizapo noHD + Stress group). Izi zinapezeka ngakhale pamene mukugwiritsa ntchito zovuta zina. Mwachitsanzo, Cifani et al. amagwiritsa ntchito kwambiri isomorphic stressor kuposa phazi losokoneza, la kulola makoswe kuti awone ndi kununkhira chakudya chokoma (a Nutella® / chow phala) koma osawalola kuti adye kwa maminiti a 15 [41, 60-62]. Izi zimapereka mwayi wotsutsana ndi ma HPA kuti adye kudya; izi zidzafotokozedwa m'munsimu mu gawo la matenda a ubongo.

Kupeza kochititsa chidwi ndi HD + Stress chitsanzo chinali chakuti ngati HD + Stress makoswe anapatsidwa chidutswa cha chakudya chokoma ndiye anasiyiratu kanthu kokha mbola chow pambuyo nkhawa, iwo adyabe. Ndipotu, amadya 160% ena a chow kcals kuposa magulu olamulira omwe amawakomera ndi chakudya chokoma [43]. Chakudya chokoma chofanana ndi chodyera chachikulu cha chow chodyeramo chinawonetsedwa mu makoswe osakhala ndi njinga ngati akadali pamalo omwe ali ndi malo omwe kale anali ndi zakudya zokoma (komanso Oreos) [63]. Izi zowonjezera kudya ngakhale zakudya zosafunika zomwe zingayambitsidwe ndi kudya chakudya chokoma [64-67], amatchulidwa ndi njira zazikulu zamaganizo mwa anthu (mwachitsanzo, malingaliro odzigonjetsa okha kapena malingaliro okhutira-kupindula kapena kulephera kutsatira ndondomeko ya zakudya) [56, 68-70]. Kuzindikira mosakayikira kumachititsa kuti anthu azidya mowa mwauchidakwa koma chakudya chachikulu chowoneka ndi makoswe a HD + Opanikizika amasonyeza kuti chakudya chokoma chingachititse kuti munthu azidya moyenera, zomwe zingakhale zovuta kuzilamulira. Zakudya zowonongeka ndi mafuta, mafuta odzaza ndi ma sodium apamwamba, ndizo zowonjezera zakudya zamakono [71-73] ndipo angakhale akuchita ngati mankhwala oyambitsa mankhwala [9, 10, 72-75]. Mu ubongo wokonzedweratu, pang'ono chabe zingayambitsenso kubwerera. Hoebel wapereka chidziwitso cha nyama zovuta kwambiri kuti pakhale "kusowa kwa zakudya", monga momwe tafotokozera m'gawo lapitalo [18, 22, 76-78]. Matenda a chakudya chokoma kwambiri omwe amachititsa kuti anthu azidya zakudya zamtundu umenewu ndi zina zotere ayenera kuziganizira pakupanga zisankho zokhudzana ndi kuyambitsa zakudya zoterozo poyang'anira matenda okhudzana ndi kudya. (Komabe, onani Murphy et al., 2010 [79], ponena za kukonza malamulo okhudzana ndi zakudya zothandizira kudya mowa).

Ndemanga pa kusiyana kwake: ndondomeko yochokera ku Binge-kudya yomwe ikuwonetsedwa ndi chitsanzo chotsutsana

Pakati pa anthu, si onse omwe ali ndi HD kapena amene akukumana ndi zowawa kapena kupsyinjika maganizo pa chakudya. Zochitika zamtundu komanso mwinamwake zaka zoyambirira zimadziwika kuti zikhoza kuonjezera chiopsezo chodyera [80-83]. Chimodzimodzinso ndi kudya zakudya zolimbitsa thupi kuti ziwonetsedwe mu makoswe kamodzi kamene kamakhala ndi HD ndi nkhawa. Pamene mukugwira ntchito ndi HD + Stress model, tazindikira kuti panali makoswe omwe amadya pansipa kapena pamwamba pa gululo amatanthauza chakudya chokoma mkati mwa gulu la HD +. Choncho, ngati sichifukwa chodyera kwambiri makoswe, gululo limatanthawuza zolowera siziyenera kukhala zosiyana ndi zolamulira. Choncho, izi zimakhala zovuta kwambiri kuti munthu adye chakudya choyenera, zomwe zimapangitsa kuti apange chinyama chosiyana, kudya zakudya zolimbitsa thupi komanso zakudya zolimbitsa thupi (BEP / BER model) [84].

Zambiri pazithunzizi zikufotokozedwa kwina kulikonse [84] Mwachidule, zinawonedwa kuti ngakhale makoswe aakazi amadya zakudya zosawerengeka, pamene chakudya chokoma chilipo (mwachitsanzo, makeke a Oreo) pafupifupi gawo limodzi mwa magawo atatu aliwonse amadya kcals chakudya chokoma kwambiri (BEPs) kuposa chakudya chopatsa thanzi chochepetsetsa kwambiri lachitatu (BERs) mu 4 yoyamba mpaka 24 nthawi ya chakudya chokoma, koposa momwe iwo amafunira chow [84]. Monga zina zotchulidwa apa, chakudya chokoma chimaperekedwa mwachindunji vs tsiku lililonse (2-3x pa sabata kwa 24 h). Chochititsa chidwi n'chakuti, phazi likadodometsa, magulu onse awiriwa amachepetsa kudya kwapadera koma kuchepa kwa BEP chifukwa cha kuchepa kwa chakudya chaching'ono pomwe BERs zimakhala chifukwa cha kuchepetsa chakudya chokoma [84]. Komanso pamikhalidwe yokhazikika, ma BEP ochulukirapo kuposa ma BER omwe amawoloka mopitilira M & Ms® omwe ali ndi BEPs nawonso amalekerera kwambiri kuposa ma BER kuti atenge M & Ms® [85]. Kudya zakudya za BEP sikumangotengera zakudya zina zakuthupi zokoma [85-87] komanso mafuta osakhala okoma (mwachitsanzo, Crisco®) ndi maswiti omwe si a mafuta (mwachitsanzo, Froot Loops®). Komanso, pamene mafupa a BEP ndi BER amaikidwa pa zakudya zachikhalidwe zomwe zimapangitsa kuti kunenepa kunenepa kwambiri kumene kumakhala mafuta okhaokha omwe amapezeka tsiku ndi tsiku [88], theka la BEPs ndi theka la BERs zimakhala zowonongeka pamene theka lina la BEPs ndi BERs amaletsa kunenepa kwambiri [84]. Izi zimakhala zothandiza kufufuza njira zomwe zimayambitsa matenda osiyanasiyana, mwachitsanzo, BED (yokonzedwanso ndi BEPs), osati kunenepa kwa BED (yosamalidwa ndi BERs zowonongeka), bulimia nervosa (yosankhidwa ndi BERs zosagonjetsedwa) komanso kulemera kwabwino kuti asadye anthu osagwirizana ndi thanzi labwino (zowonetsedwa ndi BERs zosagonjetsedwa).

Kuphatikizana ndi kusiyana kosiyana pakuyesa kudya chakudya chokoma, kusiyana komwe kumachitika pa kudya kudya kungabwererenso kuchokera ku zochitika zachilengedwe zachilengedwe. Ngakhale kuti HD + Stress yapamwamba imakhala yogwirizana kwambiri ndi kusintha kwa mayesero ndi ife ndi ena [33, 43, 53, 60-62, 89-92], sitinathe nthawi zonse kupeza chakudya chokwanira mu makoswe. Nthawi zina ena, omwe sankatha kupeza zotsatirapo ndi kupweteka kwa mapazi kapena ngati atatero, kudya mowa kwambiri kunali kovuta [91, 92]. Ngakhale zokhumudwitsa, vutoli limapereka mpata wokwanira wofufuzira zinthu zomwe zakhala zikuchitika kale. Chochititsa chidwi, Hancock et al. mwapeza, pogwiritsa ntchito HD + Stress model, izo okha makoswe amaloledwa kubereka ndi kudzikongoletsa kwa amayi monga ziphuphu pambuyo pake zitathamangitsidwa pambuyo pa HD ndi nkhawa [92]. Izi zimangochitika panthawi yaunyamata osati patapita zaka zambiri koma zimagwirizana ndi zaka zaumunthu zomwe zimayambitsa matenda ozunguza bongo [8]. Mofananamo, ziphuphu zomwe zimaphatikizapo kupatukana kwa amayi zimasonyeza chakudya chokwanira kwambiri pa nthawi yolepheretsa / kubwezeretsa msinkhu waunyamata. Makoswewa alinso ndi miyeso yapamwamba ya CORT motsutsana ndi makoti osakanikizika kwambiri oyambirira [93, 94]. Takhala tikudziŵa kuti malonda ogulitsa malonda, ngakhale m'makampani ogulitsa, sangathe kulamulira kusiyana kwa ma pups omwe amathandizidwa ndi amayi kapena zinthu zina. Ngakhalenso zovuta za kutumiza zingakhale ndi zotsatira zosiyana zotsalira zinyama. Izi ndizimene zakhala zikudziwika kuti zimakhudza zotsatira zazinthu zowonongeka zowonongeka [95-100]. Poganizira izi, sitingathe kuwonetsa kuti zochitika zakale zoyambirira zimatha kuyendetsa kusiyana kwa chakudya chokoma mu BEP / BER chitsanzo. Mwachidule, zopanikizika zoyambirira za moyo komanso mwinamwake kusiyana kulikonse kwa zakudya zomwe zimachokera kwa zovutitsazi ziyenera kuganiziridwa pogwiritsa ntchito mitundu yambiri ya kudya. Izi ndi zogwirizana ndi mgwirizano wamphamvu pakati pa ubongo pakati pa ubwana ndi mavuto oyambirira a moyo pa kudya chakudya mwa anthu [101-104].

Kupeza zakudya zosavuta kwapadera kumabweretsa zakudya zodyera

Chitsanzo chochepa choyendera chafotokozedwa mwatsatanetsatane kwinakwake [105]. Mosiyana ndi mafilimu a HD + ndi shuga odyera okhudzana ndi shuga omwe atchulidwa pamwambapa, chitsanzo chochepa choyendera sichigwiritsa ntchito chakudya cham'mbuyomu kapena chamakono chamakono kuti chidyetsedwe chodyera. Makoswe mu chitsanzo ichi palibe chakudya chosowa, chifukwa iwo ali ndi mwayi wopita ku chow ndi madzi nthawi zonse. Izi zapangitsa kuti aphunzire za kugwiritsiridwa ntchito mowa mwauchidakwa omwe sali osiyana ndi kusintha kwa neuronal komwe kungayambitsidwe ndi kugwiritsidwa ntchito kwa kusowa chakudya. Pofuna kuti anthu azidya zakudya zolimbitsa thupi, makoswe amapatsidwa sporadic (nthawi zambiri 3 nthawi pa sabata), nthawi yochepa (makamaka 1-2 h) kupeza chakudya chokoma, kuphatikizapo chow. Chitsanzo chochepa chowonekera chikuyenera kudya pamene kulibe njala, monga momwe BED [8, 106], komanso "zakudya zoletsedwa" zomwe anthu amadya kuti zakudya zomwe anthu amalephera kuzipeza ndi zakudya zomwe amadya [55, 56].

Magulu awiri a makoswe amagwiritsidwa ntchito motere, omwe ali ndifupikitsa, osachepera nthawi yopezeka chakudya chokoma tsiku ndi tsiku (gulu loyendetsa tsiku ndi tsiku), ndi omwe ali ndi nthawi yochepa yopeza chakudya chokoma nthawi zingapo (kawirikawiri Masiku a 3) pa sabata (gulu lofikira mobwerezabwereza). Chakudya chokoma kwambiri ndi mbale yowonongeka ya masamba, yomwe ndi hydrogenated mafuta olimba omwe amagwiritsidwa ntchito muzophika. Mukamafupikitsa maola a 1-2 tsiku lililonse, kusuta sikusintha kwambiri nthawi ndi zofunikira nthawi zambiri pozungulira 2 g (~18 kcal). Komabe, pamene kufupikitsa kumaperekedwa mobwerezabwereza, kuyamwa panthawi yochepa yofikira kumawonjezeka patapita milungu ingapo mpaka ~4-6 g (~36-54 kcal), ndipo imakhala yaikulu kwambiri kuposa makoswe okhala nawo tsiku ndi tsiku. Kumwa mowa kumagwiritsidwa ntchito moyenera mu chitsanzo ichi pamene kudya chakudya chokoma mu gulu lofikira pang'ono kumaposa kuposa gulu lofikira tsiku lililonse. Inde, patangotha ​​masabata a 4, gululi limadya chakudya chochuluka kapena chokoma kwambiri mu 1-2 h monga makoswe omwe amatha kupeza chakudya chokoma mu 24 h [107, 108]. Kuwonjezeka kwa chakudya chokoma chokwanira kumachitika m'gulu lachilendo ngakhale kuti nthawi zonse amakhala ndi chow; Chakudya chokoma chokha ndichokhazikika. Ng'ombe zomwe zili ndi nthawi yochepa yopeza chakudya chokoma, zimaphatikizapo kuti zikhale zovuta kuti chakudya chikhale chokoma, komanso kuti adziŵe za nthawi yochepa yomwe chakudya chokoma chiripo. Gulu la tsiku ndi tsiku limaganiziridwa kuti ndi "labwino," lomwe limayerekezeredwa ndi gulu lachilendo. Chodabwitsachi chafotokozedwa mwa amuna ndi akazi, zovuta zosiyanasiyana, komanso m'magulu angapo a zaka [107, 109, 110].

Ngakhale kuti kafupikitsidwe kawirikawiri amagwiritsidwa ntchito mu chitsanzochi, chakudya china chokoma chinayesedwa kuphatikizapo mankhwala a sucrose, mafuta osiyanasiyana omwe amaperekedwa monga emulsions olimbitsa thupi, zakudya zapamwamba kwambiri, ndi mafuta / sucrose mixtures [111-118]. Kufupikitsa kumagwira ntchito monga chakudya chokoma cha maphunzirowa, monga makoswe amachidya mosavuta [119] ndipo kusiyana pakati pa magulu kungayesedwe. Kuonjezera apo, ngakhale kuyambira kumayandikira padenga la mphamvu ya m'mimba ya makoswe (monga momwe anawerengera molingana ndi Bull ndi Pitts [120]) samapeza kwenikweni mimba yodzaza. Izi zimathandiza kuti azindikire zochepetsetsa komanso zokopa zogwiritsira ntchito mankhwala opangira mankhwala (mwachitsanzo, [121]).

Ndikofunika kugwiritsira ntchito chakudya chokoma mwachitsanzo chomwe chimagwiritsidwa ntchito mosavuta, koma izi sizingalimbikitse zochitika zazikuluzikulu kuti kusiyana kwa gulu sikudziwika. Ngati magulu onse a tsiku ndi tsiku amatha kudya zambiri, ndiye kuti kudya mowa mwauchidakwa sikungathe kusiyanitsa ndi zomwe zimapangidwira ndi chakudya chokoma, monga momwe tafotokozera m'maphunziro ena. Mwachitsanzo, makoswe amadya kwambiri (5-9 g) ya emulsions olimba kwambiri panthawi yochepa yopeza mu phunziro limodzi, ndipo zozizwitsa sizinali zosiyana pakati pa masiku onse ndi magulu ochepa [116]. Kusiyana kwa kusiyana pakati pa magulu a tsiku ndi tsiku ndi otha msinkhu kumatchulidwanso pamene chow chochuluka, mafuta a shuga / mafuta, ndi zowonjezera shuga zakhala zikugwiritsidwa ntchito ngati chakudya chokoma [111-115, 117, 118]. Chochititsa chidwi ndi chakuti kusiyana pakati pa makhalidwe ndi ma pharmacy pakati pa magulu opatsirana ndi osapatsirana tsiku ndi tsiku awonetsedwa, ngakhale pamene kudya panthawi yopereŵera sikunali kusiyana pakati pa magulu (mwachitsanzo [115, 116, 121, 122]). Komabe, ngakhale m'mayesero amenewa, zakudyazo zinali zazikulu. Ngati zimakhala zochepa-zochepa (zomveka) panthawi yoyamba ya 5 yochepetsa kufikitsa (makoswe amaloledwa kudyetsa 2 g), ndiye kuti kubwerera kumbuyo kumakhala kuchepetsedwa pamene kudya sikunamveka [108]. Choncho, kungodziwa chakudya chokoma, ndi kuloledwa kuyesa, sikokwanira; makoswe ayenera kuloledwa kuti 'adye' pamene adayambitsa chakudya chokoma kuti adziwe bwinobwino.

Makoswe okhala ndifupipafupi chakudya chokoma sapeza phindu, ndipo samadziunjikira mafuta ochuluka kwambiri, kusiyana ndi chow controls [107, 109]. Izi ndi chifukwa cha kuchepetsa kudya kwa chow komwe kumachitika. Zakudya zam'madzi zowonjezera kapena zowonjezera, zomwe zimakhala ndi mphamvu za tsiku ndi tsiku zimayamba kumakhala ndi makoswe chifukwa chodya chakudya chokoma chifukwa chakuti amadya chakudya chamasiku odya chakudya chokoma, komanso ngati chakudya sichingaperekedwe [107, 109, 112-115, 123]. Zotsatira zake zimakhala kuti kuchuluka kwa mphamvu zopatsa mphamvu (chow + kuchepetsedwa) ndi kulemera kwa thupi sizasiyana pakati pa makoswe otha msinkhu komanso maulamuliro a chow (mwachitsanzo [107, 109, 112, 113, 115]. Popeza kuti makoswe oledzeretsa amadya masiku ambiri, ndipo mosapitirira nthawi masiku osaphatikizapo, amaphunzira pofuna kudziwa ngati kumwa mowa kumayambitsa chifukwa chodzipangira mphamvu zowonjezera mphamvu zomwe zimachitika masiku ambuyomu. Izi sizikuwoneka ngati zili choncho; Kuledzera kukupitirizabe, ngakhale pamene kusamvetsetsa sikukuchitika tsiku lapitalo [124]. Kukonzekera kwa mphamvu yowonjezera mphamvu ndi kulemera kwa thupi kumagwiridwe ndi zofanana ndi zaumunthu monga bulimia nervosa momwe kumwedzeretsa kumachitika, koma kulemera kwa thupi kumakhalabe kosiyana chifukwa cha khalidwe lopeputsa ngati kusokoneza [8]. Zoonadi, kulephera kulemera kwa thupi ndi chinthu chodziwika bwino cha zitsanzo zomwe zafotokozedwa muzokambirana izi ndipo zimakhala za kudya kwa anthu; Pafupifupi 35% ya anthu omwe amadya ndi BMI ≥30 [5].

Kuphatikiza pa kudya mofupikitsa panthawi yopereŵera yochepa, makoswe oledzeretsa amakhalanso ovuta pofupikitsa mu magawo opitilira. Kukula kwa chiŵerengero chapakati pafupipafupi kumawonjezeka pakapita nthawi mu makoswe okhala ndifupipafupi kuti afupikitse [125], ndipo ndi yaikulu kwambiri kuposa ya makoswe a tsiku ndi tsiku [122]. Kuchuluka kwa chiwerengero cha kudya kwa sucrose pambuyo pa nthawi ya chakudya chosowa chakudya chinakula kwambiri mpaka makoswe okhala ndifupipafupi kuti azifupikitsa masamba ndi makoswe ndi kupeza tsiku lililonse [115]. Kuyanjana kwa chiŵerengero chofulumira kumaonedwa kuti ndi khalidwe lolimbikitsa [126] kutanthauza kuti oyendetsa zokhudzana ndi mphoto angagwirizane mosiyana ndi makoswe okhala ndi zozizwitsa ndi zosavuta tsiku ndi tsiku za chakudya chokoma.

Kodi ndi zotani zokhudzana ndi zakudya zopatsa thanzi zomwe zingachititse kusintha kotereku? Mwachiwonekere, makoswe amaphunzira kumwa mowa mwauchidakwa, koma ma neurocircuitry omwe akuphatikizidwa mu njira yophunzirirayo ayamba kudziwika. Chotheka ndi chakuti njira ina yopezera mphamvu yopezera chakudya ikhoza kuchitika. Makoswe mu chizoloŵezi cha shuga ndi HD + Opanikizika amaphunzira kudya chakudya chokoma pamene chakudya chimachotsedwa. Choncho, gawo limodzi la zomwe zimayendetsa gwiritsirani ntchito mowa mwachitsulo muzojambulazo ndizourojekiti zowonjezera zomwe zimayenera kuyanjana ndi chiyanjano pakati pa chilengedwe ndi chakudya chokoma pamene ali ndi mphamvu zowononga mphamvu, monga momwe Holland ndi anzake amagwiritsira ntchito [127]. Dongosolo laposachedwapa kuchokera ku lab lab Boggiano likuwonetsa kuti kuphunzira koteroko kungachitenso ngakhale kulibe chakudya chokwanira [63]. Choncho, nkotheka kuti kutengeka kochokera ku chakudya kumagwiritsidwa ntchito mwachitsanzo, ngakhale kuti makoswe alibe chakudya.

Ngakhale kutengeka koyambitsa kudya kungakhale kofala kwa onse atatu, ndizotheka kuti njira zosiyanasiyana zimakhudzidwanso. Mtengo wa shuga woterewu umapatsa shuga tsiku ndi tsiku kwa makoswe omwe amalephera kudya maola angapo kumdima. Choncho, kufotokoza kwa shuga n'kosayembekezeka kwambiri muchitsanzo chimenecho. Mosiyana ndi zimenezo, kuwonetsa chakudya chokoma ndichabechabe, ndipo sichidziŵika bwino, mu mafilimu a HD + Stress ndi Limited Access. Timakonza kuti chakudya chosayembekezereka chodyetsa chimapangitsa kuti munthu azidya mowa. Kafukufuku waumunthu amachirikiza lingaliro ili. Mapiko sangapangidwe nthawi zonse [8] komanso kumwa mowa mwauchidakwa kumasiyana kwambiri kwa munthu aliyense [128]. Kuonjezerapo, malo omwe amalimbikitsa zakudya zosadalirika zikuwoneka kuti akulimbikitsanso kudya. Mwachitsanzo, atsikana achikulire nthawi zambiri amadya chakudya chamadzulo pamodzi ndi abambo, mwayi wokwera mowa ndi wotsika kuposa pamene amayi achichepere samadya chakudya chamadzulo ndi banja [129]. Njira imodzi yokhala ndi chithandizo chochiritsira imapangitsa kuti anthu asadye zakudya zokhazokha komanso kuti azidya zakudya zokhazikika poyesa kudya nthawi zonse monga gawo la njira ya mankhwala [79].

Mu njira yoperewera yofikira, kudya kwambiri kumakhala ndi makoswe osakudya omwe amangotenga chakudya choledzeretsa masiku atatu pa sabata, mwachitsanzo, mwachisawawa. Ambiri mwa maphunzirowa apereka chakudya chodyera pa Mon, Weds, ndi Fri sabata iliyonse. Kotero, nthawizina pali tsiku limodzi lokha pakati pa mabingeni ndipo nthawizina awiri. Ndondomekoyi yowonjezereka pamtundu wina wosatsimikizika pokhudzana ndi mwayi wotsalira. Timayesetsanso ndondomeko zosawerengeka zofanana ndi zotsatira zofanana [36]. Kuwonjezera pamenepo, makoswe okhala ndi chakudya chokoma mobwerezabwereza amakhala mu chipinda chomwecho monga makoswe omwe amapezeka tsiku ndi tsiku. Choncho, makoswewa amadziwika kuti ali ndi chakudya chokoma tsiku ndi tsiku, koma amangodya chakudya chokoma mobwerezabwereza. Chotsatira chake, mayanjano odyera-chakudya amathandizidwanso ndi kusatsimikizika. Fiorillo et al. [130] adalemba moto wosiyana wa DA neurons m'dera la ventral tegmental (VTA) monga ntchito yosatsimikizika mu ndondomeko yomwe pulojekitiyi inaneneratu kuti kubweretsa chakudya cha madzi. Choncho, dopaminergic kuzindikiritsa malo a VTA (NAC, prefrontal cortex) ingakhale yosiyana ndi makoswe omwe amadziwika bwino (osatsimikiziridwa / osadziwika) ndi makoswe okhala ndi chakudya chokoma tsiku ndi tsiku (zina / zodziwika). Zoonadi, deta yamagetsi yomwe imagwiritsidwa ntchito ndi Limited Access chitsanzo ikugwirizana ndi izi (onani m'munsimu).

Dopamine

Kuphatikizidwa kwa DA ndi maulendo ake obwezeretsa m'mabwinja kwafotokozedwa kwina [131, 132], ndipo ntchito ya Bart Hoebel yakhudzidwa kwambiri pa zofufuzazi. Mankhwala osokoneza bongo angasinthe DA receptors ndi DA kumasulidwa m'mapiri a mesolimbic a ubongo [133, 134]. Kusintha kotereku kunawonetsedwa pogwiritsira ntchito mankhwala osokoneza shuga (onani [19, 21] kuti awonenso). Mwachindunji, kujambula kumawulula kuwonjezeka kwa D1 receptor kumangiriza mu NAc ndi kuchepa kwa D2 kulandira cholowa mu striatum poyerekeza ndi makoswe odyetsedwa [76]. Ena adanena kuti kuchepa kwa D2 kulandira mankhwala mu NAC ya makoswe ndi mwayi wopita ku sucrose ndi chow poyerekeza ndi makoswe odyera chow chokha [135]. Makoswe okhala ndi shuga komanso chow kupeza amachepetsanso D2 receptor mRNA mu NAC, ndipo anawonjezera mzere wa D3 receptor mRNA ndi caudate-putamen poyerekeza ndi maulamuliro odyetsa [78]. Komabe, chimodzi mwa zofanana kwambiri pakati pa shuga ndi kumamwa mankhwala osokoneza bongo ndi zotsatira za DA excellarlar. Kuwonjezeka kambiri mobwerezabwereza DA m'kati mwa NAc shell ndi zotsatira za mankhwala osokoneza bongo [136], komabe nthawi zambiri panthawi ya kudyetsa, mayankho a DA amatuluka pambuyo pobwereza chakudya mobwerezabwereza pamene icho chimasokonekera [137]. Pamene makoswe akudya shuga, yankho la DA likufanana ndi kumwa mankhwala osokoneza bongo kusiyana ndi chakudya, ndipo DA atamasulidwa panthawi iliyonse yodyera [77]. Makoswe oletsa kudya shuga kapena chow ad libitum, makoswe okhala ndi kamba kochepa chabe, kapena makoswe omwe amakwanira shuga kawiri kokha, kumayankha yankho la DA lopanda pake lomwe ndilo chakudya chomwe chimataya zachilendo zake. Choncho, kudya kwambiri shuga kumayambitsa matenda a shuga omwe ndi osiyana kwambiri ndi omwe amagwiritsa ntchito shuga popanda kudya, ngakhale kuti shuga wamba umakhala wofananamo muzinthu zonsezi. Zotsatira izi zimathandizidwa ndi zofufuza pogwiritsira ntchito mitundu ina ya shuga kudya kwambiri komwe kusintha kwawonjezeka kwa chiwerengero cha DA ndi woyendetsa DA akudziwika [138, 139].

Muzitsulo zochepa zowonjezereka, mankhwala opangira mankhwala a D1 ndi D2 receptors ayesedwa. Utsogoleri wazengereza wa wotsutsa wa D1 SCH23390 kudya kochepa kwa mafuta ndi shuga m'kudyera ndi makoswe, koma zotsatirazi nthawi zambiri zimaperekedwanso ndi kuchepetsa chakudya cha chow [121]. Choncho, zotsatira za D1 blockade zikhoza kukhala chifukwa cha kuponderezedwa kwathunthu kwa khalidwe. Utsogoleri wa pulogalamu ya D2-wotsutsana ndi raclopride, kumbali inayo, anali ndi zotsatira zomwe sizinafotokozedwe ndi chizoloŵezi chokhalitsa khalidwe. Raclopride amachepetsetsa shuga njira zothetsera shuga pa makoswe omwe amatha kupeza tsiku ndi tsiku kapena kupezeka mosavuta, koma amasiyana chifukwa chodya zakudya zonenepa. Mwachindunji, kudyetsa zakudya zonenepa kwambiri kunkachepetsedwa ndi raclopride pa mlingo waukulu wa makoswe ndi zovuta tsiku lililonse koma sizinasokonezedwe kapena kuwonjezeka ndi raclopride pa mlingo wochepa mu makoswe okhala ndi mpata wochepa wopeza [121]. Zotsatira izi zimapangitsa kuti D2 receptors muzogwiritsa ntchito zakudya zamtundu, koma zimasonyezanso kusiyana kwa D2 kuzindikiritsa mu makoswe ndi mazenera. Popeza kuti mlingo wa m'munsi umakhala ndi makoswe ochepa kwambiri komanso amadzipiritsi ochepa omwe amawathandiza kuchepetsa, zotsatirazi zimaperekanso zizindikiro zotsutsana ndi D2 musanayambe kusindikizidwa. Zotsatirazi zikugwirizana ndi mauthenga a anthu ndi makoswe omwe amachititsa kusintha kwa DA kugwiritsira ntchito zakudya za mafuta [3] ndi kudya mowa kwambiri [15, 131].

Kuwonjezera pa NAC, VTA dopamine neurons imagwira ntchito kumadera a prefreal cortex omwe amagwira ntchito kupanga zisankho ndi ntchito yogwira ntchito (anterior cingulate), komanso kuwonetsetsa (kapenanso kwa Fr2; [140]; onani [141] kuti awonenso). Kafukufuku waumunthu amaonetsa kuti kugwirizanitsa kwa anterior kumaganiziridwa mwa anthu omwe amamwa mowa [142-146], ndikuphatikizidwa kwa zigawo zam'mlengalenga zam'mimba pofunafuna [147]. Choncho, posachedwapa maphunziro ayambitsidwa pogwiritsira ntchito Limited Access chitsanzo chomwe kutsutsidwa kwachindunji kwa otsutsana ndi antchito a DA kwaperekedwa m'maderawa. Zotsatira, pakalipano, zimagwirizana ndi zotsatira zomwe zimapezeka ndi jakisoni zapachiŵeni, mwachitsanzo, mlingo wochepa wa wotsutsana ndi D2 oticlopride wochulukirapo mafuta ambiri mu makoswe odyera koma osati olamulira [148]. Kuphatikizidwa pamodzi, zotsatirazi zikuwonetsa kuti zochepa zomwe D2 amachita m'madera a cortical sichimayambitsa kubwereza, koma zimatha kuonjezera kumangidya. Mwachidule, zotsatira zimasonyeza kuti kudzimana ndi vutoli kungasokoneze chiwonetsero cha DA, zomwe zimapangitsa kuti zikhale zovuta kuimitsa kamodzi kokha.

Opioid Receptors

Kuphatikiza pa zotsatira za DA, machitidwe a opioid amakhudzidwanso ndi kumwa mowa mwa njira zomwe zimagwirizana ndi zotsatira za mankhwala osokoneza bongo. Dongosolo lochokera ku shuga lachizolowezi cha shuga lawonetsa kuti kusakaniza shuga kumachepetsa enkephalin mRNA mu nucleus accumbens [78], komanso mu-opioid receptor kumanga imakula kwambiri mu nkhono ya NAC, yolemba, hippocampus ndi locus coeruleus, poyerekeza ndi machitidwe odyetsa [76]. Komanso, kuti makoswe ophika shuga amadziwa zotsatira za mdani wa opioid naloxone, zomwe zingapangitse zizindikiro za kuchotsa [22], amasonyeza kuti kugwiritsidwa ntchito mobwerezabwereza kwa shuga wambiri kungasinthe machitidwe a ubongo opioid.

Zotsatira za mafilimu a HD + Opanikizika ndi Operewera Ochepa Amathandizanso kuti opioid azikhala ndi makhalidwe odyera. Kugonjetsa kwa HD + kumabweretsa nkhawa kumathetsa ndi nayxone, wotsutsana wa kappa / mu-receptor. Ngakhale kuti ndizochita mwachidule, palibe zakudya zowonongeka pa 24 hrs; Choncho, kufotokozera opioid-receptor kungakhale kofunikira kuti kudya chakudya chodyera kuti chichitike [89]. Njira imodzi imene HD imawonekera kuti ubongo umapangidwanso ndi kuyambitsa opioid-receptors [149]. Kuchepetsa matendawa kungakhalepo chifukwa cha kuchepa kwa opioid receptors chifukwa makoswe odyera amasonyeza kuti akutha kusokoneza chiopsezo cha mu / kappa-receptor blockade ndi naloxone [89]. Receptor-downregulation idzapereka blockade yokwanira kwambiri ya bilexone monga momwe zimachitikira opiate toxic [150-152]. Mogwirizana ndi kukhudzidwa kwa opioid-receptor, opioid-receptor agonist butorphanol imakwaniritsa hyperphagia yochuluka mu makoswe odyera okhudzana ndi magulu olamulira ngakhale atakhala kale owonjezera kudya [89]. Chifukwa cha kuwonjezeka kwa DA kumasulidwa ndi opioid-receptors mu mesolimbic neurons [153] komanso maudindo awo pofuna ndi kukonda [132] motero, n'zosadabwitsa kuti kusintha kwa HD-kusintha kwa opioid-receptors kumathandizira kudya. Chofunika kwambiri, zomwe apezazi zikuwonjezera mapepala a apainiya a Hoebel pa mgwirizano wosiyana pakati pa kudya chakudya ndi mphotho ndi chenjezo kuti ngakhale kusadyetsa chakudya cham'mbuyo chisanapangitse kusintha kosatha kumalo ozungulira mphoto.

Ngakhale HD ingachititse kuti ubongo ukhale wobwezeretsa pogwiritsa ntchito opioid receptors, HD imakhala yosafunika kuti chitetezo chiti chichitike. Mu Limited Access chitsanzo, wotsutsa opioid naltrexone kuchepetsa kudya kwa 100% mafuta (kufupikitsa) olimbitsa thupi, emulsions olimba opangidwa ndi zofupikitsa zochepa (32%, 56%), ndi ma mix fat sucrose pamene mazira a sucrose anali otsika mu makoswe kuchepa kwa tsiku ndi tsiku komanso makoswe okhala ndi zochepa zokhala ndi chakudya chokoma [116, 121]. Choncho, naltrexone inali yothandiza kuchepetsa kudya zakudya zonenepa mosasamala kanthu koyendera. Mosiyana ndi zimenezi, makoswe omwe amamwa sucrose amakhala osiyana kwambiri ndi zotsatira za naltrexone. Mwachindunji, naltrexone kudya kochepa kwa 3.2% ndi 10% kuyamwa njira mu makoswe okhala ndi zochepa zofikira, koma osati mu makoswe okhala ndi mwayi wopeza tsiku lililonse [118]. Izi zimagwirizana ndi mauthenga ena omwe amasonyeza kuti ophioid receptors amagwiritsidwa ntchito mowa mwauchidakwa m'makoswe [76, 78, 89] komanso anthu [154]. Choncho, pamene kutsekedwa kwa opioid receptors kumachepetsa kuchepetsa kugwiritsidwa ntchito kwa mafuta ochepa pansi pa zosakanizidwa komanso zolimbitsa thupi, opioids angakhale ndi gawo lapadera mukumwa mowa mwa zakudya zomwe zili ndi shuga.

Kuphatikizidwa pamodzi, zotsatirazi zapitazo zimasonyeza kuti kudya mowa kumakhala kosakanikirana ndi opioid-receptor supersensitivity (mwina chifukwa cha kubwereza kwa opioid kobwerezabwereza chifukwa cha zakudya zopatsa thanzi, zomwe zimatulutsa opioid yodalirika [155-160]. Ichi ndi chofanana ndi opiate oledzera kumene opiates, osati chakudya chokoma, amasefukira mu ubongo ndi zokopa zowopsa za opioid zomwe zimapangitsa kuti chiwerengero cha receptor downregulation [150-152]. N'zochititsa chidwi kuti anthu ambiri amadziletsa kuti asatenge shuga mwina m'malo mwa opiates pa ubongo. Kuthamanga kwawo kwa shuga ndi kotere kuti kungachititse kuti mukhale wonenepa kwambiri komanso shuga lopweteka [161-163]. Choncho, kutsata mankhwala osokoneza bongo omwe amagwiritsidwa ntchito pa opiate mowa umathandiza kwambiri pakudya zakudya zolimbitsa thupi (mwachitsanzo, ndi buprenorphin [164], buprenorphin / naloxone [165] D, phenylalanine / L-amino-acids / naloxone [163]). Kuzindikiritsa mitundu yambiri yomwe imakhalapo pakati pa opiate ndi kumwa mowa (osati kunenepa kwambiri) kungathandizenso kupita patsogolo kwa chithandizo. Thandizo la lingaliro limeneli laperekedwa ndi maphunziro a zachipatala omwe amachepetsanso kuchepa kwa insula mu-receptor mu bulimia nervosa odwala [166] komanso mafupipafupi ambiri a mu-receptor A118G yosiyana (yolembedwa mu mphoto ndi chizoloŵezi) pakati pa BED kwambiri ndi onse omwe sali a BED maphunzirowa [17].

Acetylcholine (ACh)

Kuwonjezeka kwa ACh ya extracellular kwagwirizanitsidwa ndi kuyamba kwachisomo [167]. Mu mtundu wa chizoloŵezi cha shuga, makoswe obweretsa shuga amayamba kuchedwa kuwonjezeka kwa ACh, yomwe ingakhale chifukwa chimodzi chomwe kukula kwa chakudya chowedzeretsa kumawonjezera nthawi [77]. Kuphatikizidwa ndi neurons cholinergic kumawonekeranso kukhala ndi mbali m'makhalidwe osadziwika. Zizindikiro zokhudzana ndi kuchotsa mankhwala nthawi zambiri zimatsatizana ndi kusintha kwa DA / ACh mu NAC; DA imachepetsa pamene ACh ikuwonjezeka. Kusalinganika kumeneku kwawonetsedwa panthawi yochotsera mankhwala osokoneza bongo angapo, kuphatikizapo morphine, chikonga ndi mowa [168-170]. Makoswe omwe amawotcha shuga amasonyezanso kusamvetsetsana kwa matendawa mu DA / ACh panthawi yosiya. Zotsatira izi zimachitika pamene makoswe amaperekedwa ndixone kuti athetseretu opiate-ngati kuchotsa [22] ndipo pambuyo pa 36 h ya chakudya chosowa [19].

Serotonin

Hoebel ndi anzake ankachita masewera olimbitsa thupi amphaka omwe anathandiza kukhazikitsa maziko a serotonin kuti azitha kudya zakudya zopanda malire [171, 172]. Mu HD + Stress model fluoxetine, serotonin reuptake inhibitor (SSRI) imene imavomerezedwa kuti imuchulukitse bulimia, kuchepa kwa mafilimu a HD + kwachangu mofanana ndi kudya zakudya za HD + Magulu ovutika maganizo pa 2 h. Pa 4 h chithandizo chamankhwala, fluoxetine anali adakali ndi luso lodyera makoswe, koma osati mu HD + ndi Stress controls [53]. Choncho, HD ingapangitse kusintha kosatha pa malamulo osokoneza bongo, ntchito yaikulu ya serotonin, ngakhale kuti thupi ndi lolemera. Kupsinjika maganizo kumadziwika kuti kumawonjezera masankhulidwe a syaptic serotonin mwapang'onopang'ono zomwe zingathe kufotokozera mphamvu ya fluoetine yaitali yomwe imapezeka mu HD + Makoswe opsinjika maganizo [53]. Mosiyana ndi zimenezi, fluoxetine sichitha kuthana ndi kuchepetsa kudya zakudya zamagulu ngati makoswe ali ndi mphamvu zowonongeka, mwinamwake chifukwa cha syaptic serotonin yokwanira ya SSRI [173]. Kuphatikizanso apo, fluoxetine inachititsa kuti tizilombo toyambitsa matenda tizilombo toyambitsa matenda tizilombo toyambitsa matenda (24h) tipeze chakudya chokoma chogwirizana ndi makoswe omwe ali ndi HD omwe analibe chakudya chokoma kapena tsiku lililonse [54]. Choncho, ntchito ya chakudya chosakanikirana kuti iwonetsedwe ndi HD kuti iwononge ntchito ya serotonin sayenera kudedwa.

GABA ndi Glutamate Receptors

Msonkhanowu wa GABA-B wakhala watcheru muzaka 10 zapitazi chifukwa cha mphamvu za agonist kuchepetsa kudzipangira mankhwala osokoneza bongo m'maphunziro a zinyama, komanso chifukwa chothetsera vuto la mankhwala osokoneza bongo [174, 175]. Pogwiritsa ntchito njira yochepa yofikira, GABA-B agonist baclofen yachepetsa kuchepa, komanso mafuta olemera (56%) emulsions olimba, mu makoswe ndi awiri tsiku ndi tsiku komanso nthawi yochepa yopeza mankhwala omwe amachititsa kapena osakhudzidwa ndi chakudya cha chow [116, 121]. Mosiyana ndi zimenezi, baclofen sanakhale ndi zotsatira zowonjezera katatu njira zowonjezera (3.2%, 10%, 32%) mu makoswe okhala ndi zovuta zowonjezera kapena zosatheka tsiku lililonse [121]. Pamene mafuta ndi sucrose anali osakanikirana pamodzi ndi baclofen amachepetsa kudya ndi makoswe pogwiritsidwa ntchito mosasamala kapena tsiku ndi tsiku pamene asprose ndondomeko inali yochepa (3.2%, 10%) koma sizinathandize mu gulu lililonse pamene msinkhu wa sucrose unali waukulu (32%) [118]. Zotsatira zofanana zafotokozedwa ndi ena. Mwachitsanzo, baclofen sanachepetse chakudya chokoma chomwe chili ndi 40% mafuta ndi ~16% sucrose muchitsanzo cha mouse chodyera [112]. Pa ntchito yomwe inanenedwa ndi Hoebel ndi anzake, baclofen anachepetsanso masamba osakanikirana ndi makoswe omwe ali ndi 2-h tsiku lililonse, koma sanagwire ntchito yothetsera shuga [111]. Motero, kuchepetsa kuchepetsa zotsatira za baclofen mu makoswe kumawonekeratu kuti ndi zakudya zomwe zimakhala ndi mafuta ambiri, ndipo zimakhala zowonongeka chifukwa cha kuwonjezeka kwa shuga.

Palibe-zochepa, mayesero atsopano a zachipatala amasonyeza kuti baclofen angakhale othandizira pakuthandiza kudya mowa kwambiri [176, 177]. Mwachindunji, baclofen yachepetsetsa kukula kwa binge mu bolote lotseguka [176] komanso maphunziro olamuliridwa ndi placebo [177]. Mitundu ya chakudya chomwe chinkadya komanso zojambula bwino zamabwa sizinayesedwe pa mayesero. Komabe, chiwerengero cha makoswe chimasonyeza kuti baclofen ikhoza kukhala yothandiza kwambiri kwa anthu omwe amadya kwambiri chakudya chambiri chomwe sichikwera mu shuga.

Gwiritsani ntchito mankhwala opangira mankhwalawa amasonyeza kuti ntchito zowonongeka mu GABA-A ndi zakudya zopatsa thanzi zimatha kudya zakudya zolimbitsa thupi zopangidwa ndi HD ndi nkhawa. Pogwiritsa ntchito njira yawo yosinthika ya HD + HD, Cifani et al. anapeza kuti, pamene fluoxetine ndi sibutramine amalepheretsa kudya zakudya zamtundu wambiri, topiramate amayamba kuchepetsa kudya kwa HD + Gulu lopanikizika popanda kuthana ndi zakudya zowonongeka, Kupsinjika maganizo, komanso magulu a HD okha [60]. Olembawo akuganiza kuti zikhoza kukhala zotsutsana ndi zilakolako za topiramate zomwe zimalimbikitsidwa ndi kuyambitsidwa kwa GABA-A zofunira komanso kuletsedwa kwa ma receptors AMPA / kainate glutamate omwe amaletsa mwachangu kudya zakudya zolimbitsa thupi [60, 178]. Kulimbana ndi maonekedwe oopsa omwe amawoneka bwino, topiramate yakhala yothandiza kuchepetsa kupititsa patsogolo zakudya zamankhwala [179]. Komabe, zotsatira zake zimakhala zofunika kwambiri chifukwa zimagwira ntchito yodabwitsa kwambiri yokhudzana ndi ubongo. Kufufuzanso kwina pa udindo wa GABA ndi glutamate pa kudya moyenera kumayenera.

HPA axisiti

Kuwonjezera pa chikoka champhamvu chomwe HD imakhala nacho pakadyedwe kudya, umboni wamakono umasonyezanso kuti kudya mowa kwambiri kumachepetsa nkhawa zomwe zimapangitsa kuti zikhale zovuta kuthetsa khalidwe loledzera. Bart Hoebel adalosera kuti "kumasulidwa kwa DA kungawononge maulendo ku NAC ndi malo ena omwe akuyambitsa zokondweretsa ndi mayankho" ([57], pg. 182). Inde, nkhawa ndi CORT makamaka, zakhala zikuwonetseratu kuti DA idzamasulidwa ku NAC [58, 59]. Monga tanenera kale, miyeso ya CORT yowonjezera ndiyo makina odyera mavitamini mu HD + Stress model [41, 61]. Cifani et al., Anaona kuti zigawo za CORT zinasintha kwambiri pogwiritsa ntchito maonekedwe a HD + Stress model [60, 90]. Zakudya zopatsa thanzi zakhala zikuwonetsedwa kuti zowoneka bwino za hypothalamic-pituitary-adrenal (HPA) axis [114, 180, 181]. Mu mbewa, mphamvu zothetsera mphamvu zitha kuwonjezera mphamvu za opanikizika (zotsatiridwa ndi CORT yotulutsidwa) komanso zikhoza kuonjezera kudya zakudya zamtengo wapatali pothana ndi mavuto [182]. Chofunika kwambiri, CORT ikuwonjezerekanso panthawi ya kuchotsa zakudya zamatenda [2], chifukwa chosiya kumwa mankhwala osokoneza bongo [183]. Izi zingachititse kuti munthu asamadye chakudya chokoma ngati akuvutika maganizo, ndiye kuti ali ndi vuto lokhalitsa chakudya,180].

Kuti muyankhe izi, Cottone et al. anapeza kuti makoswe omwe ali ndi mwayi wopeza chakudya chokoma mtima amachititsa kuti zizindikiro zisawonongeke ngati chakudya chokoma sichipezeka, zizindikiro zomwe zimatsutsidwa ndi anti-corticotropin-release factor (CRF) -1-receptors [4]. Mchitidwe womwewo ukhoza kukhala ukuchitika m'mabvuto odya omwe amadziwika ndi kubwereka. Mu anthu olemera kwambiri omwe ali ndi ma cortisol a BED ali apamwamba kuposa anthu olemera kwambiri popanda BED [184, 185]; Mankhwala a cortisol a magazi poyankha nkhawa amasonyeza kuti kudya maswiti wambiri [186]; ndipo magulu a cortisol osakaniza amakhala ogwirizana kwambiri ndi kudya mowa kwambiri [187]. Kuwonjezera pa kuyambitsa mayankho a maganizo, CORT imakhudzidwanso ndi cholinga chofuna zinthu zopindulitsa [158, 188-190]. Choncho, chirichonse chomwe chingathe kumanga izi (mwachitsanzo, kusinthanitsa chakudya chokoma ndi mphotho yowonjezera komanso / kapena mankhwala okhudza HPA-activation) angakhale othandiza kwambiri pochiza mowa mwa kubwezeretsa kubwerera. Kafufuzidwe kafukufuku amafunika kudziwa ngati machitidwe oopsa a HMM osakanikizika kuti asokonezeke ndi omwe amakhalapo kale kuti ali ndi chiopsezo chodyera kudya monga momwe phunziro limodzi likuwonetsera kuti mwina [185].

Komabe chiwerengero cha CORT mu HD + Stress model komanso anthu omwe ali ndi BED chimasonyeza kuti kudya zakudya zolimbitsa thupi zomwe zimagwirizanitsidwa ndi nkhawa zimaphatikizapo kulephera kugwira ntchito mu HPA. Choncho, kuyang'ana mahomoni opanikizika angakhale othandiza pochiza kudya mowa kwambiri. Nociceptin / orphanin ndilo lingaliro losatha la nociceptin opioid-receptor (aka, OP4, ORL1). Kulimbana kwake ndi kupanikizika ndi kuda nkhawa, zomwe zimasinthidwa ndi CRF zatchula kuti wotsutsa CRF wothandiza [191]. Chochititsa chidwi ndi chakuti kuchepa kwapansi koma kosavuta kwambiri kumachepetsanso kuchepetsa kudya zakudya za HD + Magulu amphaka [192]. Ngakhale kuti zotsatira zake zinali "zochepa" ndi ofufuzawo, zimasonyeza kuti sitiyenera kunyalanyaza njira yopezera kudya ndi kudya mowa kwambiri, ngati atha kuchepetsa nkhawa. Choncho, kuchepetsa vutoli kungakhale kovuta. Mbali ina yokongola ya molekyulu iyi ndi yoti mosiyana ndi antagonists a CRF, zikhoza kukhala zovuta kuchiza popanda kulepheretsa a HPA axis [191].

Salidroside ndi glucoside ku Rhodiola rosea L. (aka, Golden Root, Roseroot), chomera chodziwika ku East Europe ndi Asia chifukwa cha 'adaptogenic'193, 194]. Mu HD + Stress model, mlingo wa mankhwalawa sunakhale ndi mphamvu pa chow kapena chakudya chopatsa thanzi chokhala ndi mphamvu zoyenera, Kupsinjika maganizo, kapena makoswe a HD okhaokha koma kuthetseratu kudya mowa kwambiri kudya chakudya chokoma mu HD + Stress makoswe. Komanso chifukwa chakuti sizinakhudzire kudya kwa makoswe osagwiritsidwa ntchito panthawi yomwe yanyamulidwa kapena chakudya chinachotsedwa [62] zotsatira zake sizingatheke chifukwa cha kuwonjezereka kwa chiwerengero cha njala (njala kapena kulumikizidwa) monga momwe zimakhalira ndi antotonergic agents [62]. Ngakhale kuti mankhwalawa amatha kuwonjezera monoamines komanso B-endorphin, mphamvu yake yotsutsa binge imayesedwa ndi kusokoneza maganizo [195] popeza kampaniyo inathetsanso kukwera kwa CORT kwa makoswe odyera [62]. Kutsutsana kwachindunji kwa obwebweta a CRF-1 kungakhalenso malonjezano omwe amapereka umboni wakuti amachepetsa kufunafuna zakudya zopatsa thanzi m'ma rats [190, 196].

• Mitundu itatu yokhala ndi makina oledzeretsa ndi zotsatira zawo za neuronal ndifotokozedwa
• Zotsatira zomwe zimagwirizanitsidwa ndi kuledzera ndizosiyana ndi zomwe sizinabwere.
• Kudya zakudya zolimbitsa thupi kumachitika popanda kutaya kwambiri.

Thandizo la maphunziro omwe tafotokozedwa pano operekedwa ndi MH67943 (RLC), MH60310 (RLC), Penn State Institute ya Shuga ndi Kutaya Kwambiri (RLC), National Eating Disorders Association (NMA) ndi DK079793 (NMA), DK066007 (MMB), P30DK056336 (MMB ) ndi NEDA Laureate Award (MMB).

Chodzikanira cha Wosindikiza: Imeneyi ndi fayilo ya PDF ya zolembedwa zosavomerezeka zomwe zavomerezedwa kuti zifalitsidwe. Monga ntchito kwa makasitomala athu ife tikupereka malemba oyambirira a zolembedwazo. Mipukutuyi idzayambanso kujambula, kufotokozera, ndi kubwereza umboni umene umapezekapo musanatulutsidwe mawonekedwe ake omalizira. Chonde dziwani kuti panthawi yopanga zolakwika zingapezeke zomwe zingakhudze zomwe zili, komanso zotsutsana ndi malamulo zomwe zimagwiritsidwa ntchito pa magaziniyo.