Monehelo oa bokopi moputso lipotoloho ho botenya seoa (2013)

Eric Stice,^a Dianne P. Figlewicz,^b Blake A. Gosnell,^c Allen S. Levine,^d 'me Wayne E. Pratt^e

Boitsebiso ba Mongoli ► Tlhahisoleseding ea Copyright le License ►

E 'ngoe ea litšobotsi tse hlalosang tsa Ann E. Kelley e ne e le ho ela hloko hore thuto ea motheo ea thuto ea motheo le ts'ebetso ea ts'ebetso e boetse e fana ka leseli le leholo holim'a mekhoa ea ho lemalla lithethefatsi le mekhoa ea ho ja lijo tsa maladaptive. Tlhahlobisong ena, re hlahloba ho tšoana ho teng litseleng tsa mekhoa ea litsela tse sebetsanang le moputso oa lijo le lithethefatsi, joalokaha ho hlophisitsoe ke liphuputso tsa morao-rao liphoofolong tsa liphoofolo le litekong tsa manonyeletso tsa batho. Re tšohla lipatlisiso tsa morao-rao tse bontšang hore phekolo ea hyperphagia e isang botenya e amahanngoa le liphetoho tse kholo tsa kelello bokong. Liphuputso tsena li netefatsa bohlokoa ba litsela tsa ho khothaletsa ho sebelisoa ha lijo tse matlafatsang, tse nang le matla a mangata, 'me li lebisa ho potso ea bohlokoa ea hore na liphetoho tsa potoloho ea moputso ho arabela ka ho ja lijo tse joalo li thusa ho nts'etsopele le ho boloka maemong a mang botenya. Qetellong, re buisana ka bohlokoa ba lithuto tsa nakong e tlang mohatsong oa seoa sa botenya le bothata ba tšoaetso ea tšusumetso, hammoho le lintho tse ka 'nang tsa tšoenyeha tse bakoang ke ho shebella lijo tse feteletseng joaloka "ho lemalla". Re fana ka maikutlo a hore ho ka 'na ha e-ba molemo haholo ho tsepamisa mohopolo ho ho ja haholo ho tlisoang ke botenya bo botle, le liphello tse mpe tsa bophelo bo botle, tsa batho ba bang le tsa mesebetsi ea bona e le mofuta oa "tlhekefetso" ea lijo.

3.1. Liphello tsa Tšebeliso ea Lithethefatsi le Lijo Tse Phathahaneng Tlhahlobo ea Mesolimbic Circuitry

Lipapong tse peli le liphoofolo, lipapiso tse 'maloa li bontšitsoe pakeng tsa liphello tsa tšebeliso ea lithethefatsi tsa tlhekefetso le lijo tse monate tse kenyang liphutheho tsa maoto. Ntlha ea pele, tsamaiso e matla ea lithethefatsi tse hlekefetsoang e baka ts'ebetso ea VTA, nucleus accumbens, le libaka tse ling tse hlaselang ho latela lithuto tsa batho le liphoofolo tse ling (Volkow et al., 2002; Koob le Bloom, 1988). Ho sebelisa lijo tse monate le hona ho etsa hore ho be le ts'ebetso e eketsehileng har'a li-midbrain, insula, dorsal striatum, subcallosal cingulate, le prefrontal cortex ho batho mme likarabo tsena li fokotseha ka mokhoa oa ho phekola le ho fokotsa monate oa lijo tse jeoang (Tse nyenyane le al., 2001; Kringelbach et al., 2003).

Ntlha ea bobeli, batho ba nang le litsebo tse sa tšoaneng tsa tšebeliso ea lithethefatsi, ba bontša ts'ebetso e kholo ea meputso ea libaka (mohlala, amygdala, dorsolateral prefrontal cortex [dlPFC], VTA, prefrontal cortex) ka ho arabela litabeng tsa tšebeliso ea lithethefatsi (mohlala, Due et al., 2002; George et al., 2001; Maas et al., 1998; Myrick et al., 2004; Tapert et al., 2003). Ho labalabela ho arabela likarolo tsa correlates le boholo ba dorsal striatum dopamine ho lokolloa (ho qetela ho fanoa ka tekanyo ea ¹¹C-raclopride e fumanoa; Volkow et al., 2006) le ka ts'ebetso ea amygdala, dlPFC, ACC, nucleus accumbens, le orbitofrontal cortex (OFC; Childress et al., 1999; Maas et al., 1998; Myrick et al., 2004). Ka mokhoa o ts'oanang, batho ba bangata le ba nang le boikokobetso ba bonts'a ts'ebetso e kholo ea libaka tse etsang karolo ea ho kenyelletsa bohlokoa ba moputso oa litlhaselo, ho kenyeletsa le striatum, amygdala, orbitofrontal cortex [OFC] le bohareng ba insula; ho ela hloko libaka (ventral lateral prefrontal cortex [vlPFC]); le libakeng tse ling tse sa tšoaneng, ho arabela litšoantšo tse ngata tsa mafura a lijo-tsoekere tse amanang le ho laola litšoantšo (mohlala, Bruce et al. 2010; Martin et al., 2009; Nummenmaa et al., 2012; Rothemund et al., 2007; Stoeckel et al., 2008; Stice et al., 2010). Liphuputso tsena ho batho ba haufi le libaka tse ts'oanang le tsona tse nkiloeng ke lits'oaetsano tse amanang le lithethefatsi le lijo tse monate likokoanyana (Kelley et al., 2005b). Hape ho na le bopaki bo bongata ba hore batho ba bangata le ba nang le bokooa ba fokotseha ho fokotsa ts'ebetsong libakeng tse thibelang ho itšireletsa ka ho arabela litšoantšong tsa lijo tse monate ho fapana le ho laola litšoantšo (mohlala, Nummenmaa et al., 2012; Stice et al., 2008). Batho ba nang le bokoenehi le bona ba bonahatsa kamolo e phahameng ka ho lekanngoa ha moputso le tlhokomelo ea libaka tse arabelang li-cues pontšo e atamelang chelete e ngata ea lijo tse nang le mafura a phahameng / a tsoekere a phahameng ho feta ho fumana tharollo e sa thabiseng (Ng et al., 2011; Stice et al., 2008). Tlhahlobo ea meta-analytics e fumane karolo e ngata ea libaka tsa tekanyo ea moputso e sebelisitsoeng ho arabela litšoantšo tsa lijo tse monate ho batho le libakeng tsa boipheliso tsa boko bo susumelitsoeng ke lithethefatsi har'a batho ba itšetlehileng ka lithethefatsi (Tang et al., 2012).

Litlaleho tsena li tiisa hore lithethefatsi tsa tlhekefetso le lijo tse monate, hammoho le li-cues tse bolelang esale pele moputso oa lithethefatsi le lijo, etsa hore libaka tse tšoanang li kenyelelitsoe moputsong le moputso oa ho ithuta. Lipotoloho tse amehang li kenyeletsa tsamaiso ea dopamine ea mesolimbic, e leng merero e tsoang ho VTA ho ea ho mekhahlelo ea boipheliso. Likarolo tse latelang li totobatsa tlhaho e fetellanang ea liphello tsa lijo le lithethefatsi moputso ho dopaminergic le opioid pontšo ka har'a tsela ena e kholo ea moputso.

3.2. Liphello tsa Tšebeliso e Mpe ea Lithethefatsi le Lijo Tse Ts'oanelang ho Atleha Ho Etsoa ka Pontšo ea Dopamine

Ho phaella ho ho tšoana ho hlokometsoeng ho ja lijo le ho sebelisa lithethefatsi mesebetsing ea neuronal, ho na le ho tšoana ho tsotehang ho latela liphello tsa lithethefatsi tsa tlhekefetso le ho ja lijo tse monate ka ho fetisa dopamine. Taba ea pele, ho ja lithethefatsi tse atisang ho hlekefetsoa ho etsa hore dopamine e lokolloe ho statum le libakeng tse ling tse amanang le mahlo a maholo (Dayas et al., 2007; Di Chiara, 2002; Heinz et al., 2004; Kalivas le O'Brian, 2008; Volkow et al., 2002, 2008). Ho ja lijo tse khonehang ho boetse ho etsa hore dopamine e lokolloe nucleus accumbens liphoofolong (Bassareo le Di Chiara, 1999). Ho sebelisoa ha lijo tse nang le mafura a mangata le a tsoekere a phahameng haholo ho amana le ho lokolloa ha dopamine ka dorsal striatum le boholo ba ho lokolloa ha li-correlates le litekanyo tsa lijo tse monate ho batho (Tse nyenyane le al., 2003). Ntlha ea bobeli, dopamine e lokolloa dorsal striatum ea rat nakong ea boits'oaro ba ho batla lithethefatsi (Ito et al., 2002). Ka mokhoa o ts'anang, ho arabela ho fumana lijo tse monate ho boetse ho amahanngoa le ho eketseha ha pontšo ea dopamine (Schultz et al., 1993). Ntlha ea boraro, ho pepesehela lits'ebeletso tse bontšang ho ba teng ha lithethefatsi tse tloaelehileng tse hlekefetsoang, tse kang lithane kapa leseli, ho etsa hore phasic dopamine e bontše kamora nako ea maemo a litoeba (Schultz et al., 1993). Leha ho le joalo, ho pepeseha ha lintho tse bonahalang le tse hlakileng lijong ha lia bontšoa hore li fetola ho fumanoa ha li-receptor tsa D2 ho statum lithuto tse peli tse fapaneng (Volkow et al., 2002; Wang et al., 2011), ho fana ka maikutlo a hore tlhahiso ea lijo ea lijo ha e hlahise liphello tse hlakileng ho extracellular dopamine ho statum, bonyane lithutong tsa batho ka mehlala e nyane haholo.

3.3. Karolo ea Li-opioids Lijong Tsa Lijo

Lipatlisiso li bontšitse hore li-peptide tsa opioid le li-receptor tsa tsona li phetha karolo ea taolo ea phepelo ea lijo, le hore tsamaiso ea opioid e bonahala e ameha haholo ho phelisang moputso oa lijo (bona Bodnar, 2004; Gosnell le Levine, 1996, 2009; Kelley et al., 2002; Le Merrer et al., 2009 bakeng sa litlhaloso). Bopaki ba ho ameha hona ho kenyeletsa liphuputso tseo li-agonists le bahanyetsi ba opioid ka kakaretso li atlehang ho eketseha le ho fokotseha, ka ho latellana, ho ja lijo tse monate kapa metsi ho feta a chow kapa metsi a tloaelehileng. Liphuputso tsa batho li bontša hore bahanyetsi ba opioid ka kakaretso ba fokotsa litekanyetso tsa monate oa thabo ntle le ho ama temo ea maikutlo (Li-geom le Grey, 2002). Mefuta ea liphoofolo, li-opioid agonist DAMGO li tla etsa hore lijo li kenngoe ha likokoana-hloko li kenngoa libakeng tse 'maloa tsa boko, ho kenyeletsa le nucleus ea sekhahla se ikemetseng, sekoti sa parabrachial, li-nuclei tse ling ka hare ho hypothalamus (haholo-holo mokokotlo oa limela), amygdala (haholo-holo nucleus e bohareng ), nucleus accumbens, le VTA (bona Bodnar, 2004; Gosnell le Levine, 1996; Le Merrer et al., 2009). Qetellong, liphuputso tse 'maloa li bontša phapang pakeng tsa li-peptide tsa bokopi le li-receptor likokoanyana tse tšeptjoang lijo tse nang le likhallelo tse ngata haholo (ha li bapisoa le likhoho tse fepehang; Alsio et al., 2010; Barnes et al., 2003; Colantuoni et al., 2001; Kelley et al., 2003; Olszewski et al, 2009; Smith le al., 2002).

Ka kakaretso, ho kenngoa ha lijo tse monate haholo ho amahanngoa le ho eketseha ha polelo ea liphatsa tsa lefutso ea opioid receptor ka libakeng tse ngata tsa boko, le liphetoho (ho eketsa kapa ho fokotseha) ka moriana oa pele oa peptide oa opioide libakeng tse ngata. Ho 'nile ha boleloa hore ho eketsoa ka har'a li-receptor tse ka' nang tsa bonahala ho fokotsoe ho fokotsoa peptide (Smith le al., 2002) le tse fokotseng polelo ea enkephalin e ka 'na ea e-ba tekanyetso e tlaase ea tefo (Kelley et al., 2003). Hape ho na le bopaki bo bong ba phapang ea peptide ea opioide kapa polelo ea liphatsa tsa lefutso e ka tsejoang ka lithahasello tsa lijo tse fanoeng ho fapana le ho sebelisoa ha lijo tseo. Ka mohlala, Chang le al. (2010) likarolo tse khethiloeng tse phahameng kapa tse fokolang haholo bakeng sa lijo tse mafura tse thehiloeng ho mehato ea ho noa ka nako ea 5. Ka mor'a nako ea ho hlokomeloa ha 14 feela ho rat ea rat, ho ile ha eketsoa polelo ea proenkephalin PVN, nucleus accumbens le nucleus e bohareng ea amygdala lipotheng tse nang le lithahasello tse phahameng tsa mafura a mafura. Bangoli ba fana ka maikutlo a hore phello ena e emela tšobotsi ea tlhaho ea likhoto tse khethang mafura, ho fapana le phello e bakoang ke ho ja lijo. Ka ho tšoanang, likhoho tsa Osborne-Mendel, tse tsejoang hore li na le botenya bo bakoang ke ho ja haholo, ha li bapisoa le likhoto tsa bothata bo tsejoang e le bo khahlanong le botenya bo bakoang ke lijo (S5B / Pl) li bontšitse ho eketseha ha mRNA ea receptor mRNA ho hypothalamus (Barnes et al., 2006).

Karolo e rarahaneng ea li-opioid tse laolang ho fepa e na le bohlokoa bo boholo bakeng sa kutloisiso ea mathata a ho ja le botenya. Bahanyetsi ba li-opioid, haholo-holo naloxone le naltrexone, ba 'nile ba bontšoa ho fokotsa ho ja lijo ka boima bo tloaelehileng le ho ba le ba bang ba kenang litekong tsa nakoana (Li-geom le Grey, 2002; de Zwaan le Mitchell, 1992). Ka bomalimabe, bahanyetsi bana ba na le litla-morao tse mpe (mohlala, ho nyekeloa ke pelo le ho phahama ha liteko tsa sebete) tse thibelitseng ho sebelisoa ha bona ho phekola botenya le mathata a ho ja; ho ile ha boleloa hore bahanyetsi ba bacha ba opioid ba ka 'na ba fana ka karolelano e ntle haholo / melemo (de Zwaan le Mitchell, 1992). Sehlopha se seng se bonts'ang tšepiso tabeng ena ke GSK1521498, e leng agopist inverse ea opioid receptor. Lithethefatsi tsena, tse tlalehoang hore li na le tšireletso e ntle le boleng ba boemo bo botle, li bontšitsoe ho fokotsa litekanyetso tsa hedonic tsa lihlahisoa tsa lebese tse phahameng le tse mafura a phahameng, ho fokotsa ho ja lijo tse hlahisang li-snack, ho fokotsa ts'ebetso ea fMRI Amygdala e bakoa ke lijo tse monate (Nathan et al., 2012; Rabiner le al., 2011). Qetellong, lihlahisoa tsa morao tjena tsa liphatsa tsa lefutso li bontša hore mefuta e fapaneng ea liphatsa tsa lefutso tsa opioid receptor (OPRM1) e amahanngoa le ho fapana hoa lijo tse monate le tse mafura. Batho ba nang le genotype ea G / G ea ts'ebetso ea A118G ea lefutso lena ba ile ba tlaleha lithahasello tse phahameng tsa lijo tse nang le mafura a mangata le / kapa tsoekere ho feta batho ba nang le genotypes ea G / A le A / A (Davis et al., 2011a). Ho ile ha boela ha hlokomeloa hore, ho batho ba bangata haholo, sehlopha se nang le bothata ba ho ja lijo tse nang le li-binge se ne se eketseha ka makhetlo a mangata a G lelekong ea A118G ea liphatsa tsa lefutso la opioid receptor ha li bapisoa le lihlooho tse feteletseng ntle le ho tšoaroa ke bothata ba ho ja (Davis et al., 2009). Ka hona, liphatsa tsa lefutso li hlahloba liphello tsa lithuto tsa meriana tse bontšang karolo ea li-opioids ho phelisang lijo le ho fumana moputso, le ho fana ka maikutlo a hore mefuta e fapaneng ea li-receptors ea opioid e amahanngoa le ho ja lijo tse sa tšoaneng. Ho eketsa karolo ea li-opioids ho phelisang moputso oa lijo, li ka boela tsa thusa ho ja ka ho thibela satiety le / kapa ts'oaetso. Phello ena e ka 'na ea e-ba moemeli ka mokhoa o thibelang tsamaiso ea central oxytocin (OT). OT e fokotsa ho ja lijo, 'me tšebetso ea OT neuronal e kholo ho ea qetellong ea ho fepa ho feta nakong ea ho qala ho fepa (Sabatier et al., 2006; Olszewski le Levine, 2007). Opioid agonist butorphanol e ile ea fokotsa ts'ebetso ena ea OT (Olszewski le Levine, 2007). E ka 'na ea e-ba le ketso e amanang le eona, TL e nahanngoa hore e tlatsetsa ho thehoa ha boikutlo ba ho latsoa litlolo, le ho itokisetsa pele ho li-opioid receptor ligands e thibelang mosebetsi oa li-neurons tsa OT tse kenngoeng ke lithium chloride ka mokhoa o nang le mekhoa ea ho latsoa aversion (CTA)Olszewski et al., 2010; Olszewski et al., 2000). Ho fokotseha ha mokokotlo oa opioid oa mesebetsi ea OT neuronal ho ne ho amahanngoa le karohano e fokolang ea ho amoheloa ha likhoto. Tumellanong le kamano e hlalositsoeng pakeng tsa mefuta ea phepo ea phepo ea opioid le tsamaiso ea OT, ho pepesa nako e telele lijo tsa tsoekere e phahameng ho entse hore ho be le taolo e tlase ea phepelo ea OT neuronal ho mojaro oa lijo, phello e ka tlatsetsang ho kenngoa ha lijo tse monate tse monate (Mitra et al., 2010). Khopolo ena e tšehetsoa ke tlaleho ea hore litloaelo tsa OT tse ts'oanang le li-carbohydrate li rarolla mathata, empa eseng li-emulsions tsa lipilisi (Sclafani et al., 2007).

3.4. Likamano Tse Ntle Pakeng tsa Lijo / Litlhahiso Tse Latsoang le Lithethefatsi Tsa Tlhekefetso

Liphuputso tsa boitšoaro le likhoto li bontša hore mokhoa o lekanyelitsoeng oa ho ja (kapa ho itlhokomela) lijo tse monate hangata li amana hantle le ho itlhokomela ha lithethefatsi. Li-rats li khethile ho khetha lithahasello tse phahameng kapa tse tlaase, kapa li khethiloe motheong oa saccharin kapa li-sucrose, li bonts'a ho noa joala, cocaine, amphetamine le morphine (Carroll et al., 2002; DeSousa et al., 2000; Gosnell et al., 1995; Kampov-Polevoy et al., 1999). Ho nkela li-sucrose ho boetse ho ntlafatsa liphello tse khotsofatsang le tse fapaneng tsa morphine (D'Anci et al. 1997; Lett 1989), e eketsa boikutlo ba ho ba le tšusumetso ho DR2 agonist quinpirole, cocaine le amphetamine (Foley et al., 2006; Gosnell, 2005; Avena le Hoebel, 2003), 'me e ntlafatsa liphello tsa khethollo tsa khethollo ea nalbuphine, e leng opioid receptor agonist (Jewett et al., 2005). Joalokaha ho boletsoe, ho kenngoa ha sucrose le lijo tse ling tse natefisang haholo ho etsa hore ho be le melao-motheo ea li-receptors; phetoho ena e ka 'na ea e-ba tlas'a liphello tse ngata tse boletsoeng ka holimo.

Ho batho, khetho e eketsehileng bakeng sa tharollo e monate e 'nile ea bonoa litabeng tse nang le tahi le / kapa pale ea malapa ea tahi (Kampov-Polevoy et al, 1997, 2003; Krahn et al, 2006), le hoja kamano ena e sa ka ea hlokomeloa lithutong tse ling (Kranzler et al., 2001; Scinska et al., 2001). Ho thahasellisang ke hore ho khetha lithahasello tse monate ho phahamiselitsoe hore ho ka etsahala hore ho se ke ha e-ba le boithaopo litabeng tse itšetlehileng ka joala (Krahn et al., 2006) le kamoo ho ka khonehang hore ho be le katleho ea naltrexone ho fokotsa ho khutlela morao ho noa haholo (Laaksonen et al., 2011). Lihlooho tse itšetlehileng ka li-opioid li boetse li tlaleha ho eketseha ha takatso, lijo le / kapa lithahasello tsa lijo tse monate (Morabia et al., 1989; Willenbring et al., 1989; Weiss, 1982; Zador et al., 1996).

3.5. Tlhaloso ea Karolo ea Moputso Boikarabelo ba ho Eketsa Nakong e Tlang ea Tšebeliso ea Meriana le Boima ba Boima

Bopaki bo hlahelang bo fana ka maikutlo a tšoanang le ho khetholla ka bomong ho amohela boikarabelo ba libaka tse tlang ho sebelisoa ha tšebeliso ea lithethefatsi nakong e tlang le phaello ea pele ea boima bo bobe. Batho ba bangata ba neng ba tla ithuta ka bacha ba 162 ba fumane hore boikarabelo bo phahameng ba ho fumana moputso oa lichelete bo ne bo bolela esale pele hore tšebeliso ea tšebeliso ea tšebeliso ea tšebeliso ea tšebeliso ea lichelete e ne e tla qala nakong ea bocha ba neng ba sa sebelise bacha (Stice, Yokum, & Burger, khatisong). Liphello tsena li lumellana le ho fumanoa hantle hore ho ba le boikarabelo bo boholo ba meputso le tlhokomelo libakeng tsa ho sebelisa lithethefatsi ho batho ho boetse ho amahanngoa le kotsi e eketsehileng ea ho khutlela morao hape (Gruser et al., 2004; Janes et al., 2010; Kosten et al., 2006; Paulus et al., 2005). Le hoja phaello ea phaello ea libaka sebakeng se phahameng e sa ka ea bolela esale pele phaello e boima ea boima bo boima har'a boima ba boima ba bocha lilemong tsa thuto Stice et al., (Ka mochine oa khatiso), ditaba tseo li eketsa bopaki bo fanoeng pele bo fumanoa hore boikarabelo bo boholo ba sebaka se kenyelletsoang moputso oa tekanyetso (orbitofrontal cortex) ho bontša hore ho na le ho hlahisa litšoantšo tse monate ho bolela esale pele ho fumana boima ba nakong e tlang (Yokum et al., 2011).

3.6. Liphello tsa Tšebeliso ea Mokhoa oa Boipheliso oa Mokhoa oa Tšebeliso e Mpe le Lijo Tse Tloaelehang Tlhahlobo ea Dopamine Circuitry le Signal

Hape ho na le bopaki ba hore mekhoa e tloaelehileng ea tšebeliso ea lithethefatsi le ho ja lijo tse monate li amahanngoa le polasetiki e mengata ea moputso oa potoloho. Liteko tsa liphoofolo li bontša hore mokhoa o tloaelehileng oa tšebeliso ea lithethefatsi o fokotsa li-receptor tse hlaselang tsa D2 (Nader le al., 2006; Porrino et al., 2004) le kutloisiso ea potoloho ea moputso (Ahmed le al., 2002; Kenny et al., 2006). Lits'ebeletso li boetse li bontša hore mokhoa o tloaelehileng oa kelello ea psychostimulant le opiate o baka ho eketseha ha DR1, ho fokotsa kutloisiso ea DR2 ho amohela mofuthu, ho amohela li-receptor tse tlamang, ho fokotsa phetisetso ea basophyine ea basal, le ho ntlafatsoa ho bokella karabo ea dopamine (Imperato et al., 1996; Unterwald et al., 2001; Vanderschuren le Kalivas, 2000). Tumellanong le sena, batho ba baholo ba nang le, khahlanong le ntle le joala, joala, k'hok'heine, heroin, kapa ho itšetleha ka methamphetamine ho bontša ho fokotseha ho fumanoa ha D2 receptor e fumanehang le kutloisiso (Volkow et al., 1996, 1997, 2001; Wang et al., 1997). Ho phaella moo, batho ba hlekefetsang k'hok'heine ba bontša hore ba lokolohile dopamine ka lebaka la lithethefatsi tse susumetsang tse amanang le taolo (Martinez et al., 2007; Volkow et al., 2005) le ho mamella liphello tse phahameng tsa k'hok'heine (O'Brian et al., 2006).

Mabapi le ho nona haholo, lithuto tse tharo tsa batho li fumanoe hore batho ba mahlahahlaha le ba nang le bokooa ba bonts'a matla a ho thibela D2 ho striatum (de Weijer et al., 2011; Wang et al., 2001; Volkow et al., 2008;; le hoja litho tsa boima bo feteletseng le tse phetseng hantle li ne li sa tsamaisane ka lihora tse ngata ho tloha ka nako ea ho qetela ha li ntse li ithuta 'me ho ne ho e-na le karolo e itseng ho barupeluoa lithutong tse peli tse qetellang), ho fana ka maikutlo a hore fokoliso ea D2 e fumanoa, e bile le phello e matla haholoanyane li-rats (Thanos et al., 2008). Ho khahlisang, Thanos et al. (2008) e boetse e fumane hore ha likhoto li ntse li boima, li ile tsa bontša ho fokotseha ho eketsehileng ka matla a ho thibela D2, ho fana ka maikutlo a hore ho ja ho tlatsetsa ho tlatsetsa ho fokotseha ho fumaneha ha mokete oa D2. Colantuoni et al. (2001) o fumane hore khase e tloaelehileng e kenang lenaneong le fokolang ea ho kenyeletsa ho eketsa DR1 ho tlamisa ho striatum le nucleus accumbens le ho fokotsa DR2 ho tlama ho striatum le nucleus accumbens, ho phaella ho liphetoho tse ling tsa CNS rateng. Ho thahasellisang, ho ja lijo tse monate ho ile ha fella ka ho theola taolo ea li-receptor tse hlaselang D1 le D2 likokoanyana tse amanang le ho noa ha isocaloric ea mafura a tlaase /Alsio et al., 2010), ho fana ka maikutlo a hore ke phepelo ea lijo tse matla tse matla tse matlafatsang ho fapana le ho leka-lekanya matla a matla a etsang hore polasetiki ea moputso o be le moputso. Liphello tsena li ile tsa etsa hore ho be le phuputso e bapisoang le boikarabello ba batho ba nang le bokooa (n = 152) ho tlalehoa ha bona ea ice cream ka libeke tse fetileng tsa 2 (Burger le Stice, 2012). Ho noa ice cream ho ile ha hlahlojoa hobane e na le mafura a mangata haholo le tsoekere ebile e ne e le mohloli o ka sehloohong oa limatlafatsi tsena lebeseng le sebelisitsoeng papaling eo ea fMRI. Ho ja ice cream ho ne ho amana hampe le ts'ebetso ea striatum (bilateral putamen: right r = -.31; left r = -30; caudate: r = -.28) and insula (r = -.35) in response to milkshake rasiti (> rasiti e se nang tatso). Leha ho le joalo, palo e felletseng ea kcal nakong ea libeke tse 2 tse fetileng ha ea ka ea tsamaellana le dorsal striatum kapa insula activation ho arabela risiti ea milkshake, e fana ka maikutlo a hore ke ho ja lijo tse matlafatsang, ho fapana le ho ja ka kakaretso khalori e amanang le moputso oa ts'ebetso ea potoloho. Liphuputso tsena li tsamaellana le se hlokometsoeng ke taolo ea endocrine ea tšusumetso ea sucrose e hlalositsoeng kaholimo - haholo-holo, hore litlamorao tsa insulin le leptin li hlaha litekanyetsong tse fokotsang ho ja le `mele oa boima ba 'mele oa khalori - mme e hatisa kutloisiso e hlahelletseng ea potoloho ea moputso le polasetiki ea eona mabapi le meputso ea lijo.

Ho lokela ho hlokomeloa hore basebelisi ba bangata ba lithethefatsi ha ba finyelle boemo ba ho itšetleha, leha ho le joalo ba sebelisa lithethefatsi tsa tlhekefetso ka litsela tse kotsi ho bona le sechabeng. Khang ea "ho lemalla" lijo e ka 'na ea se ke ea e-ba le likhang haeba tšebetso ea DSM-IV-TR ea tšebeliso e mpe ea lithethefatsi e ne e sebelisoa, e lebisang tlhokomelo ea liphello tse mpe tse amang motho ka mong le malapa a bona ho e-na le ho itšetleha ka physiologic ka ntho (ho mamellana le ho tlosoa). E 'ngoe le e' ngoe ea mekhoa ea DSV-IV-TR e ka khotsofatsoa ka hare ho lenane lena la likarolo bakeng sa ho tšoaneleha ho sebelisa lithethefatsi hampe; lintlha tse peli tse ikhethang ke:

"Ho sebelisoa ha lithethefatsi tse tloaelehileng ho fella ka ho hlōleha ho phethahatsa boikarabelo bo boima mosebetsing, sekolo, kapa lehae (mohlala, ho ba sieo ka makhetlo a mangata kapa ts'ebetsong e mpe ea mosebetsi o amanang le tšebeliso ea lithethefatsi; ho sieo ha lintho tse amanang le lithethefatsi, ho belaela kapa ho lelekoa sekolong; kapa ba ntlo) "P. 199.

'me

"Ho tsoela pele ho sebelisa lithethefatsi ho sa tsotellehe mathata a tsitsitseng kapa a tloaelehileng a sechaba kapa a boikemelo a bakoang kapa a fetisitsoeng ke liphello tsa motsoako (mohlala, likhang le molekane ka liphello tsa botahoa le lintoa)." P. 199.

Hobane ho bile thata ho fana ka bopaki ba likarolo tsa bohlokoa tsa ho itšetleha e sebelisoa ho lijo (ho mamellana le ho tlohela), mohlomong ho ba le mekhoa e metle ka ho fetisisa mabapi le boitšoaro bo etsang hore ho be le lijo tse ngata ho ka 'na ha e-ba ho sebelisa moelelo oa DSM bakeng sa lithethefatsi Ho hlekefetsoa. Re fana ka maikutlo a tlhaloso e latelang ea nakoana ea "tlhekefetso ea lijo": mokhoa o sa foleng oa ho ja ho tlisoang ke litlamorao tse sa hlahiseng feela BMI (> 30) empa hape le litlamorao tse ngata tse mpe tsa bophelo bo botle, maikutlo, boits'oaro ba batho, kapa tsa mosebetsi (sekolong kapa mosebetsing). Ho hlakile hore ho na le lintlha tse ngata tse ka lebisang mononong o sa pheleng hantle, empa ho tloaeleha ke hore li baka matla a tsoelang pele a matla. Ho na le litlamorao tse ngata tsa bophelo bo botle tse atisang ho amahanngoa le botenya, ho kenyeletsoa lefu la tsoekere la mofuta oa 2, lefu la pelo, dyslipidemia, khatello ea kelello le mefuta e meng ea mofetše. Litlamorao tse mpe tsa maikutlo a botenya / botenya li kenyeletsa ho ikhella fatše, ho ikutloa u le molato le ho hlajoa ke lihlong le ho tšoenyeha ho hoholo ka setšoantšo sa 'mele. Mathata a ho sebelisana le batho a ka kenyelletsa likhohlano tse etsahalang khafetsa le litho tsa lelapa ka ho hloleha ho boloka boima ba 'mele bo phetseng hantle. Mohlala o mong oa litlamorao tsa mosebetsi o tlisoang ke ho nona ho tlosoa litšebeletsong tsa sesole ka lebaka la boima bo feteletseng, ketsahalo e amang masole a fetang 1000 selemo se seng le se seng. Batho ba bang ba ka ja ho tlōla 'me ba se ke ba ba le boima ba' mele bo seng botle; 'me batho ba bang ba kanna ba se ke ba ba le boima ba' mele bo sa pheleng empa ba ka fumanoa ka nepo ba e-na le bothata ba ho ja, joalo ka bulimia nervosa (e kenyelletsang boits'oaro bo seng botle bo botle, joalo ka ho hlatsa kapa boikoetliso bo fetelletseng ba ho laola boima ba 'mele) kapa ho itlopa joala (e ka' nang ea se e amanang le botenya nakong ea karolo ea pele ea boemo bona). Re amohela hore ntle le ho ja ho tlōla, lintlha tse ling (mohlala, liphatsa tsa lefutso) li kenya letsoho kotsing ea ho kula ho amanang le botenya. Leha ho le joalo, mabaka a mang ntle le ts'ebeliso e mpe ea joala le lithethefatsi a tlatsetsa liphellong tse mpe ts'ebelisong e mpe ea lithethefatsi, joalo ka likhaello tsa taolo ea boits'oaro ka mohlala, tse eketsang kotsi ea mathata a amanang le ts'ebeliso ea molao.

Lithuto tsa 4.1 tse sebelisitsoeng lipatlisisong tsa lithethefatsi tsa lithethefatsi

Ho sa tsotellehe menyetla ea liphello tse mpe ho hlalosang mekhoa ea phepo e lebisang ho nona ho tlōla e le "ho lemalla ho lemalla", ho bile le liphetoho tse ntle tse bakiloeng ke boitšoaro bo boletsoeng le bo bong bo tšoanang pakeng tsa ho fepa (haholo-holo ka lijo tse monate) le ho ja ea lithethefatsi tsa tlhekefetso. Nakong ea lilemo tse fetileng tsa 50, tšimo ea tšebeliso e mpe ea lithethefatsi e thehile le / kapa ho hloekisa palo e mengata ea liphoofolo le mekhoa ea boitšoaro e sa tsoa sebelisoa ke bafuputsi ba thahaselloang ke boitšoaro bo susumelletsoeng ka ho pharaletseng. Ka mohlala, ho na le li-labs tse ngata hona joale tse hlahlobang lijo tsa ho ja lijo tse lekaneng ha lijo tse joalo li thibetsoe (joalo ka ha ho tloaelehile tabeng ea lithuto tsa tšebeliso e mpe ea lithethefatsi; mohlala, Corwin le al., 2011). Ho phaella moo, mekhoa ea "ho lakatsa" e qalileng ho hlahisoa lithutong tsa ho itšireletsa lithethefatsi e amohetsoe ho hlahloba takatso ea sucrose le lijo tse ling tse khahlisang (mohlala, Grimm et al., 2005, 2011). Mefuteng ea liphoofolo tse peli le batho, ho khutlela mokhoeng oa ho batla lithethefatsi ho ka bakoa ke ho ipapisa le lits'ebeletso tse bolelang esale pele hore na meriana eo ke efe, ka maemo a sithabetsang bophelong kapa ka ho khahloa ke tekanyo e le 'ngoe e sa lebelloang ea lithethefatsi. Ho tsosolosoa ho joalo ho ka bonoa ka mehlala ea liphoofolo ea boits'oaro ba ho batla lijo, 'me li-paradigms tse tsosolositsoeng li sebelisetsoa ho hlahloba karolo ea boipheliso ba bokooa ba boko ba ho potlakisa ho khutlela morao hangata ho batho ba lekang ho boloka lijo (Floresco et al., 2008; Nair et al., 2009; Pickens et al., 2012; Guy et al., 2011). Ha lijo li ka ts'oaetsanoa ho ba le tebello ea likaroloana tsa "phepo" le lijo tse fanang ka phepo, li-paradigms tsa boitšoaro li fapane tse ka fokolang phello ea phekolo ea meriana ka likarolo tsena tse arohaneng (sheba Baldo et al, taba ena; Berridge, 2004; Kelley et al., 2005a). Liteko tse eketsehileng, ho sebelisa li-paradigms tsena le tse ling, li ka fana ka temohisiso ka maemo le mekhoa ea methapo e tlatsetsang ho tlōla lijo tse ngata, tseo ka linako tse ling li ka lebisang botenya.

Mabapi le lithuto tsa batho tsa mehleng ea kajeno, ho amohela karolo ea litsela tsa basal ganglia meketeng ea moputso e tlatsetsang ho jang lijo, haholo-holo ha ho tobane le lijo tse lekaneng, ho entse hore ho be le nako e monate ea ho hlahloba karolo ea potoloho ena ha ho sebetsoa lijo tsa moputso le lits'ebeletso tse bolelang esale pele. Ho phaella moo, liteko tse ngata tsa morao-rao tsa lisele tsa bokooa li sebelisitse mokhoa o tšoanang, ka mokhoa o ts'oanang le ho hlahisa maikutlo, joalokaha ho 'nile ha etsoa nakong ea libuka tsa tšebeliso e mpe ea lithethefatsi. Ka hona, liphoofolong tse peli le liphoofolo, ho ba le maikutlo a phahameng a ho shebella lijo tse monate, le ho lemalla lithethefatsi e le "mathata a ho susumetsa maikutlo" (ebang ke karolo ea "lithethefatsi", kapa ntho e 'ngoe) e lebisitse mekhoa e mecha le temohisiso mabapi le hore na lipotoloho tsa moputso li ka tlatsetsa joang ho qalella le ho boloka mekhoa e sa nepahaleng ea ho fepa ka pel'a mehloli e mengata ea lijo.

Matšoao a 4.2 ka ho talima botenya e le lefu la "lemalla"

Ke batho ba seng bakae feela ba laolang botenya le lijo tse kenang lijo tse ka tlatsetsang ho boima ho feta litšobotsi tse hlakileng, tse neng li le tšoaetsano ea lijo le tse ling tseo e ka 'nang ea e-ba "ho lemalla lijo" (' me mohlomong e se). Kahoo, joalokaha ho boletsoe, esita le haeba ho thehiloe hore lijo tse ling li na le bokhoni ba ho hlekefetsa, ho ka etsahala hore batho ba nang le botenya ba ka 'na ba bitsoa "li-addicts tsa lijo", ha seo se ka etsahala kapa ha se joalo. Ho na le likotsi tse ka 'nang tsa e-ba teng ho khetholla joalo. Ho fana ka maikutlo a hore batho ba na le lefu kapa kelello ea kelello ho ka fella ka tlhekefetso ea sechaba ('me batho ba feteletseng ba se ba ntse ba e-na le mekhoa e mebe le ea boiketlo), ba na le maikutlo a ho hloka taolo kapa khetho holim'a boitšoaro ba bona, kapa ho itšoara kalafo ea lefu (" ke sitoa ho iphelisa, ke lemaletse "). Ho utloisisa meeli ea liphuputso tsa lipatlisiso tšimong ena ke tsa bohlokoa joaloka liphuputso tsa lipatlisiso ka boeona, 'me li-caveats li lokela ho tsebisoa phatlalatsa.

Tlhokomeliso e 'ngoe bakeng sa tšimo ke hore tlhaloso ea liphoofolo ea liphoofolo e hlalositsoeng ke anthropomorphic-le ho hlalosa sepheo ho liphoofolo tseo ho hlakileng hore li ke ke tsa tiisoa-li lokela ho qojoa. Ntho e 'ngoe e fokolang ea lithuto tsa liphoofolo ke hore litaba tsa taolo le khetho, e leng karolo e khōlō ho fepa batho ho tloha lilemong tsa bocha, ha ho joalo ebile hangata ha li sebetsane le tsona. Ka sebele, ho rarahana ha tikoloho ea batho ha hoa etsoa ka bongata ba lithuto tsa liphoofolo ho fihlela joale, kahoo e emela phephetso le monyetla oa lithuto tsa liphoofolo tsa nakong e tlang. E le ho fana ka papiso e tobileng, mocha oa morao-rao US o ka 'na a khetha lipakeng tsa lipapali, a bapala lipapali tsa video, a etsa mosebetsi oa sekolo o etsetsoang hae, kapa a' qeta 'a bile a ja lijo tse hlaselang. Tsena tsohle li ka 'na tsa e-ba le boleng bo lekanang le theko e boima' me ho ja lijo tse sa hlajoang ke lijo tse sa hlahisang lijo ho ka ' Lipatlisisong tsa liphoofolo, phoofolo e ka 'na ea ba le khetho ea ho ja kapa ea sa je lijo tse monate, empa ha e na matla a ho laola hore na lijo tseo ke life, li na le mekhoa e fokolang ea boitšoaro, ebile ha e na matla a ho laola ha lijo tseo li le teng.

Ho feta moo, ho fana ka maikutlo a hore lijo li "lemaletse" li ka 'na tsa lebisa lipotsong tsa "lijo life tse lemalang?" Ho latela maikutlo a seoa sa botenya haholo, lipotso tse joalo li fetola maikutlo ho feta ho khothalletsa mokhoa o nepahetseng oa ho ja le ho ikoetlisa. lijo. Joalokaha ho se ho bontšitsoe pele (Rogers le Smit, 2000), ho bitsa likamano tsa mofuta o itseng oa lijo (esita le tse nang le caloric le tse ratehang haholo) e le "ho lemalla" ho fokotsa boemo bo tebileng le bo ferekanyang ba boemo ba ba nang le ts'oaetso ea lithethefatsi kapa ho lemalla lithethefatsi. Batho ba fokolang haholo ba isoa boitšoarong bo mabifi ka lebaka la takatso ea tsokolate.

4.3. Maikutlo a ho qetela le litaelo tsa nakong e tlang

Kaha ho ja lijo hoa hlokahala hore motho a phele 'me moputso oa ho potoloha o ka' na oa fetoha ho tsamaisa mokhoa ona oa ho pholoha, ho nyatsoa ha lijo (esita le ho hongata ho hongata ho lijo tse sa thabiseng empa ho sa phelloe hantle) ho ka bonahala e le sepheo se fosahetseng sechabeng. Joalokaha ho boletsoe ka holimo, ho tsepamisa maikutlo ho nepahetseng ho ka bonahala eka ke ho lemoha hore na ke hobane'ng ha batho ba kopanela ho sebelisoa ho ja ho tlōla kapa ho sebelisa lithethefatsi ho fihlela bocha ba potoloho ea neural e fetoloa ka mokhoa o ba bolokang ba kopanela boitšoarong nako e telele. Leha ho le joalo, ntlha ea bobeli bakeng sa lipatlisiso, thuto le mohlomong phekolo e ka ba holim'a khetho ea phepo e nepahetseng le ho leka-lekanngoa ka ho hatisoa ka boitšoaro ("ho lemala"), empa liphellong tsa pathophysiological tse ka tlaase, tse bonahatsoang ka mokhoa o moholo ho batho ba teng hona joale , le ha a le monyenyane (palo ea bana). Ho hatelloa haholo fructose e nang le liphello tse ikhethileng tsa ts'ebetso, le hoja liphuputso tse ling li thehiloe ho sebelisoa ha fructose haholo, liphoofolong kapa litlelong tsa meriana (bonang tlhahlobo ea morao tjena Stanhope, 2012). Monehelo o susumelletsang motho ka mong hore a noe lino tse monate, le ho matlafatsa sucrose tšusumetso ka lijo tse tsoang mofuteng oa mafura (Figlewicz et al., 2006, 2008, 2012) e fana ka maikutlo a hore lipatlisiso le thuto mabapi le liphello tsa ts'ebetsong tsa macronutrients li lokela ho ba tsepamisitsoeng pele, mme mekhoa ea ho romela melaetsa e sebetsang lihlopheng tse fapaneng e lokela ho ntlafatsoa.

Phuputso e eketsehileng ho batho le eona ha e lakatsehe feela empa e hlokahala haholo. Hona joale hore 'moloko' oa pele oa lipatlisiso o 'nile oa etsoa ho tiisa hore ho tla lebelloa ts'ebetsong ea potoloho ea moputso, ke nako ea lithuto tsa bobeli le tsa boraro tse thata haholo: ho hlahloba motheo oa neural oa khetho ho phaella ho sepheo sa motheo sepheo. Taba e boima le e hlokahalang e tla ba ho atolosoa ha lithuto tsa ka hare-hare ho nako, hammoho le ho khetholla baahi ba tlokotsing bakeng sa ho ithuta pele ho qala ho ja lijo tse sa pheleng, botenya bo botle, kapa bobeli. E shebisitsoe ka tsela e 'ngoe, tšimo e tlameha ho tloha lithutong tsa ho shebella liphuputso tse qalang ho rarolla bothata (ke hore, ebang CNS e fetola liphetoho tse itekanetseng tsa boitšoaro, kapa li khotsofatsa kapa liphello tsa liphetoho tsa boitšoaro) li sebelisa mekhoa e meholo le ea liteko.

Ho phaella moo ho hlahlojoa liphetoho tse amanang le botenya ho fapana le liphetoho tse amanang le lijo, joalokaha ho totobatsoa ke liphuputso tse ncha tse tsoang ho Stice le basebetsi-'moho, hape ho hlokahala. Joalokaha ho boletsoe ka holimo, lithuto tsa litoeba li bontša lijo tse mafura tse matla ho eketsa tšusumetso ea sucrose, e sa ikemetseng ka ho feteletseng kapa liphetoho tsa ts'ebetso, ho hatisa phello ea limatlafatsi kapa macronutrients ka se le ho fetola li-circuits tsa moputso oa CNS. Ka hona, sena se emela tataiso e 'ngoe ea lipatlisiso moo lipatlisiso tsa liphoofolo tsa phetolelo le lipatlisiso tsa batho / litleleniki li ka fetolang. Qetellong, le hoja ho ka 'na ha e-ba le liketsahalo tse tloaelehileng tse bakang ho ja lijo tse ngata tlas'a maemo a ho fumaneha ha lijo, ho na le lintho tse ka sehloohong tsa' maemo a ts'oaetsano 'a ka' nang a phetha karolo ea polelo ka 'ngoe ea lijo. Tlhahiso ena ea ho etsa lithuto tse tsoelang pele ho kopanya liphatsa tsa lefutso, mme mohlomong epigenetics, ka ho nahana ka boko le lithuto tsa kelello tsa kelello. Ho tseba hore liphatsa tsa 'tlokotsi' li ka 'na tsa etsa hore' li fetole lithuto tsa ho fetolela 'liphoofolong, li sebelisa mefuta e loketseng ea mefuta kapa lipapali ho etsa bonnete ba hore na karolo ea liphatsa tsa lefutso ke efe, ka mohlala, ho khetha lijo tse bonolo. Ka ho hlakileng, sebaka sena sa thuto ke nakong eo lipatlisiso tsa morao-rao tsa lipatlisiso, hammoho le lisebelisoa le thekenoloji bakeng sa lipatlisiso tsa batho le liphoofolo li ka sebelisoa.

Eric Stice ke setsebi se phahameng sa thuto lefapheng la lipatlisiso la Oregon Research Institute; phuputso ea hae e boletsoeng mona e tšehetsoa ke NIH e fanang ka R1MH064560A, DK080760, le DK092468. Dianne Figlewicz Lattemann ke setsebi se phahameng sa ho etsa lipatlisiso ho bafuputsi, Setsi sa Lipatlisiso sa Lipatlisiso tsa Lipatlisiso, Lefapheng la Bahlabani ba Puget Sound Health Care System, Seattle, Washington; mme lipatlisiso tsa hae tse boletsoeng ka pampiri ena li tšehetsoa ke thuso ea NIH DK40963. Phuputso ea Blake A. Gosnell le Allen S. Levine e tšehetsoa ke NIH / NIDA (R01DA021280) (ASL, BAG) le NIH / NIDDK (P30DK50456) (ASL). Wayne E. Pratt hona joale o tšehetsoa ke DA030618.

Boitlhotlhollo ba Mohoeletsi: Ena ke faele ea PDF ea mongolo o ngotsoeng ka letsoho o sa amoheloang o amoheletsoeng bakeng sa ho hatisoa. Joaloka tšebeletso ho bareki ba rona re fana ka phetolelo ena ea pele ea mongolo o ngotsoeng ka letsoho. Mongolo o ngotsoeng ka letsoho o tla ba le ho kopitsa, ho kenya lihlopha le ho hlahloba bopaki bo hlahang pele o hatisoa ka mokhoa oa oona oa ho qetela. Ka kopo hlokomela hore nakong ea mekhoa ea tlhahiso ea lihlahisoa e ka fumanoa e ka amang litaba, le litsebiso tsohle tsa molao tse sebetsang koranteng e amanang le eona.

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