Karolo ea dopamine e kotsing ea ho nka: ho shebahala ka mokhoa o tobileng ho lefu la Parkinson le papali ea chelete (2014)

Pele Behav Neurosci. 2014 May 30; 8: 196. doi: 10.3389 / fnbeh.2014.00196. eCollection 2014.

Sehlooho sena se bile teng e boletsoeng ke lihlooho tse ling ho PMC.

inahaneloang

Mohlala o nang le tšusumetso o fana ka maikutlo a hore dopamine e bontša phapang lipakeng tsa moputso o boletsoeng esale pele le o nang le boiphihlelo. Ka tsela ena, dopamine e ka sebetsa e le lets'oao la ho ithuta le ka etsang boits'oaro ho ntlafatsa meputso le ho qoba likotlo. Dopamine e boetse e nahanoa e matlafatsa boitšoaro ba ho batla moputso. Ho lahleheloa ke dopamine ho supa letsoalo le leholo ho lefu la Parkinson. Li-agonists tsa Dopamine li bile le tšusumetso ho hlaha ha mathata a taolo ea ts'usumetso ho bakuli ba lefu la Parkinson, ntho e atileng ka ho fetisisa ke ho becha ka methapo, boitšoaro bo qobelloang ho tsa thobalano le ho reka ka mokhoa o qobelloang. Haufinyane tjena ho hatisitsoe lithuto tse ngata tse sebetsang tsa lipatlisiso tse mabapi le mathata a taolo ea ts'usumetso ho lefu la Parkinson. Mona re lekola lingoliloeng tsena, 'me re leka ho li beha ka har'a moralo oa ho etsa liqeto moo ho ka fumanoang melemo le tahlehelo ho fihlela liqeto tse nepahetseng. Re fana ka mofuta oa hypothetical empa o ntse o sa phetheha ka phello ea kalafo ea dopamine agonist ka boleng bona le litlhahlobo tsa kotsi. Likarolo tse peli tsa mantlha tsa boko tse nahanoang hore li kenella ho computing likarolo tsa moputso le tahlehelo ke li-ventral striatum (VStr) le insula, ka bobeli libaka tsa prooption tsa dopamine. Likaho tsena ka bobeli li na le moelelo o tšoanang lipatlisisong tsa ts'ebetso ea ts'ebetso ea ts'ebetso ea ho becha ha pathological ho lefu la Parkinson.

Keywords: mathata a taolo a ho susumetsa, ho hloka toka, moputso, ho felloa ke tahlehelo, ho kenella, ho kenella ka hare

Ho becha e le pherekano ea moputso le ts'ebetso ea kotlo

Ho becha ka tsela ea tlhaho ho ka hlalosoa e le pherekano ea moputso le ts'ebetso ea kotlo, moo motho ea betang a khethang monyetla o potlakileng empa o le kotsi oa ho fumana chelete holima monyetla o moholo oa monyetla oa ho boloka chelete (Ochoa et al., 2013). Ho joalo, ho becha ho hlalosoa ka mokhoa o makatsang e le tšitiso ea maikutlo, moo ho nka liqeto ho potlakileng ho bileng ho sa senoloeng ke litlamorao tsa nako e tlang. Batho ba betang ka mokhoa oa pathological ba bonts'a ho ts'oaroa ho hoholo le ho fokotsa ho theotsoeng hanyane ka mehato ea laboratori (Verdejo-Garcia et al., 2008). Ho kopanngwa ha boitshwaro bo ntseng bo eketseha ba ho batla moputso ka ho se ananele litlamorao tse mpe ho ka hlalosa ho phehella ha papali ea chelete ha ho talingoa le tahlehelo ea chelete ka kakaretso (Vitaro et al., 1999; Petry, 2001b; Cavedini et al., 2002). Moralo ona oa khopolo-taba o ts'oana le o sebelisoang bokhobeng ba lithethefatsi, moo ho fumana menyetla ea hanghang ha o ntse o fokotsa likotsi tse ka ba teng. Matšoao a bokhoba ba ho lemalla a kenyelletsa ho lakatsa kapa ho qobelloa, tahlehelo ea taolo, le boitlamo bo tsoelang pele boits'oarong bo bolokang temallo le ha e na le litlamorao tse mpe khafetsa (American Psychiatric Association, 2000). Ka mokhoa o ts'oanang, ts'ebeliso ea ts'ebeliso ea marang-rang ea kelello e ka bitsoa tlhekefetso ea boitšoaro hobane e arolelana likarolo tse ngata tse lemalloang ke lithethefatsi, joalo ka ho qobelloa le ho lahleheloa ke taolo holim'a boitšoaro ba motho, hammoho le ts'ebetso ea boitšoaro nakong ea litlamorao tse mpe (Grant et al., 2006; Goodman, 2008). Batho ba betang ka mokhoa oa Pathological ba bonts'a litakatso tse sa laoleheng, mamello, bolulo le matšoao a ho tlohela, a ts'oanang le a ba lemaletseng lithethefatsi (Wray le Dickerson, 1981; Castellani le Rugle, 1995; Duvarci le Varan, 2000; Potenza et al., 2003). Ntle le moo, papali ea chelete ea thobalano le tšebeliso e mpe ea lithethefatsi li amahanngoa le botho bo ts'oanang, e leng ho batla maikutlo le ho susumetsa (Zuckerman le Neeb, 1979; Castellani le Rugle, 1995), e ileng ea phahamisa litšobotsi tse khahlisang meputsong e ka fokotsoang le ho fokotsa boitšoaro le tšibollo ea tšebetso. Phapang e kholo lipakeng tsa ts'ebeliso ea lithethefatsi (lithethefatsi le joala) le papali ea papali ea kelello (Petry, 2001a; Petry et al., 2005), le bopaki ba lintlha tse tloaelehileng tsa liphatsa tsa lefutso, supa mathata ao a mabeli a nang le etiology e fetang (Slutske et al., 2000; Goodman, 2008).

Mohlala o mong o sebetsang o nka ho ithuta ka moputso le ho ithuta ka kotlo e le likarolo tsa tlhaho ts'ebetsong ea ho etsa liqeto. Ho etsa liqeto ho ka fokotsoa ho boima ba menyetla le boleng ba moputso khahlano le litšenyehelo tse ka bang (mohlala, litlamorao tse mpe). Lintho tse ling tse kang ho fetoha ha sepheo le phapang (ka linako tse ling ho thoe ke kotsi) li ama le likhetho tsa motho ka mong (Huettel et al., 2006), empa mona re tla sheba feela menyetla le tahlehelo e ka bang likheo tsa ho etsa liqeto nakong ea papali ea chelete. Re tla nka “kotsi” ho bolela tahlehelo e ka bang teng boikhethong bofe kapa bofe. Kotsi, joalo ka ha e hlalositsoe, e eketseha ka boholo le menyetla ea tahlehelo e ka bang teng. Ebile, ho ipeha kotsing ho ka bonoa e le sesupo sa botsitso bo teng lipakeng tsa likhakanyo tsa meputso le tahlehelo e ka bang teng. Likarolo tse peli tsa mantlha tsa boko tse nahanoang hore li kenya letsoho likhokahanong tsena ke li-ventral striatum (VStr) le insula, ka bobeli libaka tsa prooption tsa dopamine. Ka bobeli li hokahane le li-computations tsa boleng, VStr e ntse e arabela haholo ho phutha phoso ea ho bolela (RPE), e kenyeletsa ho fumana tebello e ntle le ho lahleheloa ke tebello e mpe (Rutledge et al., 2010; Bartra et al., 2013), le insula e arabelang haholo tahlehelong le tahlehelong lithutong tse ling (Knutson le Greer, 2008) kapa ka liphetho tse ntle le tse mpe ho ba bang (Campbell-Meiklejohn et al., 2008; Rutledge et al., 2010). Tlhatlhobo ea meteo ea Bartra et al. (Setšoantšo (Figure1) 1) e fana ka maikutlo a hore ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso e hokahanya kapa e boreleli ho fapana le boleng, kaha e arabela ka mokhoa o hlakileng ho melemo le tahlehelo. Tlhatlhobo ena ea meta e boetse e phahamisa monyetla oa karolo e kholo bakeng sa ts'ebetso ea tlhahlobo tekong ea likotsi le tahlehelo ho feta ho fumana (bapisa liphanele tsa A le B ho Setšoantšo. Figure1) .1). Phetoho ea botsitso lipakeng tsa lits'ebetso tsena tsa tebello le tahlehelo ea tahlehelo e ka baka mekhoa e sa lokelang ea boits'oaro e bang teng litsietsing tse kang bokhoba ba tahi, papali ea chelete le mathata a taolo.

Setšoantšo sa 1 

Tlhatlhobo ea Meta ea lithuto tsa fMRI tsa boleng (tse nkiloeng ho Bartra et al., 2013). Bangoli ba qotsitse likhokahanyo tsa tlhalo-tlamiso ho tsoa lithutong tse 206 tse phatlalalitsoeng tsa FMRI tse neng li fuputsa lipalo tsa boleng. (A) Khokahano ea bohlokoa ea likarabo tse ntle. (B) Bohlokoa ...

Patlisiso ea morao tjena e bontša hore phapang ea tšebetso ea bokong, sebopeho, le biochemistry li teng ho ba hlahisang mathata a papali ea chelete, ka dopamine e le lebaka le tloaelehileng la etiology. Lithuto tsa ho ts'oasa li bonts'itse keketseho ea tokollo ea mesolimbic dopamine nakong ea mesebetsi ea papali ea chelete lithutong tse phetseng hantle (Thut et al., 1997; Zald et al., 2004; Hakyemez et al., 2008). Leha ho le joalo ho lokela ho hopoloa hore mesebetsi e sa lebelloang ea moputso e na le bokhoni ba ho baka khatello le ntlafatso ea phetisetso ea dopamine libakeng tse fapaneng tsa striatum (Zald et al., 2004; Hakyemez et al., 2008). Phuputso ea pejana mabapi le ba bechang ea methapo ea methapo e khothalelitse litsamaiso tse fetotsoeng tsa dopaminergic le noradrenergic, joalo ka ha li fumanoe ka ho fokotseha hoa khatello ea dopamine le keketseho ea litekanyetso tsa methapo ea methapo ea methapo ea 3,4-dihydroxyphenyl-acetic acid le Homovanilic acid (Bergh et al., 1997). Barekisi ba pathological le bona ho tlalehiloe hore ba na le mekhahlelo e mengata ea mokelikeli oa "cerebrospinal" ea 3-methoxy-4-hydroxyphenylglycol, metabolite e ka sehloohong ea norepinephrine, hammoho le tlhahiso ea norepinephrine e kholo haholo ho bapisoa le lits'ebetso (Roy et al., 1988), sesupo sa pherekano e sebetsang ea sistimi ea noradrenergic. Ntle le moo ho na le bopaki ba hore liphatsa tsa lefutso tse amang dopaminergic neurotransication li etsa lintho tse ka behang motho kotsing ea ho becha ka mathata (Lobo le Kennedy, 2006).

Dopamine ka matlafatso

Bopaki bo ka fumanoang bo tsoang liphuputsong tsa liphoofolo, dopamine e kenyang ts'ebetsong ea boitšoaro bo fana ka karolo ea methapo e ka kenyelletsang ts'ebetso ea meputso ea tlhaho, joalo ka lijo le thobalano, le lithethefatsi tsa tlhekefetso le papali ea chelete ea methapo (Di Chiara le Imperato, 1988; Bohlale le Rompre, 1989; Bohlale, 1996, 2013). Se hlokometsoeng ke Schultz le ba bang (Schultz et al., 1998;; Schultz, 2002) e netefalitse karolo ea li-dopamine neurons ho arabela meputso; leha ho le joalo mohlala oa hona joale oa dopamine ho supa o ka latela pampiri ea seminal ke Montague, Dayan le Schultz (Schultz et al., 1997), moo ho neng ho phehisanoa hore mokhoa oa ho thunya oa dopamine neurons ha o supe moputso ka bobeli, empa letšoao la RPE, le ts'oanang le le sebelisitsoeng ho ithuta mochini. Ho fumana hona, hammoho le bopaki ba hore dopamine e ka fetola polasetiki ea synaptic (Calabresi et al., 2007; Surmeier et al., 2010) e lebisitse khopolong ea hore dopamine e sebetsa e le sesupo sa ho ithuta (kapa ho tiisa) se bopetsang boitšoaro bo susumetsang ba nako e tlang. Patlisiso e ileng ea latela e bonts'a hore dopamine e kanna ea kenyelletsa likhakanyo mabapi le meputso e tlang le sekhahla sa moputso, ka tsela eo ea sebetsa e le lets'oao la boleng ho mesocortical le mesolimbic dopaminergic pathways (Montague le Berns, 2002).

Sebaka sa mantlha sa "dopamine neurons" ke "striatum" e ikopantseng le "cortex" e ka pele, e nang le "cortex", e amanang le diketso tse nang le sepheo se hlakileng sa ho khanna thuto ea "Go", e amanang le liketso tse nang le litholoana tse ntle. No Go "kapa ho ithuta ho qoba, e amanang le liketso tse lebisang kotlong kapa ho se be teng moputsong. Taba ea pele, dopamine signaling e sebetsa ka mekhoa e 'meli (Mohau, 2000): Ho lokolloa butle-butle ha dopamine ho laola maemo a tonic, a atisang ho supa ka dopamine D2 li-receptor ho striatal medium spiny neurons; Phasic burchip ea dopamine ho thunya e lebisa ho keketseho e kholo ea synaptic dopamine e letsang ka bobeli ba D1 le D2 litsamaiso tsa receptor. D1 li-receptors li na le kamano e tlase bakeng sa dopamine (Marcellino et al., 2012) 'me re arabe feela ka keketseho e kholo ea li-dopamine tsa synaptic tse lokollotsoeng nakong ea mokokotlo oa phasic dopamine neuron tse bontšang li-RPE tse ntle, tse tšehetsang ho ithuta ho atamela ts'usumetso e khotsofatsang (Frank, 2005). Dopamine D2 li-receptors, ka lehlakoreng le leng, li na le tumellano e phahameng ea dopamine, e li lumella ho arabela ho lets'oao la tonic dopamine, le ho bona phokotso ea nakoana maemong a dopamine ea tonic e latelang likhefu ho thunya ha dopamine nakong ea li-RPE tse mpe. Sena se thusa ho ithuta ho qoba sephetho se sebe (Frank, 2005). Sistimi ea cortico-striatal e ka aroloa ka tsela e tobileng le e sa tobang (Setšoantšo (Figure2), 2), tse nang le litlamorao tse fapaneng thalmus le ka hona cortex (Albin et al., 1989). Ka dorsal striatum, li-receptors li arohane, le D1 li-receptors kahare ho tsela e otlolohileng, e amanang le khetho ea ketso, ha D2 li-control receptors control inhibition kahare ho tsela e sa tsejoeng (Mink, 1996). Karohano ena e lumella dopamine ho khanna moputso ka bobeli (ho eketseha ha dopamine ho supa sephetho se betere ho feta se lebelletsoeng) le kotlo (ho fokotseha hoa tonic dopamine ho bontšitse sephetho se sebe ho feta se lebelletsoeng). Frank o ile a etsa tlhahiso ea hore na phasic dopamine e phatloha ka mor'a meputso e khothaletsa matlafatso e matla ha litheko tsa litekanyetso tsa tonic dopamine li lebisa ho matlafatso e mpe, e 'ngoe le e' ngoe e laoloang ke D1/ tsela e e tsamaisang le D2/ tsela e sa tsamaelaneng, ka ho latellana (Cohen le Frank, 2009). Moetso ona oa computational o fana ka tlhahiso ea hore RPE dopamine sign e khothaletsa ho ithuta ho tsoa liphellong tse ntle ka ho hlohlelletsoa ha D1 li-receptors, athe ho ithuta ho qoba litlamorao tse mpe ho kenelletsoa ka ho lahla tsela e sa tsamaellaneng ea methapo ea kutlo e bohareng ebe ho fokotsa D.2 ho hlohlelletsoa ha li-receptor nakong ea khefu ea dopamine (Cohen le Frank, 2009). Phello e mpe (kotlo kapa ho haella ha moputso o lebelletsoeng) ho lebisa ho khutsufatso ea ho thunya ha methapo ea kutlo ea dopamine, ebe e lebisa phokotso ea nakoana ho tonic dopamine. Hape ho lokela ho hlokomeloe hore D2 ho hlohlelletsa li-receptor ho fokotsa thabo ea li-neurons tseleng e sa tsejoeng (Hernandez-Lopez et al., 2000), ka hona, phokotso ho D2 li-receptor signaling li na le phello ea ho kenya tšebetsong tsela e thibelang "No Go". Sena se lumella ho akofisa ho saena le ho khothaletsa ho saena ka matla le ho se sebetse hantle ka manonyeletso a dopamine. Ts'ehetso ea mofuta ona e fanoe ke liteko tse ngata. Bakuli ba lefu la Parkinson ba bonts'a thuto e ntlafalitsoeng ha ba sebelisa meriana ea bona, empa ba ntlafalitse thuto e seng ntle ha ba ntse ba sa sebetse (Frank et al., 2004). Lingoloa tsa meriana le tsona li tšehetsa mohlala (Frank le O'Reilly, 2006; Pizzagalli et al., 2008). Ho lokolloa ha dopamine ho kopantsoe le ho ithuta le ho tloaelana le tloaelo ea tloaelo ka taolo ea "corticostriatal synaptic plasticity" e anngoeng ka tsela e fapaneng.1 le D2 ho saena (Shen et al., 2008). D1 dopamine receptor signaling e nts'etsapele bokhoni ba nako e telele (Reynolds et al., 2001; Calabresi et al., 2007), athe D2 letšoao la receptor le khothalletsa khatello ea maikutlo ea nako e telele (Gerdeman et al., 2002; Kreitzer le Malenka, 2007). Hlokomela hore mohlala ona o lekoa haholo litekong tsa striatum. Ts'ebetso ea Multivariate ea lintlha tsa fMRI e bonts'a hore matšoao a matlafatsang le a kotlo a hoholo ka ho fetisisa bokong, haholo ka kotloloho le li-striatum tsa pele (Vickery et al., 2011). Ho nyane ho tsejoa ka tlhahisoleseling e tšoaetsoang ke dopamine e lebisitsoeng libakeng tsa bokong ntle le striatum, joalo ka cortex ea ka pele, insula, hippocampus le amygdala, kapa hore na pontšo ea RPE e sebelisoa joang ke libaka tsena.

Setšoantšo sa 2 

Mohlala oa gangal. Mohlala o ka etsahalang oo ka oona basal ganglia e kopanyang ts'ebetso ea katleho le tahlehelo ka litsela tse peli tse arohaneng ho potoloho ea corticostriato-thalamocortical. Lits'ebetso tsa methapo ea methapo ea methapo e otlolohileng ea tseleng li hlahisa li-receptors tsa D1 le projeke ...

Moputso oa Striatum le chelete

Lithutong tse sebetsang tsa batho tsa neuroimaging, liphetoho tšebetsong ea boko li bontšitsoe ka mokhoa o ts'oanang ho arabela meputso ea chelete (Thut et al., 1997; Elliott et al., 2000; Knutson et al., 2000; Breiter et al., 2001; O'Doherty et al., 2007). Ho feta moo, lithuto li qhekelletse likarolo tse fapaneng tsa boko tse kenyelletsang likarolo tse fapaneng tsa moputso oa chelete, joalo ka ho lebella, ho fana ka maikutlo, ho hapa le ho lahleheloa. Ho bonahala ho na le ts'ebetso kahare ho libaka tsa projeke tsa dopamine mabapi le moputso oa chelete: tebello ea moputso oa chelete e nyolla ts'ebetso ho VStr, e kenyelletsang li-bokellase tsa nucleus, ha liphetho tse ntle li eketsa ts'ebetso ho "cortex" ea "ventral" ea "preralal" preortal preortal cortex, dorsal striatum, le posterior cingulate , e nang le deactivation libakeng tse boletsoeng ka holimo nakong ea ho siea moputso (Elliott et al., 2000; Breiter et al., 2001; Knutson et al., 2001b; Tricomi et al., 2004). Liteko tsa Neuroimaging bathong li fana ka maikutlo a hore ts'ebetso ea VStr e lumellana hantle le boleng bo lebelletsoeng, hammoho le boholo le mohlomong (Breiter et al., 2001; Knutson et al., 2001a, 2005; Abler et al., 2006; Yacubian et al., 2006; Roll et al., 2008). E sebetsoa ke D'Ardenne et al. (2008) e tšehetsa karolo ea mesolimbic dopamine sistimi ho saena lipalo tsa RPE. Ts'ebetso ea sebaka se kenang sa likarolo tse kenang kahare, tšimoloho ea potoloho ea mesolimbic dopamine, e bonts'itse li-RPE tse ntle, athe VStr e kentse li-RPE tse ntle le tse mpe. Ka mokhoa o ts'oanang, Tom et al. (2007) e bonts'itse mosebetsi oa VStr o bonts'a phaello le tahlehelo e ka 'nang ea hlaha. Phuputso ena e boetse e bonts'a hore lipontšo tsena tsa neural li bonts'a phapang ea motho ka mong ea ho lahleheloa ke tahlehelo, tloaelo ea tahlehelo e ka bang matla ho feta phaello e ka bang teng. Kamora nako, mohlala o motle oa sebapali-motšoaea-liphoso (Sutton le Barto, 1998) e fana ka tlhahiso ea hore VStr e sebelise liphoso tsa ho bolela esale pele ho ntlafatsa tlhahisoleseling mabapi le meputso e lebelletsoeng ea nako e tlang ha dorsal striatum e sebelisa letšoao lena la phoso e boletsoeng esale pele ho kenyelletsa tlhahisoleseling mabapi le liketso tse ka lebisang moputsong. Phapang ena e fumane tšehetso ho tsoa liteko tsa fMRI (O'Doherty et al., 2004; Kahnt et al., 2009). Ho khahlisang, bokhoni ba ho ntlafatsa boitšoaro ho arabela RPE bo ile ba bontšoa hore bo lumellana le khokahano e sebetsang pakeng tsa dorsal striatum le dopaminergic midbrain (Kahnt et al., 2009). Lithuto tse nang le monahano tse boletsoeng mona li tšehetsa khopolo ea dopamine e le lets'oao la RPE, bonyane ka bohanyetsi ba lona ba litoro.

Insula le kotsi

Insula e etsoa khafetsa litekong tse sebetsang tsa neuroimaging (Duncan le Owen, 2000; Yarkoni et al., 2011). Ka ts'ebetso e ka aroloa likarolo tse tharo tse ikhethileng: sebaka se nang le "ventroanterior" se amanang le chemosensory (Pritchard et al., 1999) le ts'ebetso ea maikutlo le sechaba (Sanfey et al., 2003; Chang le Sanfey, 2009), sebaka se nang le dorsoanterior se amanang le ts'ebetso e phahameng ea kelello (Eckert et al., 2009), le sebaka se ka morao se amanang le bohloko le ts'ebetso ea sensorimotor (Craig, 2002; Moputso et al., 2004). Morero o fapaneng oa ts'ebetso ea libaka tse kenang ho lipheo tse fapaneng tsa striatal: VStr e amohela likhakanyo tsa insular tse amanang haholo le lijo le moputso, athe dorsolateral striatum e fumana litlatsetso tse kenang tse amanang le somatosroll (Chikama et al., 1997).

Cortex ea insular e kenella mekhoeng ea ho etsa liqeto e kenyang kotsi e sa tsitsang le moputso. Ka ho khetheha, lithuto tsa fMRI li tlalehile ho kenya letsoho ha cortex ea ho etsa liqeto tse fapaneng tsa kotsi (Kuhnen le Knutson, 2005), thibelo ea kotsi le boemeli ba kemeliso ea tahlehelo (Paulus et al., 2003), ho hloka botsitso ka chelete (Critchley et al., 2001), le ho kenyelletsa phoso ea ho bolela esale pele ka kotsi (Preuschoff et al., 2008). Bakuli ba nang le tšenyo ea cortex ea insular ba beha li-wager tse phahameng ha li bapisoa le barupeluoa ba phetseng hantle mme ho becha ha ho na taba le mathata a ho hapa, ka li-wager tse phahameng esita le ka mathata a sa thabiseng (Clark et al., 2008). Patlisiso e 'ngoe e fana ka maikutlo a hore liqeto tse nepahetseng tse kenyeletsang kotsi li its'etleha botšepehing ba cortex ea insular, ho bonts'a hore bakuli ba insula lesion ba fetotse liqeto tse amanang le melemo le tahlehelo e kotsi (Weller et al., 2009) (Leha ho le joalo bona Christopoulos et al., 2009). Haholo-holo, tšenyo ea insula e ne e amahanngoa le ho hloka kutloelo-bohloko ho amanang le boleng bo fapaneng lipakeng tsa likhetho. Patlisiso e fetileng e bonts'itse hore ho na le karohano lipakeng tsa insula le VStr, ka ts'ebetso ea VStr e kenelletseng likhethong tse batlang kotsi, le ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso e boletseng pele likhethong tse mabapi le likhetho tse mabapi le kotsi (Kuhnen le Knutson, 2005) e fana ka maikutlo a hore VStr e emela ho bolela esale pele (Knutson et al., 2001a), ha mokhoa oa kahare oa kantle o emela ho bolela tahlehelo (Paulus et al., 2003). Le ha lithuto tsa monahano li boetse li bonts'a karolo e akaretsang ea mohopolo oa kantle ho ho supa tlholeho (e ntle kapa e mpe) ea meputso e ka bang teng (Litt et al. 2011; Bartra et al., 2013) Lintlha tsa lesion li pheha khang ea hore anterior insular cortex e na le karolo ho lekola tlhahlobo, ka ho khetheha ho etsa liqeto tse khahlano le kotsi. Ho hantle, lithutong tse phetseng hantle, insula ke karolo ea marang-rang a boleng bo shebahalang bo latela lits'enyehelo tse ka lahlehang ka tsela e lumellanang le boemo ba ho hloloheloa ba motho ka mong (Canessa et al., 2013). Ho ka etsahala hore ho se leka-lekane pakeng tsa metlae ea pele le litekanyo tsa sepetlele ho ka lebisa ho likhetho tse nyane ha ho sekasekoa menyetla le tahlehelo e ka bang teng, joalo ka ha ho bonoa ho baphethi ba pelo. 2001a; Goudriaan et al., 2005).

Ho becha ka tsela ea tlhaho ho bakuli ba nang le lefu la Parkinson

Ho becha ka tsela ea tlhaho ho tlalehiloe ka lekhetlo la pele maemong a lefu la Parkinson le kalafo ea dopamine ka 2000 (Molina et al., 2000). Nako e atileng ea bophelo ba papali ea chelete ea marang-rang sechabeng ka kakaretso ke hoo e ka bang 0.9 ho isa ho 2.5% (Shaffer et al., 1999). Ka lefu la Parkinson, litekanyetso tsa tšoaetso li phahame, ho tloha 1.7 ho isa ho 6.1% (Ambermoon et al., 2011; Callesen et al., 2013). Lisosa tsa kotsi tse amanang le ho hlaha ha papali ea papali ea mafu a mafu a Parkinson ke botsofe ba ho qala ha lefu la Parkinson, nalane ea motho ka mong kapa lelapa la ts'ebeliso e mpe ea lithethefatsi kapa joala, khatello ea maikutlo, le ho ts'oaroa ho hoholo le ho hloka tsebo ho hoholo ka lintlha tsa botho (Voon et al., 2007b). Ho khahlisang, tsena li tšoana le mabaka a kotsi a ho lemalla lithethefatsi le papali ea chelete ea methapo ho bongata ka kakaretso. Hape, ho bile le litlaleho tsa ho lemalla L-dopa ho bakuli ba itseng (mohlala, Giovannoni et al., 2000), ketsahalo e neng e se e hlokometsoe ka bo-1980. Mohlomong qalong ho ne ho makatsa ho fumana hore bakuli ba lefu la Parkinson ba ka lemalla meriana ea bona kapa ba hlaolela mekhoeng ea boits'oaro hobane ho ne ho nahanoa hore ha ba na mofuta oa batho ba lemaletseng. Ka tloaelo li hlalosoa e le batho ba sebetsang ka thata, ba tloaetseng ho boloka nako, ba sa fetoheng, ba hlokolosi, ba sa tsilatsile, ba qhekellang, ba liehang ho etsa lintho tse ngata, ba sa tsubelletsoeng habonolo ebile ba sa batle ho tseba letho, mme ba na le menyetla e fokolang ea bophelo bakeng sa ho tsuba koae, ho nwa kofi le tšebeliso e mpe ea ts'ebeliso ea lefu la Parkinson. Menza et al., 1993; Menza, 2000).

Phekolo ea phetisetso ea Dopamine e bile le tšusumetso ho nts'etsopele ea ts'ebeliso ea marang-rang ea ho becha ho amanang le lefu la Parkinson (Gschwandtner et al., 2001; Dodd le al., 2005) le ho ts'oaroa kapa ho fokotseha ha ts'ebeliso ea papali ea methapo ea methapo ea methapo ho hlokomeloa ka mor'a ho fokotsa kapa ho khaola meriana ea dopamine agonist (Gschwandtner et al., 2001; Dodd le al., 2005). Setsi se pharaletseng sa litekanyetso tsa boits'oaro se bitsoang mathata a taolo ea tšusumetso, ho kenyelletsa empa ha se na meeli ho ts'ebeliso ea ho becha ha pathological, boitšoaro bo khothalletsang ba thobalano, le ho reka ka mokhoa o qobelloang, ho tlalehiloe ka kopanelo le kalafo ea phetisetso ea dopamine (Weintraub et al., 2006;; Voon et al., 2007a; Dagher le Robbins, 2009). Dopamine agonists (pramipexole, ropinirole le perorid) li bonahala li beha kotsi e kholo ho feta L-Dopa monotherapy (Seedat et al., 2000; Dodd le al., 2005; Pontone et al., 2006). Ho fokotsa dopamine agonist le ho eketsa L-Dopa ho fihlela karabo e tšoanang ea makoloi e felisitse papali ea methapo ea methapo ho batho ba amehang (Mamikonyan et al., 2008), ha tlhahlobo ea lipatlisiso ea bakuli ba lefu la Parkinson ba fetang 3000 e fumane hore ho nka dopamine agonist ho ekelitse menyetla ea ho ba le bothata ba taolo ea taolo e tlisoang ke 2.72 (Weintraub et al., 2010). Kamora nako, litla-morao tsena tsa kalafo ea dopamine agonist li sa tsoa bonoa maloetseng a mang, joalo ka lefu le sa foleng la leoto, fibromyalgia le prolactinomas (Davie, 2007; Mokhanni-Dunckley et al., 2007; Ho oa ka potlako le ho kotloloha, 2007; Tippmann-Peikert et al., 2007; Falhammar le Yarker, 2009; Holman, 2009). Ho lokela ho hlokomeloe leha ho le joalo hore lithuto tse ling li tlalehetse litheko tsa boits'oaro le / kapa ho potlaka le ho qobelloa ho ikamahanya le litekanyetso tse phahameng tsa L-Dopa monotherapy (Molina et al., 2000), ho hlohlelletsa ho tebileng ha boko bakeng sa lefu la Parkinson (Smeding et al., 2007), le ho bakuli ba lefu la lefu la naïve Parkinson (Antimon et al., 2011), kaofela ha ho se na dopamine agonists. Leha ho le joalo, bopaki ba bongaka bo tšehetsa haholo khopolo ea hore dopamine agonism ho D2 lelapa la receptor le lekane ho baka mathata a taolo ea ts'usumetso.

Lithuto tsa ho nahana ka Brain

Litšoantšo tsa Neurotransmitter

Positron emission tomography (PET) imaging e lumella liphetoho bakeng sa litekanyetso tsa dopamine tsa morao-rao hore li tlisoe ho tsoa liphetoho tse tlamang [11C] moraro oa dopamine D2 li-receptors. Ea pele [11C] raclopride PET thuto sebakeng sena e ne e le ho bakuli ba Parkinson ba nang le dopamine dysregulation syndrome. Dopamine dysregulation syndrome e tšoauoa ka ho nka khatello e qobelloang ea lithethefatsi tsa dopaminergic, eo hangata e leng comorbid le mathata a taolo ea tšusumetso (Lawrence et al., 2003). Bakuli ba nang le dopamine dysregulation syndrome ba bontšitsoeng ba ntlafalitsoeng ba L-Dopa ba kenyellelitse VStr dopamine ho bapisoa le bakuli ba lefu lena la Parkinson ba sa qobelloeng ho nka lithethefatsi tsa dopaminergic (Evans et al., 2006). Ena e ne e le thuto ea pele ho fana ka bopaki ba ho susumetsa ha mesolimbic dopamine circry ho bakuli ba lefu la Parkinson ba ratang ho sebelisa lithethefatsi hampe. Boithuto bo latelang bo tšehelitse 'muso o amanang le "hyperdopaminergic state" ho bakuli ba lefu la Parkinson ka ho becha ho hoholo. Lithuto tse tharo tse bonang 'mapa oa batho ba tsamaisang dopamine reuptake Transport (DAT) li bonts'itse maemo a fokotsehile ho bakuli ba lefu la Parkinson ba nang le bothata ba taolo ea tšusumetso ha bo bapisoa le bakuli ba sa sebetseng (Cilia et al., 2010; Lee et al., 2014;; Voon et al., 2014). Ka bomalimabe ho fumana ha ho hlalose, hobane ha mahloriso a theohileng a DAT a ka supa lits'ebetso tsa methapo (le ho fokotsa ho saena ka dopamine) kapa polelo e fokolitsoeng ea DAT (ka hona ho ile ha eketsa litekanyetso tsa tonic dopamine). Ho ts'ehetsa hypothesis ea morao-rao, bakuli ba laolang tšusumetso ba bontša ho fokotseha [11C] raclopride e tlamang ho VStr ha e bapisoa le taolo ea Parkinson (Steeves et al., 2009), eo hape e lumellanang le dopamine e phahameng ea tonic sehlopheng sena. Hlokomela, leha ho le joalo hore sephetho sena ha sea atleha ho phetoa thutong e tšoanang (O'Sullivan et al., 2011).

Leha ho le joalo, tsena tse peli [11C] raclopride PET lithuto li boletse ho fokotseha ho hoholo hoa bokhoni ba binding ba VStr (index ea tlhahiso ea dopamine) nakong ea papali ea chelete (Steeves et al., 2009) le ho latela ponts'o ea cue e amanang le moputso (litšoantšo tsa lijo, chelete, thobalano) ha li bapisoa le lintlha tse sa nke lehlakore (O'Sullivan et al., 2011) ho bakuli ba lefu la Parkinson ba nang le mathata a ho laola ntle ho tšitiso ha ba bapisoa le bakuli ba sa sebetseng. Sena se fana ka maikutlo a ho arabela ka mokhoa o hlakileng oa potoloho ea meputso ea papali ea chelete ea ho becha le lits'ebeletso tse amanang le moputso ho bakuli ba nang le mathata a taolo ea tšusumetso. Ho O'Sullivan et al. (2011) ho lokolloa ha dopamine ho fumanoe feela ho VStr mme ke feela ha lithuto li fumana lethal dose ea molomo oa L-Dopa esale pele ho hlahlojoa, e lumellana le data ea post-mortem ho lefu la Parkinson e bonts'a hore maemo a dopamine ea boko a tlase haholo ho dorsal ho feta VStr (Kish et al., 1988). Liphetho tsena li lumellana le maikutlo a sensitization a khothalletsoang ke Evans et al. (2006). Haufinyane tjena ho tlalehiloe hore bakuli ba lefu la Parkinson ba nang le papali ea papali ea methapo ea methapo ba na le khatello e fokolang ea dopamine autoreceptors bohareng ba mpa (Ray et al., 2012), e tsejoang ho hokahanya le karabelo e phahameng ea dopaminergic le ho eketseha ha khatello (Buckholtz et al., 2010). Kamora nako, ho bakuli ba lefu la Parkinson, matla a tlholeho a dopamine, joalo ka ha a lekantsoe ke [18F] DOPA PET, e hokahana le tekanyo ea botho ea litšila, ka boeona e le sesosa sa kotsi bakeng sa papali ea chelete ea ho becha le litlatsetso tse ling (Lawrence et al., 2013). Ka kakaretso, lithuto tsa PET li fana ka bopaki bo kopanyang ba lentsoe le phahameng la dopaminergic le karabelo e eketsehang ea dopamine ho putsa li-cue e le tlokotsi e ka bang teng ho bakuli ba lefu la Parkinson ba nts'etsopele ho ts'oaroa ha methapo ea methapo nakong ea kalafo ea dopamine.

Monahano o sebetsang oa matla a matla a khoheli

Bakuli ba lefu la Parkinson ba nang le karabo ea methapo ea methapo ea methapo ba bonts'a likarabo tse ntlafalitsoeng tsa hemodynamic ho li-visual cortsex tse amanang le papali ea methapo ea methapo ea methapo ea methapo, ea VStr, precuneus e nepahetseng le "medial prefrontal cortex" (Frosini et al., 2010). Sena se tsamaisana le liteko tse ts'oanang le tsa ho becha ha li-pathological ntle le lefu la Parkinson (Crockford et al., 2005; Ko et al., 2009) le bokhoba ba lithethefatsi (Wexler et al., 2001), e ts'ehetsang maikutlo a hore mathata a taolo a susumetsang ho lefu la Parkinson a kanna a nkuoa e le litlatsetso tsa boits'oaro.

Bakuli ba lefu la Parkinson ba nang le bothata ba taolo ea tšusumetso e sa fokotseheng ba bonts'a ts'ebetso ea BOLD ho VStr e nepahetseng nakong ea ho nka likotsi le ho fokotsa haholo phallo ea mali a likhoele ka har'a VStr e nepahetseng ho bapisoa le balekane ba bona ba bophelo bo botle (Rao et al., 2010). Ka mokhoa o ts'oanang, ho ile ha fumaneha hore bakuli ba lefu la Parkinson ba nang le mathata a taolo ea tšusumetso ba bonts'a leeme ho likotsi tse kotsi ha li bapisoa le bakuli, le hore dopamine agonists e ntlafalitse kotsi ea ho ipeha ha ba ntse ba fokotsa ts'ebetso ea VStr (Voon et al., 2011). Bangoli ba khothalelitse hore litsebi tsa dopamine agonists li ka fokotsa ts'ebetso ea boko ho tsoa leseding la kotsi ho bakuli ba tlokotsing, ka hona ba rata likhetho tse kotsi. Phuputso e 'ngoe ea FMRI e tlalehile hore, ho latela taolo ea Parkinson, bakuli ba nang le bothata ba taolo ea ts'usumetso ea Parkinson ba fokotsetse lipontšo tsa cortex RPE tsa "insterior" le "portal". Li boetse li bonts'itse hore li-agopist tsa dopamine li eketsa sekhahla sa ho ithuta ho tsoa liphelong, le ho eketsa tšebetso ea RPE, ba fana ka maikutlo a hore dopamine agonists e ka skew ts'ebetso ea neural ho kenya ts'ebetso "e ntle ho feta e lebelletsoeng" ho bakuli ba lefu la Parkinson ba kotsing ea ho kenya ts'ebetsong mathata a taolo (Voon et al ., 2010).

Le ha ho fapana ha dopamine ho saena hoa dopamine ho ka khetholla bakuli ba lefu la Parkinson ba sa etsang joalo mme ba sa nts'etsapele mokhoa oa ho becha, ts'ebetso eo ka eona dopamine agonists e fetolang tlhahlobo ea kotsi e ntse e sa hlakileng. Dopamine agonists e fetola tsela eo methapo ea kelello ea batho ba phetseng hantle e arabelang tebello le phihlelong ea moputso. Nakong ea likarabo tsa moputso, tsamaiso ea lethal e le 'ngoe la pramipexole ho batho ba phetseng hantle e ile ea etsa hore mosebetsi oa VStr o fokotsehe papaling ea lothari (Riba et al., 2008). Ka mokhoa o ts'oanang, ho ile ha fokotsoa ts'ebetso ea VStr ha bakuli ba Parkinson ba fumana tekanyetso ea L-Dopa ha e bapisoa le placebo (Cools et al., 2007). Mokhoa ona oa hypoactivation o re hopotsa seo se fumanoang ho barekisi ba methapo ntle le lefu la Parkinson (Reuter et al., 2005): nakong ea papali ea papali ea papali ea chelete e sebelisitsoeng ka ho becha, papali ea papali ea chelete e bonts'itseng e bontsitse ts'ebetso mabapi le taolo ho cortex ea ventromedial prefrontal preortal le VStr. Ho teba ha papali ea chelete ho ne ho hokahane hantle le phello ea BOLD ho VStr le cortex ea ventromedial pele, e fana ka maikutlo a hore hypoactivity ke ponelo-pele ea bosholu ba papali ea chelete. Joalokaha ho boletsoe ka holimo, bakuli ba Parkinson ba ts'usumetso ea ts'usumetso e fumanoe ba fokotse ho phomola ha mmele le ho fokotsa mesebetsi ea BOLD nakong ea kotsi ea ho kena VStr bapisoa le taolo ea Parkinson (Rao et al., 2010). Lithuto tsena li bontša hore li-dopamine agonists li etsa hore batho ka bomong ba batle meputso le ho etsa likhetho tse kotsi (Riba et al., 2008), ha u tobane le karabelo ea VStr e hatelletsoeng mabapi le moputso.

Ho lokela ho hopoloa leha ho le joalo hore ts'ebetso e fokotsang ts'ebetso ea VStr litekong tsa fMRI ha e hlile ha e bonts'e ho fokotseha ha dopaminergic signation. Ho na le bopaki ba ho ts'ehetsa letšoao la mesolimbic dopamine le sa sirelng e le eona ntho e ka bakang kotsi ea ho becha ha boloetse ba Parkinson. Taba ea pele, ho nka khafetsa moriana oa dopaminergic bakeng sa kalafo ea lefu la Parkinson ho ka lebisa tlhokomelong ea dopamine signaling. Kameho ea maikutlo ea VStr e bontšitsoe kamora ho phetoa khafetsa ho amphetamine ho batho (Boileau et al., 2006). Ho feta moo, ho lefu la Parkinson karolo ea "ventrial" ea "striatum" e bolokoa ke lefu lena ha le bapisoa le libaka tsa dorsal (Kish et al., 1988), mme ka hona phekolo ea dopamine e khutlisetsa, ha e ntse e lokisa bofokoli ba dopamine ka har'a dorsal striatum ho maemo a tloaelehileng, e na le monyetla oa ho phahamisa maemo a dopamine ho potoloho ea VStr ho ea holimo ho feta maemo a nepahetseng (Cools et al., 2007). Khopolo ena ea "ho feta" e qalile ho hlahisoa ke Gotham et al. (1988) ho hlalosa 'nete ea hore tsamaiso ea L-Dopa ho bakuli ba lefu la Parkinson, leha e ntse e ntlafatsa bofokoli bo itseng ba kelello, e ka baka likotsi tse mpe mesebetsing e meng ea ho hlaka ea kelello ea kereke. Tabeng ea mathata a taolo ea tšusumetso, re fana ka tlhahiso ea hore ts'usumetso e feteletseng ea dopaminergic ho VStr e hlokomele matamo ho dopamine ho supa ho amanang le liphoso tse mpe tse boletsoeng esale pele.

Ho kenella hape ho bile le phello e matla lithutong tsa ho nahana tsa ho becha ha li-pathological ka lefu la Parkinson. Thutong ea fMRI, Ye et al. (2010) e fumane hore nakong ea tebello ea moputso oa chelete, lethal dose le le leng la pramipexole (ha e bapisoa le placebo) e ile ea eketsa ts'ebetso ea VStr, ea ntlafatsa tšebelisano pakeng tsa VStr le infula ea ka ntle, empa ea fokolisa tšebelisano lipakeng tsa VStr le cortex ea pele, e lebisang ho ho qobelloang ho eketsehileng. Cilia et al. (2008) o fumane bakuli ba Parkinson ka ho becha ha methapo ea methapo ba bonts'itse ho phomola ho eketsehileng mesebetsing ea boko marang-rang a mesocorticolimbic, ho kenyelletsa le insula. Phuputsong ea fMRI, e amanang le taolo ea Parkinson, bakuli ba nang le bothata ba taolo ea tšusumetso ba ne ba fokotse mosebetsi oa "cortex" oa insular le insulin. 2009;; Voon et al., 2010). Qetellong, thutong ea bakuli ba lefu la Parkinson ba nang le khatello ea maikutlo ntle le tšebeliso ea matla, tekanyetso e le 'ngoe ea L-Dopa e felisitse deactivation e tloaelehileng ea tlhaho e bonoang ho arabela litšoantšo tse tsosang takatso, ho bakuli ba hypersexual feela (Politis et al., 2013). Ha ho tsamaisoa liphetho tsena ho ka supa ho se lekane pakeng tsa khokahano ea pele-pele le ho kenella, le ho susumetsa tšusumetso ea menyetla e ka bang teng ho feta ea likotsi (tahlehelo) ha ho nka liqeto.

Ho nka kotsi le ho lahleheloa ke kotsi

Moralo o nang le tšusumetso ea ho ithuta ho etsa liqeto tse kotsi ke khopolo ea ho ba le tšepo, e ntlafalitsoeng ke Kahneman le Tversky (1979). Sepheo sa mantlha sa mosebetsi oa bona ke ho se hloloheloe tahlehelo, tahlehelo ea ho lahleheloa ke e kholo ho feta menyetla e teng, le bakeng sa batho ba tloaetseng ho khetha likhetho tse kotsi ha mekhoa e meng e se nang ts'ireletso e se na thuso. Mohlala, batho ba bangata ba tla hana tlhahiso ea chelete ea tšepe ntle le haeba phaello e ka ba kholo haholo ho feta tahlehelo e ka bang teng. Ho phehella, bonyane maemong a papali ea chelete, ho ka bonoa e le phetisetso ea tahlehelo ea tahlehelo, le boima bo fetang ba meputso e ka bang teng mabapi le tahlehelo. E ntse e lokela ho bonoa hore na tahlehelo ea ho lahleheloa ke litšitiso e hlaha ka lebaka la boima ba melemo le tahlehelo ho latela axis e le 'ngoe ea boleng (Tom et al., 2007), kapa ho tsoa tlholisanong lipakeng tsa li-system tse arohaneng bakeng sa ho fumana melemo le tahlehelo (Kuhnen and Knutson, 2005; De Martino et al., 2010). Mohlomong, mefuta ena ka bobeli e nepahetse: bopaki ba morao-rao ba fMRI (Canessa et al., 2013) e bonts'a likarabo tsa maikutlo mabapi le tahlehelo le katleho ho VStr le li-cortex tse tsoang pele tsa VStr (tse ntle bakeng sa katleho) le amygdala le insula (e ntle bakeng sa tahlehelo). Maemong ana ka bobeli, ho na le ts'ebetso e kholo ho tahlehelo e ka bang teng, e tsamaellanang le tahlehelo ea tahlehelo ea motho ka mong e lekantsoeng ho sebelisoa khopolo ea tebello (Kahneman le Tversky, 1979). Leha ho le joalo ho boetse ho na le libaka tsa boko tse arabelang ka mokhoa o ikhethileng bakeng sa tahlehelo e ka bang teng, e leng insula e nepahetseng le amygdala, e boetse e bonts'a phapang e fapaneng le tahlehelo ea tahlehelo (Canessa et al., 2013). Ka kakaretso, marang-rang a libaka a thehiloeng ho VStr, insula le amygdala ho bonahala a kopanya tebello le tahlehelo ka tsela eo ka tloaelo e qetellang e le lehloeo la tahlehelo. Ho khahlisang meaho ena, hammoho le dorsal anterior cingulate, li theha marang-rang a kokelo ea khokahano joalo ka ha li khetholloa ke fMRI ea naha e phomotsang. Marang-rang ana ho nahanoa hore a nka karolo ho bona le ho sebetsana le liketsahalo tsa maikutlo a hlonephang maikutlo (Seeley et al., 2007).

Tahlehelo ea tahlehelo e ka hlalosoa motheong oa maikutlo, ka melemo le litla-morao tse ka bang le tšusumetso ea boitšoaro ka maikutlo a fapaneng (Loewenstein et al., 2001), e leng khothatso ka lehlakoreng la phaello le matšoenyeho a tahlehelo. Moetso o joalo o ka tlama ea pele ho li-bokellase tsa nucleus le ea morao-rao ho amygdala le insula. Maemong ana ka bobeli, ho ka etsahala hore batho ba sa hloloheloang ho feta tekano ba ka ba kotsing ea ho ba le boits'oaro bo bobe joalo ka ho lemalla lithethefatsi le ho becha, ka lebaka la tefiso ea tahlehelo, leha ho makatsa hore sena se ntse se lokela ho hlahlojoa ka molao.

Ho na le bopaki bo bong bo supang striatum mabapi le phetoho ea tahlehelo e tloaelehileng ea tahlehelo ho ba bechang. Ho lahleheloa ke li-neurophene tsa dopamine neurons ho lefu la Parkinson ho amahanngoa le boitšoaro bo fokotsang likotsi ha bo bapisoa le lithuto tse laoloang (Brand et al., 2004; Labudda et al., 2010), ha ts'ebetso e sa foleng ea li-dopamine agonists, haholo litekanyetso tse phahameng, e khutlisa mokhoa ona mme e khothaletse boitšoaro bo kotsi le ho susumetsoa habonolo (Dagher le Robbins, 2009). Bokong bo phetseng hantle, tsamaiso e matla ea D2 dopamine agonists e ka boela ea baka keketseho ea likhetho tse kotsi ho batho (Riba et al., 2008) le likhoto (St Onge le Floresco, 2009). Sebetsang D2/D3 ho hlohlelletsoa ha li-receptor ho fumanoe ho hlahisa liphetoho tse thata ho boleng ba tahlehelo e nkoang e le ho lelekisa (ho lelekisa ho ba papali ea chelete e tsoelang pele ea ho fumana tahlehelo) (Campbell-Meiklejohn et al., 2011). Ha ho kopantsoe hammoho, sena se fana ka maikutlo a dopamine, e sebetsang ho striatum mme mohlomong le likarolo tse ling tsa mesolimbic, e ka fetisa tahlehelo ea tahlehelo. Liphuputso tse peli ho bakuli ba lefu la Parkinson ba sa angoeng ke mathata a taolo a qobelloang li fumane hore tekanyetso e le 'ngoe ea dopamine agonist pramipexole e fokotse tahlehelo ea ho rerela phoso ka cortex ea orbitofrontal maemong a le mong (van Eimeren et al., 2009) le orbitofrontal cortex le insula ho tse ling (Voon et al., 2010). Ka kakaretso, ts'ebetso ea tonic dopamine e bonahala e fokotsa ho supa tahlehelo, ka hona e ka fokotsa ho haelloa ke tahlehelo.

Re hlahisa moralo o akaretsang o thehiloeng khopolong ea tebello, eo ho eona ho lebelletsoeng tebello ea tahlehelo le meputso, mohlomong libakeng tse arohaneng tsa boko pele, 'me li kopantsoe ho etsa boleng ba qeto (Setšoantšo. (Figure3) .3). Re fana ka maikutlo a hore tebello ea tebello e kanna ea kenyelletsoa ka "cortex" ea "psychral" pele ho lithupelo, tse ipapisitseng le lithuto tse ngata tsa monahano tse mabapi le sebaka sena ho kopanya boleng (Kable le Glimcher, 2007; Plassmann et al., 2007; Bartra et al., 2013). Joalokaha ho hlahlojoa ka holimo, amygdala le insula li ka ba le karolo ho koposeng tebello ea tahlehelo. Sebaka se ka khonehang bakeng sa pokello ea boleng ba ho qetela, bonyane ka sepheo sa ho ntlafatsa likhetho le merero ea ts'ebetso, ke striatum, e nang le ts'ebeliso e nepahetseng ea libaka tsa boko tse kenyelletsang moralo oa tšebetso (van der Meer et al., 2012). Striatum e na le karolo ea tlhaho ho mekhatlo e mebedi ea moputso (dorsal striatum) (Alexander le Crutcher, 1990) le ho theha mekhatlo e khothatsang ea moputso (VStr), e e fang monyetla o ikhethileng oa ho kopanya boleng (Packard le Knowlton, 2002). Matšoao a boleng ba Striatal a ka khothaletsa ts'ebetso ea ho matlafatsa e lebisang ho ntlafatsong ea liketso tsa nako e tlang, maano le mekhoa, e arolelanoang ke dorsal striatum, ha e ntse e khanna moputso o monate oa ho batla boitšoaro ka VStr. Bakeng sa tlhahlobo ea karolo ea "striatum ho boleng ba likh'ara" Knutson et al. (2008); Bartra le ba bang. (2013). Tekanyo pakeng tsa lits'ebetso tsa tlhahlobo ea phaello le tahlehelo e kanna ea fetoloa bonyane ka karolo ke dopamine. Re fana ka tlhahiso ea mohlala eo ho eona dopamine ea tonic, e sebetsanang le tsela e sa tobang ea basal ganglia (Setšoantšo (Figure2) 2) e laola taolo ea inhibitory e bonahatsang e le tahlehelo ea tahlehelo. Mona litekanyetso tse tlase tsa tonic dopamine li ka amahanngoa le ho eketseha ha tahlehelo ea tahlehelo. Ka lehlakoreng le leng, phasic dopamine, e sebetsa ka tsela e otlolohileng, e ne e tla eketsa boleng ba melemo. Sena se ipapisitse le ho fumana hore lithuto tse nyane tse phetseng hantle tse fuoeng tekanyetso e le 'ngoe ea dopamine agonist cabergoline li bonts'a thuto e fokotsehileng ho arabela (litekanyetso tse ntle), ka lebaka la tšusumetso e kholo (ka tekanyetso e tlase), kabergoline, D2 agonist, e fokotsa phasic dopamine neuron e thunya ka liketso ho amana haufi le D2 autoreceptor, e fumanehang pele ho li-dopamine neurons) (Frank le O'Reilly, 2006). Ka lehlakoreng le leng, haloperidol, D2 antagonist, ho eketsa ho ithuta ho tsoa ho phaello, mohlomong ka lebaka la bokhoni ba eona ba ho ntlafatsa ho thunya ha phasic dopamine. Mabapi le lefu la Parkinson, haeba mokuli a le kotsing ea ho lahleheloa ke litšenyehelo tsa motho ka mong, joale kalafo ea dopamine agonist, e ntlafatsang D2 li-receptors le li-block tse lemohang lipompo tsa phasic dopamine tse amanang le meputso e fosahetseng, (Frank et al., 2004, 2007), e ka fella ka hore o hloye le tahlehelo e tlase haholo. Tlhaloso e 'ngoe ke hore boholo ba ts'ebetso ea phasic e beha phaello holim'a boleng ba meputso e ka bang teng, ha ts'usumetso ea tonic ea D2 li-receptors li thibela maikutlo a fosahetseng a amanang le tahlehelo.

Setšoantšo sa 3 

Mohlala oa ho etsa liqeto o thehiloe khopolong ea tebello. (A) Ts'ebeliso ea menyetla le tahlehelo e ka bang teng li fanoa ke equation e latelang: u(x) = (x)α bakeng sa phaello e ka bang teng u(x) = -λ · (-x)β bakeng sa tahlehelo (Kahneman ...

Bakuli ba lefu la Parkinson ba bonts'a thuto e ntlafalitsoeng ha ba sebelisa meriana ea dopaminergic, le ho ntlafatsa thuto e fosahetseng ha ba sa sebetse, ha ba bapisoa le taolo e amanang le lilemo tsa bona (Frank et al., 2004). Phekolo ka dopamine D2 agonists e se e amoheloa e le sesosa sa mathata a taolo a susumetsang a mafu a Parkinson, moo bothata ba papali ea chelete bo kenelletseng ts'ebelisong ea meriana. Mohlaleng o boletsoeng mona, D2 tsusumetso e ne e tla fokotsa tahlehelo ea tahlehelo ka tsela e sa tobang ea corticostriatal. Re fana ka maikutlo a hore tlasa D2 kalafo ea agonist, bakuli bana ba tloaetse ho se shebe tahlehelo e tlase mme ba batla kotsi le ho feta. Sena se lumellana le tlhokomeliso ea hore bofokoli ba bakuli ba lefu la Parkinson ha ba etsa liqeto tse kotsi bo laoloa ke bokhoni ba ho sebelisa maikutlo a fosahetseng (Labudda et al., 2010). Kameho ea ho fumana phaello, kotsi le ts'ebetso ea tahlehelo ea dopamine signaling libakeng tse ling tsa sisteme ea mesolimbic le mesocortical, haholo ha vmPFC, OFC, insula le amygdala, e ntse e lokela ho hlahlojoa ka botebo bo tebileng.

Boemo ba ho lahleheloa ke mamello bo ka ameha le ho saena ha norepinephrine. Ho baithaopi ba phetseng hantle, tekanyo e le 'ngoe ea "beta blocker propranolol" e le' ngoe e fokotseng boholo ba tahlehelo (Roger et al., 2004) le diphapano tse tloaelehileng ho norepinephrine reuptake transporter ho thalamus, joalo ka ha ho hlahlojoe ke PET, correlate le tahlehelo ea tahlehelo (Takahashi et al., 2013). Tlhaloso ea sena ke hore norepinephrine e eketsa karabelo e khahlisang ho tahlehelo e ka bang teng, mme ho saena ka norepinephrine ka hona ho ka fokotsa ho lahleheloa ke kelello. Le ha li-neuron tsa norepinephrine li boetse li ameha ho lefu la Parkinson, karolo ea bona lithutong tsa lefu lena e ntse e lokela ho hlahlojoa (Vazey le Aston-Jones, 2012).

fihlela qeto e

Mokhatlo oa causal o lipakeng tsa dopamine D2 agonism ea receptor le mathata a taolo ea ts'usumetso ho lefu la Parkinson a na le litlamorao tsa ho lemalla joala ka bongata. Taba ea mantlha, ha se batho bohle ba ntlafatsang li-syndromes tse lemalloang tse latelang kalafo ea ho khutlisa dopamine; bao ho bonahalang ba sa ntse ba bolokile matšoao a dopamine tseleng ea mesolimbic, mohlomong ka ho kopantsoe ha sebopeho sa bona se ikhethileng sa neurodegeneration, sensitization le tlokotsi ea pele ho morbid (joalo ka bopaki ba hore nalane ea lelapa ea ho lemalla e ka baka tšenyo). Ho ka nahanoa hore phetisetso ea mesolimbic e ntlafalitsoeng e boetse e le kotsi ho sechaba ka kakaretso (Buckholtz et al., 2010). Taba ea bobeli, ho hlakile hore D2 agonism ea receptor feela e lekane bakeng sa nts'etsopele ea khatello ea maikutlo. Ha a kopantsoe D1/D2 agonists joalo ka L-Dopa le bona ba ka lemalla (Lawrence et al., 2003), D2 agonists hangata ha e lefelloe ka tieo; ho fapana le moo, ba na le bokhoni ba ho khothaletsa litheko tse ling tse kang ho becha ha li-pathological (O'Sullivan et al., 2011). Sena se ts'ehetsoa ke liteko tsa liphoofolo (Collins le Woods, 2009), mefuta ea li-neuroscience tsa khomphutha (Cohen le Frank, 2009), le bopaki ba bioloji ea molek'hule (Shen et al., 2008) fana ka maikutlo a hore D1 ts'usumetso ea li-receptor ea matlafatsa ha D2 ts'usumetso ea li-receptor e thibela tsela e sa tobang. Re fana ka maikutlo a hore D2 agonism, bathong ba tlokotsing, e na le phello ea "ho lokolla brake" lits'ebetsong tsa matlafatso, ka hona e thusa nts'etsopele ea mathata a taolo ea tšusumetso. Mofuta o notletsoeng nako ea D2 litlamorao, le taba ea hore litloaelo tse lemalloang li tloaetse ho rarolla ha ho khaoloa hoa dopamine agonist, e lumellana le khopolo ea hore tonic dopamine e na le tšusumetso e matla boitekong ba ho batla moputso (Niv et al., 2007; Dagher le Robbins, 2009).

Rea hlokomela leha ho le joalo hore mekhoa e meng ntle le tšitiso ea karabo ea dopamine e pakeng tsa ho matlafatsa liketsahalo le tse susumetsang li ka bapala karolo. Mohlala, Aouneck et al. (2014) ba hlahisitse hore bakuli ba lefu la Parkinson ba nang le mathata a taolo ea tšusumetso ha ba na bonnete ba tšebeliso ea tlhaiso-leseling ho tataisa boits'oaro, bo ka lebisang ho tsitsipano (tloaelo ea ho nka khato kapele). Hape, likhaello tsa pele tsa lobe (Djamshidian et al., 2010) e ka boela ea lebisa ho ho potlakisa ka boits'oaro bo bobebe. Mechine ena ha ea lokela ho ikhetholla ka tsela e tšoanang.

Khohlano ea polelo ea thahasello

Bangoli ba bolela hore lipatlisiso li ne li etsoa ka ho se be le likamano leha e le life tsa khoebo kapa tsa lichelete tse ka nkoang e le khohlano e ka 'nang ea e-ba le thahasello.

lumela hore baa fokola

Mosebetsi ona o ile oa tšehetsoa ka lithuso ho tsoa ho Canadian Institutes of Health Research and Parkinson Society Canada ho ea ho Alain Dagher le likamano ho tsoa Lekhotleng la Sechaba la Saense le Boenjiniere ba Canada ho ea Crystal A. Clark.

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