PLoS One. 2013; 8 (9): e74645.
Ipapashwe kwi-intanethi ye-2013 Sep 10. doi: 10.1371 / journal.pone.0074645
PMCID: PMC3769238
UJohannes W. de Jong,1 Karin E. Meijboom,1 Louk JMJ Vanderschuren,1,2 kwaye URoger AH Adan1,*
USilvana Gaetani, uMhleli
Abstract
Ubhubhani wokutyeba emhlabeni wonke usesisongelo esikhulu nesandayo kwimpilo yoluntu. Nangona kunjalo, iindlela ze-neurobehavioral zokutya kakhulu kunye nokukhuluphala aziqondwa ngokupheleleyo. Kuye kwacetywa ukuba iinkqubo ezinjengomlutha zinokuba phantsi kweendlela ezithile zokutyeba, ngakumbi ezo zinxulunyaniswa nengxaki yokutya ngokugqithisileyo. Ukuphanda indima yeenkqubo ezinjengomlutha ekutyebeni, silungelelanise imodeli yokuziphatha okufana ne-cocaine kwiimpuku eziphendula ukutya okunencasa kakhulu. Apha, sivavanye ukuba ingaba iimpuku ziphendula itshokolethi enencasa kakhulu. Siphinde saphanda ukuba ukuvezwa kwimodeli yokuzinkcinkca (ukutya okubandakanya amaxesha okutshintshana kofikelelo lokutya okulinganiselweyo kunye nokufikelela ekutyeni okunencasa kakhulu), ikhuthaza inkangeleko yokuziphatha okunjengokutya. Idatha yethu ibonisa iyantlukwano enkulu yomntu ngamnye kulawulo lokufuna ukutya okunencasa kunye nokuthatha, kodwa akukho qela lahlukileyo lezilwanyana ezibonisa ukuziphatha okufana nokukhobokisa kunokuchongwa. Endaweni yoko, siye sabona uluhlu olubanzi olusuka kulawulo oluphantsi ukuya oluphezulu kakhulu lokutya okunencasa. Ukuvezwa kwimodeli ye-binge akuzange kuchaphazele ulawulo lokufuna ukutya okunencasa kunye nokuthatha, nangona kunjalo. Izilwanyana ezibonise ulawulo oluphantsi lokutya okunencasa (okt, amanqaku aphezulu kwiikhrayitheriya ezintathu zokuziphatha okufana nomlutha) azizange zibe nobuntununtunu ekuthotyweni komvuzo wokutya kwaye zithambekele ngakumbi ekubuyiseleni okubangelwa kukutya kokuphendula okucinyiweyo, nto leyo ebonisa ukuba ulawulo olumnandi. Ukutya okudliwayo kunxulunyaniswa nokutya okuqhelekileyo kunye nokuba sesichengeni sokubuyela umva. Ukuqukumbela, sibonisa imodeli yezilwanyana ukuvavanya ulawulo lokufuna ukutya kunye nokuthatha. Kuba ukuncitshiswa kokulawulwa kokutya yeyona nto iphambili kuphuhliso lokutyeba, ukuqonda indlela yokuziphatha kunye ne-neural underpinnings kungaququzelela ulawulo oluphuculweyo lobhubhani wokutyeba.
intshayelelo
Ukutyeba kakhulu sisisongelo esikhulu kwimpilo yoluntu, kuba kwandisa umngcipheko wesifo seswekile, isifo sentliziyo kunye nomhlaza [1,2]. Amazinga okuxhaphaka kokutyeba aye anyuka ngokuthe ngcembe ngokunyuka okulindelekileyo ngo-2030 wezigidi ezingama-65 kunye ne-11 yezigidi zabantu abadala abatyebe kakhulu e-USA nase-UK, ngokulandelanayo [2]. Ukuxhaphaka kwangoku kokukhuluphala (kuchazwa njengesalathisi somzimba> 30 kg / m2) malunga ne-33% e-US kwaye ngaphezu kwesiqingatha samazwe angamalungu e-EU anamanqanaba okutyeba > i-20% [3,4]. Ngaphandle kokuxhaphaka kwayo okuphezulu, i-neural kunye nokuziphatha okungaphantsi kokutyeba akuqondwa ngokupheleleyo.
Kuye kwacetyiswa ukuba iindlela ezithile zokutya okugqithisileyo okuhambelana nokutyeba kulungelelaniswe yinkqubo efana nomlutha [1,2,5-11]. Nangona ubungakanani bobukhoboka bokutya obunokuchaza ubhubhani wokutyeba kuxhomekeke kwingxoxo-mpikiswano enkulu [2,12-14]. Ukuxhasa indima yeenkqubo ezinjengomlutha wokutyeba, kukho ukugqithelana phakathi kwenkqubo ye-DSM-IV yokuxhomekeka kweziyobisi kunye neendlela ezicetywayo zokuphazamiseka kokutya kokutya [3,4,15,16] kunye nokutyeba [1,2,17]. Ngaphaya koko, i-comorbidity phakathi kokuphazamiseka kokutya kunye nokusetyenziswa kakubi kweziyobisi kunokuba phezulu ukuya kuma-40% [18]. Ngokubhekiselele koku kuye kwacetyiswa ukuba (ngaphezulu) ukutya kunye nokusetyenziswa kweziyobisi kuxhomekeke kwi-neural circuitry efanayo [19]. Enye indlela ekwabelwana ngayo ye-neural kukuncipha kokufumaneka kwe-dopamine D2 receptor kwi-striatum efumaneka kuzo zombini iziphazamiso [20-24], ukufunyaniswa okuqinisekisiweyo kwimodeli yezilwanyana yokutya okunyanzelekileyo [25]. Okunye ukufana kubandakanya ipateni efanayo yomsebenzi wobuchopho emva kokunqwenela kunye nokucinezelwa kwenkanuko [26-30[31-36].
Siye saxoxa ngaphambili ukuba iimodeli ezisandul 'ukuphuhliswa ezivela kwindawo yokulutha iziyobisi kunokuba luncedo ukuphanda ingqikelelo yokukhotyokiswa kokutya [15]. Kwi-2004, uDeroche-Gamonet et al. uphuhlise imodeli yokuziphatha okufana nokulutha kwiimpuku, ngokusekwe ekuphulukaneni nolawulo lokusela i-cocaine [37]. Kule modeli, iimpuku zizinika i-cocaine yonke imihla kangangeenyanga ezininzi. Izilwanyana zavavanywa kwiiparamitha zokuziphatha ezintathu ezisekelwe kwiikhrayitheriya ze-DSM-IV zokuxhomekeka kwento, okt 1) Ubunzima bokunciphisa ukufuna ngexesha lokungafumaneki okuphawulweyo. 2) Inkuthazo ephezulu kakhulu yokufuna kunye nokuthatha ichiza. 3) Ukuqhubeka nokufuna ichiza ngaphandle kweziphumo ezibi. Kwafunyaniswa ukuba iqelana leempuku (17,2%) lafumana amanqaku ngaphakathi kwitertile ephezulu kwikhrayitheriya nganye, engaphezulu lee kunoko bekulindelekile ngamabona-ndenzile (okt, 3,6%). Ukongeza, ezi zilwanyana zibonakala ngathi zisesichengeni sokubuyiselwa kweziyobisi ezicinyiweyo, imodeli yokubuyela ekusebenziseni kakubi iziyobisi emva kokukhutshwa kwetyhefu [38].
Kwesi sifundo sikhoyo, sivavanye ukuba isimilo esikhobokisayo esijoliswe ekutyeni singabonakaliswa kusetyenziswa indlela efanayo neDeroche-Gamonet et al. Ukuze kuququzelelwe ukubonakala kokutya okufana nokuziphatha, sibonise izilwanyana kwi-binge-model equka amaxesha okutshintshana kokutya kunye nokufikelela ekutyeni okunencasa. Imifuziselo yokutya kakhulu equka ukufikelela okuphakathi kokutya okunencasa [39,40] okanye ukutshintshana (12h/12h) ukufikelela kwi-sucrose kunye nokunqongophala kokutya kubonakaliswe ukulamla ukuzintyintya [41] kunye nemiba ethile yokukhotyokiswa njengeempawu zokurhoxa [42,43] kunye notshintsho kuphawu lwe-dopamine olubonwa emva kokuvezwa kweziyobisi ixesha elide [44,45].
Kuye kwacetywa ukuba ukuphuhliswa komlutha kuququzelelwe ngotshintsho olusuka kwisiphumo esiqhutywayo, ekuziphatheni okujoliswe kwinjongo ukuya kwindlela yokuziphatha, ukuvuselela-impendulo yendlela yokuziphatha [46,47]. Ukuze kuvavanywe indima yesiqhelo sokuziphatha kwimodeli yethu ecetywayo yokuziphatha okunjengokutya, siye savavanya ukuphendula ngokutya emva kokuthotywa kwexabiso lokunyanyiswa kokutya okunencasa [48]. Ngapha koko, ekubeni isimilo esifana nesomlutha sinxulunyaniswa nokwanda kokuba sesichengeni sokubuyiselwa kokufuna iziyobisi [37], sicinge ukuba izilwanyana ezinolawulo oluncinci malunga nokutya kwazo ziya kuba lula ekujongeni kunye nokubuyiselwa okubangelwa kukutya okufuna emva kokuphela.
Impahla nenkqubo
Statement Ethics
Iimvavanyo zavunywa yiKomiti yeZimilo zeZilwanyana zeYunivesithi yase-Utrecht kwaye zaqhutywa ngokuvumelana nemithetho yamaDatshi (Wet op de Dierproeven, 1996) kunye nemimiselo yaseYurophu (Isikhokelo 86/609/EEC).
izilwanyana
Iigundane ze-6 zeveki ezidala ze-Wistar (uCharles River, iSulzfeld, eJamani) ezinobunzima be-150-200 grams ekuqaleni kovavanyo zazigcinwe ngabanye kwiikheji ze-Macrolon (L = 40 cm, W = 25 cm, H = 18 cm) phantsi kweemeko ezilawulwayo. iqondo lobushushu yi-20–21 °C, 55±15% ukufuma okunxulumeneyo) kwaye phantsi komjikelo obuyisiweyo weyure ezili-12 wokukhanya-ubumnyama (izibane zikhanya nge-19.00 h). I-Chow kunye namanzi zazifumaneka simahla. Zonke iimvavanyo zenziwa ngexesha lobumnyama bomjikelo wemini nobusuku.
Isishwankathelo sovavanyo
Ukulungelelanisa imodeli ye-Deroche-Gamonet yokulahlekelwa kulawulo lwe-cocaine efuna ukutya okunencasa, sifumene kuphononongo lokulinga ukuba nokushukuma kweenyawo okuthambileyo kombane kucinezele konke ukufuna ukutya. Ke ngoko sikhethe ukulinganisa 'ukuqhubeka sifuna nangona sisohlwaywa' sisebenzisa iquinine yokukrexeza kokutya okunencasa [49]. Olu vavanyo lokulinga luthelekisa izidlo ezi-4 (ezichazwe ngezantsi) ukuze zikwazi ukuvuselela ukuziphatha okufana nokukhotyokiswa kokutya. Kule meko izilwanyana ezingama-24 (n = 6 ngeqela ngalinye) zaqeqeshwa kwaye zavavanywa kwiindlela ezintathu zokuziphatha njengoko kuchazwe ngu [37]. Okubangela umdla kukuba, xa izilwanyana zivavanyelwa ikhrayitheriya yesithathu (ukuchasana ne-footshock encinci yombane), ukunyanzeliswa okupheleleyo kokufuna i-tshokoleta kwafunyanwa, nangona ukutshatyalaliswa kokutshatyalaliswa kwehliswa kwi-0.35 mA. Akukho mmahluko ekuphenduleni phantsi kweparadigm yokutshatyalaliswa kwafunyanwa phakathi kwamaqela ahlukeneyo okutya (ANOVA p = 0.1146 F = 2.243 df = 23). Ukongezelela, asizange sibone umehluko omkhulu ekuphenduleni phantsi kweshedyuli yomlinganiselo oqhubekayo wokuqiniswa phakathi kwamaqela amane okutya (idatha engaboniswa). Siye, nangona kunjalo, sabona umkhwa obhekiselele ekunyukeni kokuziphatha okufana nokukhobokisa kwizilwanyana ezivezwe kwimodeli yokuzitika xa sizithathela ingqalelo zontathu iindlela. Ukusukela oko ukushukuma kweenyawo zombane kucinezele wonke umntu ofuna umvuzo, sikhethe ukulinganisa inqobo yokumelana nobunzima ngendlela eyahlukileyo, okt ngokubeka izilwanyana ekutyeni okunencasa okungxengwe nge-quinine eyi-2 mM. Kuvavanyo oluphambili oluchazwe kuphononongo lwangoku, sithelekisa iqela elivezwe kwimodeli ye-binge (n = 36) kwiqela le-chow-fed control (n = 12). Ngolu vavanyo, izilwanyana zaziqeqeshelwa kwangaphambili kwiikhrayitheriya ezintathu kwiiveki ze-5 zilandelwa iiveki ze-8 zokufikelela kwisondlo. Asizange sibone umehluko ekuphenduleni okusebenzayo phakathi kwamaqela okutya ngaphambi kokutya. Emva koko saqhubeka ngokuqeqeshwa kwakhona kunye nokuvavanya kwiikhrayitheriya ezintathu ezilandelwa yi-10 yeeseshoni zokucima kunye neeseshoni ezimbini zokubuyisela (i-cue- kunye ne-chocolate) iseshoni.
Ukutya
Izidlo ezine ezahlukeneyo zisetyenzisiwe kolu phononongo, kwaye izilwanyana zavezwa kwizidlo ezichaphazelekayo kwiiveki ezisi-8. Ukutya okulawulwayo kwakuquka i-ad libitum chow (SDS, 3.3 kcal / g, 77.0% carbohydrate, 2.8% fat, 17.3% protein). Ufikelelo oluthintelweyo lokutya lubandakanya i-ad libitum chow eyongezwa nge-3h yokufikelela kwitshokolethi.TM (Abbott Laboratories, Abbott Park, IL, USA), iintsuku ezi-5 ngeveki (ukusuka kwi-12.00-15.00h). I-fat high-fat high-sucrose choice diet iquka i-ad libitum chow ngokudibanisa ne-ad libitum egcwele amafutha (Beef tallow (Ossewit/Blanc de Boeuf), iVandemoortele, eBelgium, 9.1 kcal/g) kunye ne-30% yesisombululo se-sucrose (ibakala lorhwebo. sucrose emanzini ompompo, 1.2 kcal / ml). Ukutya okudliwayo kwakuquka iintsuku ezi-4 ze-15.0-15.5g chow / imini etshintshwe kunye neentsuku ze-3 ze-ad libitum chow ezongezwayo kunye ne-ad libitum Oreo cookies (Nabisco, East Hanover, NJ, USA, 4.7 kcal / g, 74% carbohydrates, 21% amafutha, i-3% yeprotheni). Kule meko iikuki zeOreo bezifumaneka nge-24h/ngosuku iintsuku ezintathu. I-15g chow / imini yayisekelwe kumsebenzi wangaphambili nguHagan et al. apho izilwanyana zithintelwe kwi-66% ye-ad-lib chow. Lo mzekelo yinguqulelo elungisiweyo kaHagan et al. ngaphandle kwecandelo loxinzelelo lwemodeli yokuzingxala [39,50]. Amanzi etephu ayefumaneka ngawo onke amaxesha, ngaphandle kwangexesha lovavanyo. Uphononongo olulingwayo luthelekise zone ukutya. Izilwanyana zavavanywa ngaphambi nangemva kweeveki ze-8 zokufikelela kwizidlo. Olona vavanyo luphambili lweli nqaku luthelekisa iiveki ezisi-8 zokutya okuziinkozo kwiiveki ezisi-8 ze-ad-lib chow. Siqhubekile nokutya ngokutya kuba idatha evela kuncwadi, kunye nedatha yethu yomqhubi wenqwelomoya iphakamise ukuba ukutya ngokuzingxamela njengoko kuchaziwe apha ngasentla kunokwenzeka ukuba kuvuselele indlela yokuziphatha efana nokudyola [39].
izixhobo
Iigundane zaqeqeshwa kumagumbi okusebenza okusebenza (30.5 x 24.1 x 21.0 cm; Med Associates Inc, St. Albans, VT, USA). Igumbi ngalinye lalixhotyiswe ngeentsimbi ezimbini ezirhoxiswayo (4.8 x 1.9 cm). Ngaphezulu kweleva nganye bekubekwe isibane sokukhanya (ENV-221M stimulus light kwiimpuku, 28V, 100mA; Med Associates Inc) kunye nesibane sendlu (ENV-215M isibane sendlu samagumbi empuku, 28 V, 100mA; Med Associates Inc) yabekwa. kudonga oluchaseneyo. Umgangatho wegumbi wawugqunywe ngegridi yentsimbi kunye nemivalo ehlukaniswe ngu-1 cm. Igumbi libekwe kwityhubhile ethomalalisa isandi exhotyiswe ngefeni yokungenisa umoya ukunciphisa ingxolo yangaphandle. I-Chocolate Ukuqinisekisa kuhanjiswe kwisitya sokutya, esiphakathi kwezitshisi ezibini, ngetyhubhu enayiloni edityaniswe kwimpompo yesirinji enye yesantya (PHM-100-3.33; Med Associates Inc) ebekwe ngaphandle kwegumbi. Igumbi elisebenzayo lilawulwa yi-MED-PC (inguqulo IV) yoLawulo loPhando kunye neNkqubo yokuFumana idatha.
Ukufumana itshokolethi Qinisekisa ukuzilawula
Izilwanyana zaqeqeshelwa ukusabela ekutyeni njengoko kuchaziwe ngaphambili [51,52]. Iimpuku zaqala zafumana iiseshini zoqeqesho zokusebenza ezili-10 ezithatha iyure enye. Ebudeni bezi seshoni, iilever ezimbini zazikho, enye yazo yayichongwe njengesebenzayo. Isikhundla se-levers esebenzayo kunye nengasebenziyo yayichasene phakathi kwezilwanyana. Iseshoni yaqala ngokufakela zombini iilevers kunye nokukhanya kwesibane sendlu. Ngexesha leseshoni yokuqala, i-fixed ratio (FR) ishedyuli ye-1 yokuqinisa isetyenziswe, oku kuthetha ukuba i-lever nganye icinezela i-lever esebenzayo ibangele ukuhanjiswa kwe-chocolate ye-1 ml Qinisekisa, ukuhlehliswa kwee-levers zombini ze-0.2 sec kunye nokukhanya kokukhanya kwe-cue ngaphezu kokusebenzayo. i-lever ye-20 sec ngexesha apho ukukhanya kwendlu kuye kwacinywa. Imfuno yokuphendula yandiswe kwishedyuli yeFR10 yokuqinisa ngexesha leseshoni yesibini neyesithathu. Ukususela kwiseshoni yesine ukuya phambili, ishedyuli yeFR2 yokuqinisa yanyanzeliswa.
Ukuphuma kwexesha ukuphendula
Inkqubo yokuphuma kwexesha yayisekwe kwi [37], nangona ixesha elifutshane leseshoni lisetyenziselwa ukuthintela iziphumo zokuhlutha ekuphenduleni. Iiseshini beziqulathe iibhloko ezi-5 zetshokholethi emizuzu eli-10. Qinisekisa ukufumaneka okutshintshiswayo kunye neebhloko ezi-4 zemizuzu emi-5 apho itshokholethi ibingafumaneki. Ngexesha lokufumaneka kweebhloko, ubukho bempendulo yomvuzo bubonakaliswe kwizilwanyana ngokukhanyisa ukukhanya kwendlu. Inkqubo yokuzilawula ngexesha lokufumaneka kweebhloko yayifana nechazwe ngasentla, oko kukuthi, ishedyuli ye-FR5 yokuqinisa isetyenziswe. Ngexesha lokungafumaneki kwebhlokhi isibane sendlu besicimile kwaye iimpendulo kuzo zombini iilever bezingenaziphumo ezicwangcisiweyo. Ukuphendula kuye kwatshintsha ngakumbi ngexesha leebhloko zokugqibela kwiseshoni, mhlawumbi ngenxa yokuhlutha. Ngoko ke sisebenzise inani leempendulo ezenziwe ngexesha lokuqala le-5 min ibhloko yokungafumaneki njengepharamitha ebalulekileyo, kuba le bloko yayifakwe kwiibhloko ezimbini zokufumaneka apho izilwanyana zihlala zifumana ubuninzi bemivuzo ngaphakathi kwexesha elikhoyo. Izilwanyana zafumana iiseshoni ze-10 ngaphambi kokutya kunye neeseshoni ze-15 emva kokutya. Iimpendulo zeempendulo ngexesha lokuqala lokungafumaneki kweeseshoni zokugqibela ze-4 zisetyenziswe njengenqaku lokuphuma kwexesha lesilwanyana.
Ishedyuli yomlinganiselo oqhubekayo wokuqiniswa
Ngaphantsi kweshedyuli eqhubekayo yokuqiniswa, izilwanyana kwafuneka zihlangabezane nemfuneko yokuphendula kwi-lever esebenzayo eyanyuka ngokuqhubekayo emva kwetshokolethi nganye efunyenweyo Qinisekisa umvuzo (1, 2, 4, 6, 9, 12, 15, 20, 25, njl.53]). Iseshoni yaqala ngokukhanyisa isibane sendlu (umqondiso wokufumaneka komvuzo) kunye nokufakwa kokubini okusebenzayo kunye ne-lever engasebenzi. Ukuhlangabezana nemfuno yokuphendula kwi-lever esebenzayo kubangele ukurhoxiswa kwazo zombini ii-levers, ukukhanya kokukhanya kwe-cue ngaphezulu kwe-lever esebenzayo ye-10 sec kunye nokuhanjiswa kwe-0.2 ml yetshokolethi Qinisekisa. Emva kwemizuzwana engama-20, umjikelo omtsha uqalile. Iseshoni yaphela xa izilwanyana zahluleka ukufumana umvuzo ngaphakathi kwe-60 min. Izilwanyana zafumana iiseshini ze-4 ze-PR ngaphambi kunye neeseshoni ze-PR emva kokutya. Kuzo zombini iimeko umyinge weempendulo ze-lever ezisebenzayo kwiiseshoni ze-4 zisetyenziswe njengenqaku le-PR yesilwanyana.
Wohlwaywa ephendula
Inkqubo yatshintshwa ukusuka kwiDeroche-Gamonet et al. (2004). Ngethuba le nkqubo, izilwanyana zavavanywa kumagumbi okusebenza okusebenza okwahlukileyo kulawo asetyenziswa ngexesha loqeqesho, ixesha lokuphuma kunye neeseshoni ze-PR. Iseshoni yaqala ngokukhanyiswa kokukhanya kwendlu kunye nokuboniswa kwazo zombini iilevers. Ngethuba lezi seshoni, izilwanyana ziphendule phantsi kweshedyuli ye-FR5 yokuqinisa, apho i-1st lever press nganye ibangele ukunikezelwa kwethoni kunye ne-4 nganye.th Kunye ne5th i-lever press ibangele umboniso womothuko weenyawo zombane (0.35mA, 2sec), olawulwa ngomgangatho wegridi. Ngamnye 5th i-lever press ibangele ukuhanjiswa kwe-chocolate ye-0.2 ml Qinisekisa. Ithoni yacinywa emva ko4th i-lever press okanye xa izilwanyana zihluleka ukwenza iimpendulo ze-4 ngaphakathi kwe-1 iminithi, apho umjikelezo omtsha we-FR5 waqala. Umlinganiselo wesiphumo wawuyimali ye-lever presses eyenziwa yizilwanyana ngexesha leseshoni njengepesenti yokuphendula okusisiseko (umyinge we-4 FR5 iiseshoni kwiintsuku zangaphambili). Sivavanye ukuphendula phantsi kwale paradigm kwisifundo sokulinga (esichazwe ngasentla), apho i-footshock yombane iphantse yacinezela ukuphendula ngokutya kuzo zonke izilwanyana.
Ukukrexeza kwe-quinine
Izilwanyana zanikwa ukufikelela simahla nokuba kungangxengwanga okanye kugqwethiweyo (usebenzisa i-quinine eyi-2 mM; eSigma, eNetherlands) itshokolethi Qinisekisa kwikheji yasekhaya kangangemizuzu engama-30 ngeentsuku ezahlukeneyo. Uvavanyo olulingwayo lubonise ukuba umyinge we-2 mM wequinine ubangele ukuguquguquka okukhulu komntu ngamnye, ngelixa ugxininiso oluphezulu lucinezele ukuthathwa kwazo phantse kuzo zonke izilwanyana, kwaye ugxininiso olusezantsi lube nefuthe elincinane kakhulu kwitshokholethi. Umlinganiselo wokunyanzeliswa ubalwa ngolu hlobo lulandelayo: ((ukusetyenziswa okungaxutywanga - ukusetyenziswa kakubi) / ukusetyenziswa okungaxutywanga) * 100, ukwenzela ukuba umlinganiselo wokunciphisa we-100 uquka ukunyanzeliswa okupheleleyo kokuthatha, kwaye umlinganiselo we-0 wawuthetha ukuba akukho ngcinezelo kwaphela. .
Ukuthotywa komvuzo
Izilwanyana zanikwa i-2 h yokufikelela kwamahhala kwitshokolethi Qinisekisa kwi-cage yasekhaya ngokukhawuleza ngaphambi kweseshoni yokusebenza ye-20 min, apho ukukhanya kwendlu kwakhanyiswa kwaye zombini iilevers zikhona kwiseshoni yonke. Zombini iimpendulo ezisebenzayo nezingasebenziyo bezingenaziphumo ezicwangcisiweyo. Umlinganiselo wokulinganisa ubalwa njengomlinganiselo we-lever presses esebenzayo eyenziwa sisilwanyana emva kokunciphisa. Iziphumo zafaniswa nesixa se-lever press ngexesha le-20 min ye-non-devalued FR5 iseshoni ngosuku olungaphambili.
Ukuphela kunye nokubuyiselwa
Izilwanyana zafumana i-12 imihla ngemihla iiseshini zokusebenza ze-1 ngexesha apho i-lever presses yayingenazo iziphumo ezicwangcisiweyo. Isibane sendlu (esasibonakaliswe ngaphambili ngokufumaneka komvuzo) silayitiwe kuyo yonke iseshoni. Ngomhla we-13, ukubuyiselwa kwe-cue-induced reinstatement kwavavanywa ngolu hlobo lulandelayo. Iseshini iqale ngokukhanya kwesibane esingaphezulu kwelever esebenzayo ye-10 sec. Ngexesha lale seshoni, ukuhlangabezana nemfuno ye-FR5 kwi-lever esebenzayo kubangele ukurhoxiswa kwazo zombini iilevers kunye nokukhanya kokukhanya kwe-cue ye-10 sec, kodwa akukho mvuzo unikezelweyo. Izilwanyana zafumana iiseshoni zokuphela eziqhelekileyo ngosuku lwe-14 kunye ne-15. Ngomhla we-16, i-tshokoleta Ukuqinisekisa ukubuyiselwa kwakhona kwavavanywa. Iseshoni yaqala ngokuziswa kwe-0.6 ml yetshokolethi Qinisekisa. I-Lever press ngexesha leseshoni yayingenazo iziphumo ezicwangcisiweyo.
Uhlalutyo lwedatha
Ngokusekelwe kwiikhrayitheriya ezintathu, 'amanqaku omlutha' abalwe ngokutsho kukaBelin et al. [54]. I-normalization yenziwa ngokususa intsingiselo yazo zonke izilwanyana kwisilwanyana ngasinye kwaye yahlulwe ngokutenxa okusemgangathweni kweqela lonke. Oku kubangele inqaku lekhrayitheriya kunye ne-avareji ye-0 kunye nokutenxa okusemgangathweni kwe-1 kwikhrayitheriya nganye. Amanqaku omlutha emva koko abalwa njengesixa samanqaku amathathu aqhelekileyo. Siphinde sahlulahlula izilwanyana ngokwe-Deroche-Gamonet et al., oku kuthetha ukuba sibale inani leenqobo apho isilwanyana safumana amanqaku phakathi kwama-66th Kunye ne99th ipesenti yonikezelo [37]. Amaqela amabini okutya athelekiswe elinye kwelinye kusetyenziswa iimvavanyo zoMfundi. Amaqela eenqobo zokugweba athelekiswe kusetyenziswa ii-ANOVA zendlela enye elandelwa luvavanyo oluninzi lwaseTurkey lokuthelekisa emva kwe-hoc, apho kufanelekileyo. Iiseti zedatha ekrwada ziyafumaneka xa uceliwe.
iziphumo
Iqela lezilwanyana (n = 48) lavavanywa kwiikhrayitheriya ezintathu zokuziphatha okufana nomlutha. Ukuze uvuse ukuphuhliswa kokutya okungalawulwayo, i-subgroup (n = 36) ibonakaliswe kumzekelo wokuzinkcinkca. Akukho mahluko ubalulekileyo kuyo nayiphi na imilinganiselo emithathu phakathi kokulawulwa kunye nezilwanyana ezizityayo ziye zabonwa (ixesha lokuphendula (TO): p=0.6 t=0.53 df = 46; umlinganiselo oqhubekayo (PR): p=0.9 t=0.1128 df = 46 iquinine: p=0.3 t=1.048 df = 46) (Umzobo 1A-C). Imodeli ye-binge yenza, nangona kunjalo, ibangele ukwanda okukhulu kwesisindo somzimba (p <0.0001 t = 6.105 df = 46) (Umzobo 1D). Emva koko, sahlulahlula zonke izilwanyana zibe ngamacandelwana ama-4 ngokusekwe kubungakanani bekhrayitheriya abafumene kuzo amanqaku phakathi kwama-66th Kunye ne99th percentile, ngokutsho Deroche-Gamonet et al. (2004). Kwimeko yethu, i-3-critt subgroup yayingekho nkulu kunokuba bekulindelwe ngethuba (okt, 3,6%) (Umzobo 2). Oku bekuyinyani kuwo omabini iqela lokuzinkcinkca (Umzobo 2A) kunye neqela lonke (Umzobo 2B). Amacandelwana eenqobo okugweba ahlukile elinye kwelinye kwikhrayitheriya nganye (ANOVA UKUYA: p<0.0001 F=11.42 df = 47; PR: p<0.0001 F=9,850 df = 47; iquinine: p=0.0006 F=6.932 df = 47) (Umzobo 3A-C). Kwiqela le-binge sivavanye ukuba ukunciphisa ukulawulwa kwesisindo somzimba ngexesha lokutya, okwakungenjalo (Umzobo 3D).
Okubalulekileyo, ukungafani phakathi kwamaqela eenqobo azibangelwa kukwahluka kwe-satiety okanye imfuno yamandla njengoko onke amaqela asebenzisa inani elifanayo letshokolethi ngexesha le-70 min FR5 iseshoni (ANOVA p = 0.3 F = 1.266 df = 47) (Umzobo 4A) okanye xa unikwe i-2h ye-ad libitum ukufikelela kwitshokolethi Qinisekisa (ANOVA p=0.4 F=0.9651 df = 47) (Umzobo 4B). Siphinde sabala inqaku lokulutha ngokwe [54]. Oku kubangele uluhlu olubanzi lwamanqaku (Umzobo 5).
Kuye kwacetyiswa ukuba ukubunjwa kwemikhwa evuselelayo, ekhokelwa ngamachiza-ndlela yokuphendula inyathelo elibalulekileyo ekuphuhliseni ukuziphatha okukhobokisayo [46,47]. Ukuvavanya ukuba ukuziphatha okubonakaliswe zizilwanyana bekujoliswe ekujoliswe kuko okanye ngokwesiqhelo, sijonge phantsi itshokolethi Qinisekisa umvuzo ngokunika izilwanyana i-2 h yokufikelela simahla kwindawo yazo yasekhaya ngaphambi kweseshoni yovavanyo esebenzayo ye-20 ngexesha apho i-lever icinezela apho ingaqiniswanga. . Izilwanyana ezenziwe nge-avareji ye-63% iimpendulo ezingaphantsi xa i-tshokoleta ihlanjululwa xa ithelekiswa neseshoni yemizuzu engama-20 apho i-lever presses apho iqiniswe kwaye i-tshokoleta ayizange ihlaziywe.Umzobo 6A). Uxinzelelo lwe-Lever olwenziwe emva kokuthotywa kwexabiso elihambelana namanqaku okulutha (r2=0.2, p<0.001) (Umzobo 6B). Akukho mahluko phakathi kokutya kunye neqela lolawulo labonwa (idatha ayiboniswanga).
Emva koko, siye savavanya ukuba izilwanyana ezinolawulo oluncitshisiweyo lokutya zithande ukubuyisela ukuphendula okucinyiweyo. Silinganise iintlobo ezi-2 zokubuyiselwa. Xa kuthelekiswa nokuphendula ngexesha lokuphela (Umzobo 7A), unikezelo lwempendulo yetshokolethi Ukuqinisekisa-iimpawu ezihambelanayo zenze ukubaluleka (p=0.0035 t = 3.077 df = 47) ukubuyiselwa kokuphendula phezu kweqela lonke, kodwa akukho mahluko phakathi kwamaqela emilinganiselo (ANOVA p = 0.865 F = 0.2442 df = 47) (Umzobo 7B). Ngexesha le-tshokoleta Ukuqinisekisa ukubuyisela ukubuyisela kwakhona, siye sabona ukubuyiselwa okubalulekileyo (p <0.0001 t = 12.35 df = 47) kunye nokwahlukana okukhulu ekubuyiselweni phakathi kwamaqela, kunye neqela le-2 elibonisa amanqanaba aphezulu okuphendula kune-0 kunye ne-1 yezilwanyana zezilwanyana (ANOVA p=0.01 F=4.225 df = 47) (Umzobo 7C).
ingxoxo
Kwesi sifundo sikhoyo, silungelelanise imodeli yesilwanyana sokuziphatha okufana ne-cocaine ukuvavanya ukwenzeka kokuziphatha okukhobokisayo okujoliswe ekutyeni okunencasa. Ukuze kuququzelelwe ukuphuhliswa kokutya okungalawulwayo, iqela elincinane lezilwanyana (n = 36) libonakaliswe kwimodeli yohlobo lokuzinkcinkca olubandakanya iintsuku ze-4 ze-66% ye-ad libitum chow ehambelana neentsuku ze-3 zokufikelela kwi-ad libitum chow ngokudibeneyo. kunye neOreo Cookies. Emva kovavanyo lweendlela ezintathu zokuphulukana nolawulo, sikwalinganise ukuphendula emva kokuthotywa kwexabiso kunye nokuthambekela kokubuyisela impendulo ecinyiweyo ebangelwe yinkcazo-mpendulo exhomekeke kumvuzo wokutya ohambelana nomvuzo okanye itshokolethi Qinisekisa umvuzo ngokwawo.
Imodeli ye-binge ayichaphazeli ulawulo lokufuna ukutya
Asizange sibone impembelelo yemodeli yokuzinkcinkca kuyo nayiphi na imilinganiselo emithathu yokuziphatha okufana nokulutha (Iimpawu ze1 kwaye And2) .2). Siye sabona, nangona kunjalo, ukonyuka kobunzima bomzimba emva kokuvezwa kumzekelo wokuzinkcinkca. Ukutya okukhoyo ngoku kusekwe kuphononongo olwenziwa nguHagan et al., Obonise ukonyuka kokutya ukutya okunencasa kwezilwanyana eziye zachatshazelwa kukutya okuthelekisekayo nasemva kokuba ziye zarhoxiswa koku kutya kangangeentsuku ezingama-30 [50]. Ngokwahlukileyo kuHagan et al., Sasebenzisa iimpuku zamadoda. Ke ngoko asinakukhuphela ngaphandle ukuba sinokuba sifumene iziphumo ezicacileyo zokutya ngokuzintyintya xa sisebenzise iimpuku zabasetyhini. Inene, iBED ixhaphake kakhulu kumabhinqa angabantu kunamadoda [55]. Kwelinye icala, kuye kwaboniswa ngokuphindaphindiweyo ukuba, xa kunikwa iimeko ezifanelekileyo, zombini iimpuku zamadoda nemazi ziya kuzitya ngokutya okunencasa [56-58]. Enye imodeli ye-binge esetyenziswa ngokuqhelekileyo, ebangela ukuzinkcinkca kuzo zombini iigundane zesini, isebenzisa amaxesha e-12h / 12h atshintshanayo yokutya okudityaniswa nokufikelela kwi-10% yesisombululo se-sucrose [59,60]. Uphando lwangaphambili luye lwabonisa ukuba ukufikelela rhoqo kwi-fat-high-high sucrose diet kwandisa ukuphendula phantsi kweshedyuli ye-PR kunye nokuphendula phantsi kweshedyuli ye-PR ngaphambi kokufikelela kwisondlo esifanelekileyo sihambelana nokugcinwa kwamafutha esiswini emva kwe-4weeks yokufikelela kwi-fat-fat high- ukutya iswekile kwiimpuku amadoda [51]. Ke, ukuvezwa kwiintlobo ezithile zokutya okune-obesogenic kunokukhokelela ekuzingxaleni nasekunyuseni ukukhuthaza ukutya. Nangona kunjalo, idatha yethu ibonisa ukuba ukuvezwa ixesha elide ekutyeni ngokuzinkcinkca kukodwa akwanelanga ukuvuselela indlela yokuziphatha ecacileyo.
Akukho bungqina 'bokukhotyokiswa kokutya', kodwa ukuguquguquka okuphezulu komntu kulawulo lokutya okunencasa
Ngokuchaseneyo noko kufunyenweyo kwi-cocaine, iqela leempuku eziqhube kwi-tertile ephezulu kuzo zontathu iinqobo zokugweba belingekho likhulu kunokuba bekulindelwe ngethuba (3,6%). Ke ngoko, kunengqiqo ukugqiba kwelokuba akukho zimpawu zicacileyo zokuziphatha okufana nokukhobokisa okujoliswe kwitshokholethi Qinisekisa ukuba kuphuhliswe kwisifundo sethu. Nokuba akukho 'iqela-likhoboka' elinjalo, uluhlu lolawulo lokufunwa kokutya oluqatshelwe kuphononongo olukhoyo lubaluleke kakhulu. Oko kukuthi, ukunciphisa ukulawulwa kokutya kwabantu, nokuba akukho kuziphatha okucacileyo okufana nokulutha, kunokubangela ukutya kakhulu kunye nokutya kakhulu okuthambileyo okukhokelela ekutyebeni ngokugqithiseleyo kwabanye abantu. Kuphononongo lwangoku, ukunciphisa ukulawulwa kokutya okunencasa akuzange kuqikelele ukufumana ubunzima bomzimba, okunokwenzeka ngenxa yokuba iigundane (ngokungafaniyo nabantu) azizami ukukhusela ubunzima bomzimba. Ke, iindlela ze-neural ezisemva kolu qhubekeko lolawulo lokufuna ukutya kunye nokuthatha kubalulekile ukuphanda kwaye imodeli yethu yangoku ibonelela ngezixhobo zokuziphatha ukwenza oko.
Izilwanyana ezibonisa ulawulo oluncitshisiweyo lokutya ukutya azikhathali kangako ekuthotyweni komvuzo
Siye sabona ukwehla okukhulu ekuphenduleni emva kokunciphisa ixabiso kwinqanaba leqela (Umzobo 6a). Okubangela umdla kukuba, bekukho iyantlukwano enkulu yabantu malunga nefuthe lokuthotywa kwexabiso, elihambelana namanqaku okulutha (Umzobo 6b). Kuye kwacetywa ukuba ukuphuhliswa komlutha kuququzelelwe ngotshintsho olusuka kwinjongo ekhokelwa sisiphumo sokuziphatha okujoliswe ekuziphatheni okuqhutywa yi-stimulus [46]. Eyangaphambili kucingelwa ukuba ilamlwa ziinxalenye ze-ventral kunye ne-medial ye-striatum, ngelixa le yokugqibela ixhomekeke kwi-dorsolateral striatum [61]. Ewe, kubonakaliswe ngokuphindaphindiweyo ukuba ixesha elide lokuzilawula kwe-cocaine liqesha iindlela ze-dorsolateral striatal eziphantsi kokufuna iziyobisi [62-65] kwaye izilonda okanye ukungasebenzi kwe-dorsolateral striatum kunciphisa ukuziphatha okuqhelekileyo [66-69]. Kuba izilwanyana ezibonisa ukulawulwa okuncinci kokutya zivakalisa ukuziphatha okuthe kratya, ezi ziphumo zibonisa ukuba ulawulo oluncitshisiweyo lokutya lunxulunyaniswa nokubandakanyeka okukhulu kwe-dorsolateral striatal kulawulo lokutya.
Izilwanyana eziphantsi kolawulo zityekele kakhulu ekubuyiseleni ukufuna ukutya okucinyiweyo
Olona phawu lubalaseleyo lokukhotyokiswa ngumngcipheko omkhulu wokuphinda ubuyele kwakhona [70,71]. Oku kunokuphandwa kusetyenziswa imifuziselo yezilwanyana ephonononga ukuthambekela kwesilwanyana ukubuyisela iyeza elifunayo emva kokuphela kwempendulo esebenzayo. Ukufuna iziyobisi kunokubuyiselwa kusetyenziswa isicatshulwa esinxulumene neziyobisi, isixa esincinci 'sokuqala' sechiza okanye ngoxinzelelo [38]. Ukuvavanya ukuba ngaba izilwanyana ezinolawulo oluncinci ekufuneni kwazo ukutya zinokuthi zibuyisele ukufuna ukutya okucinyiweyo, siye savavanya izilwanyana ukuba zibuyiswe zombini kunye nomvuzo. Njengoko kubonakala kwi Umzobo 7C, kuphela ukunyusa izilwanyana kunye nomvuzo wetshokolethi-flavored kubangele umahluko omkhulu ekubuyiselweni phakathi kwamaqela e-4. Kule meko i-2 imilinganiselo yezilwanyana iphendule ngokuphawulekayo ngakumbi ngexesha lokubuyiselwa. Kungenzeka ukuba izilwanyana ezi-3 ziyakwazi ukubuyisela kwakhona, kodwa oku kwakunzima ukubonisa ngokwezibalo ngenxa yenani elincinci lezilwanyana kweli qela.
Ukuqukumbela, sibonisa imodeli engasetyenziselwa ukulinganisa utshintsho kulawulo lokuziphatha kokutya. Imodeli ivelisa ukuqhubeka kokuziphatha ukusuka kulawulo oluphezulu kakhulu ukuya kulawulo oluphantsi, ugqithiso olunokubizwa ngokuba likhoboka lokutya, kodwa ubuncinci kuvavanyo lwangoku, akukho mda ucacileyo phakathi kwezilwanyana 'ezilikhoboka' kunye 'nokungekho mlutha' unokutsalwa. , kwaye asiloqela elincinane lezilwanyana ezinokuthi zichazwe njengezibonisa ukuziphatha okufana nokukhobokisa kunokuba kulindelwe ngamabona-ndenzile. Kwelinye icala, sifumanise ukuba ulawulo oluphantsi lokutya lunxulunyaniswa nokuthambekela okuphezulu kokutya okunencasa okubangelwa kuphinda kuphinde kuphinde kuphinde kwenyuka ngokwesiqhelo sokuphendula itshokolethi, nto leyo ebonisa ukuba utshintsho lokuziphatha olunxulunyaniswa nokuziphatha okukhobokisayo lunokubonwa kwizilwanyana ezinolawulo oluphantsi ngaphezulu kokunencasa. ukutya. Imodeli ke ngoko ibonelela ngesixhobo esixabisekileyo sokufunda ukulawula ukutya kunye ne-neural underpinnings. Oku kubaluleke kakhulu xa sicinga ukuba ulawulo oluncitshisiweyo lokutya, nangaphandle kokuhlelwa okungqongqo kokukhobokisa kokutya, kunokubangela iingxaki zempilo.
Ingxelo Yenkxaso
Ixhaswa yi-NeuroFAST Foundation (i-neurobiology edibeneyo yokutya, umlutha kunye noxinzelelo). I-NeuroFAST ixhaswa ngemali yi-European Union Seventh Framework Programme (FP7/2007-2013) phantsi kwemvumelwano yesibonelelo n ° 245009. Abaxhasi babengenayo indima ekuyilweni kokufunda, ukuqokelela idatha kunye nokuhlalutya, isigqibo sokupapasha, okanye ukulungiswa kombhalo wesandla.
Ucaphulo
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