Igalelo leengqungquthela zemivuzo yengqondo kwisifo se-obesity (2013)

U-Eric Stice,^a UDianne P. Umzobi,^b Blake A. Gosnell,^c UAllen S. Levine,^d kwaye Wayne E. Pratt^e

Ulwazi loMbhali ► Ulwazi lobunikazi kunye neelayisensi ►

Olunye lweempawu ezichazayo zophando luka-Ann E. Kelley kukunakana kwakhe into yokuba isifo se-neuroscience esisiseko semfundo esisiseko kunye neenkqubo zenkxaso sikwakhanyisela ukukhanya kwiinkqubo ezenza ukuba likhoboka leziyobisi kunye neepateni zokutya zingalunganga. Kolu phononongo, sivavanya ukufana okukhoyo kwiindlela ze-neural ezisebenza ngokufumana umvuzo wokutya kunye neziyobisi, njengoko kumiselweyo kwizifundo zamva nje kwiimodeli zezilwanyana kunye nokuvavanywa komntu kwezilwanyane. Sixoxa ngophando lwangoku olibonisa ukuba i-hyperphagia ekhokelela ekutyebeni kakhulu inxulunyaniswa notshintsho olukhulu engqondweni. Ezi ziphumo ziqinisekisa ukuhambelana kweendlela zomvuzo zokukhuthaza ukusetyenziswa kokutya okuthandekayo, ukutya okune-calorical dense, kwaye kukhokelela kumbuzo obalulekileyo wokuba ngaba utshintsho kumjikelezo womvuzo ekuphenduleni ukuthathwa kokutya okunjalo kunendima ebangelwa kukuphuhliswa nokulondolozwa kwemeko ezithile ukutyeba kakhulu. Okokugqibela, sixoxa ngexabiso elinokubakho lezifundo ezizayo kwincam yesifo sokutyeba kakhulu kunye ne-neuroscience yenkuthazo, kunye nezinto ezinokubangela inkxalabo ezinokubangelwa kukujonga ukutya okugqithileyo njengo "kukungakwazi". Sicebisa ukuba kunokuba luncedo ngakumbi ukugxila ekuzondleni kakhulu okukhokelela ekutyebeni kakhulu, nakwimpilo eyahlukeneyo, phakathi kwabantu, nakwiziphumo ezibi zomsebenzi njengendawo yokutya.

3.1. Iziphumo zokuSebenzisa iziyobisi kunye nokuTya okuLungeleleneyo kokutya kwiSekethe yeMesolimbic

Kuzo zombini izilwanyana kunye neemodeli zabantu, ukufana okuninzi kubonisiwe phakathi kweempembelelo zokusetyenziswa kweziyobisi zokuxhatshazwa kunye nokutya okufumanekayo kokutya kwi-mesolimbic circry. Okokuqala, ukuphathwa ngamandla kwamachiza ahlukumezekileyo kubangela kusebenze i-VTA, i-nucleus accumbens, kunye neminye imimandla ye-striatal ngokwezifundo zabantu kunye nezinye izilwanyana (Volkow et al., 2002; I-Koob kunye neBhloko, 1988). Ukusetyenziswa kokutya okunencasa ngokufanayo kubangela ukuba kusebenze ngakumbi ukubelekisa, i -ula, isisu, isithsaba esincinci, kunye ne-cortex yangaphambili ebantwini kwaye ezi mpendulo ziyancipha njengomsebenzi wokuthambisa kunye nokunciphisa ubumnandi bokutya okuchithiweyo (Encinci et al., 2001; I-Kringelbach et al., 2003).

Okwesibini, abantu abane, ngokuchaseneyo, ngaphandle kweziphazamiso ezahlukeneyo zokusetyenziswa kweziyobisi babonisa ukusebenziseka okukhulu kwemimandla yomvuzo (umzekelo, amygdala, dorsolateral preortal cortex [dlPFC], VTA, preortal cortex) kunye nemimandla yokuthathela ingqalelo (i-anterior cingulate cortex [ACC]) kwaye banike ingxelo yokunqwenela okungakumbi. ukuphendula ukusetyenziswa kweziyobisi (umz. Ngenxa et al., 2002; UGeorge et al., 2001; Maas et al., 1998; UMyrick et al., 2004; Tapert et al., 2003). Umnqweno wokuphendula izinto ezihambelana nawo kunye nobungakanani bokubakhutshwa kwe-dorsal striatum dopamine (eyokugqibela isuselwa kumgangatho ¹¹Ukuthathwa kwe-C-raclopride; Volkow et al., 2006) kunye nokwenza intsebenzo kwi-amygdala, dlPFC, ACC, i-nucleus accumbens, kunye ne-orbitofrontal cortex (OFC; Childress et al., 1999; Maas et al., 1998; UMyrick et al., 2004). Ngendlela efanayo, abantu abatyebileyo xa kuthelekiswa nabantu abangaqhelekanga babonisa ukusebenza kweengingqi ezidlala indima ekufakweni kwexabiso lomvuzo wokukhuthaza, kubandakanya i-striatum, i-amygdala, i-orbitofrontal cortex [OFC], kunye ne-mid-insula; kwimimandla yokuthathela ingqalelo (i-cralex yangaphambili yecortal yangaphambili [vlPFC]); nakwimimandla enomxholo othile UBruce et al. 2010; UMartin et al., 2009; I-Nummenmaa et al., 2012; URothemund et al., 2007; I-Stoeckel et al., 2008; I-Stice et al., 2010). Ezi zinto zifunyanisiweyo kwiindawo ezingumntu ezihambelana ngqo neziye zenziwa zezi zinto zihambelana neziyobisi kunye nokutya okuthandekayo kwiigundane (UKelley et al., 2005b). Kukho obunye ubungqina bokuba umntu otyebileyo ngokuchaseneyo nabantu aboyisayo abonisa ukusebenza okucothisiweyo kwimimandla yolawulo lwe-inhibitory ekuphenduleni kwimifanekiso ethandekayo yokutya ngokuchaseneyo nemifanekiso yolawulo (umz. I-Nummenmaa et al., 2012; I-Stice et al., 2008). I-Obese xa kuthelekiswa nabantu abanqabileyo ngokubonakalayo i-activation ephezulu yokuxabisa umvuzo kunye nemimandla yokuthathela ingqalelo ukuphendulwa kwezinto ezibonisa ukufunyanwa kwamanqatha aphezulu / iswekile yokutya ngokuchasene neendlela zokulawula ezibonisa ukuba kufunyenwe isisombululo esingenakonakala.Ng et al., 2011; I-Stice et al., 2008). Uhlalutyo lwe-meta-analytic olufunyenwe lubanzi kwimimandla yoqingqo lwamaxabiso eyenziwe yaphendulwa kwimifanekiso yokutya ethandekayo ebantwini kunye nemimandla yobuchopho yomvuzo ovuselelwa ziindidi zeziyobisi phakathi kwabantu abaxhomekeke kwiziyobisi (I-Tang et al., 2012).

Ezi datha ziqinisekisa ukuba iziyobisi zokuxhatshazwa kunye nokutya okuthandekayo, kunye neendlela ezixela kwangaphambili ngomvuzo wamachiza kunye nokutya, zenza ukuba loo mimandla ifakwe kumvuzo nasekufundeni umvuzo. Imijikelezo echaphazelekayo ibandakanya inkqubo ye-mesolimbic dopamine, neeprojekthi ezivela kwi-VTA ukuya kwi-medial ventral striatum. La macandelo alandelayo agxininisa ubume obunqamlezayo bemiphumo yokutya kunye nomvuzo weziyobisi kwi-dopaminergic kunye ne-opioid signaling ngaphakathi kwendlela yomvuzo obalulekileyo.

3.2. Iziphumo zoSetyenziso lweziyobisi kunye nokutya okukutya okuqinisekileyo kwi-Dopamine Signaling

Ukongeza kokufana okubonakalayo ekutyeni nasekutyeni iziyobisi kwimisebenzi ye-neuronal, kukwakho ukubakho okufanayo ngokuhambelana nemiphumela yeziyobisi zokusetyenziswa gwenxa kunye nokutya okuthandekayo kokutya okutyikityayo kwi-dopamine signaling. Okokuqala, ukuthatha iziyobisi eziqhelekileyo ezixhatshaziweyo kubangela ukukhutshwa kwe-dopamine kwi-striatum kunye nemimandla ye-mesolimbic ehambelana nayo (Imini et al., 2007; Di Chiara, 2002; UHeinz et al., 2004; IKalivas kunye ne-O'Brian, 2008; Volkow et al., 2002, 2008). Ukutya okunokuthenjwa ngokufanayo kubangela ukukhutshwa kwe-dopamine kwi-nucleus accumbens kwizilwanyana (I-Bassareo kunye ne-Di Chiara, i-1999). Ukusetyenziswa kokutya okunamafutha aphezulu kunye neswekile eneswekile kuhambelana nokukhutshelwa kwe-dopamine kwi-dorsal striatum kunye nobungakanani bokukhutshwa okuhambelana nemilinganiselo yokutya okuthandekayo ebantwini (Encinci et al., 2003). Okwesibini, i-dopamine ikhutshwa kwi-dorsal striatum ye-rat ngexesha lokuziphatha kweziyobisi (Ito et al., 2002). Kwangokunjalo, ukuphendula ngokufumana ukutya okutyebileyo kunxulunyaniswa nokwanda kokubonisa phasic dopamine (Schultz et al., 1993). Okwesithathu, ukubhencwa kwiimpawu ezibonakalisa ubukho bolawulo lweziyobisi ezisetyenziswa gwenxa, ezinje ngetoni okanye isibane, zenza iphasic dopamine isayine emva kwethuba lokubhalwa kweentonga (Schultz et al., 1993). Nangona kunjalo, ukubonakaliswa kokubonakalayo kunye ne-olodoory kukutya okunesondlo akuboniswanga ukutshintsha ukubakho kwe-D2 receptors kwi-striatum kwizifundo ezibini ezahlukeneyo (Volkow et al., 2002; Wang et al., 2011), ukucebisa ukuba ukubonakaliswa kwe-cue yokutya akuvelisi iimpembelelo ezibonakalayo kwi-dopamine ye-extracellular kwi-striatum, ubuncinci kwizifundo zabantu abaneesampuli ezincinci kakhulu.

3.3. Indima yeeOpioids kumvuzo wokutya

Uphando luveze ukuba i-opioid peptides kunye nee-receptors zazo zidlala indima kulawulo lokutya, kwaye nenkqubo ye-opioid ibonakala ibandakanyeka kakhulu ekulamleni umvuzo wokutya (jonga I-Bodnar, 2004; UGosnell noLeviine, 1996, 2009; Kelley et al., 2002; I-Le Merrer et al., 2009 yoqwalaselo). Ubungqina bolubandakanyeko lubandakanya ukufumanisa ukuba i-opioid agonists kunye nabachasi ngokubanzi iyasebenza ngakumbi ekunyukeni nasekunciphiseni, ngokulandelelana, ukutya okuthandekayo okanye ulwelo kunolo lomgangatho okanye amanzi aqhelekileyo. Izifundo zabantu ziphakamisa ukuba ii-opioid antagonists ngokubanzi ziyanciphisa iireyithingi zokunambitheka kobumnandi ngaphandle kokuchaphazela ukuqonda kokungcamla (I-Yeomans kunye ne-Grey, 2002). Kwimodeli yezilwanyana, i-mu opioid agonist DAMGO iya kukhuthaza ukutya xa i-microinjected isiza kwiindawo ezininzi zobuchopho, kubandakanya i-nucleus yendlela yokuhamba yodwa, i-parabrachial nucleus, i-nuclei ehlukeneyo ngaphakathi kwe-hypothalamus (ngokukodwa i-nucleus ye-patriyo ), i-nucleus accumbens, kunye ne-VTA (jonga I-Bodnar, 2004; UGosnell noLeviine, 1996; I-Le Merrer et al., 2009). Okokugqibela, uphononongo oluninzi lubonisa umahluko kwii-pioides zobuchopho kunye nama-receptors kumagundane atyhilwe kukutya okuthandekayo (xa kuthelekiswa namagundane atyetyileyo; Alsio et al., 2010; UBarnes et al., 2003; Colantuoni et al., 2001; Kelley et al., 2003; I-Olszewski et al, 2009; Smith et al., 2002).

Ngokubanzi, ukumiliselwa kokutya okunencasa kakhulu kunxulunyaniswa nokwandiswa kwe-mu opioid receptor gene kwiindawo ezininzi zobuchopho, kunye notshintsho (ukunyusa okanye ukuncipha) kwi-opioid peptide preursor mRNA kwiindawo ezininzi ezifanayo. Kucetyisiwe ukuba ukunyuka kwee-receptors ze-opioid kungabonakalisa ukukhutshwa kwepeptide okuncitshisiweyo (Smith et al., 2002) kunye nentetho encitshisiweyo yenkephalin inokuba ngummiselo ophantsi wokumisela umthetho (Kelley et al., 2003). Kukho nobungqina bumehluko kwi-opioid peptide okanye i-gene receptor gene enokuchongwa kukukhetha ukutya okunikiweyo kunokuba kusetyenziswe ngqo oko kutya. Umzekelo, Chang et al. (2010) Iigundane ezikhethiweyo ezinokukhethwa okuphezulu okanye okuphantsi kokutya okunamafutha aphezulu ngokusekwe kumanqanaba okungena ngexesha leentsuku ze-5. Emva kwexesha le-14 leentsuku zolondolozo kuphela kwi-rat chow, kwabakho intetho ye-proenkephalin kwi-PVN, i-nucleus accumbens kunye ne-nucleus esembindini kwi-amygdala kumagundana ngokukhetha okuphezulu kokutya okunamafutha aphezulu. Ababhali bacebisa ukuba esi siphumo simele imeko eyenzeka kwiigundane ezikhetha amanqatha, ngokuchasene nesiphumo ngenxa yokutya okutyayo. Ngokufanayo, i-Osborne-Mendel rats, eyaziwa ngokuba sesichengeni sokutya kakhulu, xa kuthelekiswa namagundane esistres eyaziwa ngokuba ayakwazi ukumelana nokutya kakhulu (S5B / Pl) ibonise inqanaba le-mu opioid receptor mRNA kwi-hypothalamus (UBarnes et al., 2006).

Indima entsonkothileyo yee-opioids kulawulo lokondla inokubaluleka kokuqonda kokuphazamiseka kokutya kunye nokukhuluphala. Iintshaba ezichasene ne-opioid, ngakumbi i-naloxone kunye ne-naltrexone, ziye zaboniswa ukunciphisa intengo yokutya kumthamo oqhelekileyo kunye nabathathi-nxaxheba abatyebileyo kuvavanyo lwexesha elifutshane (I-Yeomans kunye ne-Grey, 2002; de Zwaan noMitchell, 1992). Ngelishwa, ezi zinto zichasene neziphumo ebezingalindelekanga (umzekelo, isicaphucaphu kunye nokuphakama kovavanyo lwesibindi) eziye zabangela ukusetyenziswa kwazo ngokubanzi kunyango lokukhuluphala kunye nokuphazamiseka kokutya; kwacetyiswa ukuba abachasi abatsha be-opioid banokubonelela ngomngcipheko ofanelekileyo / umrhumo wenzuzo (de Zwaan noMitchell, 1992). Ikhomputha enye ebonisa isithembiso malunga noku yi-GSK1521498, i-mu opioid receptor inverse agonist. Eli chiza, ekuxelwa ukuba likhuselekile kwaye linyamezele iprofayili, kubonisiwe ukuba inciphisa imilinganiselo ye-hedonic yokutya okuneswekile eninzi kunye neemveliso zobisi ezinamafutha aphezulu, ukunciphisa ukucekeka kokutya okune-caloric, ukunciphisa inkqubo yokuvavanywa kwe-fMRI i-amygdala ebangelwa kukutya okuthandekayo (UNathan et al., 2012; URabiner et al., 2011). Okokugqibela, uhlalutyo lwofuzo lwakutsha nje lubonisa ukuba iyantlukwano kwi-opioid receptor gene (OPRM1) yokudityaniswa nokuguquguquka kokukhetha ukutya okumnandi nokunamafutha. Abantu abane-G / G genotype yokusebenza kwe-A118G yolu phawu luchazwe ngokukhethekileyo kwizidlo ezinamafutha aphezulu kunye / okanye iswekile kunabantu abane-G / A kunye A / A genotypes (UDavis et al., 2011a). Kwaye kwaqwalaselwa ukuba, kubantu abatyebe kakhulu, ingxaki yokutya ngokutya okuneengxaki zokutya ngokufuthi kuye kwaba nokunyuka rhoqo kwe-allele e-A118G uphawu lophawu lwe-mu opioid receptor genes xa kuthelekiswa nezifundo ezikhuluphele ngaphandle kokuphazamiseka kokutya.Davis et al., 2009). Ke ngoko, uhlalutyo lwemfuzo lomntu luxhasa iziphumo zezifundo zekhemikhali ezibonisa indima ye-opioids ekulamleni ukutya kunye nomvuzo, kwaye iphakamise ukuba ukwahluka kwi-op opioid receptors kunxulumene nokutya okungalunganga. Ukongeza kwindima yee-opioids ekulamleni umvuzo wokutya, banokuqhubekeka nokutya ngokuthambisa kunye / okanye ukujija. Iziphumo ezinokuthi zidityaniswe ngaphakathi kuthintelo lwenkqubo ye-oxytocin (OT) esembindini. I-OT inciphisa ukutya, kwaye i-OT ye-neuronal activation ikhulu ukuya esiphelweni sokondla kunokuba kuqalile ukondla (Sabatier et al., 2006; I-Olszewski kunye neLevine, 2007). I-opioid agonist butorphanol iyinciphisile le activation ye-OT (I-Olszewski kunye neLevine, 2007). Kwintoni enokuthi ibe sisenzo esinxulumene noko, i-OT kucingelwa ukuba inegalelo ekwakhiweni komkhwa othile wokucamngca, kunye nokuzenzisa okunento yokwenza ne-opioid receptor ligands ethintelweyo yomsebenzi we-OT neurons owenziwe yinkqubo ye-lithium chloride kwinkqubo yokuthintela ukunambitha (CTA).I-Olszewski et al., 2010; I-Olszewski et al., 2000). Oku kuncipha kwe-opioid okubangelwa kukusebenza kwe-neuron ye-OT kwakudityaniswa nokunciphisa ukuphendula okuphakathi kweempuku. Ngokuhambelana nolwalamano oluphakanyisiweyo phakathi komvuzo wokuqhutywa kwe-opioid kunye nenkqubo ye-OT, ukuvezwa kwexesha elide kukutya okuneswekile eninzi kubangele ukumiswa kokuphendula kwe-OT ye-neuronal kumthwalo wokutya, isiphumo esinokuthi sibe negalelo kukunyuka okuphezulu kwe- abanambitha abanomdla (UMitra et al., 2010). Olu luvo luxhaswe yingxelo yokuba i-OT ye-knockout yeempuku idla ngokusetyenziswa kwesisombululo se-carbohydrate, kodwa hayi nge-lipid emulsions (Sclafani et al., 2007).

3.4. Ubudlelwane obuqinisekileyo phakathi koKutya / Ukukhetha iziTayile kunye nokuSebenzisa kakubi iziyobisi

Izifundo zokuziphatha kakuhle kwiigundane zibonisa ukuba ubungakanani bokutya (okanye ukuzilawula) ukutya okunokutya kuhlala kuhambelana nokuzilawula iziyobisi. Iigundane ezikhethwe ngokukhethekileyo kukhetho oluphezulu okanye olusezantsi olukhethiweyo, okanye lukhethwe kwisiseko sedakethi yabo yesakancharin okanye ye-sucrose, bonisa ukuthambeka okuphezulu okanye okusezantsi kotywala, icocaine, amphetamine kunye ne morphineUCarroll et al., 2002; UDeSousa et al., 2000; UGosnell et al., 1995; Kampov-Polevoy et al., 1999). Ukutya kwe-Sucrose kukhulisa nemiphumo emihle kunye ne-analgesic ye morphine (UD'Anci et al. 1997; Ileta ye1989), yandisa imvakalelo yokuziphatha kwi-DR2 agonist quinpirole, cocaine, kunye ne-amphetamine (UFoley et al., 2006; IGosnell, 2005; IAvena kunye neHoebel, 2003), kunye nonyusa ifuthe lokuvuselela lucalucalulo lwe-nalbuphine, i-mu opioid receptor agonist (UJewett et al., 2005). Njengoko sele kuphawuliwe, ukutya i-sucrose kunye nokunye ukutya okunomdla kakhulu kubangela ukunyuswa komgaqo wolwelo we-op opioid receptors; olu tshintsho lunokubangela uninzi lweziphumo zokuziphatha ezichazwe ngaphambili.

Emntwini, ukuthanda okonyukayo kwezisombululo ezimnandi kuye kwabonwa kwizifundo ezinotywala kunye / okanye nembali yosapho yotywala (I-Kampov-Polevoy et al, 1997, 2003; Krahn et al, 2006), nangona olu lwalamano lungakhange lubonwe kwezinye izifundo (UKranzler et al., 2001; I-Scinska et al., 2001). Into enomdla kukuba, ukhetho oluphezulu lweencasa ezimnandi ziphakanyisiwe njengokuqikelela kwangaphambili kokungabunqabeli kwizifundo ezixhomekeke ku-alcohol (Krahn et al., 2006) kunye nesangqa esisebenzayo sokusebenza kwe-naltrexone ekunciphiseni ukubuyela kwakhona kwisiselo esinxilisayo (U-Laaksonen et al., 2011). Izifundo ezixhomekekileyo zeOpioid zikwaxela ukwanda kokunqwenela, ukutya kunye / okanye ukhethoUMorabia et al., 1989; UWillenbring et al., 1989; Weiss, 1982; UZador et al., 1996).

3.5. Ukudityaniswa koXanduva lweNgingqi yokuXhasa uKonyuka okuSetyenzisiweyo kweziyobisi kunye nokuButha kwesisindo

Ubungqina obuqhubayo bubonisa ukufana ngumahluko okwahlukileyo ekuphenduleni kwemimandla yomvuzo ukuqala kwexesha lokusetyenziswa kweziyobisi kunye nokufumana ubunzima okokuqala. Uphononongo olukhulu olulindelekileyo kulutsha olufikisayo lwe162 lufumanise ukuba ukuphakanyiswa kokuphendula kwi-caudate kunye ne-putamen kumvuzo wemali oqikelele ukuqala kokuqala kokusetyenziswa kweziyobisi phakathi kolutsha olungasebenzisi nto ngaphambili (Stice, Yokum, & Burger, kumaphephandaba). Ezi ziphumo ziyaqaqanjelwa ngokufumana okuphindeneyo ukuba impendulo yokuphendula okukhulu kunye nemimandla yokuqwalaselwa kokusetyenziswa kweziyobisi kubantu ikwanxulunyaniswa nomngcipheko owandileyo wokuphinda ubuye kwakhona (Gruser et al., 2004; UJanes et al., 2010; Kosten et al., 2006; UPaulus et al., 2005). Nangona ukuphakanyiswa kokuphendula kwengingqi kungakhange kuqikelele ukufunyanwa kwesisindo okungekuko phakathi kweshumi elivisayo elinempilo UStice et al., (Ngoshicilelo), ezo datha zongeza ubungqina bangaphambili obufumanisileyo bokuba ukuphendula okuphezulu kwommandla kuphembelela ukuxabiseka komvuzo (orbitofadal cortex) kumfanekiso otyhidiweyo wokuboniswa kwemifanekiso yokutya ethandekayo waxela kwangaphambili ukufunyanwa kwesisindoYokum et al., 2011).

3.6. Iziphumo zokusetyenziswa kwesiyobisi esiqhelekileyo kunye nokutya okutyayoayo kwi-Dopamine Circuitry kunye nokusayina

Kukho ubungqina bokuba ukusebenzisa iziyobisi ngendlela eqhelekileyo kunye nokutya okuthandekayo kuyinxulunyaniswa neplastical ye-neural efanayo yokujikeleza komvuzo. Uvavanyo lwezilwanyana lubonisa ukuba ukusetyenziswa rhoqo kweziyobisi kunciphisa ii-striatal D2 receptors (UNader et al., 2006; I-Porrino et al., 2004) nemvakalelo yokujikeleziswa kwemivuzo (Ahmed et al., 2002; UKenny et al., 2006). Idatha ikwabonisa ukuba ukusetyenziswa kwe-psychostimulant kunye nokusetyenziswa kwe-opiate kubangela ukunyuka kokubopha kwe-DR1, kunciphise ukuziva kwe-DR2 receptor, ukunyusa i-mu-opioid receptor yokubambisa, ukunciphisa ukuhanjiswa kwe-basal dopamine, kunye nokuphuculwa kwe-dopamine yokusabela (Imperato et al., 1996; I-Unterwald et al., 2001; Vanderschuren kunye neKalivas, i-2000). Iyahambelana nale nto, abantu abadala abanayo, ngaphandle kotywala, i-cocaine, i-heroin, okanye ukuxhomekeka kwemethamphetamine kubonisa ukunciphisa ukubakho kwesithambisi se-striatal D2Volkow et al., 1996, 1997, 2001; Wang et al., 1997). Ukongeza, abantu abaxhaphaza i-cocaine babonisa ukukhutshwa kwe-dopamine ebonakalisiweyo ekuphenduleni iziyobisi ezivuselelayo ezinxulumene nolawulo (UMartinez et al., 2007; Volkow et al., 2005) kunye nokunyamezeleka kwimiphumela euphoric yecocaine (O'Brian et al., 2006).

Ngokumalunga nokukhuluphala, izifundo ezintathu zabantu zifumanise ukuba ukutyeba ngokuchaseneyo nokungakhathali kubonakalise ukunciphisa i-D2 yokubopha okunokwenzeka kwis striatum (de Weijer et al., 2011; Wang et al., 2001; Volkow et al., 2008; Nangona abathathi-nxaxheba abatyeba nabanempilo bengathathwanga ngokulandelelana iiyure ukusukela okokugqibela ukuthatha inxaxheba kophando kwaye bekukho ukugcwala kwabathathi-nxaxheba kwizifundo ezibini zokugqibela), kucebisa ukuba ukubakho kwe-D2 receptor ukutholakala, isiphumo esivele ekuthetheni ngokuchaseneyo. amagundaneThanos et al., 2008). Okubangela umdla, Thanos et al. (2008) bafumanise ukuba njengoko iorenji ifumene ubunzima, babonisa ukunciphisa okungaphaya kokudibanisa i-D2, becebisa ukuba ukuchitha ixesha elininzi kunegalelo ekunciphiseni ukubakhona kwe-D2 receptor. Colantuoni et al. (2001) ifumene ukuba i-glucose ethatha ixesha elide kwishedyuli yokufikelela engapheliyo inyusa i-DR1 ibopha kwi-striatum kunye ne-nucleus accumbens kwaye iyancipha ukubopha kwe-DR2 kwi-striatum kunye ne-nucleus accumbens, ukongeza kwezinye iinguqu ze-CNS kwi-rat. Into ebangela umdla kukuba, ukutya ukutya okuthandekayo kuye kwabangela ulawulo lwe-striatal D1 kunye ne-D2 receptors kwiigundane ezinxulumene nokuthatha isocaloric kwamafutha asezantsi / iswekile ye-chow (Alsio et al., 2010), kuthetha ukuba kukufumana ukutya okunamandla okunokutya xa kuthelekiswa nomgangatho wamandla ombane obangela ukuqina komjikelo wempepha. Ezi ziphumo zikhuthaze ukufundwa ukuthelekisa ukuphendula kwengingqi yokuvuzwa kwabakwishumi elivisayo (n = 152) ekunikeni ingxelo yabo ye-ayisikhrim kwiiveki ezi-2-ezidlulileyo (Burger kunye Stice, 2012). Ukutya i-ice cream kwavavanywa kuba inamafutha aphezulu kunye neswekile kwaye yayingowona mthombo uphambili wezi zondlo kwi-milkshake esetyenziswe kule fMRI paradigm. Ukutya i-ice cream kwakuhambelana ngokunxulumene nokusebenza kwi-striatum (i-putamen yamazwe amabini: ekunene r = -.31; ekhohlo r = -30; caudate: r = -.28) kunye ne-insula (r = -.35) ukuphendula ubisi irisithi (> irisiti engenancasa). Okwangoku, inani elipheleleyo le-kcal kwiiveki ezi-2 ezidlulileyo azilungelelananga ne-dorsal striatum okanye i-insula activation ekuphenduleni i-milkshake irisithi, iphakamisa ukuba kukutya ukutya okuxineneyo kwamandla, endaweni yokutya okwekhalori iyonke okunxulumene nokuvuselelwa kokusebenza kwisekethe. Ezi zinto zifunyanisiweyo ziyahambelana nokuqwalaselwa kommiselo we-endocrine wokhuthazo lwe-sucrose oluchazwe apha ngasentla-ngakumbi, ukuba iziphumo ze-insulin kunye ne-leptin zenzeka ngeedosi ezingaphantsi kokunciphisa inani lokutya kunye nobunzima bomzimba- kwaye kugxininisa ubuntununtunu obuphambili bokujikeleza komvuzo kunye Iiplastikhi zayo ngokubhekisele kwimivuzo yokutya.

Kufuneka iqatshelwe into yokuba uninzi lwabasebenzisi beziyobisi abahlangabezani nenqobo yokuxhomekeka, kwaye nangona kunjalo basebenzisa iziyobisi zokuphathwa gadalala ngeendlela eziyingozi kubo kunye noluntu. Impikiswano yokutya "kwesiyobisi" inokuba yinto ephikisanayo xa kusetyenziswe ukuhlelwa kweziyobisi ze-DSM-IV-TR, kugxila kwiziphumo ezinxulumene nokusetyenziswa komntu kunye nosapho kunokuba kuxhomekeka kubomi bomzimba kwinto leyo (ukunyamezeleka kunye urhoxiso). Nawuphi na umntu weenkqubo ze-DSV-IV-TR unokwaneliswa ngaphakathi kule nkqubo yokuhlelwa ukuze akulungele ukusetyenziswa gwenxa kweziyobisi; Iindlela ezimbini eziphawulwayo zezi:

Ukusetyenziswa kweziyobisi okwenziwa rhoqo okukhokelela ekusilele ekufezekiseni uxanduva oluphambili emsebenzini, esikolweni, okanye ekhaya (umzekelo, ukungaphangeli rhoqo okanye ukungasebenzi kakuhle ngokunxulumene nokusetyenziswa kweziyobisi; ukungahambelani nezinto ezinxulumene nokuhamba, ukunqunyanyiswa, okanye ukugxothwa esikolweni; okanye umzi) ”P. 199.

kwaye

"Ukusetyenziswa gwenxa kweziyobisi nangona kukho ukuqhubeka okanye iingxaki eziqhubekayo zentlalo okanye phakathi kwabantu zibangelwa okanye zongezwa ziziphumo zento (umzekelo, ukuxabana neqabane malunga nemiphumela yokunxila kunye nokulwa ngomzimba)." P. 199.

Ngenxa yokuba bekulucelomngeni ukubonelela ngobungqina bezinto eziphambili ze kuxhomekeka njengoko isetyenziswa kukutya (ukunyamezelana kunye nokurhoxa), mhlawumbi iluncedo ngakumbi ngokubhekisele kwindlela yokuziphatha ekhokelela kukuziselela kokutya kungasetyenziswa isicelo somgaqo weDSM Xhatshazwa. Sicebisa le nkcazo ilandelayo yethutyana "yokusetyenziswa gwenxa kokutya": ipateni engapheliyo yokutya kakhulu okukhokelela kungekuphela kwe-BMI etyebileyo (> 30) kodwa kunye neziphumo ezibi zempilo, ezemvakalelo, zokunxibelelana, okanye ezomsebenzi (esikolweni okanye emsebenzini). Ngokucacileyo zininzi izinto ezinokukhokelela ekufumaneni ubunzima bomzimba obungenampilo, kodwa into eqhelekileyo kukuba zikhokelela kumandla alinganisiweyo amandla. Zininzi iziphumo zempilo ezihlala zinxulunyaniswa nokutyeba, kubandakanya uhlobo lweswekile 2, isifo sentliziyo, idyslipidemia, uxinzelelo lwegazi kunye nezinye iindlela zomhlaza. Iziphumo ezingalunganga zeemvakalelo zokutyeba kakhulu / ukutyeba kakhulu kubandakanya ukungazithembi, iimvakalelo zokuba netyala kunye neentloni, kunye nokukhathazeka komzimba. Iingxaki zokunxibelelana nabantu zinokubandakanya ukungqubana okuphindaphindayo namalungu osapho malunga nokusilela ukugcina ubunzima obusempilweni. Omnye umzekelo wesiphumo somsebenzi ekutyebeni kakhulu uyakhutshwa kwinkonzo yasemkhosini ngenxa yobunzima obugqithisileyo, isiganeko esichaphazela ngaphezulu kwama-1000 emkhosini minyaka le. Abanye abantu banokutya kakhulu kwaye bangabi namava okufumana ubunzima; kwaye abanye abantu banokungafumani bunzima obunempilo kodwa banokuchongwa ngokufanelekileyo ukuba banengxaki yokutya, njenge-bulimia nervosa (ebandakanya iindlela zokuziphatha ezingalunganga, njengokugabha okanye ukuzilolonga ngokweqile kulawulo lobunzima) ehambelana nokukhuluphala ngexesha lesigaba sokuqala sale meko). Siyavuma ukuba ukongeza kukutya kakhulu, ezinye izinto (umz., Imfuza) zinegalelo kumngcipheko wokugula kakhulu. Nangona kunjalo, izinto ngaphandle kotywala neziyobisi zinegalelo kwiziphumo ezibi ekusetyenzisweni gwenxa kweziyobisi, ezinje ngokusilela kulawulo lokuziphatha umzekelo, okwandisa umngcipheko weengxaki zomthetho ezinxulumene nokusetyenziswa.

Izifundo ze4.1 zisetyenziswe kuphando lweziyobisi

Ngaphandle kokubanemiphumela emibi ekuchazeni iindlela zokutya ezakhokelela ekutyebeni kakhulu njenge- "addiction-", kubekho izinto ezenzekayo ezinokubakho kwindlela yokuziphatha neyokomzimba ebonakalayo phakathi kokondla (ngakumbi ukutya okutyayo) kunye nokutya iziyobisi zokuxhatshazwa. Ngexesha elidlulileyo le-50, icandelo lokusebenzisa iziyobisi liye laqulunqa kwaye / okanye lacokisa inani leemodeli zezilwanyana kunye neendlela zokuziphatha ezisandula ukusetyenziswa ngabaphandi abanomdla kwindlela yokuziphatha ebanzi ngakumbi. Umzekelo, kukho iilebhu ezininzi ngoku ezivavanya ukutya okulinganayo kokutya okuzinzisayo xa ukutya kunokuthintelwa (njengoko kunjalo kwizifundo zokusetyenziswa gwenxa kweziyobisi; umzekelo, UCorwin et al., 2011). Ukongeza, iimodeli "zokunqwenela" ezazenziwe okokuqala kwizifundo zokutya iziyobisi zamkelwe ukuba zivavanye umnqweno wokufuna ukuzimela kunye nokunye ukutya okuthandekayo (umzekelo, uGrimm et al., 2005, 2011). Zombini imodeli yezilwanyana kunye nabantu, ukuphinda ubuye kwisimo sokufuna iziyobisi kunokubangelwa kukuchatshazelwa kwiimpawu ezixela kwangaphambili ngesiyobisi, ngokuxinezeleka ebomini, okanye ngokuhambisa idosi enye engalindelekanga. Ukubuyiselwa okufanayo kuya kujongwa kwiimodeli zezilwanyana zokufuna ukutya, kwaye iindlela zokubuyiselwa zisetyenziselwa ukujonga indima yokujikeleza komvuzo wobuchopho ekukhuthazeni ukubuyela kwakhona okuxhaphakileyo kubantu abazama ukugcina ukutya (Floresco et al., 2008; UNair et al., 2009; Ukukhetha i-et al., 2012; UGuy et al., 2011). Njengokuphikiswa kokutya kunokuxoxwa ngokuba nezinto ezilindelekileyo "zokutya" kunye necandelo lokondla, iindlela zokuziphatha ezahlukileyo ezinokuqulunqwa zinokuchaphazela iimpembelelo zonyango lwe-pharmacological kula macandelo ahlukanayo (jonga uBaldo et al, ngalo mbandela; EBerridge, 2004; UKelley et al., 2005a). Olunye uvavanyo, ukusebenzisa ezi kunye nezinye iiparadigms, zinokubonelela ngengqondo kwiimeko kunye neendlela ze-neural ezinegalelo ekusetyenzisweni kakhulu kokutya, ezinokuthi kwezinye iimeko zikhokhe ekuthumeni kakhulu.

Ngokumalunga nezifundo zabantu zala maxesha, ukwamkelwa kwendima yokujikeleza kwe-basal ganglia kwiinkqubo zembuyekezo ezinegalelo ekutyeni kokutya, ngakumbi phambi kokutya okunokuthenjwa, kukhokelele kwixesha elonwabisayo lokujonga indima yale setyhula ekusebenzeni umvuzo wokutya kunye neendlela zokuxela kwangaphambili. Ukongeza, uninzi lolingo lwamva lwe-neuroimaging lusebenzise indlela efanayo, ngokwe-cue kunye nokuvezwa kokuvuselela, njengoko bekwenziwe ngaphambili kuncwadi lokusetyenziswa gwenxa kweziyobisi. Ke ngoko, kuzo zombini izilwanyana kunye neemodeli zabantu, ukuzilolonga kokujonga ukutya okugqithisileyo kokutya okuthandekayo, kunye nokusetyenziswa kweziyobisi njengengxaki yoxhaso lwenkanuko (nokuba oko kuchongwa njenge “mlutha”, okanye enye into) kukhokelele kwiindlela ezintsha kunye Ingqiqo malunga nokuba imijikelezo yomvuzo inokuba negalelo njani ekuqaliseni nasekugcinweni kweendlela zokutya okungekho mpilweni phambi kwemithombo yokutya ene-caloric.

Iingxaki ze4.2 zokujonga ukukhuluphala njengengxaki yokulutha

Bambalwa abantu abalele ekunokwenzeka ukuba babone ukutyeba kakhulu kunye neepateni zokutya ezinokuthi zibenegalelo lokutyeba kakhulu njengeziganeko ezizodwa, imeko eyayisakuba sisifo se-metabolic kunye nokunye okunokuthi kungakho "kukungabinanto yokutya" (kwaye ngokunokwenzeka kungenjalo). Ke ngoko, njengoko kuphawuliwe, nokuba kufumaniseke ukuba ezinye izidlo zinokusetyenziswa gwenxa, kunokwenzeka ukuba abantu abanengxaki yokutya kakhulu banokurekhodwa ngokuthi "kukungabinakho ukutya", xa kunokwenzeka oko okanye kungenjalo. Kukho ubungozi obunokubakho kuphawu olunje. Ukuthetha ukuba abantu banesifo okanye ukugula ngengqondo kunokubangela ukuceketheka ngokwasentlalweni (kwaye abantu abatyebileyo sele bephethwe lucalucalulo noluntu), imvakalelo yokungakwazi kulawula okanye ukukhetha ngaphezulu kwendlela abaziphethe ngayo, okanye izizathu zokuziphatha kwilebula yesifo ( Andikwazi kuzinceda, ndilikhoboka ”). Ukuqonda imida yokufumana iziphumo zophando kulo mmandla kubaluleke njengophando, kwaye ezi cawe kufuneka zaziswe esidlangalaleni.

Olunye ulumkiso ngentsimi kukuba kutoliko lwe-anthropomorphic lwezifundo zezilwanyana- kunye nokuchaza iinjongo zezilwanyana ezingenakuqinisekiswa-kufanele kuthintelwe. Olunye unyino kwizifundo zezilwanyana kukuba imiba yolawulo kunye nokukhetha, edlala indima enkulu ekondleni kwabantu kwasebusheni ukuya phambili, azikho kwaye zihlala ziqwalaselwa. Ngokuqinisekileyo, ubunzima bommandla woluntu abuqulunqwa kuninzi lwezifundo zezilwanyana ukuza kuthi ga ngoku, kwaye ke oko kubonisa umngeni kunye nethuba lezifundo zezilwanyana ezizayo. Ukubonelela ngokuthelekisa ngokuthe ngqo, umntwana wasemva kwesikolo sase-US esikolweni unokukhetha phakathi kwezemidlalo, ukudlala imidlalo yevidiyo, ukwenza umsebenzi wesikolo owenzelwa ekhaya, okanye 'ukuxhoma' kunye nokutya ukutya okulula. Zonke ezi zikhetho zinokuba nexabiso elilinganayo leendleko kunye nokutya okune-snacks akufuneki kube yinto engagqibekanga. Kwizifundo zezilwanyana, isilwanyana sinokukhetha ukutya okanye ukungakutyi ukutya okunencasa, kodwa asinakho ukulawula koko kutya kukuko, sinokuziphatha okulinganiselweyo, kwaye asinakho ukulawula okukhoyo kokutya.

Ngaphaya koko, ukucebisa ukuba ukutya "kungamakhoboka" kusenokukhokelela kwimibuzo ethi "kukuphi ukutya okukhobokisayo?" Ngokwembono yesifo sokutyeba kakhulu, imibuzo enjalo ishenxisa ugxile ekukhuseleni ukutya okusempilweni kunye neendlela zokuzilolonga kuthintelo oluthile ukutya. Njengoko bekucetyisiwe ngaphambili (Rogers no Smit, 2000), ukulebhelisha ubumbano kuhlobo oluthile lokutya (nkqu noko kunokubakho kwaye kuyathandeka) njengegama elithi "umlutha" kuthambisa imeko enkulu nophazamisayo yemeko yabo banengxaki yokuxhomekeka kwiziyobisi okanye iziyobisi. Bambalwa kakhulu abantu abaqhutywa kukuziphatha okunebundlobongela ngenxa yokulangazelela itshokolethi.

4.3. Iingcinga zokugqibela kunye nolawulo lwexesha elizayo

Ngenxa yokuba ukutya ukutya kufanelekile ukuze umntu aphile kwaye loo mvuzo ujikeleziswa ngokukhawuleza ukuqhuba le ndlela yokusinda, ukugxekwa kwemisebenzi yokutya (nkqu nokutya okuninzi okunokutya kodwa okungenampilo) kunokubonakala ngathi kukujolisa ngendlela engeyiyo ekuhlaleni. Njengoko kubhekiselwe apha ngasentla, ugxininiso olufanelekileyo luya kubonakala lucacisa ukuba kutheni abantu bebandakanyeka ekuzondleni kakhulu okanye ekusetyenzisweni kweziyobisi ukuya kuthi ga ngokutshintsha kwe-neural ngendlela ebenza ukuba bazibandakanye ekuziphatheni ixesha elide. Nangona kunjalo, ugxininiso lwesibini lophando, imfundo, kwaye mhlawumbi unyango lungaba kukukhetha okunesondlo kunye nokulinganisa kugxininiso hayi ekuziphatheni ("umlutha"), kodwa kwiziphumo zonyango lwe-pathophysiological, ezibonakaliswa kwinqanaba elikhulu kuluntu lwangoku , kwaye usemncinci (inani labantwana). Ugxininiso olukhulu lubekwe kwi-fructose eneziphumo ezizodwa ze-metabolic, nangona ezinye iziphumo zisekwe ekusetyenzisweni kwesixa esikhulu kakhulu sefreyifesi, kwizilwanyana okanye kwizifundo zeklinikhi (bona uphononongo lwakutsha nje oluvela IStanhope, i2012). Igalelo elenzelwe ngokwemvelo le-sucrose ekutyeni iziselo ezinencasa, kunye nonyuselo lwenkuthazo ye-sucrose kukutya okungasemva okuphezulu kumanqatha (I-Figlewicz et al., 2006, 2008, 2012) icebisa ukuba uphando kunye nemfundo malunga neziphumo ze-metabolic zezi macronutrients kufuneka zibe kugxilwe okuqhubekayo, kwaye iindlela zokuthumela imiyalezo ngokufanelekileyo kumaqela ojoliso ezohlukeneyo kufuneka ziphuhliswe.

Uphando olongezelelekileyo ebantwini alunqweneleki kuphela kodwa luyimfuneko kakhulu. Ngoku ekubeni 'isizukulwana' sokuqala sophando senziwe ngokuqinisekisa ukwenziwa kwenkqubo yokujikeleza komvuzo, lixesha lesifundo sesibini nesesithathu ekunzima kakhulu: uvavanyo lwesiseko sezinto ezikhethiweyo ukongeza kwisiseko iinjongo. Umceli mngeni ofunekayo kunye oyimfuneko kuya kubakho ukwandiswa kwezifundo zangaphakathi-zezifundo ngalo lonke ixesha, kunye nokuchonga ukwanda kwabantu abasesichengeni sokufunda ngaphambi kokuqala kokutya okungenampilo, ukukhuluphala ngokungathethekiyo, okanye zombini. Ukuchaza enye indlela, intsimi kufuneka isuke kwizifundo ezibonakalayo ukuya kwizifundo eziqala ukulungisa umba wokuphambuka (okt, nokuba ngaba ii-CNS zitshintsha iindlela zokuziphatha zokuziphatha, okanye ziyangqinelana okanye ziziphumo zenguqu yokuziphatha) zisebenzisa zombini uyilo olwenziwayo kunye nolingovavanyo.

Ukuvavanywa ngakumbi kweenguqu ezinxulumene nokukhuluphala xa kuthelekiswa neenguqu ezinokutya ezinxulumene nokutya, njengoko kubonakaliswa ziziphumo ezintsha ezivela kwiStice kunye noogxa, ziyafuneka. Njengoko sele kukhankanyiwe apha ngasentla, izifundo kwiintonga zibonisa isiphumo sokutya okunamafutha aphezulu okwenyusa ukunyusa ukunyanzelwa kwe-sucrose, ukuzimeleyo okanye ukutshintsha kwe-metabolic, kugxininisa isiphumo sezondlo okanye i-macronutrients ngeseti yokuguqula imijikelezo yomvuzo we-CNS. Ke, le nto imela enye indlela yophando apho izilwanyana ziguqulela khona kunye nophando lomntu kunye / nonyango. Okokugqibela, nangona kusenokwenzeka ukuba kukho imicimbi ethile eqhelekileyo ebangela ukuba utye kakhulu phantsi kweemeko zokufumaneka kokutya okuphezulu, kukho izinto eziphambili 'ezinokubeka umngcipheko' ezinokuthi zidlale indima ekubonakalisweni kweendlela zokutya. Le ntelekelelo icela ukuqhubekeka nezifundo zokudibanisa i-genetics, kwaye mhlawumbi i-epigenetics, kunye nokucinga kwengqondo kunye nezifundo zengqondo zeklinikhi. Ukuchongwa kohlobo 'lokuba semngciphekweni' kunokukhokelela 'kwizifundo eziguqulweyo' kwizilwanyana, kusetyenziswa iimodeli ezifanelekileyo okanye iiparadesi zokuqinisekisa indima yendidi enjalo, umzekelo, ukhetho olulula lokutya. Ngokucacileyo, le ndawo yokufunda ikwindawo apho iziphumo zophando zelixesha lethu, kunye nezixhobo kunye netekhnoloji yophando lomntu kunye nezilwanyana, inokuthi ifakwe.

U-Eric Stice nguSosayensi oPhezulu woPhando kwiZiko loPhando lase-Oregon; Uphando olukhankanywe apha lwaxhaswa zizibonelelo ze-NIH R1MH064560A, DK080760, kunye DK092468. UDianne Figlewicz Lattemann yiNzululwazi yezaBafundi yoPhando abaDala, iNkqubo yokuPhononongwa kweLebhu yezeMveliso, iSebe leMicimbi yeVeterans Inkqubo yeNkathalelo yeMpilo yeSeet, eSeattle, eWashington; kwaye uphando olukhankanyiweyo kweli phepha lixhaswe yi-NIH isibonelelo DK40963. Uphando olwenziwe nguBlake A. Gosnell kunye no-Allen S. Levine baxhaswa yi-NIH / NIDA (R01DA021280) (ASL, BAG) kunye ne-NIH / NIDDK (P30DK50456) (ASL). U-Wayne E. Pratt ngoku uxhaswa yi-DA030618.

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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