Uhlangothi olumnyama lokulutha kokudla (2011)

I-Physiol Behav. Umbhalo wesandla; kutholakala ku-PMC 2012 Jul 25.

Ishicilelwe efomini lokugcina ehleliwe njenge:

Physiol Behav. I-2011 Jul 25; I-104 (1): 149-156.

Ishicilelwe ku-intanethi i-2011 May 8. doi: 10.1016 / j.physbeh.2011.04.063

I-PMCID: PMC3304465

I-NIHMSID: I-NIHMS297622

Sarah L Parylak,^a,^b,^c UGeorge F Koob,^a,^c futhi U-Eric P Zorrilla^a,^b,^c,¹

abstract

Kumlutha wezidakamizwa, ukuguquka kusuka ekusetshenzisweni kwezidakamizwa okwejwayelekile kuya ekuxhumekeni kuye kwaxhunyaniswa ekuguqukeni kude nasekuqinisweni okuhle nasekuqiniseni okungekuhle. Okusho ukuthi, izidakamizwa ekugcineni zincike ekuvikeleni noma ekunciphiseni imibiko engemihle ebangelwa ngenye indlela ngokuziyeka (isb. Ukuhoxa) noma ezimweni ezingezinhle zemvelo (isib. Ukucindezela). Umsebenzi wakamuva uphakamise ukuthi lolu shintsho “olubi” nalo lubalulekile ekuthuthukiseni umlutha wokudla. Kuqala, ukusetshenziswa kokudla okuthandekayo kunokuqinisa okuqinisayo, imiphumela ethokozisayo nokuqiniswa okungekuhle, "okudumisayo" okungenza kube nokuphendula okuphelele kwento yomzimba ekucindezelweni. Ukudla okuphindwayo okuphindaphindekayo, okuqhubeka ngezikhathi ezithile kungakhulisa ukujikeleza kwengqondo futhi kunciphise izindlela zokubuyiselwa kobuchopho okuqhubeka njengokubandakanyeka okuqhubekayo okuphoqelekile ukuvikela amazwe angathandeki emizweni ngokuqiniswa okungekuhle. Ukuxineka, ukukhathazeka kanye nemizwa yokudangala kukhombisile ukuthokomala okuphezulu kanye namandla okuthi adale izindlela zokudla ezifana nokudla ebantwini. Izinhlobo zezilwane zibonisa ukuthi ukufinyelela okuphindaphindiwe, okuphakathi kokudla okudla okungahle kuholele ekubonakaleni okungokomzwelo nokwenqatshelwa kokuthile lapho ukudla kungasatholakali, ukubekezelela kanye nokucekelwa phansi komjikelezo womvuzo wobuchopho, ukufuna okuphoqayo kokudla okuthandekayo naphezu kwemiphumela emibi engase iphinde ibuye, -ukudla okudingayo ukuphendula ukukhathazeka okufana ne-anxiogenic. I-neurocircuitry ekhonjwe kuze kube manje ohlangothini "olumnyama" lokulutha kokudla zifana kahle nezihambisana nokuncika kwezidakamizwa notshwala. Ukubuyekezwa okukhona lapha kufingqa iqhaza likaBart Hoebel elisisekelo nelinamandla lokuqonda iqhaza lendawo “emnyama” ekuluthweni kokudla kanye nomsebenzi ohambelana nalawo amlandelayo.

Amagama angukhiye: Ukulutha kokudla okuthandekayo, ukuhoxisa noma ukungazinaki noma ukuncika, ukuthinta okubi noma ukukhathazeka noma ukudangala, ingcindezi, ukuphazamiseka kokudla noma i-bulimia, ushukela noma i-sucrose noma ushukela noma ushokoledi noma amafutha amaningi

1. Isingeniso

Ukulutha kwezidakamizwa kuyinkinga engapheli, ebuyela emuva enezigaba ezintathu ezihlukene: isigaba sokudakwa ngokweqile esiqhutshwa futhi esiboniswa yizici zomvuzo zomuthi, isigaba sokuhoxa esihambisana nesimo esibi ngokomzwelo njengoba izakhiwo zomuthi ovuza kakhulu ziphela, futhi ukukhathazeka isigaba sokulindela esandulela ukuvuselelwa kokudla izidakamizwa. UDkt. Bartley Hoebel uphakathi kwamaphayona okuqala kakhulu afaka lokho kudla ushukela, mhlawumbe nokunye ukudla okunomsoco, nakho kungalawulwa yilezi zigaba ezintathu zokulutha. Ubuholi bakhe abuzange bube nesandla nje kuphela ekuvaleni imikhakha yokuluthwa nokuzondla ngomsebenzi wakhe wokuhlola, kodwa futhi nasemizameni yakhe yokwandisa ukuqwashisa nokugunyaza lokho okwake kwaba yinto engathandeki futhi eyimpikiswano emphakathini wesayensi - ukuthi umuntu angaba "Umlutha wokudla." Manje, izingqungquthela zokuluthwa kokudla, ezifana neFood & Addiction Conference on Eating and Dependence isingathwe yiRudd Center for Food Policy and Obesity eYale, iseshini ethi “Addiction Food: Fact or Fiction” emhlanganweni we-2008 Experimental Biology eSan Diego, kanye ne-Obesity and Food Addiction Summit ka-2009, njalo kuhlanganisa ososayensi, odokotela, abenza izinqubomgomo zomphakathi, kanye nabameli bezempilo abavela ezindaweni ezahlukahlukene. Ngaphezu kwalokho, umsebenzi kaDkt Hoebel wokuqhaqhaqhaza usize ukugqugquzela ukwakhiwa kwezikhungo ezinikele ngokukhethekile ekuqhubekiseleni phambili ucwaningo lokuluthwa kokudla, kufaka phakathi iFood Addiction Institute kanye neRefined Food Addiction Research Foundation.

Njengoba abasebenzisi bezidakamizwa bethuthuka besuka ekusetshenzisweni nje kokuya ekuluthwaleni, izinto ezishukumisa ukusetshenziswa kwezidakamizwa ziqondiswa emzimbeni ukuze ziguquke ngokubaluleka. Ngenkathi ukusetshenziswa kokuqala kushukunyiswa yizakhiwo ezizuzisayo zomuthi, ukusetshenziswa komlutha kuyabekeka ukuze kugqugquzelwe amandla amancane ngokuqiniswa okuhle (isib. Ukuphakama okuphezulu), kepha kunalokho ngokuqiniswa okungekuhle: ukuvimbela noma ukukhulula isimo esingesihle sokomoya esivelayo ekuyekeni (isib. ukuhoxiswa kwezidakamizwa) noma ekuhlangenwe nakho okuphambene nemvelo (isib. ukucindezela) [1]. Ezingeni le-neurobiological, lokhu kugudluka kufana nokwehliswa phansi kwezinhlelo zemivuzo yobuchopho ezihlinzeka ngezimpendulo ezisebenzayo kulo muthi kanye nokukhulisa kanyekanye kwengcindezi yobuchopho noma izinhlelo ze- “antireward”. Kulolu hlaka, ukushintshela "ohlangothini olumnyama" lomlutha wokudla kungacaciswa ngokufanayo njengenguquko ebalulekile kwinqubo yokulutha. Njengoba abantu bethuthukela ekudleni okuphoqayo kokudla okuthandekayo, inani elifanele lokuvuza lezinto zokudla lingabamba ukubaluleka okuncane kokugqugquzela ukungena okungaphezulu kunokuvimbela noma ukunambitheka kwezindawo ezingezinhle (isib. Ukukhathazeka, ukudangala, ukungabekezeleleki, futhi mhlawumbe nezimpawu zokuhoxa). Uthole lapho ukudla okunjalo okuthandayo kungatholakali noma lapho izimo zimbi.

I-2. Ubufakazi “ohlangothini olumnyama” obuvela ezifundweni zabantu

Ukunquma ukuthi ngabe "uhlangothi olumnyama" olungumlutha lukugqugquzela ukudla okutholakalayo, iphuzu lokuqala eliwusizo ukukhomba inani labantu (imikhuba yabo yokudla) efana kakhulu nokuziphatha okuluthayo. Yize ukukhuluphala nokuziphatha okufana nokudla kungaba njengendikimba, "umlutha wokudla" cishe awunakuchaza wonke amacala okukhuluphala kwabantu, futhi abanye abantu abajwayelekile ngokweqile bangabandakanyeka kumaphethini wokudla angumlutha. Azikho izindlela zokuxilonga zokuvumelana "zokulutha kokudla" okwamanje ezikhona [2, 3]. Kodwa-ke, muva nje, i-Yale Food Addiction Scale (YFAS) yethulwe njengenkomba yokuziphatha okufana nokudla okulingisa izindlela zokuxilonga zokuncika kwento ku-DSM-IV-TR [4]. I-YFAS ilinganisa ukuthi (a) abantu abadla ngokweqile ukudla okuthile noma bezama kaninginingi ukunciphisa umkhawulo, (b) izindlela zabo zokudla ziphazamisa imisebenzi yezenhlalo nezobuchwepheshe, futhi (c) kuqhamuka nezimpawu zokuhoxa lapho kugwema ukudla okuthile. Ukusetshenziswa kokuqala kwalezi zindlela kusikisela ukuthi ukudla okuphoqayo, okungalawuleki kokudla okulindelwe okukulindelekile kumamephu wokuphazamiseka kokudla okungenamikhawulo kahle kakhulu kunqubo yamanje yokuxilongwa kokuthenjwa kwento. Ngakho-ke, izikolo ku-YFAS zibikezele ngokuziphatha kokudla okuthe xaxa nokudla okungokomzwelo [4] kepha akazange ahambisane nenkomba yomzimba (BMI) kwabesifazane ababambe iqhaza ocwaningweni lokugcinwa kwesisindo ababike ukuthi akukho nkinga yokudla [5]. Le miphumela isikisela ukuthi "uhlangothi olumnyama" lomlutha wokudla, njengoba lusetshenziswa yi-YFAS, lungafundiswa ngokuthe xaxa kubantu abanokudla okulingene kunabantu abakhethwe ngendlela engakhethwanga.

I-2.1 Psychiatric comorbidity ekudleni kokuzidla

Ngokuhambisana nendima engaba khona yokuthi kube “ohlangothini olumnyama” kumlutha wokudla, abadla ngokweqile banamazinga amaningi okuxilongwa kwezifo zengqondo kubandakanya nezimo zemizwa ezingezinhle ngokuqhathaniswa neningi labantu. Isibonelo, abantu abadala nentsha ene-bulimia amanosa noma inkinga yokudla kokudla ikhombisa ukwanda kwesifo esikhulu sokudangala, ukuphazamiseka kwengqondo okuguquguqukayo, ukuphazamiseka kokukhathazeka, notshwala noma izidakamizwa kunabantu abangenangxaki yokudla [6-8]. Amanani okucindezelwa okukhulu nawo ayaphakanyiswa kwabakhuluphele, kepha ukuzihlanganisa kokudla okudla ngamazinga okucindezelwa okuqhubekayo kuhlala kukuqhathanisa okunesisindo kwabantu abakhuluphele nabakhuluphele ngokweqile [9]. Izinga eliphakeme kakhulu lemibono yokuzibulala kwabadli bokulunywa lifakazela ubulukhuni bokuphazamiseka kwemizwelo kulesi sizwe. Ngaphezu kwesigamu seziqhwaga zentsha nengxenye eyodwa kwezintathu yalabo abanenkinga yokudla kokudla okubikiwe babika umbono wokuzibulala, kanti nokwesithathu kwemibiko yezibonelo zentsha ezazama ukuzibulala [6]. Ukuqondiswa kokudonswa kokudla phakathi kokudla okufufusayo nokudangala okukhulu akukasungulwa ngokuqinile futhi kungahle kuphindaphinde [10-12]. I-comorbidity enjalo yezengqondo ihlotshaniswa nemiphumela emibi yokwelashwa yesikhathi eside [13] imvamisa enkulu yokudla kokudla kakhulu [14]. Ngakolunye uhlangothi, ama-antidepressant amaningi, njengama-SSRIs noma ama-tricyclics, anganciphisa imvamisa nobukhali bezimpawu zokudla kokuzidla [15].

Izimo ezingokomzwelo ze-2.2 ezingezinhle zikhulisa ukudla okutholakalayo ezithandekayo kubantu abasengozini

Ukwanda nobukhulu bokudana nokukhathazeka kwabadli bokuzitika kubonisa ukuthi umbono wokuthi isimo esingesihle ngokomzwelo singakubangela ukubuyela ekuziphatheni okuthe xaxa. Ngempela, izici zokuzizwa ezingezinhle ezingokomzwelo zokudangala, ukuzithemba okuphansi, ne-neuroticism kuhlotshaniswa nokudla kokuzidla okulingene kwabesilisa nabesifazane [16]. Ngenkathi yezimo ezingezinhle zemizwelo nezimo, abantu abajwayelekile nabakhubazekile babika ukuthi badla ukudla okuncane kunangezikhathi zezimo nezimo ezakhayo. Ngokuphambene nalokhu, lokhu kungaphenduki okuphendula imibiko engemihle akubonwa kubantu abakhuluphele ngokweqile, ababika ukuthi badla kakhulu ngesikhathi sombuso ongemuhle kunamanye amaqembu [17]. Ngokuhambisana nendima yezindawo ezingezinhle zemizwelo ekushayweni kokuziphatha okulimazayo, izikolo zemizwa ezinobungqabavu ziphansi ngokushesha ngaphambi kokulunywa kunangezinsuku lapho kungenzeki khona ukulunywa kakhulu [18].

Okunye ukwakhiwa okufaka ingcindezi nemizwelo engemihle njengokuqala kokudla ngokweqile kungukuvimbela ekudleni. Imizamo yokulawula isisindo somzimba (isib. Ngokudla, ukuzivocavoca, izithasiselo zokudla, noma ama-laxatives) kuhlotshaniswa ngokumangazayo nokwanda kwesisindo kwentsha yabesifazane [19]; Ukuvinjelwa kokudla ngokufanayo kuhlotshaniswa nokuzuza kwesisindo isikhathi eside kubantu abadala besifazane [20]. Ukuchazwa okungenzeka kwalokhu kungqubuzana okubonakalayo ukutholakala okungaguquki okuvinjelwe abadli bokudla ngokweqile ekuphenduleni ezimweni ezahlukahlukene ezicindezelayo [21]. Isibonelo, ukulindelwa kwengcindezelo yenhlalo (umsebenzi wokukhuluma esidlangalaleni) kwandise ukudla okuningi ekudleni okuvinjelwe ngenkathi kungashintshwa lokho kwabadli abangavinjelwe amandla [22]. Ngokufanayo, abadli abakhawulelwe ababike ukucindezelwa okuphezulu kokuphazamiseka nokuthinta okubi kulandela uchungechunge lwemisebenzi yokuqonda kukhombise ukuphuza okukhulu ngemuva kwengcindezi kunalabo ababika amazinga aphansi wokucindezelwa okungukuthi [23]. Ukuvinjelwa kokudla nakho kungahle kube nomkhawulo wesikhashana kubadli bokudla ngoba inhloso yokunciphisa ukunqotshwa kukhulu ngaphambi kokuphazamiseka uma kuqhathaniswa nezinsuku okungekho kuzo ukulunywa kuzo [18].

Noma izifundo zokulethwa kwemizwa elebhu zingagxekwa njengokungezona izindlela zokudla komhlaba wangempela ngaphansi kwezimo zemvelo zemvelo [24], baphinde basekele kabanzi i-hypothesis “emnyama” yokuthi ukudla okudlayo kungabangelwa izimpendulo zomzwelo ezicindezelayo noma ezingezinhle kuma-subsets abantu. Isibonelo, abadli bokuzidla ngokweqile baphuza kakhulu ushokolethi ngemuva kokubuka ifilimu edabukisayo endaweni yokucwaninga kunokulandela ifilimu elingathathi hlangothi [24]. Bonke ababambiqhaza kulolu cwaningo babike ukujabha njengenye yezimbangela zabo zokudla, “ukudangala” noma “ukudabuka” okuvame kakhulu ukugcizelelwa. Kwabesifazane abangawona omkhulu, labo abanezimpendulo ezinkulu ze-cvisis cortisol ebhethri labacindezeli bezenhlalo badla okuningi ngemuva kwesipiliyoni esicindezelayo kunaleso esinezimpendulo ze-cortisol ephansi [25]. Ukwethulwa kwesimo esingesihle sokomzwelo nge-memory ye-autobiographical yememori edabukisayo futhi kwandise inani lokudla okulula okudla okuphuzwa ocwaningweni lwezinto ezingadli ngokudla, futhi umphumela wawubonakaliswa ikakhulukazi kulabo ababambe iqhaza ababike “ukudla okungokomzwelo” okukhulu [26]. Ngokungafani nokutholakele okubuyekeziwe nokwenzekile ekudleni okuvinjelwe, abadli abangavinjelwe kuncishisiwe ukudla kwabo okungenamsoco ngemuva kokubuka ifilimu elidabukisayo [27, 28].

Ukudla okungahambi kahle okunjalo okuhambisana nokutholwa kungaphazamisa ukulungiswa kwesisindo somzimba. Ukuvuselela isisindo ezinyangeni ze-6 kulandela ukwehliswa kwesisindo okuphumelelayo kuhlotshaniswa nokudla ngokuphendula izehlakalo zokuphila ezicindezelayo, ukudla ngokuphendula imizwa engemihle, nokusetshenziswa kokudla ukulawula imizwa [29]. Mhlawumbe ngokufanele, ukungeza ukwelashwa kwengqondo ukusiza ukuphatha imizwa ejwayelekile nokubhekana nakho, futhi hhayi kuphela indlela yokuziphatha nokudla, kunganciphisa ukubuyela esimeni sokukhuluphala kakhulu [30]

Ithonya le-2.3 lokudla okungathandeki kokudla kumood yemizwa nomsebenzi wokuvuza

Ukudla uma uphendula ezimweni ezingezinhle zemizwelo kusikisela ukuthi ukudla ngokweqile kungaba umzamo wokuzindla “ngokudla okunethezekayo.” Ukudla okujwayelekile okudla ngesikhathi sokuncwaba kuvame ukuba mnandi futhi kube namandla aminyene; kuqhubeke, zivame ukuba yizinto ezithwelwe carbohydrate ezinjengezinkwa, i-pastas, namaswidi [31]. Ekuqaleni, lokho kudla okunotha okunama-carbohydrate kungahle kube nomphumela ongemuhle wokuqinisa, ngoba kunciphisa imibiko yokuthukuthela [32] nokungezwani [33] futhi ukhulise ukuzola ngaphakathi kwe-1-2 hr ukusetshenziswa. Ukucabanga okuphindaphindiwe kokudla okunambithekayo, noma kunjalo, kungahle kube nokukhiqiza isikhathi eside emvuzweni wobuchopho kanye nezindlela zokucindezela ezikhuthaza izimpendulo ezidabukisayo noma ezikhathazayo lapho lokho kudla kungasatholakali noma kudliwe. Ngokuhambisana nalesi hypothesis “emnyama”, ngemuva kokudla ukudla okunamafutha amaningi (i-41%) inyanga eyodwa, amadoda nabesifazane abashintshelwa emafutheni aphansi (i-25%), ukudla okune-carbohydrate ephezulu kubike ulaka nentukuthelo ngenkathi ngenyanga eyalandela kunezifundo ezaqhubeka nokudla ukudla okunamafutha amaningi [34]. Ukukhuphuka kwentukuthelo kungahle kube nomphumela kusuka ekunciphiseni kwamafutha wokudla (noma ukuqondwa kokuqonda) noma kusuka kuma-neuroadaptations kuya kumakhilo e-carbohydrate.

Ukusetshenziswa ngokweqile okuphindaphindekayo kokudla okunambitheka kakhulu kungabukela phansi ukujikeleza komvuzo we-dopaminergic ngezindlela ezibonisa lokho okuvame ukubonwa kumlutha wezidakamizwa: ukutholakala kwe-dopamine ye-dopamine D2 receptor receptor kanye nokukhishwa kwe-dopamine okuvuthiwe [35, 36]. Ngempela, abantu abakhuluphele bakhombisa ukutholakala okuphansi kwe-dopamine D2 receptor kunokwenza izilawuli ezingezona ezinamafutha, futhi lokhu kuncishiswa kwe-striatal D2 kuhlangene ngqo neBMI [37, 38]. Ukwenza kusebenze nge-Caudate ekuphenduleni kweshizi ye-chocolate ye-chocolate kuyancishiswa nesihlobo esicebile kubantu abazondayo [39]. Leli zinga lomsebenzi ongahluziwe libonakaliswa ngokukhethekile kubantu abane-polymorph ye-TaqIA A1 ye-D2 receptor, ehlotshaniswa ne-D2 receptor expression [39]. Enye i-polymorphism exhumene nomsebenzi we-dopamine oncishisiwe, i-7R allele ye-dopamine D4 receptor, ihlotshaniswe nesikhathi esiphakeme kakhulu se-BMI ephezulu kuma-bulimics [40] kanye nokuziphatha okulungene kokudla kwabesifazane abanokudangala kwesikhathi esithile [41]. Idatha ehlanganisiwe yezakhi zofuzo iphakamisa ukubonwa kusengaphambili kokuthola isisindo kubantu abanophawu oluphansi lwe-driamal dopaminergic, futhi kuye kwavezwa ukuthi labo bantu badla ngokweqile bezama ukubuyisa imali esileleyo yomholo. Imininingwane yakamuva iphakamisa ukuthi, isisindo sokuthola isisindo (noma i-correlate yenzuzo yesisindo, mhlawumbe ukudla okudla okuthe xaxa) ibeka phansi umsebenzi we-striatal dopamine. Abesifazane abane-BMI yabo ekhuphuke ngesikhathi sezinyanga ze-6 bakhombise ukwehliswa kwamandla kwe-caudate ekusebenziseni i-chocolate shake kunabesifazane abama-BMI abahlala bezinza, kanti ukuncipha kokuqalisa kwe-caudate kuhlotshaniswa nokwenyuka kwe-BMI enkulu [42]. Ngakolunye uhlangothi, ukudlula kwe-gastric kukhuphule ukutholakala kwe-D2 etholakalayo ngaphakathi kwamaviki e-6 wokuhlinzwa kwe-bariatric esifundweni esincane sabesifazane abakhuluphele kakhulu [43].

Ukutholakala kwe-Striatal D2 receptor ukutholakala kwezifundo ezikhuluphele kubuye kuhlobane ngokuthe ngqo ne-glucose metabolism ezindaweni zangaphambi kwecortical ezihlinzekela ukulawulwa kokuvinjwa, kufaka phakathi i-dorsolateral pre kwangaphambilial, orbitof Pambal, ne-anterior cingulate cortices [38]. Lokhu ubudlelwano kuphakamisa i-hypothesis eye yanciphisa ukuguquguquka kwe-dopaminergic kusuka ku-striatum kungaholela ekuvinjelweni kokuthikamezwa kokuvinjwa kokudla futhi ngaleyo ndlela kwandise ubungozi bokudla ngokweqile. Mhlawumbe nge-analog, ukuhlangana okuqondile phakathi kokutholakala kwe-DriNUMX ye-striatal kanye ne-glucose metabolism ku-dorsolateral kanye ne-anterior cingate cortices nakho kuye kwaqashelwa kwiziphuzo ezinotshwala, kepha hhayi ezilawulweni ezingezona ezidakayo noma ezingekho esimweni esibi [38, 44].

Kuhambisana nokuhlukahluka kokuziphatha okubuyekeziwe ekuphenduleni okungaphakathi kokucindezelwa, isitayela sokudla sibuye sihlukanise okufakwayo ngamaphrofayili wesistimu ye-dopamine ehlukile. Abantu abangawona omkhulu abakhulu ababike "ukudla okungokomoya" okukhulu okukhombisa ukwehla kwesisekelo se-D2 ukutholakala kwe-receptor ku-dorsal striatum njengoba kuqhathaniswa nokudla okungekho emphefumulweni; lezo eziphezulu ekuvinjelweni kokudla zazikhulise ukubopha kwe-D2 ku-dorsal striatum ngokuphendula ukukhuthaza kokudla ngokuqhathaniswa nalawo aphansi ekuvinjelweni kokudla [45]. Ekugcineni, abadli bokuzidla ngokweqile bakhombise ukwanda kwe-D2 receptor ebopha ku-caudate ngokuphendula inhlanganisela yokuvuselela ukudla kanye nenselelo ye-methylphenidate njengoba kuqhathaniswa nabadli abangamathe nolaka [44, 46].

I-3. Ubufakazi “ohlangothini olumnyama” obuvela kumamodeli wezilwane eziluthayo lokudla

Ukuthuthukiswa kwamamodeli ezilwane bekuyisihluthulelo sokuqinisekisa umqondo wokuluthwa kokudla futhi kuqale ukubonakalisa "uhlangothi lwalo olumnyama." Iqembu likaBart Hoebel liholele indlela ekuboniseni izici zokuluthwa kokudla emaqongeni [47]. Ngenkathi amamodeli ezilwane engakwazi ukufaka phakathi zonke izinto eziyinkimbinkimbi zenhlalo ezithonya indlela yokuziphatha ekudleni kubantu, banethuba lokuhlukanisa kalula phakathi kwezenzo nemiphumela yokudla okufana nomlutha, ukumisa ukulawula ukudla okuqinile, nokuvumela ukuhlolwa okuningiliziwe izindlela ezihambisana namangqamuzana.

I-3.1 Induction yezindawo ezihoxayo ngemuva kokuqedwa kokutholakala kokudla okuthandekayo

Ngokuhambisana "nemlutha wokudla" we-hypothesis osungulwe nguHoebel nozakwabo, ucwaningo oluningi kumamodeli wezilwane manje selubonile amaphrofayli wokuziphatha nawokuzenzisa afana nezindawo ezinjengokuhoxa ezilwaneni ezihoxisiwe ukufinyelela kokuhamba kwesikhathi kokudla okuthandekayo. Isibonelo, uHoebel nozakwabo bahlinzeka ngobufakazi bokuthi ukunqotshwa nsuku zonke kwezixazululo ezinoshukela (isib. I-25% ushukela noma i-10% sucrose) kungaholela ekuthembekeni kwe-opoid opioid. Amagundane ahlinzekwe ukufinyelela kwe-12-hr nsuku zonke ukufinyelela kweglucose futhi kufakwe enye esikhundleni sokudliwayo kokudla kwe-12-hr kuboniswe izimpawu ezithile ezihlobene nokuhoxiswa kwe-opiate, kufaka phakathi ukubhuqa kwamazinyo, ukuthuthumela kwangaphambilini, nokuqhaqhazela kwekhanda, lapho kuphonswa inselelo ne-opioid antagonist naloxone [48]. Ukuhoxa okuvikelekile nge-pretxment ye-naloxone kubuye kwandise nokuziphatha okufana nokukhathazeka ku-12-hr izilwane ezihamba nge-glucose nsuku zonke, njengoba kuboniswa yancishiswa isikhathi esivulekile sengalo ku-plus-maze ephakeme, kepha hhayi ezilwaneni ezitholwayo i-ad lib ukufinyelela i-chow noma ushukela [48]. Kuvele ukungabibikho kokuqunjelwa kwe-naloxone, izimpawu zokuhoxa futhi kwenzeka "ngokuzenzakalelayo" i-24-36 hr ngemuva kweseshini yokugcina yokungena kweglucose. Uma kungekho inselelo ye-naloxone, indlela yokuziphatha ekhathazekile efana ne-maze nayo ibonakale ezilwaneni ezihamba nge-cycled ngemuva kwe-36-hr esheshayo, njengoba kuqhathaniswa i-ad lib Izilawuli ze-ok zidle, zinikeza ubufakazi besimo esikhathazekile-esifana nesezilwane ezihamba ngamabhayisekili ezikhishwe ekuhambeni ukufinyelela kwesisombululo sikashukela [49].

U-Hoebel nozakwabo babonile ukuthi ukwehlisa ukusebenza kwemvuzo kanye nokuziphatha okufana nokukhathazeka ngesikhathi sokuhoxa kungaqhamuka engxenyeni yezinguquko ekulinganiselweni kwe-dopaminergic ne-acetylcholinergic (ACh) phakathi kwe-striatum. Bathole ukuthi inselelo ye-naloxone ivusele ukukhululwa kwe-ACh enkulu kakhulu kuma-nucleus accumbens (NAc) wamagundane anomlando we-cyclic we-12-hr glucose yansuku zonke kanye nokufinyelela kwe-kulandelwa ukuncishiswa kokudla kwe-12 hr kunokwezilwane ezigcinwe ku i-ad lib chow [48]. Lokhu kukhuliswa kwempendulo ye-ACh kuhambisana nokuncishiswa kwama-dermamine we-extracellular dopamine kulandela inselelo ye-naloxone, efana nalokho okwenzeka ngesikhathi sokuhoxiswa kwe-morphine [50, 51]. Ngemuva kokushesha kwe-36-hr, izilwane ezi-glucose / chow-cycled zine-dopamine ephansi kanye namazinga aphezulu we-ACh extracellularly ku-NAc ngisho noma kungekho naloxone, iphinde ifane nesimo sokuzikhipha esinjenge-pontaneous opiate-like state ngesikhathi sokuyeka ukudla kwe-glucose [49]. U-Hoebel nozakwabo baphakamisa ukuthi lokhu kuguqukela ekuthuthukisweni kwe-ACh ekhulisiwe kanyekanye nokuncipha kokukhishwa kwe-dopamine kungakhombisa ukuguquguquka kokuziphatha okude kude nokuziphatha kwendlela ye-dopamine-mediated kanye nokugwema ukulimala [52].

Sebenzisa ukudla okuqinile okunoshukela, kunokudla koketshezi, i-Cottone et al. ngokufanayo kutholwe nokuzenzakalelayo okufana nokuziphatha okufana nokukhathazeka kumagundane ahoxisiwe ukufinyelela kokuhamba kwesikhathi kokudla okune-sucrose ephezulu, enambitheka ushokoledi. Amagundane ahlinzekwe ngokushintshana kokufinyelela kosuku lwe-5-day / 2-day labour ejwayelekile nokudla okumnandi kusetshenziswe isikhathi esincane ezingalweni ezivulekile ze-plus-maze nesikhathi esithe xaxa ngaphakathi kwegumbi lokukhipha emsebenzini wokuzivikela lapho uvivinywa ngesikhathi se-chow isigaba somjikelezo wabo wokudla [53, 54]. Ukwanda kokuziphatha okufana nokukhathazeka kuhambisane nokukhonjiswa okwandisiwe kokuxineka okuhlobene nokucindezela kwe-neuropeptide corticotropin-releasing factor (CRF) ku-nucleus ephakathi ye-amygdala (CeA), uhlelo olusetshenziswayo futhi ngenkathi kuhoxiswa utshwala [55-59], opiates [60-63], i-cocaine [64], cannabinoids [65], ne-nicotine [66, 67]. Ukuqagela nge-CRF ekhethiwe₁ i-antagonist R121919 ivimbele ukukhathazeka okuhlobene nokukhishwa kokudla kumthamo ongashintshanga ukusebenza kwezilawuli ezi-chow-fed [68-70]. Nge-analogingly, CRF₁ Abaphikisi bakhulisa iziphithiphithi zezindawo eziphikisayo- noma ezikhathazayo ngesikhathi sokuhoxiswa kotshwala [59, 71, 72], opiates [73, 74], benzodiazepines [75], i-cocaine [76, 77], ne-nicotine [66]. CRF₁ Isenzo sokuphikisa futhi siphikise izinga lapho izilwane ezihamba ngamabhayisekili zigcwalisa ekudleni okune-sucrose lapho zivuselelwa ukufinyelela kumithamo engashintshanga ukusetshenziswa kwezilawuli ezi-chow-feed noma kwezilwane ezidle ukudla okune-sucrose, kepha ngaphandle komlando wokuhamba ngamabhayisekili . Nge-analogingly, CRF₁ Abaphikisi banciphisa ukuphuza ngokweqile [57, 78-82], i-cocaine [83], opiates [84], ne-nicotine [66] kumamodeli wokulutha, ngenkathi kunemiphumela emincane ekuzilawuleni kwezidakamizwa notshwala bezilwane ezinganciki.

Lapho kufundwa izilwane ezihamba ngamabhayisekili ngenkathi zithola ukufinyelela kokudla okuncamelayo, okunotha nge-sucrose, izindlela zokuhlanganisa zombili kanye namazinga weCeA CRF ejwayelekile, kusekelwa i-hypothesis ekhulisa ukusebenza kohlelo lwe-amygdala CRF nokuziphatha okufana nokukhathazeka kubonise ukuhoxa kakhulu izwe [53, 54]. Ekugcineni, amagundane adonswe ekudleni futhi akhombise ukuzwela okukhulayo kwama-CeA GABAergic neurons ukuze kuguqulwe nge-CRF₁ ukubekezelela. I-R121919 inciphise amandla e-inhibitory e-inhibitory e-inhibitory e-CeA afike ezingeni eliphakeme kumagundane ahamba ngokudla ngamabhayisekili kunakulawulo oludliwe ngotshwala₁ Abaphikisi ngokudluliselwa kweCeA GABAergic synaptic okubonakala ngesikhathi sokuhoxiswa kotshwala [58]. Ngakho-ke, iphethini yokwanda okuhambisana nokukhishwa kokudla okuhambisana nokuchazwa kokuchazwa kwe-CeA CRF nokuziphatha okufana nokukhathazeka, ukukhuphuka kokudliwayo kokufinyelela okuvuselelekile, kanye nokuhlehliswa kokuziphatha nge-CRF₁ Ukuphikisana nomuntu ophikisana naye kufana nokutholakele kokuluthwa izidakamizwa notshwala [68-70].

Esifundweni esehlukile, uCottone et al. futhi ngithole ukuthi amagundane abesifazane anomlando wokuthola okulinganiselwe kakhulu (i-10 min / day) ukufinyelela kokunambitheka koshokolethi owodwa, ukudla okucebile kwe-sucrose akubonisanga kuphela ukwanda okumangazayo kokudla kwabo kokudla okuthandekayo (kudla ngaphezulu kwe-40% yokudla kwabo kwansuku zonke ukudla ngaphakathi kwe-10 min), kodwa futhi nokunciphisa okufana ne-anxiogenic ngesikhathi sokuhlanganisa se-plus-maze lapho kufundwa i-24 hr ngemuva kweseshini yabo yokugcina yokufinyelela [85]. Ukudla okuphathelene nokudla okwenziwe ngebhayisikile okuchitha isikhathi esincane kakhulu ezingalweni ezivulekile nakho kwakuyinto ebambe kakhulu ekudleni okuthandekayo, ukuxhumeka kungabonakali ezilawulweni ze-chow-fed. Le miphumela isekela i-Hoebel hypothesis etholakala kancane kancane ekudleni okunothe kahle kwe-sucrose okuholela hhayi ekudleni okufana nokudla, kepha futhi nesimo sokuhoxa sokukhathazeka okukhulayo maqondana nokudla okufana nokudla.

I-3.2 Sugar vs. umlutha wamafutha: Ingabe ukhona umehluko?

UHoebel nozakwabo nabo basanda kuphakamisa ukuthi kungenzeka kube nokuthile okuhlukile mayelana nekhono loshukela olulula (vs. amafutha) ukukhuthaza "umlutha wokudla"86]. Ngenkathi kunezimpawu zokuhoxa okubonakalayo noma okuxakayo kulandela ukubanjwa kwesikhashana kokuthola izisombululo zikashukela noma ukudla okuqinile, icala lezimpawu zokuhoxa elandela ukudla okubandakanya ikakhulu ukuhlanganiswa kwamafutha noma okunamafutha amnandi alicacile. Njengokudla ushukela, amagundane athuthukisa amaphethini okudla njenge-binge lapho ethola ukufinyelela ngezikhathi ezithile emafutheni ahlanzekile njengokuqunjelwa imifino [87] kanye nokuhlanganiswa kwamafutha amnandi [88]. Ngokungafani nokutholakele okunamandla kokuhoxa kwe-opiate-gcled ngamagundane ahamba noshukela, inselelo ye-naloxone nokuzila yehlulekile ukukhiqiza izimpawu zokuhoxa ezifana ne-somatic efana namagundane ngokufinyelela okuphakathi kwamafutha emifino noma i-sweet-fat chow [86].

Noma kunjalo, ukuntuleka kwezimpawu zokuhoxa njenge-somatic opuate akuvimbeli ukuthuthuka kwesimo esingesihle sokomzwelo ezilwaneni ezihlukaniswe nokudla okunamafutha aphezulu (okusho ukuthi “ukuhoxa kwesibambiso”). Ngempela, abanye baye babona izimpendulo eziguquliwe zokuziphatha kuma-stressors amnene ngemuva kokususwa kokudla okunamafutha amaningi. Amagundane agcinwe ngokuqhubekayo ekudleni okunamafutha amaningi akhombisa umsebenzi owengeziwe esivivinyweni esivulekile se-24 hr ngemuva kokushintshelwa ku-chow ejwayelekile, umphumela ongabonakali kumagundane ahoxisiwe ekudleni okuphezulu kwe-sucrose [89]. Ngaphezu kwalokho, ukuhoxa kwe-24-hr ekudleni kwamafutha aphezulu nakho kuholele ekukhuleni kwamazinga we-CRF mRNA ku-CeA [89], kufana nokutholakele kweCottone et al. ngokudla okune-sucrose ecebile [53]. Ngakolunye uhlangothi, umehluko weqembu awuzange ubonwe kwezinye izinkomba zokuziphatha okunexhala, kufaka nokungcwatshwa kwemabula noma isimilo esiphakeme se-plus-maze. Ukucatshangelwa okwengeziwe kwemiphumela yokuhumusha kulolu vivinyo lwe-vis-à-vis oluhlaziwe ngaphambilini lokuhlolwa kweshukela "ukuhoxisa" kufaka phakathi ukuthi ukudla okuthandekayo bekuhlinzekwa ngokuqhubekayo kunokuba kube njalo; ukuthi ukudla okunamafutha amaningi lapha bekuthandeka kakhulu kunokudla okune-high-sucrose; nokuthi ukudla okuphezulu-kwe-sucrose kwakuyisihlanganisi sama-macronutrients, kunokudla noma ushukela omningi.

Izimpawu ezihoxayo ezifana nokukhathazeka lapho kususwa isidlo esithandekayo nazo zingalungiswa yizakhi zofuzo. I-Cottone et al. babone ukungafani okuzinzile komuntu ngamunye ngezinga lamagundane ancike kuwo ekudleni okuphezulu okuhambelana nezinga lokuziphatha okufana nokukhathazeka 24-hr post-ukufinyelela [85]. I-Pickering et al. uthole ukuthi ukuthambekela kokukhuluphala ngokweqile, kepha hhayi ukumelana nokukhuluphala, amagundane akhombisa umsebenzi owenziwe wancipha enkabeni yenkundla evulekile yama-2 amasonto ngemuva kokushintshwa ekudleni okujwayelekile okulandelayo okwalandela amaviki e-7 wokuthola ukudla okunamafutha aphezulu, okunoshukela omningi [90]. Izilwane ezivame ukukhuluphala ziqhubeke nokudicilela phansi isihlobo se-chow kuzo zombili izilawuli ze-chow-nezilwane ezilwa nokukhuluphala kumaviki amathathu okuhoxa.

Imicibisholo ekhishwe ekudleni oyithandayo nayo izokhuthazelela imiphumela emibi yokuthola ukufinyelela okuvuselelwa [89, 91]. Isibonelo, amagundane ahoxisiwe ekudleni okunamafutha amaningi achithe isikhathi esiningi endaweni enobuhlakani obukhanyayo lapho angadla khona ipisi elinamafutha amaningi kunokuthi amagundane angahlukanga ekudleni okunamafutha aphezulu noma ezilawulweni ze-chow-fed [89]. Amagundane anomlando wokufinyelela okuwedliwe ekudleni okunempilo kwe-yokudlela futhi awukunciphisanga ukuphendula ngokudla okunempilo yize bekukhona induku enezimpiko [91]. Lokhu kugcina kufana nokuphikelela kokuziphatha okufuna i-cocaine kuma-rodents yize kukhona ikhebula elibikezela ngezidladla. Imiphumela iphakamisa ukuthuthukiswa kwamaphethini wokudla okuphoqayo, mhlawumbe i-analogous ekuphoqeleleni ukudakwa kwezidakamizwa, okumelana nemiphumela engahle iphazamise [92].

I-3.3 yokufuna ukudla nokudla okufunwa yingcindezi

Ngoba ukudla okuthandekayo kungaba nemiphumela emibi yokuqinisa, noma "eduduzayo", ukukhathazeka nokukhathazeka okuphakeme akuyona nje imiphumela yokuhoxiswa ekudleni okunempilo, kepha futhi kuyizinto ezikhuthazayo ezivuselela ukubuyela esimeni sokudla okwandisiwe ngemuva kwesikhathi sokungayeki. Ngokunwetshwa, ukwanda kwesisusa sokuthola, ukusebenzisa nokudla okudla okudumisayo okuphathekayo ngaphansi kwengcindezi yezemvelo kungenziwa kufakwe emgqomeni ukukhombisa izinqubo zokuqinisa ezingezinhle ezisebenzayo kulabo abasebenza ngesikhathi sokuhoxa kokudla okuthandekayo [49, 54, 93, 94]. Amandla asungulwe okusetshenziswa kokudla okuthandekayo ngaphansi kwezimo ezithile zokwenza kusebenze ukusebenza kwangaphandle kwezinhlelo zokucindezelwa, njengoba kufakazelwa izindlela zokuziphatha, ezizimele, ze-neuroendocrine, nezindlela ze-neurochemical [94-111], isekela kakhulu lo mqondo.

Mhlawumbe ngokufanelekile, i-alpha-2 adrenergic antagonist yohimbine, ingcindezi yemithi ekhiqiza ukukhathazeka okuphezulu kubantu nasezindongeni, futhi okudala ukubuyiselwa kokuziphatha kwe-cocaine-, utshwala-, kanye ne-methamphetamine-kumagundane [112-114], futhi kuvusa ukubuyiselwa kokuphendula izimpilo zokudla ezithandekayo nezisombululo ze-sucrose [115-117]. I-Yohimbine igxilisa ukubuyiselwa kokufuna izinhlobo ezahlukene zokudla eziqukethe amandla, kufaka phakathi i-carbohydrate engafiki, i-sucrose ne-pellets enamafutha amaningi, kepha hhayi amandla angenawo amandla futhi, mhlawumbe futhi ayithandeki, i-cellulose fiber pellets [118]. Amasistimu amaningi we-neurotransmitter afakwe umfutho njengama modulators angaphansi komphumela walo mphumela, kufaka phakathi i-CRF, i-orexin kanye nezinhlelo ze-dopaminergic. Isenzo sokuzenzisa nge-CRF₁ i-receptor antagonist antalarmin inamandla okubuyisela ukubuyiselwa okuyisisekelo kokudla okuthandekayo [115], njengoba kwenza isenzo sobunyangi ne-orexin-1 antagonist SB334867 [117]. Indawo (s) yezinyathelo zalezi zingxubevimbi ekuvinjelweni kokubuyiselwa kwe-yohimbine ihlala ingaziwa. Kususelwa ku-neuroanatomy yokuxinzelela- noma ukubuyiselwa kwe-yohimbine-kokuvuselelwa kokufuna izidakamizwa [119], noma kunjalo, izifunda ezibandakanyeka ku-amygdala enwetshiwe noma ngokulawula kokuvinjwa zingabazokhetho. Ngempela, i-microinjection ye-CRF kuma-nucleus accumbens ingaba nomthelela wokuphendula ongathandwa we-sucrose [120] kanye nokuphathwa kwe-dopamine D1 antagonist SCH23390 ngaphakathi kwe-dorsomedial prefrontal cortex kungakhipha ukubuyiselwa okuyisisekelo kwe-yohimbine kokufuna ukudla [121].

Izimo ezicindezelayo zemvelo nazo zingakhuthaza ukubamba okuqhubekayo kokudla okuthandekayo ngamagundane. Ngaphansi kwengcindezi yokuguquguquka okungamahlalakhona, amagundane akhetha kakhulu ukudla kwawo kwansuku zonke kwe-caloric ekudleni okunamafutha amaningi, kunokuphakama kwamaprotheni amaningi noma izinketho zokudla eziphakeme ze-carbohydrate [111]. CRF₂ amagundane angasebenzi kahle, akhombisa impendulo ye-HPA-axis eyeqisayo yokuxineka, andisa ukudla kwawo okuphezulu kokudla okulandelayo ngemuva kokuxineka okuguquguqukayo okufika ezingeni elikhulu kunokulawula kohlobo lwasendle, uma ukudla okunamafutha aphezulu kunikezwa i-1hr nsuku zonke kunokuba isikhangiso. Lawa amagundane abonisa ukuncishiswa kokukhishwa kwe-CORT ukuze kuvinjelwe ukucindezela ngemuva kwamaviki we-2-3 wokuchayeka ngesikhathi esisodwa kwamafutha aphezulu, i-carbohydrate, nokudla kwamaprotheni ngesikhathi sokuxineka okungafani okungapheli [111].

UBoggiano kanye nozakwabo bakhombe ubudlelwane phakathi kokuvinjelwa kokudla kanye nengcindezi yokwazisa ukudla okufana nokudla okulingene kumagundane okungase kubonise ukuhlangana kokuvinjelwe kokudambisa kokudla kanye nengcindezi ekudambiseni ukudla kokudla. Kumodeli, awukho umlando wokuvinjelwa kwe-caloric noma we-footshock stress kuphela ezanele ukukhuthaza ukudla okulingene njengokudla okuhlobene nokungena kumagundane angondlekile. Esikhundleni salokho, inhlanganisela yemijikelezo ephindaphindwe yokuvinjelwa kokudla + i-footshock iholela ekudla okwandayo kokudla okuthandekayo (amakhukhi) kulandela uxinzelelo [122, 123]. Ukudla okwandisiwe akuqhutshwa yisidingo samanje se-metabolic ngoba isheduli yokudla ivumela amaqembu akhawulelwe ukuphinda adle ku-chow isisindo somzimba esivamile ngaphambi kwenselelo ye-footshock [124]. Uma kutholakala kuphela i-chow ejwayelekile, akunakuphathwa njengokulunywa yinyama, kepha uma kunikezwa isampula elincane lokudla okutholakala eceleni kokudla okujwayelekile, amagundane ayaqhubeka nokuzumeka kwi-chow. Le mininingwane ifaka okutholakele okuvela kubanikazi babantu, okungenzeka kakhulu ukuthi baqale ukulunywa (kunoma yikuphi ukudla) uma beqala ukudla okufisayo [125]. Amanye amaqembu abonile ukufana kokudla okufana nalokhu kulandela umlando wokuvinjelwa kokudla okwenziwa nge-cyclic uma ukucindezelwa kwe-footshock kuthathelwa indawo isikhathi se-15-min sokuchayeka kokubuka nokudla kokudla okuphathekayo, lapho ukusetshenziswa kungavunyelwe [126]. Yize ushintsho oluqondile lwe-neurobiological oluvuselelwa yimijikelezo ephindaphindwe yokuvinjelwa, ukucindezelwa, nokuphinda kubuye kukhishwe kusacacisiwe, ama-opioids endo native angaba nengxenye ekuziphatheni okucindezelekayo okubangelwa ukucindezela. Inselelo ye-Naloxone iyancipha futhi i-mu / kappa agonist butorphanol inyusa ukudla okungathandeki eqenjini elinqunyelwe + elicindezelwe ngokuqondile [127],

Ukulahleka kwe-3.4 yenani le-hedonic lesikhuthazo esasinomvuzo ngaphambili

Enye yezimpawu eziwuphawu “ohlangothini olumnyama” lomlutha wezidakamizwa ukuthuthukiswa kokubekezelelana, lapho inani elikhulu nelikhulu lezidakamizwa lidala ukukhiqiza umphumela ofanayo we-hedonic. Ubuningi obuncane abasabonwa njengokunomvuzo. Ukulahleka okufanayo kokuphendula ngokweqile kwimivuzo yokudla kungenzeka ezilwaneni ezinomlando wokuthola ukudla okuthandekayo. Ngempela, uHoebel nozakwabo babone ukwanda okumangazayo kokudla kwe-glucose ngezinsuku ezilandelanayo ze-12-hr ukufinyelela okulinganiselwe nokusetshenziswa okusheshayo kwe-glucose ngehora lokuqala lokufinyelela, okuhambisana nentuthuko yokubekezelelana kanye noguquko kokudla kokudla okulingeneyo [128] Isisusa esithuthukisiwe sokuthola ukudla kweglucose sabuye sabonwa kulandela isikhathi esingamasonto amabili47]. Abanye abaphenyi selokhu bakuphinda lokhu kukhuphuka okufana nokulunywa okungakhombisa ukubekezelela kusetshenziswa izinhlobo ezahlukene zokudla namadigri wokufinyelela okulinganiselwe [85, 87, 129, 130].

Futhi kufana nokubekezelela, eminye imivuzo eyamukelekayo ngaphambili ayisebenzi kahle ekusekeleni ophendulayo ophendulayo futhi ajoyine imibuthano ye-mesolimbic. Amagundane athola ukufinyelela okuphakathi kokudla okunambitheka koshokolethi, onothile ngokugcwala komoya akhula ngokuqhubekayo lapho ebuzwa ukuthi aphendule ngohlobo oluncamelayo, kodwa kungenjalo lutholakala kalula, isiraphu yesiraphu yomhluzi eyenziwe ngohlelo oluqhubekayo lokulinganisa [53]. Ukushoda okushukumiseleka kokuthola ukudla okuncamelayo okuncishisiwe kubuyiswa ngokuzenzisa nge-CRF₁ umphikisi, mhlawumbe okuxakayo kwikhono leCRF₁ umphikisi ukuze ubuyisele emuva umsebenzi wokuvuthwa ongafanele ngesikhathi sokuhoxa kwe-nicotine [131].

Obunye ubufakazi bezimpendulo ezincishisiwe zokungatholakali kalula, eminye imivuzo ivela ocwaningweni lwe-micodialysis lapho amazinga we-dopamine angaphandle alinganiswa khona kumagundane anomlando wokufinyelela kokudla kwekhofi. Ukudla nge-cafeteria-ekudleni kuphumela kumazinga aphansi we-dopamine kuma-nucleus aqokeleleka ngemuva kwamaviki we-14 wokufinyelela, kanye nokukhishwa okuphansi kwe-dopamine kokukhipha ku-wote ama-accumbens kanye ne-dorsal striatum [132]. Emgundwini ophathwe ngokudla okod, ukwanda kwe-dopamine efflux kwabonwa ekuphenduleni ekudleni kwelebhu ejwayelekile, kanti lokhu kukhuphuka bekungasabhekwa emgundweni we-yokudlela owenziwe nge-yokudlela. I-Dopamine efflux ekuphenduleni kwesinye isisusa esivuselelayo, i-amphetamine, nayo yancishiswa kakhulu kumagundane wokudla nge-cafeteria. Ukudla kwase-yokudlela, nokho, kwaqhubeka nokukhuthaza i-dopamine efflux kuma-accumbens, aphakamisa ukuthi ukusetshenziswa okuqhubekayo kokudla kwekhofi kuyadingeka ukuze lezi zilwane zigweme ukusilela kokukhululwa kwe-dopamine [132]. Ukugxilwa kokufinyelela ekudleni okuthandekayo nakho kungathinta amandla ayo okuxhasa ukukhishwa kwe-drietal dopamine. Kumagundwane angena nge-12-hr ngezikhathi ezithile ukufinyelela ku-sucrose, i-sucrose iyaqhubeka nokukhuthaza i-dopamine efflux kuma-accumbens ngemuva kwamasonto amathathu, kepha lo mphumela ulahlekile ezilwaneni ezine isikhangiso finyelela konke133].

Izingqinamba zokuzishukumisa ze-Intracranial lateral hypothalamic zibuye zikhuphuke kumagundane anikezwe ngokudla okweluliwe, kodwa kunganqunyelwe, ukufinyelela ekudleni kokudla kwasemikhakheni yokudlela. [91]. Imikhawulo yokuzikhuthaza yokuvusa amandla, inkomba yomsebenzi wokukhubazeka kobuchopho, ivela kanyekanye ngokuthuthukiswa kokukhuluphala okugxiliswe ekudleni futhi iphikelele ngisho nangemva kokuphoqelelwa kokungayeki ekudleni kwekhofi isikhathi esingamasonto amabili. Okutholakele kokutholakele okutholwe kubantu ngaphambili, amazinga e-driamine dopamine D2 receptor nawo ancishiswe kakhulu ngemuva kokufinyelela okuningiliziwe ekudleni kwendawo yokudlela; I-lentivirus-Mediated knockdown ye-D2 receptor expression isheshise ukukhuphuka kwemikhawulo yemivuzo, yabeka iqhaza lesizathu salokhu kune-neuroadaptation edalwe kukudla kokungasebenzi kahle kohlelo lobuchopho oluzayo [91]. Ukuncishiswa kokubopha i-D2 binder [134] kanye ne-D2 receptor mRNA [135] kubhekwe futhi ekuphenduleni ukungena kwansuku zonke, okufana nokukhawulelwa kwe-sucrose, kuyilapho i-D3 receptor mRNA kanye nencazelo ye-dopamine transporter iyanda [136]. Ukudluliswa kwe-mesolimbic dopaminergic transmission kungenzeka kube nemiphumela esebenzayo engcupheni yokuthola isisindo, ngoba amagundane aphathelene nokukhuluphala ane-basal extracellular dopamine amazinga asezingeni lokuxhuma ngaphezu kwamagundane amelana nokukhuluphala ngisho nangaphambi kokuwohloka kwesisindo, nokujova kwe-emulsion ye-lipid yehluleka ukukhulisa ama-accumbens amazinga e-dopamine eqenjini lokukhuluphala [137]. Ngokuphambene, ukukhawulelwa kokudla kuhlotshaniswa nokwenyuka kwamazinga e-D2 kumagundane we-Zucker obese [138]. Sekukonke, imiphumela iphakamisa ukuthi ukusetshenziswa kokudla okuthandekayo kungaholela ekulimaleni okungapheli ezinhlelweni zemivuzo yobuchopho.

I-4. Iziphetho

Njengoba nje ukuguquka kokusebenzisa izidakamizwa kuya ekuncikeni kuhambisana nokudonswa phansi komjikelezo womvuzo wobuchopho kanye nokuthuthuka ngasikhathi sinye komjikelezo “ophindayo”, kanjalo nokuguqukela ekuluthweni kokudla kubonakala kufaka “uhlangothi olubi.” Izifundo zabantu abadla ngokuzumayo, ekuziphatheni kwabo okuhambisana kakhulu nomqondo wamanje wokulutha kokudla, kuye kwaba nomfutho omkhulu wokucabanga nezimo ezikhathazayo nezikhathazayo ekuthuthukisweni nasekugcinweni kwalokhu kuguqulwa kokudla ukudla okuthandekayo ngemiphumela yako emibi yokuqinisa.

Izifundo zezilwane, ezaqalwa yingxenye yeqembu likaBart Hoebel futhi manje sezikhula ngamandla, seziqale ukucacisa izindima ezithile zesheduli yokudla, ukwakheka kwayo, kanye nobungako ekushintsheni kwezindlela zokuziphatha, kwe-neural, kanye ne-endocrine system kanye nasekunciphiseni izimpendulo ze-hedonic ukudla neminye imivuzo. Kodwa-ke, izinselelo ezibalulekile zisasele. Kudingeka omunye umsebenzi ukuze kufinyelelwe ekuvumelaneni ngezinqubo zokuxilonga zokulutha kokudla kubantu. Ukuhlaziywa kabusha kwalezi zindlela kuzothuthukisa ukuthuthukiswa kwamamodeli ezilwane afanele ukuze afunde kangcono izici ezibaluleke kakhulu zalesi sifo.

A

Izithombe ezinhle kakhulu zokucwaninga

Ukuba umlutha wezidakamizwa kune- "ohlangothini olubi" olubandakanya ukukhululeka ezikhundleni ezingezinhle.
Uhlangothi olufanayo olumnyama lungaba lubucayi ekuthuthukiseni umlutha wokudla.
Ukuxineka nokuthinteka okungekuhle kungakubangela ukusetshenziswa ngokweqile kokudla okuthandekayo.
Ukuphindwa kokudla okuphindaphindiwe okuguqukayo kuguqula umvuzo wobuchopho kanye nokujikeleza kwengcindezi.

Ukuvuma

Ukuxhaswa kwezezimali kulo msebenzi kuhlinzekwe yiPearson Center for Alcoholism and Addiction Research, Harold L Dorris Neurological Research Institute, kanye nezibonelelo ze-DK070118, DK076896, kanye ne-DA026690 kusuka ku-NIH. Okuqukethwe kungumsebenzi wababhali kuphela futhi akumelwe kuveze imibono esemthethweni yeZikhungo Zezempilo Zwelonke.

Imibhalo yaphansi

Ukungqubuzana kwezintshisekelo

I-EPZ ne-GFK bangabasunguli kwilungelo lobunikazi elifakelwe iziphikisi ze-CRF1 (USPTO Applicaton #: # 2010 / 0249138).

Ukuzikhulula komshicileli: Leli fayili le-PDF yesandla esingenakubalwa esamukelwe ukuze sishicilelwe. Njengenkonzo kumakhasimende ethu sinikeza le nguqulo yokuqala yombhalo wesandla. Umbhalo wesandla uzothola ukukopisha, ukufaka izinhlobo, nokubukeza ubufakazi obulandelayo ngaphambi kokuba ushicilelwe efomini layo lokugcina. Uyacelwa ukuthi uqaphele ukuthi ngesikhathi sezinqubo zokukhiqiza kungenzeka ukuthi zitholakale ezingahle zithinte okuqukethwe, nazo zonke izinqamulajuqu ezisemthethweni ezisebenza kulo magazini.

Okubhekwayo

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