Icala elimnyama lokulutha kokutya (2011)

. Umbhalo obhaliweyo ifumaneka kwi-PMC 2012 Jul 25.

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PMCID: PMC3304465

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Abstract

Kumakhoboka eziyobisi, inguqu ukusuka ekusetyenzisweni kweziyobisi njengesiqhelo ukuya ekuxhomekekeni kuye kwanxulunyaniswa nokushenxa ekomelezeni kakuhle ukuya ekomelezeni okungalunganga. Oko kukuthi, amachiza ekugqibeleni kuthenjelwe kuwo ekuthinteleni okanye ekuthomalaliseni iimeko ezingalunganga ezithi ngenye indlela zibangele ukuzikhwebula (umzekelo, ukurhoxa) okanye kwiimeko ezimbi zokusingqongileyo (umz., uxinzelelo). Umsebenzi wakutsha nje ucebise ukuba olu tshintsho “lwecala elimnyama” lukwangundoqo kuphuhliso lokukhotyokiswa kokutya. Ekuqaleni, ukusetyenziswa kokutya okunencasa kunokomeleza okulungileyo, imiphumo eyonwabisayo kunye nokuqiniswa okungalunganga, "ukuthuthuzela" iziphumo ezinokuthi zilungelelanise iimpendulo zezinto eziphilayo kuxinzelelo. Ukuphinda-phindwa, ukutya okunencasa okunencasa kunokwandisa ukujikeleza koxinzelelo lwengqondo kunye nokunciphisa iindlela zomvuzo wengqondo ezifana nokuqhubeka nokuthatha kuya kuba sisinyanzelo ukunqanda iimeko zeemvakalelo ezimbi ngokuqiniswa okungalunganga. Uxinzelelo, unxunguphalo kunye noxinzelelo lwengqondo lubonise ukuhambelana okuphezulu kunye nokubanakho ukuvusa umlutha wokuziphatha okunjengokutya ebantwini. Iimodeli zezilwanyana zibonisa ukuba ngokuphindaphindiweyo, ukufikelela okuphakathi kokutya okunencasa kunokukhokelela kwiimpawu zovakalelo kunye ne-somatic zokurhoxa xa ukutya kungasafumaneki, ukunyamezelana kunye nokuthomalalisa umjikelezo womvuzo wengqondo, ukufuna ngokunyanzeliswayo kokutya okunencasa ngaphandle kwemiphumo enokubakho, kwaye ubuyele ekuthandeni. ukufuna ukutya ekuphenduleni kwi-anxiogenic-like stimuli. I-neurocircuitry echongiweyo ukuza kuthi ga ngoku kwicala “elimnyama” lokukhotyokiswa kokutya ngokusemgangathweni iyafana neyoyanyaniswa nokuxhomekeka kwiziyobisi notywala. Uphononongo lwangoku lushwankathela ingqikelelo esisiseko kaBart Hoebel kunye negalelo elinamandla lokuqonda indima “yecala elimnyama” kumlutha wokutya kunye nomsebenzi onxulumeneyo wabo bamlandelayo.

Internet: Ukukhotyokiswa kokutya okunencasa, ukurhoxa okanye ukuziyeka okanye ukuxhomekeka, ukuchaphazeleka kakubi okanye ukuxhalaba okanye ukuxinezeleka, uxinzelelo, ukuphazamiseka kokutya okanye i-bulimia, iswekile okanye i-sucrose okanye iswekile okanye itshokolethi okanye amafutha amaninzi.

1. intshayelelo

Ukukhotyokiswa ziziyobisi sisifo esinganyangekiyo, esiphinda sibuyele esinamanqanaba amathathu ahlukeneyo: isigaba sokunxila esiqhutywa kwaye siphawulwe ziipropathi ezinomvuzo zechiza, isigaba sokurhoxa esikhatshwa sisimo sengqondo esingathandekiyo njengoko iipropathi zeziyobisi ezinomvuzo ziphela, kunye nokuzixakekisa kakhulu isigaba sokulindela esandulela ukuthathwa kwechiza ngokutsha. UGqr. Bartley Hoebel ungomnye woovulindlela bokuqala abathi bathatha iswekile, kwaye mhlawumbi nokunye ukutya okunencasa, nako kunokulawulwa zezi zigaba zintathu zokukhobokisa. Ubunkokeli bakhe khange bube luncedo kuphela ekuvaleni amasimi okulutha kunye nokuziphatha ngendlela yokondla ngomsebenzi wakhe wokulinga, kodwa nakwiinzame zakhe zokwandisa ulwazi kunye nokugunyazisa into ebikade ingathandwa kwaye iphikiswana kwi-hypothesis kuluntu lwezenzululwazi-leyo umntu anokuba yiyo. "Ukutya kuxhomekeke kukutya." Ngoku, ii-symposiums zokulutha kokutya, ezifana neNkomfa yoKutya kunye noKulutha kwiNkomfa yokuTya kunye nokuxhomekeka ebanjwe yi-Rudd Centre yoMgaqo-nkqubo woKutya kunye nokutyeba kakhulu eYale, iseshoni "yokutya: iNyaniso okanye iFiction" kwintlanganiso ye-2008 ye-Biology yoMvavanyo eSan Diego, kunye neNgqungquthela ye-Obesity and Food Addiction Summit ye-2009, idibanisa rhoqo izazinzulu, oogqirha, abenzi bomgaqo-nkqubo woluntu, kunye nabameli bezempilo abavela kwiimvelaphi ezahlukeneyo. Ngaphaya koko, umsebenzi onzima kaGqr.

Njengoko abasebenzisi beziyobisi beqhubela phambili ukusuka ekusetyenzisweni okuqhelekileyo ukuya ekubeni likhoboka, izinto ezikhuthaza ukusetyenziswa kweziyobisi zicingelwa ukuba zitshintshe ukubaluleka. Ngelixa ukusetyenziswa kokuqala kukhuthazwa ziipropathi ezinomvuzo zechiza, ukusetyenziswa kwiziyobisi kucingelwa ukuba kukhuthazwe kancinci ngokuqiniswa okulungileyo (umzekelo, ukuphakama kwe-euphoric), kodwa endaweni yokomelezwa okungalunganga: ukuthintela okanye ukukhulula imeko yeemvakalelo engalunganga evelayo. ukuzikhwebula (umzekelo, ukuyeka iziyobisi) okanye kumava angalunganga okusingqongileyo (umz., uxinzelelo) []. Kwinqanaba le-neurobiological, olu tshintsho luhambelana nokuthotywa kweenkqubo zokuvuza zobuchopho ezigcina iimpendulo ezikhangayo kwichiza kunye nokwandiswa okufanayo koxinzelelo lwengqondo okanye iinkqubo "ezichasene nomvuzo". Kwesi sikhokelo, ukutshintshela “kwicala elimnyama” lokukhotyokiswa kokutya ngokufanayo kunokuthi kujongwe njengenguqu ephambili kwinkqubo yokukhobokisa. Njengoko abantu beqhubela phambili ekuthatheni ngokunyanzeliswa kokutya okunencasa, ixabiso elinomvuzo elibukhali lezinto zokutya linokubamba ukubaluleka okuncinci ekukhuthazeni ukuthatha okongeziweyo kunokuthintela okanye ukunciphisa iimeko ezingalunganga (umzekelo, ixhala, ukudakumba, ukucaphuka, kunye nokuba neempawu zokurhoxa) namava xa oko kutya kukhethwa kungafumaneki okanye xa iimeko ezingqongileyo zingalunganga.

2. Ubungqina "kwicala elimnyama" kwizifundo zabantu

Ukufumanisa ukuba iziyobisi ezifana "necala elimnyama" zikhuthaza ukutya okunencasa, isiqalo esiluncedo kukuchonga abantu (abantu) abandlela yabo yokutya ifana kakhulu neyokuziphatha. Nangona ukutyeba ngokugqithiseleyo kunye nokuziphatha okunjengokutya okufana nokutya kunokwenzeka ukuba kudlule, "ukukhotyokiswa kokutya" akunakwenzeka ukuba kuchaze zonke iimeko zokutyeba kwabantu, kwaye abanye abantu abanobunzima obuqhelekileyo banokubandakanyeka kwiipatheni zokutya ezinjengomlutha. Akukho ndlela yokuxilonga yokuxilonga "yokukhotyokiswa kokutya" ekhoyo ngoku [, ]. Kutshanje, nangona kunjalo, iYale Food Addiction Scale (YFAS) iye yaziswa njengesalathiso sokuziphatha okufana nokutya okufana neendlela zokuxilonga zokuxhomekeka kweziyobisi kwi-DSM-IV-TR []. I-YFAS ilinganisa ubungakanani bokuba (a) abantu batya kakhulu ukutya okuthile nangona bezama ngokuphindaphindiweyo ukunciphisa ukutya kwabo, (b) indlela abatya ngayo iphazamisana nemisebenzi yentlalontle neyobuchwephesha, kunye (c) neempawu zokurhoxa zivela xa bezinqanda ekutyeni okukhethekileyo. Ukusetyenziswa kwangaphambili kwezi nqobo zokugweba kubonisa ukuba ukunyanzeliswa, ukuthathwa okungalawulekiyo kokutya okungaphezulu kunoko bekulindelwe kubonwa kwiimephu zokuphazamiseka kokutya ngokucocekileyo kakhulu kwiikhrayitheriya zokuxilonga zangoku zokuxhomekeka kwiziyobisi. Ngokufanelekileyo, amanqaku kwi-YFAS aqikelele indlela yokutya kakhulu kunye nokutya ngokweemvakalelo [] kodwa ayizange ihambelane nesalathisi sobunzima bomzimba (BMI) kubasetyhini abathatha inxaxheba kwisilingo sokugcina ubunzima ababika ukuba akukho ngxaki yokutya []. Ezi ziphumo zibonisa ukuba "icala elimnyama" lokukhotyokiswa kokutya, njengoko lisetyenziswa yi-YFAS, linokufundwa ngokuneziqhamo kubantu abatya kakhulu kunabantu abatyebe ngokungakhethiyo.

2.1 I-Psychiatric comorbidity ekutyeni ngokugqithisileyo

Ngokungqinelana nendima enokubakho "kwicala elimnyama" kumlutha wokutya, abatya kakhulu banamazinga aphezulu oxilongo lwengqondo olubandakanya iimeko zeemvakalelo ezimbi xa kuthelekiswa noluntu ngokubanzi. Umzekelo, abantu abadala kunye nabakwishumi elivisayo abane-bulimia nervosa okanye ingxaki yokutya kakhulu babonisa ukwanda kokuxhaphaka koxinzelelo olukhulu, ukuphazamiseka kwengqondo, ukuphazamiseka kokuxhalaba, kunye nokusetyenziswa kakubi kotywala okanye iziyobisi kunabantu abangenangxaki yokutya.-]. Rates of major depression are also elevated in the obese, but the association of binge eating with increased depression scores remains even in weight-matched comparisons of overweight and obese individuals []. Amazinga aphezulu kakhulu okucinga ukuzibulala kubantu abatya ngokugqithisileyo angqina ubuzaza bokuphazamiseka kweemvakalelo kolu luntu. Ngaphezu kwesiqingatha sabantwana abakwishumi elivisayo abanebulimics kunye nesinye kwisithathu sabo banengxaki yokutya kakhulu baxela ukuba bafuna ukuzibulala, kwaye isithathu kwishumi elivisayo i-bulimics ichaza ukuzama ukuzibulala []. Isalathiso sesizathu phakathi kokutya kakhulu kunye nokudakumba okukhulu akumiselwanga ngokuqinileyo kwaye kusenokubuyelana [-]. I-comorbidity enjalo yengqondo inxulunyaniswa nesiphumo esibi sonyango lwexesha elide [] kunye namaxesha amaninzi okuzinkcinkca ngokutya []. Ngapha koko, uninzi lwe-antidepressants, njenge-SSRIs okanye i-tricyclics, inokunciphisa ukuphindaphindeka kunye nobunzima beempawu zokutya ngokuzintyintya.].

2.2 Iimeko zeemvakalelo ezingalunganga zonyusa ukutya okunencasa kubantu abasengozini

Ukuxhaphaka kunye nobuzaza boxinzelelo kunye nokuxhalaba kwabo batya kakhulu kucebisa i-hypothesis yokuba imeko yeemvakalelo engalunganga inokuthi iqalise ukubuyela ekuziphatheni ngokuzinkcinkca. Inene, iimpawu zeemvakalelo ezimbi ezizixelile ngokwazo zokudakumba, ukuzithemba okuphantsi, kunye ne-neuroticism zinxulunyaniswa nokutya kakhulu kumadoda nabasetyhini []. Ngexesha leemeko zeemvakalelo ezingathandekiyo kunye neemeko, abantu abaqhelekileyo nabangaphantsi kobunzima baxela ukuba batya ukutya okuncinci kunangexesha lemeko entle yeemvakalelo kunye neemeko. Ngokwahlukileyo koko, oku kuncipha ekuphenduleni amazwe angalunganga akubonwa kubantu abatyebileyo, abaxela ukutya kakhulu ngexesha leemeko ezimbi kunamanye amaqela []. Ngokuhambelana nendima yeemvakalelo ezingathandekiyo ekuqhubeni ngokuzinkcinkca ngokuziphatha, amanqaku emood kwibulimics asezantsi kwangoko ngaphambi kokuzinkcinkca kuneentsuku apho kungekho kuzintyintya.].

Olunye ulwakhiwo oluchaphazela uxinzelelo kunye neemvakalelo ezingakhiyo njengezinto ezibangela ukutya kakhulu kukunqanda ukutya. Iinzame zokulawula ubunzima bomzimba (umzekelo ngokutya ukutya, ukwenza umthambo, izinto ezinciphisa umdla wokutya, okanye iilaxatives) zinxulunyaniswa ngokumangalisayo nokunyuka kobunzima bokukhula kwabasetyhini abafikisayo []; Uthintelo lokutya ngokufanayo lunxulunyaniswa nokufumana ubunzima bexesha elide kubantu abadala ababhinqileyo []. Inkcazo enokwenzeka yezi zinto ziphikisanayo kukufumanisa okuhambelanayo ukuba abadli abanqandayo batya ngokugqithisileyo ekuphenduleni kwiimeko ezahlukeneyo zoxinzelelo []. Umzekelo, ukulindela uxinzelelo lwentlalo (umsebenzi wokuthetha esidlangalaleni) ukwanda kokutya kokutya okuthintelweyo ngelixa kungaguquki oko kwabatya abangathinteliyo []. Ngokufanayo, abadli abathinteleyo abaxela uxinzelelo oluphezulu kunye nefuthe elibi emva koluhlu lwemisebenzi yokuqonda babonise ukuthatha okukhulu emva koxinzelelo kunabo baxela amanqanaba aphantsi oxinzelelo lwengqondo []. Uthintelo lokutya lunokuba nokubaluleka okwexeshana kubantu abatya kakhulu kuba injongo yokuthintela ukutya inkulu ngaphambi kokuzinkcinkca xa kuthelekiswa neentsuku ekungekho kuzinkcitha ngazo [].

Nangona izifundo zokungeniswa kwemo yelabhoratri zinokugxekwa njengokungalandeli indlela yokutya ekwenyani phantsi kweemeko zemo yendalo [], baxhasa ngokubanzi ingcamango ethi "icala elimnyama" lokuba ukutya ngokugqithiseleyo kunokubangelwa yingcinezelo okanye iimpendulo ezingathandekiyo zeemvakalelo kwii-subsets zabantu. Umzekelo, abatyebileyo abatyebileyo batya itshokolethi ethe kratya emva kokubukela ifilimu elusizi kwindawo yaselabhoratri kunokulandela ifilimu engathathi hlangothi []. Bonke abathathi-nxaxheba kolu phononongo bachaze isimo sengqondo njengenye yezinto ezibangela ukuba batye ngokutya, kunye "noxinzelelo" okanye "usizi" oluhlala lubandakanyeka. Kwabasetyhini abangatyebanga kakhulu, abo baneempendulo ezinkulu ze-cortisol ye-salivary kwibhetri yoxinzelelo lwentlalontle batya kakhulu emva kwamava oxinzelelo kunabo baneempendulo ezisezantsi ze-cortisol []. Ukungeniswa kwemeko yeemvakalelo engalunganga ngokukhumbula i-autobiographical yenkumbulo elusizi ikwanyuse isixa sokutya okutyiwayo kuphononongo lwe-non-dieters, kwaye isiphumo savakaliswa ngakumbi kubathathi-nxaxheba abachaze "ukutya ngokweemvakalelo" okukhulu []. Ngokungafaniyo neziphumo ezihlaziyiweyo kunye nento eyenzekayo kubadli abathintelweyo, abadli abangathinteliyo ncitshiswa ukutya kwabo okuneshwankana emva kokubukela ifilimu elusizi [, ].

Ukutya okunjalo okunefuthe elibi kunokuphazamisa ukugcinwa kobunzima bomzimba. Ubunzima bokubuyisela kwiinyanga ze-6 emva kokulahlekelwa kwesisindo esiyimpumelelo kudibaniswa nokutya ekuphenduleni iziganeko zobomi ezixinzelelekileyo, ukutya ngokuphendula isimo sengqondo esibi, kunye nokusetyenziswa kokutya ukulawula isimo sengqondo []. Mhlawumbi ngokufanelekileyo, ukongeza unyango lokuqonda ukunceda ukulawula isimo sengqondo kunye nokujongana, kwaye kungekhona nje ukutya kunye nokuziphatha, kunokunciphisa ukuphinda utyebe []

2.3 Ifuthe lokutya okunencasa kwindlela yokuziva kunye nomsebenzi womvuzo

Ukutya ekuphenduleni kwiimeko ezimbi ngokweemvakalelo kubonisa ukuba ukutya kakhulu kunokuba ngumzamo wokuzinyanga "ngokutya okuthuthuzelayo." Ukutya okuqhelekileyo okutyiwa ngexesha lokuzinkcinkca kudla ngokuba nencasa kwaye kuxinene ngamandla; ukuqhubela phambili, zihlala zizinto ezinekhabhohayidrethi ezinje ngezonka, ipasta, neelekese []. Ekuqaleni, ukutya okutyebileyo kwe-carbohydrate kunokuba nesiphumo esicetywayo sokuqinisa, kuba kunciphisa iingxelo zomsindo [] kunye noxinzelelo [] kunye nokwandisa ukuzola ngaphakathi kwe-1-2 yeyure yokusetyenziswa. Ukuphindaphindwa kokutya okunencasa okunjalo, nangona kunjalo, kunokuvelisa i-neuroadaptations yexesha elide kumvuzo wobuchopho kunye neendlela zoxinzelelo ezithi ekugqibeleni zikhuthaze iimpendulo ezidakumbisayo okanye ezixhalabileyo xa oko kutya kungasafumaneki okanye kusetyenzisiwe. Ngokuhambelana nale ngcamango "yecala elimnyama", emva kokutya ukutya okunamafutha aphezulu (41%) kwinyanga enye, amadoda kunye nabasetyhini abatshintshelwe kwi-fat-fat (25%), ukutya okune-carbohydrate ephezulu kubike ukwanda komsindo kunye nobutshaba ngexesha lokukhulelwa. kwinyanga elandelayo kunezifundo eziye zaqhubeka nokutya ukutya okunamafutha aphezulu []. Umsindo owongeziweyo usenokuba nesiphumo sokuncitshiswa kwamafutha okutya (okanye okuqondwa ukuba kuyathandeka) okanye ukusuka kwi-neuroadaptations ukuya kwi-carbohydrates eyandisiweyo yokutya.

Ukusetyenziswa okuphindaphindiweyo kokutya okunencasa kakhulu kunokuthoba i-dopaminergic umvuzo wesekethe ngeendlela ezibonisa ezo ziqhele ukubonwa kumlutha weziyobisi: kuncitshiswe ukufumaneka kwe-striatal dopamine D2 receptor kunye nokukhutshwa kwe-dopamine blunted [, ]. Ewe, abantu abatyebe kakhulu babonisa ukufumaneka okusezantsi kokufumaneka kwe-dopamine D2 receptor kunokwenza ulawulo olungatyebayo, kwaye oku kuncitshiswa kwe-D2 ye-striatal ihambelana ngqo ne-BMI [, ]. Ukusebenza kwe-Caudate ekuphenduleni kwi-milkshake yetshokholethi kukwancitshisiwe ekutyebeni kakhulu kubantu ababhityileyo []. Eli nqanaba lomsebenzi libonakaliswe ngokukodwa kubantu abane-polymorphism ye-TaqIA A1 ye-D2 receptor, ehambelana nokunciphisa i-D2 receptor expression []. Enye i-polymorphism edityaniswe nokunciphisa ukusebenza kwe-dopamine, i-7R allele ye-dopamine D4 receptor, iye yanxulunyaniswa ne-BMI ephezulu yokuphila kwi-bulimics [] kunye nokuzinkcinkca ngokuziphatha kwabasetyhini abanoxinzelelo lwamaxesha onyaka []. Idatha edibeneyo yemfuza icebisa ukuba umntu ajonge ekufumaneni ubunzima kubantu abanophawu oluphantsi lwe-striatal dopaminergic, kwaye kuye kwacingelwa ukuba abantu abanjalo batya kakhulu kwiinzame zokubuyisa umvuzo wokusilela. Idatha yamva nje icebisa, nangona kunjalo, ukuba ukunyuswa kobunzima (okanye ukuhambelana kokufumana ubunzima, mhlawumbi ukutya ukutya okunencasa) yehlisa umsebenzi we-striatal dopamine. Abasetyhini abane-BMI eyonyukileyo ngexesha leenyanga ezi-6 babonise ukunciphisa ukusetyenziswa kwe-caudate ekusebenziseni i-milkshake yetshokolethi kunabasetyhini abane-BMI ehlala izinzile, kunye nokunciphisa ukusebenza kwe-caudate kuhambelana nokunyuka kwe-BMI enkulu []. Ngokwahlukileyo, i-gastric bypass inyuse ukufumaneka kwe-D2 ye-striatal receptor ngaphakathi kweeveki ze-6 zotyando lwe-bariatric kwisifundo esincinci sabasetyhini abatyebe kakhulu [].

Ukufumaneka kwe-Striatal D2 receptor kwizifundo ezityebileyo ikwanxibelelana ngokuthe ngqo kunye ne-glucose metabolism kwimimandla ye-cortical yangaphambili egcina ulawulo lwe-inhibitory, kubandakanya i-dorsolateral prefrontal, i-orbitofrontal, kunye ne-anterior cingulate cortices []. Obu budlelwane bucebisa i-hypothesis yokuba kuncitshiswe ukumodareyithwa kwe-dopaminergic ukusuka kwi-striatum kunokukhokelela kulawulo oluthintelekileyo lokuthintela ukutya kwaye ngoko konyusa umngcipheko wokutya kakhulu. Mhlawumbi ngokulinganayo, ulungelelwaniso oluthe ngqo phakathi kokufumaneka kwe-D2 yokubulala kunye ne-glucose metabolism kwi-dorsolateral kunye ne-anterior cingulate cortices nayo ibonwe kwiziselo ezinxilisayo, kodwa hayi kulawulo olunganxiliyo okanye olungatyebi kakhulu [, ].

Ngokuhambelana nokuphononongwa kweyantlukwano yokuziphatha kwimpendulo yokungenisa kuxinzelelo, isitayile sokutya sikwahlula ukwahlula kwabantu ngeeprofayili zenkqubo ye-mesolimbic ye-dopamine eyahlukileyo. Abantu abangatyebanga kakhulu abachaze "ukutya ngokomzwelo" okukhulu babonise ukuncipha kwesiseko se-D2 receptor efumanekayo kwi-dorsal striatum xa kuthelekiswa nabantu abangadli ngokweemvakalelo; abo baphezulu ekuthinteleni kokutya baye bandisa i-D2 yokubopha kwi-dorsal striatum ekuphenduleni ukuvuselela ukutya xa kuthelekiswa nezo ziphantsi ekuthinteleni kokutya []. Ekugqibeleni, abatyebileyo abatyebileyo babonise ukunyuka kwe-D2 receptor ebophelelayo kwi-caudate ekuphenduleni indibaniselwano yokutya kunye nomceli mngeni we-methylphenidate xa kuthelekiswa nabantu abangadli ngokugqithisileyo., ].

3. Ubungqina "becala elimnyama" kwiimodeli zezilwanyana zokukhobokisa kokutya

Uphuhliso lweemodeli zezilwanyana lwalubalulekile ekuqinisekiseni ingqikelelo yokukhotyokiswa kokutya kunye nokuqala ukubonakalisa “icala elimnyama” layo. Iqela likaBart Hoebel likhokele indlela ekufanekiseni imiba yokukhotyokiswa kokutya kwiimpuku []. Ngelixa iimodeli zezilwanyana zingenako ukubandakanya zonke izinto ezintsonkothileyo zentlalo eziphembelela indlela yokutya ebantwini, zinenzuzo yokwahlula ngokulula phakathi kwezinto ezingaphambili kunye neziphumo zokuziphatha okufana nokutya, ukuseka ulawulo lokutya okungqongqo, kunye nokuvumela uviwo oluneenkcukacha ngakumbi. iindlela ezinxulumene nemolekyuli.

3.1 Ukungeniswa kweemeko ezifana nokurhoxa emva kokupheliswa kokufumaneka kokutya okunencasa

Ngokungqinelana ne-hypothesis "yokukhotyokiswa kokutya" eqalwe nguHoebel kunye noogxa bakhe, izifundo ezininzi kwiimodeli zezilwanyana ngoku ziye zabona iiprofayili zokuziphatha kunye ne-somatic ezifana nelizwe lokurhoxa kwizilwanyana ezirhoxisiweyo ekufikeleleni okwethutyana ekutyeni okunencasa. Ngokomzekelo, u-Hoebel kunye noogxa banikezela ubungqina bokuba imihla ngemihla ukuxhamla kwizisombululo eziphezulu zeswekile (umzekelo, i-25% ye-glucose okanye i-10% ye-sucrose) inokukhokelela ekuxhomekeke kwi-opioid engapheliyo. Iigundane ezibonelelwa nge-12-hr yemihla ngemihla yokufikelela kwi-glucose kunye ne-chow etshintshwe kunye ne-12-hr yokunqongophala kokutya ibonakaliswe iimpawu ze-somatic ezinxulumene nokuhoxiswa kwe-opiate, kubandakanywa ukuthetha kwamazinyo, ukungcangcazela kwe-forepaw, kunye nokuxubha kwentloko, xa ucelomngeni kunye ne-opioid antagonist naloxone []. Ukuhoxiswa okukhawulezileyo nge-naloxone pretreatment kuye kwandisa ukuziphatha okuxhalabisayo kwi-12-hr yezilwanyana ezijikelezayo ze-glucose imihla ngemihla, njengoko kuboniswe ngokunciphisa ixesha lengalo evulekileyo kwi-plus-maze ephakamileyo, kodwa kungekhona kwizilwanyana ezifumanayo. i-ad lib ukufikelela kwichow okanye iswekile []. Ukungabikho kwe-naloxone pretreatment, iimpawu ze-somatic zokuhoxiswa nazo zenzeke "ngokuzenzekelayo" i-24-36 hr emva kweseshoni yokugqibela yokufikelela kwi-glucose. Ukungabikho komceli mngeni we-naloxone, ukunyuka kokuziphatha okuxhalabisayo kwi-plus-maze kwabonwa kwizilwanyana ezijikelezayo emva kwe-36-hr ngokukhawuleza, xa kuthelekiswa i-ad lib i-chow feeded controls, ibonelela ngobungqina bemeko efana nexhala eliphakamileyo kwizilwanyana ezihamba ngeebhayisikile zihoxisiwe ekufikeleleni okwethutyana kwisisombululo seswekile [].

U-Hoebel kunye noogxa baye bacingela ukuba umsebenzi ocuthiweyo womvuzo kunye nokwanda kokuziphatha okuxhalabileyo ngexesha lokurhoxa kunokuvela ngokuyinxenye kutshintsho kwibhalansi ye-dopaminergic kunye ne-acetylcholinergic (ACh) yokusayina ngaphakathi kwe-striatum. Bafumene ukuba umngeni we-naloxone ukhuthaze ukukhululwa kwe-ACh enkulu kakhulu kwi-nucleus accumbens (NAc) yeegundane ezinembali ye-cyclic yemihla ngemihla ye-12-hr glucose kunye nokufikelela kwe-chow elandelwa yi-12 hr yokunqongophala kokutya kunezilwanyana ezigcinwe kuyo. i-ad lib chow []. Oku kwandiswa kwempendulo ye-ACh kukhatshwa kukuncitshiswa kwe-extracellular accumbens dopamine kulandela umngeni we-naloxone, efana nokwenzekayo ngexesha lokurhoxiswa kwe-morphine [, ]. Emva kwe-36-hr ngokukhawuleza, izilwanyana ze-glucose / i-chow-cycled zine-dopamine ephantsi kunye namanqanaba aphezulu e-ACh e-extracellularly kwi-NAc nangona ukungabikho kwe-naloxone, kwakhona kufana nesimo esizenzekelayo sokurhoxiswa kwe-opiate ngexesha lokuyeka ukutya kwe-glucose []. UHoebel kunye noogxa bacebisa ukuba olu tshintsho lubhekiselele ekukhululweni kwe-ACh ephuculweyo kunye nokuncipha kokukhutshwa kwe-dopamine kunokubonakalisa inguqu ebanzi yokuziphatha kude ne-dopamine-mediated approach behavior kunye nokuphepha ingozi [].

Ukusebenzisa ukutya okuqinileyo okutyebileyo ngeswekile, endaweni yokutya okungamanzi, iCottone okqhubekayo. ngokufanayo kufunyanwe ngokuzenzekela ukonyuka kokuziphatha okuxhalabileyo kwiimpuku ezirhoxisiweyo ekufikeleleni okwethutyana kwi-high-sucrose, ukutya okunencasa yetshokolethi. Iigundane ezibonelelwe ngokutshintshana kwe-5-day / 2-day ukufikelela kwi-chow yebhubhoratri eqhelekileyo kunye nokutya okunencasa okuchitha ixesha elincinci kwiingalo ezivulekileyo ze-plus-maze ephakamileyo kunye nexesha elingakumbi ngaphakathi kwegumbi lokurhoxisa kumsebenzi wokurhoxisa okhuselayo xa uvavanywa ngexesha le-chow. isigaba somjikelo wabo wokutya [, ]. Ukonyuka kokuziphatha okufana nokuxhalaba kukhatshwa kukonyuka kokubonakaliswa kwento enxulumene noxinzelelo lwe-neuropeptide corticotropin-releasing factor (CRF) kumbindi we-amygdala (CeA), inkqubo ekwasebenza ngexesha lokurhoxa etywaleni.-], amayeza [-], icocaine [], ii-cannabinoids [], kunye nenikotini [, ]. Unyango lwangaphambili ngeCRF ekhethiweyo1 umchasi we-R121919 uthintele ukurhoxiswa kokutya okunxulunyaniswa nokuxhalaba kwiidosi ezingazange zitshintshe indlela yokuziphatha yolawulo lokondliwa kwe-chow [-]. Analogously, CRF1 abachasi baphucula i-aversive- okanye ixhala-lilizwe ngexesha lokurhoxa etywaleni [, , ], amayeza [, ], benzodiazepines [], icocaine [, ], kunye nicotine []. CRF1 I-Antagonist pretreatment iphinde yaphazamisa inqanaba apho izilwanyana ezijikeleza ngokutya zigqithise ukutya okutyebileyo kwe-sucrose ekufumaneni okuhlaziyiweyo kwiidosi ezingazange zitshintshe ukulawulwa kwe-chow-feed okanye izilwanyana ezondla ukutya okutyebileyo kwe-sucrose, kodwa ngaphandle kwembali yokutya ibhayisekile. . Ngokulinganayo, CRF1 abachasi banciphisa ukusela utywala ngokugqithisileyo [, -], icocaine [], amayeza [], kunye nicotine [] kwimifuziselo yokukhotyokiswa, ngelixa uneziphumo ezincinci kwiziyobisi notywala ukuzilawula kwezilwanyana ezingaxhomekekanga.

Xa izilwanyana ezijikeleza ngokutya zazifundisiswa ngelixa zifumana ukufikelela kokuthandwayo, ukutya okutyebileyo kwe-sucrose, zombini i-plus-maze yokuziphatha kunye namanqanaba e-CEA CRF aqhelekile, exhasa i-hypothesis yokwandisa ukusebenza kwenkqubo ye-amygdala ye-CRF kunye nokuziphatha okufana nokuxhalaba kubonisa ukurhoxa. chaza [, ]. Okokugqibela, iigundane ezijikeleza ngokutya zikwabonise ukonyuka kobuntununtunu be-CeA GABAergic neurons ekumodareyithweni yiCRF.1 inkcaso. I-R121919 icuthe amandla e-postsynaptic e-evoked inhibitory inhibitory kwi-CeA ukuya kwinqanaba elikhulu kwiimpuku ezijikeleza ngokutya kunolawulo lokutyiswa, ebonisa impembelelo eyongeziweyo yokumodareyitha yeCRF.1 abachasi kwi-CeA GABAergic synaptic transmission ebonwa ngexesha lokurhoxa etywaleni []. Ke ngoko, ipateni yokurhoxa kokutya okunencasa okuhambelana nokunyuka kwentetho ye-CeA CRF kunye nokuziphatha okuxhalabileyo, ukunyuka kokungena ekufikeleleni okuhlaziyiweyo, kunye nokuguqulwa kwendlela yokuziphatha ngeCRF.1 I-antagonist pretreatment ifana neziphumo kuzo zombini iziyobisi kunye notywala [-].

Kwisifundo esahlukileyo, iCotton okqhubekayo. Kwakhona kwafumanisa ukuba iimpuku zabasetyhini ezinembali yokufumana umda kakhulu (i-10 min/day) ukufikelela kwi-chocolate-flavored efanayo, ukutya okutyebileyo kwe-sucrose kubonisa kungekuphela nje ukunyuka okumangalisayo kokutya okunencasa (ukutya ngaphezulu kwe-40% yemihla ngemihla. Ukungenisa ngaphakathi kwe-10 min), kodwa kunye nokunciphisa okufana ne-anxiogenic kwi-plus-maze evulekileyo yengalo evulekileyo xa kufundwa i-24 hr emva kweseshoni yabo yokugqibela yokufikelela []. Iigundane zebhayisikile yokutya ezichitha ixesha elincinci kwiingalo ezivulekileyo nazo zazizitya kakhulu kwisidlo esinencasa, ulungelelwaniso olungabonakali kulawulo lwe-chow-fed. Ezi ziphumo zixhasa ingqikelelo kaHoebel yokuba ufikelelo ngethutyana kukutya okunencasa okutyebileyo kwe-sucrose kukhokelela kungekuphela nje ekutyeni okufana nokutya, kodwa nakwimeko efana nokurhoxa yokuxhalaba okwandileyo ngokunxulumene ngqo nokutya okufana noko.

3.2 Iswekile xa ithelekiswa nokukhotyokiswa ngamafutha: Ngaba kukho umahluko?

U-Hoebel kunye noogxa nabo basandul 'ukucebisa ukuba kunokubakho into eyahlukileyo malunga nekhono leswekile elula (vs. amafutha) ukukhuthaza "umlutha wokutya" []. Ngelixa iimpawu ezifana ne-somatic kunye nexhala-ezifana nokurhoxa ziye zabonwa emva kokuyekwa kofikelelo okwethutyana kwizisombululo zeswekile okanye ukutya okuqinileyo, imeko yeempawu zokurhoxa ezilandela izidlo ezibandakanya uninzi lwamafutha okanye imixube yamafutha aswiti ayicacanga kangako. Njengokutya kweswekile, iimpuku ziphuhlisa iipateni zokutya xa zifumana ufikelelo ngamanqatha asulungekileyo anje ngokuncipha kwemifuno [] kunye nemixube ye-chow yamafutha aswiti []. Ngokungafaniyo neziphumo eziqinileyo zokurhoxiswa kwe-opiate-efana ne-glucose-cycled rats, nangona kunjalo, umngeni we-naloxone kunye nokuzila ukutya akuphumelelanga ukuvelisa iimpawu zokurhoxisa ezifana ne-opiate-efana ne-somatic kwi-rats kunye nokufikelela okuphakathi kwi-fat fat or sweet-fat chow [].

Sekunjalo, ukunqongophala kweempawu ezinjengokurhoxa kwe-somatic opiate akuthinteli uphuhliso olunokwenzeka lwemeko yeemvakalelo engalunganga kwizilwanyana ezirhoxiswayo ekutyeni okunamafutha aphezulu (okt "ukurhoxa okusebenzayo"). Ewe, abanye baye babona iimpendulo ezitshintshileyo zokuziphatha kuxinzelelo oluthambileyo emva kokususwa kokutya okunamafutha aphezulu. Iigundane zigcinwe ngokuqhubekayo kwi-fat-fat diet zibonise umsebenzi owandisiweyo kuvavanyo oluvulekileyo lwe-24 hr emva kokutshintshwa kwi-chow eqhelekileyo, umphumo ongabonakali kwiigundane ezihoxisiweyo kwi-high-sucrose diet []. Ngaphezu koko, ukurhoxa kweyure ezingama-24 ekutyeni okunamafutha aphezulu nako kubangele ukonyuka kwamanqanaba eCRF mRNA kwi-CeA [], ezifana neziphumo zeCottone okqhubekayo. ngokutya okutyebileyo kwi-sucrose []. Kwelinye icala, iyantlukwano yeqela ayizange ibonwe kwezinye izikhombisi zokuziphatha okuxhalabileyo, kubandakanya ukungcwatywa kwebhastile okanye ukuziphatha okuphakamileyo kwe-plus-maze. Iingqwalasela ezongezelelweyo zokutolika iziphumo ezivela kolu vavanyo lwe-vis-à-vis kwizifundo eziphononongwe ngaphambili zeswekile "ukurhoxiswa" zibandakanya ukuba ukutya okunencasa kwabonelelwa ngokuqhubekayo kunokuba ngamaxesha athile; ukuba ukutya okunamafutha aphezulu apha kwakuthandwa kakhulu kunokutya okune-sucrose ephezulu; kwaye ukutya okune-sucrose ephezulu kwakuyingxubevange ye-macronutrients, kunokuba kukutya okuninzi kweswekile okanye okucocekileyo.

Iimpawu ezinjengokurhoxa zokuxhalaba xa kususwa ukutya okunencasa nako kusenokumodareyithwa yimiba yemfuzo. Umqhaphu okqhubekayo. wabona ukungafani komntu ngamnye kwiqondo apho iigundane zixhamla kwi-high-sucrose yokutya ehambelana neqondo labo lokuziphatha okuxhalabileyo kwe-24-hr emva kokufikelela []. Ukuchola okqhubekayo. yafumanisa ukuba ukutyeba, kodwa kunganyangeki ukutyeba, iigundane zibonise umsebenzi oncitshisiweyo phakathi kwebala elivulekileyo kwiiveki ze-2 emva kokutshintshelwa kwisidlo esiqhelekileyo se-chow emva kweeveki ze-7 zokufikelela kwi-fat high-fat, yokutya okushukela ophezulu. []. Izilwanyana ezityebileyo ziqhubekile nokutya i-chow enxulumene nolawulo lwe-chow kuphela kunye nezilwanyana ezixhathisa ukutyeba kwiiveki ezintathu zokurhoxiswa.

Iimpuku eziyekiweyo kwizidlo ezikhethwayo nazo ziyakunyamezela iziphumo ezibi zokufumana ufikelelo ngokutsha [, ]. Umzekelo, iimpuku eziye zarhoxiswa kukutya okunamafutha aphezulu zichitha ixesha elininzi kwindawo ekhanyayo ekhanyayo apho zinokutya i-pellet enamafutha aphezulu kunokuba iimpuku ezingarhoxiswanga ekutyeni okunamafutha aphezulu okanye ulawulo olutyiswe kakhulu []. Iigundane ezinembali yokufikelela okwandisiweyo kwisidlo sokutya esinencasa nazo azizange zinciphise ukuphendula ngokutya okunencasa ngaphandle kobukho be-footshock-conditioned cue []. Ukuziphatha kokugqibela kufana nokuzingisa kokufuna i-cocaine kwiimpuku ngaphandle kobukho be-cue exela kwangaphambili ukothuka kweenyawo. Iziphumo zibonisa ukuphuhliswa kwendlela yokunyanzeliswa yokutya, mhlawumbi ifana nokunyanzeliswa kweziyobisi, ezixhathisayo kwiziphumo ezinokuthi zithintele [].

3.3 Ukufuna ukutya kunye nokutya okubangelwa luxinzelelo

Ngenxa yokuba ukutya okunencasa kunokuba nefuthe elibi, okanye "intuthuzelo," imiphumo, ukuxhalaba okuphezulu kunye noxinzelelo alukho nje imiphumo yokuhoxiswa ekutyeni okunencasa, kodwa kunye nezinto ezikhuthazayo ezikhuthaza ukuphinda uthabathe emva kwexesha lokuyeka. Ngokwandiswa, ukunyuka kwenkuthazo yokufumana, ukutya kunye nokukhetha ukutya okunencasa "okuthuthuzelayo" phantsi koxinzelelo lwendalo kunokucingelwa ukubonisa iinkqubo zokuqinisa ezingalunganga ezifana nezo zisebenza ngexesha lokurhoxiswa kokutya okunencasa [, , , ]. Ukukwazi okusekwe kakuhle kokusetyenziswa kokutya okunencasa phantsi kweemeko ezithile ukuze kuthintelwe ukusebenza kwangaphandle kweenkqubo zoxinzelelo, njengoko kungqinwa kukuziphatha, ukuzimela, i-neuroendocrine, kunye nemilinganiselo ye-neurochemical [-], ixhasa ngamandla le ngcamango.

Mhlawumbi ngokufanelekileyo, i-alpha-2 adrenergic antagonist yohimbine, i-pharmacological stressor evelisa ukuxhalaba okuphezulu ebantwini kunye neempuku, kwaye oko kubangela ukubuyiselwa kwe-cocaine-, utywala-, kunye nokuziphatha kokufuna i-methamphetamine kwiimpuku [-], kwakhona kubangela ukubuyiselwa kokuphendula kwiipellets zokutya okunencasa kunye nezisombululo ze-sucrose [-]. I-Yohimbine ibangela ukubuyiselwa kokufuna iipellets zokutya eziqulethe amandla ahlukeneyo, kubandakanywa ne-non-sucrose carbohydrate, i-sucrose kunye ne-fat-fat pellets, kodwa kungekhona amandla angenawo amandla kwaye, mhlawumbi kunye ne-fiber pellets engathandekiyo.]. Iinkqubo ezininzi ze-neurotransmitter ziye zabandakanyeka njengeemodyuli ezisezantsi kwesi siphumo, kubandakanya iCRF, i-orexin, kunye neenkqubo ze-dopaminergic. Unyango lwangaphambili olucwangcisiweyo kunye neCRF1 i-receptor antagonist i-antalarmin inqanda ngamandla ukubuyiselwa kwe-yohimbine-indeed yokubuyiselwa kokutya okunencasa okufunayo [], njengoko kwenza unyango lwangaphambili kunye nomchasi we-orexin-1 u-SB334867[]. Indawo (s) yezenzo zale mixube ekuthinteleni i-yohimbine-induced reinstatement ayisaziwa. Ngokusekwe kwi-neuroanatomy yoxinzelelo- okanye i-yohimbine-indeed ukubuyiselwa kokufuna iziyobisi [], nangona kunjalo, imimandla echaphazelekayo kwi-amygdala eyandisiweyo okanye ekulawuleni inhibitory ngabaviwa abafanelekileyo. Ewe, i-microinjection yeCRF kwi-nucleus accumbens inokwenza i-cue-induced response for sucrose [] kunye nolawulo lomchasi we-dopamine D1 SCH23390 kwi-dorsomedial prefrontal cortex inokuthoba i-yohimbine-induced ukubuyiselwa kokufuna ukutya [].

Iimeko zokusingqongileyo ezinoxinzelelo nazo zinokukhuthaza ukutyiwa okuthe gqolo kokutya okunencasa ziimpuku. Ngaphantsi koxinzelelo oluguquguqukayo oluguquguqukayo, iimpuku zikhetha ngaphezulu kwekhalori yazo yemihla ngemihla ekutyeni okunamafutha aphezulu, kunokuba zisuka kwiprotheyini ephezulu okanye kwiindlela zokutya eziphezulu zecarbohydrate []. CRF2 iimpuku ezinqongopheleyo, ezibonisa impendulo ebaxiweyo ye-HPA-axis kuxinzelelo, zonyusa ukutya kwazo okunamafutha aphezulu kulandela uxinzelelo oluguquguqukayo oluguquguqukayo ukuya kwinqanaba elikhulu kunolawulo lohlobo lwasendle, ukuba ukutya okunamafutha aphezulu kubonelelwa nge-1hr yonke imihla kunokuba ad adum. Ezi mpuku zikwabonisa ukunciphisa ukukhutshwa kwe-CORT ekuthinteleni uxinzelelo emva kweeveki ze-2-3 zokuvezwa ngaxeshanye kunamafutha aphezulu, i-carbohydrate, kunye neprotheyini yokutya ngexesha loxinzelelo oluguquguqukayo [].

U-Boggiano kunye noogxa bakhe bachonge ubudlelwane be-synergistic phakathi kokuthintelwa kokutya kunye noxinzelelo ekukhuthazeni ukutya okufana nokutyiwa kweempuku ezinokuthi zibe ngumzekelo wobudlelwane obuhlaziyiweyo bokuthintela ukutya kunye noxinzelelo ekuqaliseni ukutya kakhulu ebantwini. Kulo mzekelo, akukho mbali yesithintelo se-caloric okanye i-footshock yodwa yanele ukukhuthaza ukutya okufana nokutya okuhlobene nokungaxinzelelwanga + okungathintelwanga iigundane ezondliwa nge-chow. Endaweni yoko, indibaniselwano yemijikelo ephindaphindiweyo yesithintelo sokutya + ukushukuma kweenyawo kukhokelela ekwandeni kokutya okunencasa (icookies) kulandela uxinzelelo [, ]. Ukutya okwandisiweyo akuqhutywa yimfuno yangoku ye-metabolic kuba ishedyuli yokutya ivumela amaqela athintelweyo ukuba aphinde azondle kwi-chow kubunzima bomzimba obuqhelekileyo ngaphambi komngeni we-footshock []. Ukuba kuphela i-chow eqhelekileyo ekhoyo, akukho kuziphatha okufana nokuzingxala okwenzekayo, kodwa ukuba isampulu encinci yokutya okunencasa ibonelelwa ecaleni kokutya okuqhelekileyo kwe-chow, ke iigundane ziyaqhubeka nokuzintyintya kwi-chow. Ezi datha zifana neziphumo ezivela kwibulimics yabantu, abanokuthi baqalise ukuzinkcinkca ngotywala (nakuphi na ukutya) ukuba baqale batye ukutya okunqwenelekayo []. Amanye amaqela aqaphele ukuziphatha okufana nokufana nokulandela imbali yokuthintela ukutya okujikelezayo ukuba i-footshock stressor ithathelwa indawo yi-15-min yexesha lokuvezwa okubonakalayo kunye nokuvumba kokutya okunencasa, ngexesha apho ukusetyenziswa akuvumelekanga []. Nangona utshintsho oluchanekileyo lwe-neurobiological olubangelwa yimijikelo ephindaphindiweyo yothintelo, uxinzelelo, kunye nokondla kusafuneka kucaciswe, i-opioids engapheliyo inokuba negalelo ekuziphatheni okufana noxinzelelo. Umceli mngeni weNaloxone uyancipha kwaye i-mu/kappa agonist butorphanol yonyusa ukutya okunencasa kwiqela elithintelweyo+ elinoxinzelelo ngokukodwa [],

3.4 Ilahleko yexabiso le-hedonic yezivuseleli ezivuzayo ngaphambili

Olunye lweempawu “zecala elimnyama” lokukhotyokiswa ziziyobisi kukukhula kokunyamezelana, apho izixa ezikhulu nezikhudlwana zechiza kufuneka zivelise isiphumo esifanayo se-hedonic. Imiyinge emincinci ayisabonwa njengomvuzo. Ilahleko efanayo yokuphendula kwe-hedonic kwimbuyekezo yokutya inokwenzeka kwizilwanyana ezinembali yokufikelela kokutya okunencasa. Enyanisweni, u-Hoebel kunye noogxa babona ukunyuka okukhulu kwe-glucose kwimihla elandelelanayo ye-12-hr ukufikelela okulinganiselweyo kunye nokunyuka kokusetyenziswa kwe-glucose ngokukhawuleza ngexesha leyure yokuqala yokufikelela, ehambelana nokuphuhliswa kokunyamezela kunye nokutshintshela ekudleni okufana nokutya.] Inkuthazo eyandisiweyo yokufumana ukutya kweglucose iye yabonwa emva kweeveki ezimbini zokuzila []. Abanye abaphandi baye baphinda baphindaphinda ukunyuka okufana nokunyuka okunokuthi kubonise ukunyamezela usebenzisa iintlobo zezidlo kunye namaqondo okufikelela okulinganiselweyo [, , , ].

Ikwanokufana nonyamezelo, eminye imbuyekezo eyamkelekileyo ngaphambili iye ingasebenzi kakuhle ekuxhaseni ukuphendula kwabasebenzi kunye nokubandakanya umvuzo we-mesolimbic. Iigundane ezifumana ukufikelela okwethutyana kwi-chocolate-flavored, ukutya okutyebileyo kwe-sucrose kukhula ngokuqhubekayo kwamanqaku okuphumla aphantsi xa ucelwa ukuba aphendule ngokuthandwa kancinci, kodwa ngenye indlela emnandi, i-chow ye-corn-syrup eneswiti kwishedyuli yomlinganiselo oqhubekayo []. Iintsilelo zenkuthazo zokufumana ukutya okungathandwa kakhulu kuyayekwa ngonyango lwangaphambili ngeCRF1 umchasi, mhlawumbi ngokufana nesakhono seCRF1 umchasi wokubuyisela umva umsebenzi womvuzo ongafanelekanga ngexesha lokurhoxiswa kwe-nicotine [].

Obunye ubungqina beempendulo ezincitshisiweyo kwizinto ezingemnandanga kangako, enye imbuyekezo ivela kuvavanyo lwe-microdialysis apho amanqanaba e-extracellular dopamine alinganiswa kwiimpuku ezinembali yokufikelela kwisidlo sokutya. I-Cafeteria-isondlo sokutya iziphumo kumanqanaba asezantsi e-basal ye-dopamine kwi-nucleus accumbens emva kweeveki ezili-14 zofikelelo, kunye nokukhutshwa kwe-dopamine esezantsi yokuvuselela kuzo zombini i-accumbens kunye ne-dorsal striatum []. Kwiimpuku ezondliwe, ukonyuka kwe-dopamine efflux kwajongwa ekuphenduleni kwisidlo se-chow yelabhoratri eqhelekileyo, ngelixa oku kunyuka kwakungasajongwa kwi-cafeteria-diet feed rats. I-Dopamine efflux ekuphenduleni enye inkuthazo evuzayo, i-amphetamine, nayo yancitshiswa ngokuphawulekayo kwi-cafeteria-diet feed rats. Ukutya kwe-cafeteria, nangona kunjalo, kuqhubekile nokuvuselela i-dopamine efflux kwi-accumbens, iphakamisa ukuba ukuqhubeka nokutyiwa kokutya kwe-cafeteria kuyafuneka ukuze ezi zilwanyana zithintele ukukhutshwa kwe-dopamine engapheliyo []. Ukuphazamiseka kokufumana ukutya okunencasa kunokuchaphazela amandla ayo okugcina ukukhutshwa kwe-striatal dopamine. Kwiimpuku ezine-12-hr yokufikelela okwethutyana kwi-sucrose, i-sucrose iyaqhubeka nokuvuselela i-dopamine efflux kwi-accumbens emva kweeveki ezintathu, kodwa esi siphumo siyalahleka kwizilwanyana ezine. ad adum ukufikelela kwi-sucrose [].

I-Intracranial lateral hypothalamic self-stimulation thresholds nayo yonyuka kwiimpuku ezibonelelwa ngofikelelo olwandisiweyo, kodwa olungasikelwanga mda, ekutyeni okunencasa yecafeteria. []. Ukunyuswa komda wokuzivuselela, isalathiso sokungasebenzi kakuhle komvuzo wobuchopho, sivela ngaxeshanye nophuhliso lokutyeba okubangelwa kukutya kunye nokuqhubekeka nasemva kokuba uyekile ukunyanzelwa ekutyeni isithuba seeveki ezimbini. Ngokufana neziphumo eziphononongiweyo ngaphambili ebantwini, amanqanaba e-striatal dopamine D2 receptor nawo ancitshiswe ngokuphawulekayo emva kokufikelela okwandisiweyo kwisidlo sokutya; I-lentivirus-mediated knockdown ye-D2 receptor expression ikhawulezise ukonyuka komvuzo, ibandakanya indima ebangela le neuroadaptation ebangelwa kukutya kwinkqubo yomvuzo wengqondo elandelayo []. Ukunciphisa ukubopha i-D2 yokubulala [] kunye ne-D2 receptor mRNA [] ziye zabonwa ekuphenduleni kwimihla ngemihla, ukuxhamla-okufana nokufikelela okulinganiselweyo kwi-sucrose, ngelixa i-D3 receptor mRNA kunye ne-dopamine transporter expression yonyuka []. Ukuhanjiswa kwe-mesolimbic dopaminergic encitshisiweyo kunokuba nefuthe elisebenzayo kumngcipheko wokufumana ubunzima, kuba iigundane ezityebileyo zinamanqanaba asezantsi e-basal extracellular dopamine kwi-accumbens kunokwenza iigundane ezixhathisa ukutyeba nangaphambi kokuhlukana kobunzima, kwaye inaliti ye-lipid emulsion ayiphumelelanga ukunyusa i-accumbens. Amanqanaba e-dopamine kwiqela elithanda ukutyeba kakhulu []. Ngokwahlukileyo, uthintelo lokutya lunxulunyaniswa nokunyuka kwamanqanaba e-D2 kwiigundane ezityebileyo zeZucker []. Lilonke, iziphumo zibonisa ukuba ukutya okunencasa kunokukhokelela kukuphazamiseka okuhlala ixesha elide kwiinkqubo zomvuzo wobuchopho.

4. Izigqibo

Kanye njengoko utshintsho olusuka kusetyenziso lweziyobisi luye ekuxhomekekeni lukhatshwa kukuthotywa komvuzo wokujikeleza kwengqondo kunye nokwandiswa ngaxeshanye komjikelo wesekethe “yokungarholi”, kunjalo ke ukuguqukela ekubeni likhoboka lokutya kubonakala ngathi kubandakanya “icala elimnyama.” Uphononongo lwabantu abatya kakhulu, abasimilo sabo sisondelelene kakhulu nengqikelelo yangoku yokukhotyokiswa kokutya, luchaphazele uxinzelelo kunye nexhala kunye nemeko yoxinzelelo kuphuhliso kunye nokugcinwa kolu tshintsho lokutya ukutya okunencasa ngenxa yeziphumo ezibi zokomeleza.

Izifundo zezilwanyana, eziqalwe ubukhulu becala liqela likaBart Hoebel kwaye ngoku zizuza ngamandla, sele ziqalisile ukucacisa iindima ezithile zeshedyuli yokutya, ukwakheka, kunye nokuthanda ukuguqula iinkqubo zoxinzelelo lwendlela yokuziphatha, i-neural, kunye ne-endocrine kunye nokuthomalalisa iimpendulo ze-hedonic ukutya nezinye iimbuyekezo. Nangona kunjalo, imingeni ebalulekileyo isekhona. Umsebenzi othe kratya uyafuneka ukufikelela kwimvumelwano kwiikhrayitheriya zokuxilonga ukukhotyokiswa kokutya ebantwini. Ukucokiswa kweendlela ezinjalo kuya kuqhubela phambili uphuhliso lweemodeli zezilwanyana ezifanelekileyo ukufunda ngcono eyona miba ibaluleke kakhulu kwesi sifo.

​ 

Iziphumo eziphambili zophando

  • Ukukhotyokiswa ziziyobisi “kunecala elimnyama” elibandakanya ukukhululeka kwiimeko ezimbi.
  • Icala elimnyama elifanayo linokubaluleka ekuphuhliseni umlutha wokutya.
  • Stress and negative affect can trigger excess consumption of palatable foods.
  • Ukutya okuphindaphindiweyo okunencasa kuguqula umvuzo wobuchopho kunye nokujikeleza koxinzelelo.

Imibulelo

Financial support for this work was provided by the Pearson Center for Alcoholism and Addiction Research, the Harold L Dorris Neurological Research Institute, and grants DK070118, DK076896, and DA026690 from the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Imihlathi

 

Ukugqubana kwemidla

I-EPZ kunye ne-GFK ngabaqambi kwi-patent efakwe kwi-CRF1 abachasi (USPTO Applicaton #: #2010/0249138).

 

 

Iphepha elichazayo ukuba awusenanto oyifunayo: Le fayili yeFayile yombhalo wesandla ongabhalwanga owamkelwe ukushicilelwa. Njengenkonzo kumakhasimende ethu sinika le ngcaciso yokuqala kwincwadi yesandla. Umbhalo wesandla uza kufumana ukukopishwa, ukufakela, nokuphonononga ubungqina obunokubakho ngaphambi kokuba kukhutshwe kwifomu yayo yokugqibela. Nceda uqaphele ukuba ngexesha lokuveliswa kweeprogram ezinokuthi zifumaneke ezinokuthi ziphazamise umxholo, kunye nazo zonke izisemthethweni ezichasayo ezisetyenziswa kwiphephancwadi.

 

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