Boko ba bokooa boa je: Liphutheho tse thabisang le tse lakatsehang ka botenya le mathata a ho ja (2010)

Kent C. Berridge, Chao-Yi Ho, Jocelyn M. Richard, 'me Alexandra G. DiFeliceantonio

Seo re se jang, ka nako le ho feta hakae, kaofela li susumetsoa ke mekhoa ea bokooa ea boko e etsang hore 'ho rata' le 'ho batla' bakeng sa lijo. E le ho fokolisa, ho se sebetse ho lipotoloho tsa moputso ho ka tlatsetsa ho eketseha ha morao-rao oa botenya le mathata a ho ja. Mona re hlahloba lisebelisoa tsa boko tse tsejoang ho hlahisa 'ho rata' le ho 'batla' lijo, le ho hlahloba ho sebelisana ha bona le mekhoa ea taolo ea tlala le satiety, e amanang le litaba tsa bophelo bo botle. 'Ho rata' lisebelisoa ho kenyeletsa lipotoloho tsa hedonic tse kopanyang li-hotspots tsa cubic-millimeter libopeho tse kang li-nucleus accumbens le ventral pallidum (moo li-sign opioid / endocannabinoid / orexin li ka eketsang menyaka ea maikutlo). 'Ho batla' mekhoa e kenyelletsa marang-rang a maholo a opioid a nucleus accumbens, striatum, le amygdala e fetisang ka ntle ho li-hotspots tsa hedonic, hammoho le tsamaiso ea mesolimbic dopamine, le lisebelisoa tsa mahlaseli a maiketsetso a lumellanang le mekhoa eo. Re nahanisisa ka litsela tseo boko ba tsona bo putang lipotoloho ka tsona ho ka 'na ha kenya letsoho ho botenya haholo kapa mathateng a ho ja.

Ho se sebetse ha moputso e le sesosa

Ntlha ea pele, ho ka etsahala hore likarolo tse ling tsa bokopi ba mosebetsi li tsamaee hampe ho baka ho ja lijo kapa ho kula ho itseng. Lijo li ka 'na tsa "rata" haholo kapa li nyane haholo ka moputso oa ho se sebetse. Ka mohlala, ho sebelisoa ha mafu a opioid kapa endocannabinoid hedonic hotspots ka nucleus accumbens le ventral pallidum e hlalositsoeng mona ka tlaase ho ka etsa hore liketso tsa 'ho rata' li ntlafatsoe ho latsoa monate ho batho ba bang. Ho ts'ebetsa ho feteletseng hoa 'ho rata' li-substrate ho tla matlafatsa tšusumetso ea hedonic ea lijo, ho etsa motho ka bobeli 'joaloka' le 'ho batla' lijo ho feta batho ba bang, 'me kahoo tlatsetsa ho ja lijo tse ngata le botenya haholo (Berridge, 2009; Davis et al., 2009). Ka lehlakoreng le leng, mokhoa o ferekanyang oa ho se sebetse ho hoholo ho ka 'na ha bonahala eka o fokotsa' ho rata 'ka ho tšoenyeha ha mofuta oa anorexia (Kaye et al., 2009).

Esita le ntle le thabo ea ho se sebetse, monyetla o mong oa ho senya moputso ke hore ho 'batla' ho ja ho ka 'na ha tsoha ka boeena, haeba ho ba le tšusumetso e matla e tsoang ho hedonic' ho rata '(Finlayson et al., 2007; Mela, 2006). Ho khetholla ha 'ho batla' ho 'ho rata' mathateng a mang hoa bonahala hobane boko bo bonahala bo hlahisa 'ho batla' le 'ho rata' ka mekhoa e arohaneng, joalokaha e hlalositsoe ka tlaase. Cues bakeng sa lijo tse monate li ka 'na tsa etsa hore motho a' batle '' me a sebelisoe ka tsela e feteletseng le haeba a se a sa tsamaee ka ho toba, mohlomong ka tsela ea hyper-reactivity ho mesocorticolimbic dopamine-glutamate mekhoa ea matla a khothatsang (kapa li-CRF kapa lipotoloho tsa opioid tse ka khonang ho sebelisa mekhoa ena). Maemong a joalo, pono, monko, kapa ts'ebetso e hlakileng ea lijo li ka etsa hore motho a batle ho ja, le hoja motho a sa fumane phihlelo ea sebele ho feta kamoo e ka khahlehang kateng qetellong. Mantsoe ana ohle a 'nile a buelloa ka nako e' ngoe. E mong le e mong oa bona o tšoaneloa ke ho hlahlojoa hobane likarabo tse fapaneng li ka sebetsana le mathata a sa tšoaneng kapa mefuta e sa tšoaneng ea botenya.

Ka mokhoa o fokolang o khelosa mosebetsi oa moputso e le sephetho

Sehlopha sa bobeli sa menyetla ke hore mekhoa ea ho putsoa ha boko e ka 'na ea se ke ea e-ba eona sesosa sa pele sa ho ja, empa e ntse e sebetsa ka tsela e sa tloaelehang e le mokhoa o sa tloaelehang oa ho ba le lijo, tlhahiso e sa tloaelehang kapa boima ba' mele bo feteletseng. Maemong a joalo, mekhoa ea boko 'ea ho rata' le ea 'ho batla' e ka 'na ea leka ho sebetsa ka mokhoa o tloaelehileng, empa e bonahala e sa tloaeleha lithutong tsa maikutlo,' me kahoo e ka ba mofubelu o mofubelu o kenyelletsang bafuputsi. Leha ho le joalo, esita le mesebetsi e fokolang ea moputso e ka fane ka lifensetere tsa menyetla ea phekolo e ikemiselitseng ho lokisa boitšoaro bo itseng ka karolo ea ho tsamaisa moputso oa mosebetsi ho khutla ka har'a maemo a tloaelehileng.

Tšepo e tloaelehileng ea moputso oa boko

Ntlha ea boraro, ho ka khoneha hore maemong a mangata mekhoa ea bokoetliso ea boko bo tla tsoela pele ho sebetsa ka mokhoa o tloaelehileng ka botenya kapa bothata ba ho ja, 'me ha bo fetohe esita le ka bobeli. Maemong a joalo, lisosa tsa khathatso ea lijo li ka be li behile ka ntle ka ho feletseng mesebetsi ea moputso ea boko. Ka sebele, moputso oa bokooa o ka 'na oa sebetsa e le lithuso ho fihlela qetellong ho thusa ho itloaetsa mokhoa o itseng oa ho ja ho sa tsotellehe phekolo.

Ho hlahisa 'ho batla' ntle ho 'ho rata'

Pontšo e tsotehang ka ho fetisisa ea ts'usumetso e ts'ebetsong e le karolo e ikhethang e tsoa litsong tseo 'ho batla' ho 'nileng ha ntlafatsoa ka bomong ho le mong, ntle le ho hlahisa hedonic' ho rata 'moputso o le mong. Ho fumanoa ha rona ka lekhetlo la pele ho 'ho hloka'-ntle le ho' batla 'ho ile ha tla lilemong tse mashome a mabeli tse fetileng ho tloha ho ithuta ka ho ja ho hlahisoang ke ho tsosoa ha motlakase oa lateral hypothalamus ka likhoto, ho tsamaisanoa le Elliot Valenstein (Berridge le Valenstein, 1991). Ho ts'oanela motlakase ho lateral hypothalamus ho etsa hore litoe tse tsosolositsoeng li je ka matla (Valenstein et al., 1970), 'me li-electrode tse joalo li sebelisa lipotoloho tsa boko tse tloaelehileng tse kenyelletsang ho lokoloha ha dopamine ea mesolimbic (Hernandez et al., 2008). Tšusumetso e tšoanang ea electrode e atisa ho batloa ke liphoofolo e le moputso, mme ts'ebetso ea motlakase e ne e fetiselitsoe ho etsa hore ho jeoe ke ho eketsa tšusumetso ea hedonic ea lijo. Na likhoto tse tsosolositsoeng li 'batla' ho ja haholo hobane li 'ratile' lijo tse ngata? Mohlomong ho makatsang qalong, karabo e ile ea e-ba 'che': ts'ebetso ea electrode ea hypothalamic e ile ea hlōleha ho ntlafatsa liketso tsa 'liking' ho sucrose (joalo ka lipilomo tsa molomo, tse hlalositsoeng ka ho qaqileng ka tlaase mona), le hoja li-rats li ne li ja habeli lijo tse ngata joaloka tse tloaelehileng (Berridge le Valenstein, 1991)(Litšoantšo 2 & 3.) Ho e-na le ho eketsa 'ho rata', motlakase o matlafatsoa feela 'ho senya' (joaloka li-gap) hore o tsoele pele ho latsoa, ​​joalokaha eka, haeba ntho leha e le efe, sucrose e fetoha e sa thabiseng. Ts'ebetso ena le tse latelang tsa ho 'batla' ho tloha ho 'ho rata' ho supa tlhoko ea ho khetholla li-substrate tsa neural tse fapaneng bakeng sa mong le e mong. Re tla hlalosa ka ho latellana mekhoa ea bokooa ea 'ho batla' le 'ho rata', 'me u hlahlobe hore na litsamaiso tsena li amana joang le litsamaiso tse ling tsa tsamaiso.

 

Setšoantšo sa 2

'Ho batla' ntlafatso e bakiloeng ke tlhahiso ea hypothalamic kapa ka ho phahamisa dopamine

 

Setšoantšo sa 3

'Ho rata' bakeng sa monate ha ho mohla ho ntlafatsoang ke hypothalamic electrodes kapa ka ho phahamisoa ha dopamine

Litholoana tse sa tsitsang tsa anorectic tsa dopamine (le liphello tse mpe tsa ho thibela dopamine)?

Leha ho le joalo, ho na le lintlha tse sa thabiseng bakeng sa khopolo ea rona ea hore dopamine e buisana le 'ho batla' lijo, 'me lintlha tseo li lokela ho amoheloa hape. Ntho e 'ngoe e sa thabiseng ke hore li-antipychotic tse kotsi tse thibelang li-receptor tsa D2 li ka eketsa lijo tsa caloric le ho etsa boima ba' mele (Cope et al., 2005; Stefanidis le al., 2009). Leha ho le joalo, tlhaloso ea sena e ka 'na ea bakoa haholo ke thibelo ea thibelo ka li-antipsychotics tse tšoanang tsa serotonin 1A le 2C receptors, le histamine H1 receptor, e ka kopanelang hantle le ho feta ho feta boima ba' mele ho feta D2 occupancy (Matsui-Sakata et al., 2005).

Mohlomong 'nete ea bohlokoa ka ho fetisisa ke hore dopamine e tlalehoa hore e na le karolo e mpe le e fapaneng ho hatella takatso ea lijo, joalo ka liketso tsa lithethefatsi tse tsebahalang tsa ho ja lijo. Bonyane, tsamaiso ea amphetamine le lik'hemik'hale tse amanang le lik'hemik'hale tse khothalletsang dopamine le norepinephrine ka botšepehi li thibela takatso ea lijo le ho ja. Leha ho le joalo, bonyane liphello tse ling tsa anorectic tsa amphetamine li ka 'na tsa bakoa ke ho lokolloa ha norepinephrine, e nang le takatso e itseng ea ho hatella karolo ea hypothalamus ea mofuthu, mohlomong ka ho susumetsa alpha-1 -adrenoreceptors (e fapaneng le liphello tse bakoang ke li-receptors tsa alpha-2) (Adan et al., 2008; Wellman et al., 1993). Hape, ke habohlokoa ho hlokomela hore dopamine ka boeona e ka ba le liphello tse fapaneng ha ho kenngoa mekhoa e fapaneng ea boko, hape le ka matla a sa tšoaneng esita le ka mohaho o le mong (Cannon et al., 2004; Kuo, 2003). Ka mohlala, dopamine e na le liphello tsa anorectic mokokoting oa hypothalamic arcuate, ka karolo e ka 'nang ea etsoa ka ho fokotsa lefu la neuropeptide Y (Kuo, 2003), 'me maemo a phahameng a dopamine a ka' na a e-na le liphello tsa anorectic hape le nucleus accumbens le neostriatum, le hoja maemo a tlase a ho phahamisa dopamine a ka fokotsa ho ja le ho 'batla' lijo (Cannon et al., 2004; Evans le Vaccarino, 1986; Inoue et al., 1997; Pal le Thombre, 1993; Wise et al., 1989). Qetellong, hape ke habohlokoa ho hlokomela hore matšeliso a dopamine a ho ba le matla a ho susumetsa hangata a lebiselitsoe ho e ts'oarellang bakeng sa meputso - ho lumella hore cue e qale ho 'batla' bakeng sa moputso o lebisang ho phehella, ho e-na le ho fetisetsa ka ho toba boholo ba lijo le lijo (Pecina et al., 2006; Smith le al., 2007; Wolterink et al., 1993; Wyvell le Berridge, 2000; Wyvell le Berridge, 2001). Ho fokotsa 'ho batla' ho ka etsa hore motho a inehele tekong ea ho ja, 'me hang ha lijo li qalile tse ling (mohlala, opioid) mekhoa ea boko e ka fetisetsa boholo ba lijo ho tloha moo. Ka kakaretso, karolo ea dopamine ho kenngoa ha eona hase feela ka holimo kapa ka tlase, empa ho e-na le hoo e ka fapana ka mekhoa e fapaneng ea boko le tlas'a maemo a sa tšoaneng a kelello.

Nucleus accumbens hotspot

Sebaka sa pele sa hotspotse se fumanoeng se fumanoe ka hare ho nucleus accumbens, moo se sebelisang lipontšo tsa opioid le endocannabinoid ho eketsa tatso 'e ratang' (Setšoantšo sa 4 & 5). Sebaka se seholo se lutse sebakeng se arohaneng le khetla ea shell ea nucleus accumbens: ka ho khetheha, ka li-cubic-millimeter boholo ba lisele tse kentsoeng ea rostrodorsal ea khetla e kholo. Sebakeng sa hedonic hotspot, 'ho rata' bakeng sa monate ho eketsoa ke microinjection ea lithethefatsi tse etsisang li-opioid tse mamellang kapa li-endocannabinoid tsa neurochemical. Sena se lumellana le tlhahiso ea bafuputsi ba 'maloa ba neng ba nahana hore tlhahiso ea li-opioid kapa ea cannabinoid receptor e etsa hore ho be le takatso ea lijo ka ho eketsa' ho rata 'bakeng sa ho utloisisa lijo (Baldo le Kelley, 2007; Barbano le Cador, 2007; Bodnar et al., 2005; Cooper, 2004; Dallman, 2003; Higgs et al., 2003; Jarrett et al., 2005; Kelley et al., 2002; Kirkham le Williams, 2001; Kirkham, 2005; Le Magnen et al., 1980; Levine le Billington, 2004; Panksepp, 1986; Sharkey le Pittman, 2005; Zhang le Kelley, 2000). Liphello tsa rona li tšehetsa maikutlo ao a hedonic, 'me, ho latela li-substrate tse itseng tsa boko, li thusitse ho fumana libaka tsa boko tse ikarabellang bakeng sa ntlafatso ea monyaka ho li-hotspots tse itseng. Liphuputso tse etelletsoeng ke Susana Peciña, laboratori ea rona pele, li fumane sebaka sa li-cubmeter hotspot sekhopong, ho sebelisa microinjection ea lithethefatsi tsa opioid agonist (DAMGO; [D-Ala², N-MePhe⁴, Gly-ol] -enkephalin). DAMGO e khetha ka ho hlaka mofuta oa opioid receptor, 'me hotspot ena e bonahala e lekane ho ntlafatsa thabo e khanyang e entsoeng ke boko ka monate o monate (Pecina, 2008; Peciña le Berridge, 2005; Peciña et al., 2006; Smith le al., 2010). Makhetlo a fetang a mabeli a tloaelehileng a likarabo tse ntle tsa 'liking' a ne a tlohelloa ho noa tatso ka likhoto tse nang le DAMGO microinjection libakeng tsa tsona tse holimo. 'Ho nyatsa' liketso tsa quinine ha ho mohla ho kileng ha ntlafatsoa, ​​empa ho e-na le hoo ho ne ho hatelloa ka ho khanya ha opioid hohle le ho potoloha ho hopotpot. Kahoo menyaka e monate e ntlafatsoa, ​​'me ho halefisoa ke khalefo hoa fokotsoa ka nako e le' ngoe, ka ho susumetsoa ha methapo ea pelo ea hedonic hotspot.

Li-endocannabinoids, lik'hemik'hale tsa boko tse tsoanang le ts'oaetso ea tetrahydrocannabinol ea marikoana, li na le li-hotspot tsa tsona tsa hedonic nucleus accumbens shell eo ka tloaelo e koahelang ka holimo ho opioid hotspot. Phuputso e entsoeng ke Stephen Mahler le Kyle Smith ka laborateng ea rona e fumane hore anandamide, e leng endocannabinoid eo ho ka etsahala hore e sebetse bokong ka ho susumetsa mofuta oa CB1 oa receptor ea kankere, e ka sebetsana le nucleus accumbens hotspot ka tsela e tšoanang le lithethefatsi tsa opioid ho phahamisa tšusumetso ea thabo ea sucrose tatso (Mahler et al., 2007; Smith le al., 2010). Anandamide microinjections ho hotspot ka makhetlo a mabeli a mabeli a mabeli a 'maloa' a etsang liketso tse ntle tse hlahisang litlatse, tse kang ho ts'oaea ha li-opioid, empa hape ho itšoara habonolo ho tatso e bohloko ha hoa ntlafatsoa. Ntho e 'ngoe e thahasellisang e ka' nang ea hokahanya le ho ntlafatsa lits'ebetso tsena ke ho hopotpot ea shell ke hore lipontšo tsa opioid le endocannabinoid li ka sebelisana kapa tsa sebelisana. Anandamide o khothalletsoa hore a nke karolo e le mokokotlo oa mothapo oa mali, o ka lokolloa ka sekhahla se seholo sa neuron sekhethong sa ho khutlela morao ho li-terminon tse haufi tsa presynaptic axon le ho tsosolosa li-receptor tsa CB1, mme mohlomong o lokolla ho lokolloa ha opioid pele ho synaptic (Cota et al., 2006; Kirkham, 2008; Piomelli, 2003). Ka ho ts'oanang, matšoao a opioid a otlang se-spin neonone ea post-synaptic ka shell e ka kopa ho lokolloa ha endocannabinoid. Liphuputso tsa nakong e tlang li ka khona ho hlahloba hore na matšoao a endocannabinoid le opioid a sebelisana joang ka mekhoa e joalo ea likarabo tse sebetsang.

Leoatle le leholo la opioid la 'ho batla' ka nucleus accumbens

Ntle ho ho eketsa 'ho rata', microinjection ea DAMGO kapa anandamide sebakeng se tšoanang sa accumbens hotspot hape ka nako e le 'ngoe' me ka ho toba e etsa hore 'ho batla' ho jeoe, ho bontšoa ke keketseho e matla ea ho ja lijo. Empa likarolo tse ling tse haufi tsa nucleus accumbens li etsa feela 'ho batla' ha li sebelisoa ke li-opioids, ntle le ho ntlafatsa 'ho rata' (Setšoantšo sa 5). Ha e le hantle, ha ho fokola ha opioid ho ea holimo ho li-cubmeter hotspot ho na le bokhoni bo ikhethang ba hedonic ho phahamisa 'liking' (ha ho bapisoa le, ho re, dopamine neurotransmission), ho susumetsa opioid ka ntle ho hotspot hase hedonic, 'me ho etsa feela ho' batla 'ntle le ho rata '(ka linako tse ling le ho fokotsa' ho rata '). Ka mohlala, ho hopotpot ea opioid hedonic e na le feela 10% ea kakaretso ea accumbens, esita le 30% feela ea khetla ea eona e kholo. Leha ho le joalo DAMGO microinjection ho pholletsa le 100% ea shell e kholo e eketsehile 'ho hloka', ho feta ho belaella hore na lijo li ja hakae. DAMGO e eketsa 'ho batla' ka tsela e atlehileng esita le ho 'coldspot' e 'ngoe ea posterior moo microinjections e tšoanang e sitisang' ho rata 'ka tlaase ho tloaelehileng (Peciña le Berridge, 2005). Tlhahiso ea Hedonic e thibetsoe ke likokoana-hloko ho ea ho li-hotspots, hammoho le li-neurochemically ho li-opioid le endocannabinoid (Peciña le Berridge, 2005). Mokhoa o atolositsoeng haholo oa ho "batla" o lumellana le liphuputso tse fetileng tseo li-opioid li susumetsang lijo ho 'batla' ho pholletsa le nucleus eohle e sebetsang le esita le mehahong e ka ntle e kenyelletsang amygdala le neostriatum (Cooper le Higgs, 1994; Kelley, 2004; Kelley et al., 2005a; Levine le Billington, 2004; Li-geom le Grey, 2002). Bongata ba libaka tseo opioid li ka 'na tsa se ke tsa e-ba hedonic.

Na neostriatum e kenyelletsa 'ho batla' kapa 'ho rata' moloko?

The ventral striatum (nucleus accumbens) e tumme ka lebaka la tšusumetso, empa morao tjena dorsal striatum (neostriatum) e kentse letsoho molemong oa lijo le moputso (ho phaella mosebetsing o tummeng oa ho itšireletsa ka maoto) (Balleine et al., 2007; Palmiter, 2007; Schultz le Dickinson, 2000; Volkow et al., 2002; Bohlale, 2009). Ka mohlala, dopamine neurons e hlahisang neostriatum litontsong tsa litšoane li fana ka liphoso tse boletsoeng esale pele (meputso e sa tsejoang ea lero) ka tsela e tšoanang le ea dopamine neurons e nucleus accumbens (Schultz le Dickinson, 2000). Dopamine ea batho e lokolloa dorsal striatum e tsamaisana le takatso e hlahisoang ke ho shebella lijo kapa lithethefatsi (liphuputsong tse ling, li kopane haholo ho feta ventral striatum) (Volkow et al., 2002; Volkow et al., 2008; Wang et al., 2004a). Neostriatal dopamine e hlokahalang ho hlahisa boitšoaro bo tloaelehileng ba ho ja, ha lijo tsa ho ja li khutlisetsoa metsong e fokolang ea dopamine e senyehileng ka ho fetola dopamine ho neostriatum (Palmiter, 2007; Szczypka et al., 2001).

Ka mokhoa o ts'oanang, tlhahiso ea opioid ea neostriatum e ka etsa hore lijo li jeoe, bonyane karolong ea ventrolateral (Zhang le Kelley, 2000). Ho holisa sephetho sena, re sa tsoa fumana hore libaka tse ling tsa neostriatum le tsona li ka kenella ho keneng ha lijo tse matlafalitsoeng ke opioid, ho kenyeletsoa le likarolo tse kholo tsa neostriatum. Haholo-holo, seo re se bonang se fana ka maikutlo a hore ts'usumetso ea opioid ea dorsomedial quadrant ea neostriatum e ntlafatsa phepelo ea lijo tse monate (DiFeliceantonio le Berridge, maikutlo a motho ka mong). Phuputsong ea haufinyane ea lifofane, re hlokometse hore likhoto li jele pheko ea chokolete makhetlo a fetang a mabeli (lipompong tsa M&M) kamora ho amohela li-microinjection tsa DAMGO ka dorsomedial striatum ho feta kamora taolo ea li-microinjection tsa koloi. Kahoo liphetho tsa rona li tšehetsa mohopolo oa hore le likarolo tse kholo tsa neostriatum li ka nka karolo ho hlahiseng tšusumetso ea tšusumetso ea ho ja moputso oa lijo (Balleine et al., 2007; Palmiter, 2007; Schultz le Dickinson, 2000; Volkow et al., 2002; Bohlale, 2009).

Orexin hedonic hotspot ho ventral pallidum?

Na ho na le li-neurotransmitter tse ling tsa hedonic tse ka hare ho ventral pallidum hotspot e ka matlafatsang 'ho rata' liketso? Motho ea ts'episitsoeng ka botšepehi ke orexin, eo ho nahanoang hore e amana le tlala le moputso sebakeng sa lateral hypothalamic (Aston-Jones et al., 2009; Harris et al., 2005). Orexin neurons e tsoang ho hypothalamus ho ventral pallidum, haholo-holo sebaka sa eona sa posterior se nang le opioid hedonic hotspot (Baldo et al., 2003). Ventral pallidum li-neurons li fumana lihlahisoa tsa orexin ka ho toba, 'me ho latela li-receptors tsa orexin (Nixon le Smale, 2007).

Litholoana tsa lipatlisiso tsa morao-rao ka laborateng ea rona li bontša hore orexin ka palralum ea ventral e ka ntlafatsa ho "rata" bakeng sa meputso e metle (Ho le Berridge, 2009). Chao-Yi Ho o fumanoe hore microinjection ea orexin-A sebakeng se le seng sa morao holimo ha opioid hedonic hotspot ea ventral pallidum e eketsa palo ea 'ho rata' ho itšoara ho latsoa tatso. Li-orexin microinjections ka ventral pallidum li hlōleha ho eketsa likarabo tse mpe tsa 'ho hanyetsa' ho quinine, ho bonts'oa hore ke feela lintho tse ntle tsa monyaka o ntseng o ntlafatsoa mme ha se litsebe tsohle -Ho le Berridge, 2009). Ha ho ntse ho hlokahala lithuto tse ling, liphello tsena tsa pele li fana ka maikutlo a mokhoa oo litlamo li bolelang hore li ka etsa lijo tse monate li latsoa le ho feta, mohlomong ka li-orexin hypothalamus-to-ventral-pallidum link.

Tlhaloso ea ho qetela ea hore ventral pallidum e ama phetoho ea hedonic ea 'ho rata' maikutlo ke hore ho thunngoa ha li-neurone ka khomphuteng ea post-hedonic hotspot 'ho rata' bakeng sa melemo e monate, e letsoai le e meng ea lijo (Aldridge et al., 1993; Aldridge le Berridge, 2010; Beaver et al., 2006; Calder et al., 2007; Tindell et al., 2004; Tindell et al., 2005; Tindell et al., 2006). Li-neurons ho hotspot ea ventral pallidum mollo ka potlako ha likhoto li ja pellet ea tsoekere, kapa li bile li kopana le mohloli oa moputso, joalo ka ha li lekanngoa ke li-electrodes tsa ho rekota tse sa feleng (Tindell et al., 2004; Tindell et al., 2005). Ho chesoa ha li-sucrose-tse hlahisitseng li-neurone ho bonahala ho totobatsa ka ho khetheha hedonic 'ho rata' bakeng sa tatso (Aldridge le Berridge, 2010). Ka mohlala, ventral pallidal neurons e chesa ha tharollo ea sucrose e kenngoa molomong empa li-neuron tse tšoanang li ke ke tsa chesa tharollo ea NaCl e nang le salate ka makhetlo a mararo ho feta metsi a leoatle le ho sa thabiseng ho noa. Leha ho le joalo, li-neurons tsa ventral pallidum hotspot ka tšohanyetso li qala ho chesa ka tatso ea metsi a mararo a leoatle haeba boemo ba 'mele ea lijo tsa letsoai bo bakoa ke likhoto (Tindell et al., 2006; Tindell et al., 2009) ka ho fana ka furosemide le deoxycorticosterone e le lithethefatsi ho etsisa li-hormone sodium-depletion lipontšo tsa angiotensin le aldosterone (Krause le Sakai, 2007), le ho eketsa seo 'se se ratang' bakeng sa tatso e matla haholo ea letsoai (Berridge le Schulkin, 1989; Tindell et al., 2006). Ka hona, neurons ka lentsoe la ventral pallidum li latsoa monate ka tsela e utloisisang tlhokahalo ea mmele ea motsotso. Tlhokomeliso ea hore li-neuron tseo tsa hedonic li le sebakeng se tšoanang sa hedonic moo ho ts'oaroa ha opioid ho etsa hore liketso tsa 'ho rata' ho latsoeha hamonate li bontša hore tekanyo ea bona ea ho thunya e ka ba karolo ea mochine o hlahisang thabo e khaphatsehang holim'a maikutlo a tatso (Aldridge le Berridge, 2010).

Nyeoe e 'ngoe eo palralum ea ventral e ka ntlafatsang' ho batla 'ntle ho' ho rata 'e bonoa ka mor'a ho thibela li-neurons tsa GABA ka ventral pallidum, (Smith le Berridge, 2005). Kyle Smith o ile a tšoaea mohanyetsi oa GABA, bicuculline, e ileng ea lokolla li-neurons ho tloha khatellong ea tonyo ea GABAergic, mohlomong e ba thusang hore ba sebelisoe ke motlakase ka mokhoa o tšoanang le o motlakase. Sephetho sa kelello sa popolarization ea ventral e ne e batla e tšoana le ea stimulating electrode lateral hypothalamic electrode stimulation. Ho ja lijo ho ne ho habeli empa ho ne ho se na keketseho e 'ngoe ea' ho rata 'ho latsoa tatso (ho fapana le ts'oaetso ea opioid ka DAMGO microinjections setsing, e ileng ea eketsa' ho batla 'le' ho rata 'hammoho) (Smith le Berridge, 2005).

Sebaka se kopanetsoeng sa nucleus accumbens le li-hotspots tsa ventral pallidum

Hase feela hore nucleus accumbens le ventral pallidum li na le li-hotspots tsa hedonic tseo ho tsona ho tsosolosa ha opioid ho matlafatsa 'ho rata,' empa li-hotspots tse peli li sebetsa hammoho ho theha marang-rang a ho hokahanya 'ho rata' (Smith le Berridge, 2007). Mosebetsing o etsoang ka laborateng ea rona, Kyle Smith o fumane hore microinjections ea opioid agonist ho e 'ngoe ea hotspot e sebelisitsoe haufi le Fos polelo e' ngoe sebakeng se seng, e leng se bontšang hore sebaka se seng le se seng se sebelisana le ho ntlafatsa hedonic 'ho rata'. Ho phaella moo, thibelo ea opioid ka naloxone ka leha e le efe ea hotspot e ka felisa 'ho rata' ho eketsehileng e hlahisoang ke DAMGO microinjection ho e 'ngoe, e bontšang hore ho nka karolo e le' ngoe ho ne ho hlokahala. Litlhaloso tse joalo li bontša hore li-hotspots tse peli li kopanngoa ka mokhoa o le mong ho potoloho e 'ngoe e' ngoe e 'ratang,' 'me potoloho eohle e hloka ho phahamisa tšusumetso ea hedonic. Leha ho le joalo, ho bokella ho sebetsa ka bohona ho ka eketsa 'ho hloka' 'me ho ja lijo ho sa tsotellehe ho kenya letsoho pallidal (le ho sa tsotellehe hore na' ho rata 'ho ts'oaroa ka nako e le' ngoe) (Smith le Berridge, 2007).

Lijo e le matla a matla a susumetsang nakong ea tlala

Ntho e 'ngoe e ka' nang eaba ke ho phahamisa 'ho batla' lijo ka ho toba nakong ea tlala, 'me mohlomong ho phahamisa khahloa eo ho batho ba bangata haholo. Ho batho, ts'ehetso e matla ea lijo bakeng sa lijo e lekantsoe liphuputsong tse ling ka maeto a mahlo a tsamaisitsoeng ka potlako kapa ka nako e telele kapa hangata ho bona lijo, kapa ka mehato e amanang le eona. Ka mohlala, batho ba mahlomoleng ba 'nile ba tlalehoa hore ba tla lebisa tlhokomelo ea bona haholoanyane mahlong a lijo ho feta batho bao e seng batho ba bolileng, haholo-holo ha ba lapetse (Kejs et al., 2009). Tlaleho e 'ngoe e fana ka maikutlo a hore tlala e phahamisa matla a ho ba le lijo tse matlafatsang boemong bo tloaelehileng ba boima le batho ba bobebe, joalo ka ha ho bonahale ka ho eketseha ha nako e telele, empa batho ba feteletseng ba na le litekanyetso tse phahameng tsa matla a khothatsang bakeng sa litšoantšo tsa lijo le ha ba sa tsoa ja (Castellanos et al., 2009). Bohlale bo matla ba ho ba le litšoantšo tsa lijo bo ka 'na ba amana le maikutlo a tloaelehileng a tsoang sechabeng sa psycholose eo ho nona ho tlōla ho amanang ka ho feteletseng kapa ho itšoara ka tsela e feteletseng ho susumelletseha (Nisbett le Kanouse, 1969; Schachter, 1968).

Li-alliesthesia tsa opioid nakong ea tlala?

Ka ho tšoanang, hedonic 'ea ratang' lijo e ntlafatsoa nakong ea tlala. Ts'ebetso ea opioid e ts'ebetsong ea li-hedonic hotspots ke mokhethoa ea ka sehloohong oa ho etsa hore lijo li latsoe hantle nakong ea tlala. Haeba tatso ea lijo ha e lapile e ntša tokoloho e phahameng ea opioid e matla ho susumetsa li-receptors, lijo li ne li tla latsoa hantle ho feta ha li sate. Mang kapa mang ea neng a e-na le mokhoa o feteletsang oa mokhoa ona oa hedonic o ne a tla fumana lijo ho latsoa haholo-holo tse ntle. Bakeng sa mokokotlo oa nucleus accumbens, re nahana hore tlhaho ea tlhaho ea opioid e ka 'na ea hlaha ka tlhaho ea tlhaho ea enkephalin. Endogenous B-endorphin ke mokhoa o atlehang haholoanyane oa ho amohela li-opioid receptors ho feta enkephalin, mme B-endorphin neurons e khothalletsoa hore e hlahe ho tloha hypothalamus ho ea ho mehaho e meng ea limilamo (Bloom et al., 1978; Zangen le Shalev, 2003), empa li-endorphins li ka 'na tsa se ke tsa e-ba teng ka shell e lekaneng ho phethahatsa mosebetsi ona (SJ Watson, puisano ea motho ka mong, 2009). Ka lebaka leo, enkephalins, ho e-na le B-endorphin, e ka 'na ea e-na le letšoao le fumanoang ka ho fetisisa ka-opioid sekheng sa nucleus accumbens shell. Enkephalin e tsoa ho batho ba bangata ba methapo e meholo ka hare ho khetla (baahi ba hlahisang enkephalin mRNA hammoho le li-receptors tsa D2 le GABA mRNA), hammoho le li-neurons tse hlahang ho tsoa ventral pallidum le mehaho e amanang le eona e fanang ka GABA le lipontšo tsa enkephalin.

Ntho e tsotehang ea hypothalamic-thalamic-e bokella potoloho ea boko bo matla ho matlafatsa likontšo tsa enkephalin nucleus accumbens shell nakong ea linaha tsa caloric tlala e ileng ea khothalletsoa ke Ann Kelley le basebetsi-'moho le eena (Kelley et al., 2005a). Kelley et al. o ile a etsa tlhahiso ea hore li-orexin neurons li sebelise morero oa lateral hypothalamus ho etsa hore li-glutamate neurons li se ke tsa e-ba teng mokokotlong oa thalamic. Ka lehlakoreng le leng, morero oa thalamic paraurricular neurons ho nucleus accumbens shell moo ba sebelisang lipontšo tsa glutamate ho thabisa li-interneurons tse kholo tsa acetylcholine. Kelley le basebetsi-'moho ba ile ba etsa tlhahiso ea hore qetellong li-acetylcholine neurons li khetholle ka ho khetheha li-enkephalin neurons. Li-neurons tse lokollang enkephalin li lokela ho kenyeletsa kahare ho li-shell tsa methapo ea li-hedonic tsa shell e kholo (ka mokhoa o makatsang, masimo a li-acetylcholine neurons a boholo ba boholo ba 1 mm bophara). Ka hona, ho ka etsahala hore tlala e khone ho etsa hore palo ea opioid e qetelle e le nucleus accumbens hotspot ho matlafatsa 'ho rata' le ho 'batla' bakeng sa lijo tse monate.

Mekhoa ea endocannabinoid ea allyesthesia?

Mokhoa o mong oa bokhoni ba ho etsa hore lijo li latsoehe hamolemo nakong ea tlala ke ho hiroa ha motho ka nako e le 'ngoe sebakeng se tšoanang sa hexic of shell shell. Bopaki bo bontša hore li-endocannabinoids li ka ngolisoa ka tlala le tlala. Ka mohlala, Kirkham le basebetsi-'moho le eena ba ile ba tlaleha hore 24-hr ka potlako ho likhoto e phahamisa maemo a endocannabinoids, anandamide le 2-arachidonoyl, glycerol ka mehaho ea li-forebrain li-structures tse akarelletsang nucleus accumbens (Kirkham et al., 2002). Ka lebaka la ho ba le tlala ea ho qetela ha ho e-ba teng nakong ea tlala ho ka ntlafatsa hedonic 'ho rata' lijo (Kirkham, 2008; Kirkham, 2005). Sena se ka 'na sa etsa hore' se rate 'haholo-holo haeba lipontšo tsa endocannabinoid tse nang le bokhoni li fihlella hotspoteng e le' ngoe ho khetla ea nucleus accumbens, moo anandamide microinjections e tsejoang ho ntlafatsa 'ho rata' ho monate (Mahler et al., 2007). Hape hoa hlokomeleha hore li-endocannabinoids li boetse li thusa ho etsa mesolombic dopamine ka sebaka sa ventral tegmental le libaka tse ling, e leng ho ka fokolisang 'ho hloka' lijo tse khotsofatsang ho itšetlehile ka hedonic 'liking' (Cota et al., 2006; Kirkham, 2005).

Mekhoa ea Orexin ea allyesthesia?

Sehlopha se seng sa menyetla e kenyelletsa orexin hape, empa e sebetsana ka tsela e tobileng ho feta ka sekhahla sa thalamic sa mohokahanyi ho etsa hore ho be le methapo ea hotspot (Kelley et al., 2005a). Li-neurone tse hlahisang orexin tse sebetsang ka ho fetisisa li fumanoa ka lateral hypothalamus, moo li 'nileng tsa hlalosoa hore li sebelise moputso bakeng sa lijo, lithethefatsi, thobalano, joalo-joalo (Aston-Jones et al., 2009; Harris et al., 2005; Harris le Aston-Jones, 2006; Muschamp et al., 2007) [li-orexin tse eketsehileng kapa li-neurons tsa hypocretin li fumanoa hape linthong tse ling tsa hypothalamic, tseo ho e-na le hoo li ka buisana ka ho tsoha le ho falimeha (Berridge le al., 2009; Espana et al., 2001)].

Ma-orexin neurons a amanang le moputso oa lateral hypothalamus a sebelisoa ka ho hlahisa lipontšo tsa neuropeptide-Y (NPY) nakong ea tlala (Berthoud le Morrison, 2008; Gao le Horvath, 2007). Mokhoa o mong oa orexin neurons bakeng sa ventral pallidum le nucleus accumbens (Baldo et al., 2003; Borgland et al., 2009; Korotkova et al., 2003; Peyron et al., 1998; Zheng et al., 2007). Joalokaha ho hlalositsoe ka holimo, re sa tsoa fumana hore orexin microinjections ka ventral pallidum hotspot e ka 'na ea e-ba le tšusumetso e tobileng ea' ho rata 'ho monate (Ho le Berridge, 2009). Ka ho khetheha, ka nako eo, ho sebetsa ha orexin nakong ea tlala ho ka ntlafatsa ka ho toba hedonic tšusumetso ka ho susumetsa li-neurons holong ea hedonic, e kang posterior ventral pallidum. Ka hona orexin e ka sebetsa ka mokhoa o atlehileng ho hokae ha hedonic e tšoanang le ka lipontšo tsa opioid tse entsoeng ventral pallidum (le ho nahanoa ka nucleus accumbens). Ho phaella moo, orexin e ka 'na ea etsa hore' ho batle 'ka bobeli ka li-hotspots tsena tse ka pele le ka likhahlelo tsa mesolambic dopamine neurons ka ventral tegmentum.

Mekhoa ea Leptin ea allyeshesia?

Ka lehlakoreng le leng, satiety e bolela ho hatella 'ho rata' le ho 'batla' lijo esita leha ho le thata ho tima ka ho feletseng moputso oa lijo (Berridge, 1991; Cabanac, 1979; Cabanac le Lafrance, 1990; Kringelbach et al., 2003; O'Doherty et al., 2001; Tse nyenyane le al., 2001). Tsela e 'ngoe ea ho etsa li-alliesthesia tse mpe nakong ea lefu la satiety ke leptin, e tsejoang ka lisele tse mafura' meleng. Leptin e sebetsa ka li-neuron ka nucleus e khutsitseng, e meng ea hypothalamic nuclei le ho brainstation, ho akarelletsa le ventral tegmentum moo e ka fetolang mesolimbic dopamine lipotoloho le 'ho batla' lijoChoi et al., 2010; Figlewicz le Benoit, 2009; Friedman le Halaa, 1998; Fulton et al., 2006; Grill, 2010; Hommel et al., 2006; Leinninger et al., 2009; Robertson et al., 2008). Leptin e ka 'na ea boela ea kenya letsoho mofuteng oa alliesthesia-o susumelletsehang ho "khaotsa" ho hatella ka ho susumetsa li-POMC / CART neurons tsa hypothalamic arcuate ho etsa hore batho ba amohele MCR4 li-neurone, kapa ka ho thibela methapo ea NPY-AGrP e thibelang ho tlosa orexin neurons ka lateral hypothalamus, kahoo e fokotsa opioid kapa orexin tsusumetso ea li-hotspots tsa hedonic ka ventral pallidum kapa nucleus accumbens.

Har'a batho, Farooqi le O Rahilly le basebetsi-'moho le bona ba tlalehile liphello tse thahasellisang tse bontšang ho se sebetse ha matla a leptin ho thibela 'ho batla' kapa ho "rata" ka mokhoa o itseng oa boima bo bongata ba liphatsa tsa lefutso: batho ba tsoetsoeng ke leptin, bao ka linako tsohle ba nang le bana batla lijo mme ka potlako e ba mafura (Farooqi et al., 2007; Farooqi le O'Rahilly, 2009). Ha ho se na leptin batho bana ba feteletse litekanyetso tse ratehang bakeng sa lijo tse amanang ka ho toba le nucleus accumbens activation ka ts'ebetso ea lijo e lekantsoeng ke fMRI. Ho fapana le batho ba bangata, ba ts'oanela ho sebetsa ha ba thibeloe ke ho ja lijo tse phetseng hantle, ho fana ka maikutlo a ho phehella ho sa tloaelehang ha 'ho rata' le ho 'batla' ho ts'oaroa esita le nakong ea ho satiety. Farooqi le basebetsi-'moho le eena ba tlaleha hore ho fa batho bana meriana e mengata ea leptin ho lumella li-caloric satiety hore li boele li khone ho thibela ho thibela likokoana-hloko ka lijo, e le hore litlhaloso tse bapang li tsamaisane le nucleus accumbens activation feela ha li lapile, 'me ha li sa ja ka mor'a lijo . Liphuputso tse joalo li bonahala li lumellana le khopolo ea hore leptin (ho sebelisana le litlaleho tse ling tsa tlala / satiety) e beha bokhoni ba lipontšo tsa satiety tsa lijo ho thibela 'ho rata' le ho 'batla' lijo (Farooqi et al., 2007).

Likokoanyana, tsamaiso ea leptin sebakeng sa ventral tegmental e ka hlahisa ho fokotsa litekanyetso tsa ho thunngoa bakeng sa mesolimbic dopamine neurons, e lumellanang le ho fokotseha ha 'ho batla', 'me ka boitšoaro ho thibela ho ja lijo tse monate (Hommel et al., 2006). Leptin le insulin li boetse li bontšitsoe sebakeng sa ventral tegmental ho thibela tšusumetso ea mokhoa oa ho ja le ho ja lijo tse ling tse sa hlahisoang ke ho tsosoa ha opioid ea mohaho o tšoanang o hlahisoang ke DAMGO microinjection (Figlewicz et al., 2007; Figlewicz le Benoit, 2009). Liketso tse kang lik'hemik'hale tsa insulin sebakeng sa ventral tegmental li bonahala li akarelletsa ho phahama ha motlakase oa dopamine (DAT) ka dopamine neurons le ho fokotseha ho itseng ha synaptic extracellular dopamine maemong a nucleus accumbens (Choi et al., 2010; Figlewicz et al., 2007; Figlewicz le Benoit, 2009). Leha ho le joalo, hoa lokela ho hlokomeloa hore tse seng kae tse hlephileng li ntse li le teng bakeng sa khopolo ea hore leptin e hatella lijo tse 'batlang' le 'ho rata'. Ka ho makatsang, ka mohlala, hoo e ka bang phello e fapaneng e 'nile ea tlalehoa ka litoeba tse nang le leptin tse fokolang (ob / ob), ka leptin eo ho ile ha bonahala ho hlasimolla likokoana-hloko tse fokolang tsa accumbens dopamine (Fulton et al., 2006; Myers et al., 2009). Karolo ena ea puzzle e ntse e tla hlalosoa.

Leqephe lena le neheloa mohopolong oa Ann E. Kelley (moeta-pele oa "neuroscience of food reward") le oa Steven J. Cooper (moeta-pele oa psychopharmacology ea moputso oa lijo). Mosebetsi oa bo-rasaense bao ba ikhethang o ile oa beha sethaleng bakeng sa litaba tse ngata tse sebetsanoang mona, 'me mafu a bona a morao tjena e ne e le tahlehelo e bohloko ea tšimo. Re leboha Ryan Selleck bakeng sa ho nchafatsa Litšoantšo 1, , 2,2, 'me Le3.3. Liphetho tse hlalositsoeng mona li tsoa mosebetsing o tšehetsoang ke litšehetso tsa DA015188 le MH63649 tse tsoang ho NIH.

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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