Ke karolo efe ea motheo ea ho ba le papali ea chelete kapa ea papali ea chelete? (2013)

Front Behav Neurosci. 2013; 7: 206.

E phatlalalitsoe ka marang-rang Dec 23, 2013. Doi:  10.3389 / fnbeh.2013.00206
PMCID: PMC3870289

Papali ea papali ea thuto ea tlhaho (PG) e seng e bitsoa "bothata ba ho becha" ho DSM-5 (APA, 2013; Petry et al., 2013)] e tšoauoa ka mekhoa e mebe ea ho becha e amanang le mathata a tebileng a ts'ebetso. Lilemong tse leshome tse fetileng, ho bile le tsoelo-pele ea bohlokoa ho utloisiseng pathophysiology ea PG (Potenza, 2013). Ho tšoana pakeng tsa PG le mathata a ts'ebeliso ea lithethefatsi (Petry, 2006; Potenza, 2006; Leeman le Potenza, 2012) e hlahisitse ho hlakoloa hoa PG ho DSM-5 e le bothata bo tlatsetsang (ho e-na le bothata ba taolo ea tšusumetso, joalo ka ha ho bile joalo ka DSM-IV).

Lisebelisoa tse ngata tsa neurotransmitter li kentse letsoho ho PG ho kenyelletsa serotonergic, noradrenergic, dopaminergic, opioidergic, le glutamatergic (Potenza, 2013). Kutloisiso ea litsamaiso tsena ka ha li amana le PG ho bohlokoa kliniking bakeng sa nts'etsopele ea lithethefatsi kaha hajoale ha ho na meriana e amoheloang ke FDA e nang le matšoao a PG. Dopamine haesale e kenella mokhoeng oa litheko tsa lithethefatsi le lingoloa tsa pele li hlahisa karolo e tšoanang ea bohlokoa bakeng sa dopamine ho PG (Potenza, 2001). Leha ho le joalo, karolo e tobileng ea dopamine ho PG e lula e sa tsejoe. Boithuto ba sampole ea fluid ea "cerebrospinal fluid" e bontšitse maemo a tlase a dopamine le litekanyetso tse phahameng tsa dopamine metabolites ho PG, ho phahamisa monyetla oa phetoho ea dopamine (Bergh et al., 1997). Leha ho le joalo, meriana e lebisang ts'ebetso ea dopamine ha e so ka e bonts'a litlamorao tsa kliniki ho PG Mohlala, meriana e thibelang dopamine D2-like receptor function (mohlala, olanzapine) e bontšitse litholoana tse mpe litekong tse fokolang, tse sa sebetseng tsa kliniki (Fong et al., 2008; McElroy et al., 2008). Ho feta moo, antxonist e kang dopamine receptor antagonist e sebelisoang haholo kalafo ea mafu a kelello (haloperidol) e fumanoe e eketsa sepheo le boits'oaro bo amanang le papali ea chelete ho batho ba nang le PG (Zack le Poulos, 2007). Leha ho le joalo, tsamaiso ea li-amphetamine tsa pro-dopaminergic (le pro-adrenergic) le tsona li lebisitse menahanong le boits'oaro bo amanang le papali ea chelete ho PG (Zack le Poulos, 2004).

Lithuto tsa morao-rao tsa monahano li se li qalile ho sebelisa li-radioligands le positron-emission tomography ho etsa lipatlisiso ka ts'ebetso ea dopamine ho PG. Ho fapana le se fumanoeng ho itšetlehileng ka koae moo ho ileng ha bonoa liphapang tsa pakeng tsa sehlopha ho [11C] raclopride-binding ho striatum, maemo a ts'oanang a ile a bonoa ho PG le lithuto tsa papiso ke lihlopha tse peli tsa lipatlisiso (Linnet et al., 2010, 2011; Clark et al., 2012). Ka mokhoa o ts'oanang, ha ho phapang pakeng tsa sehlopha pakeng tsa PG le lithuto tsa papiso tse ileng tsa bonoa li sebelisoa [11C] raclopride kapa D3-e khethang agonist-radioligand [11C] - (+) - propyl-hexahydro-naphtho-oxazin (PHNO) (Boileau et al., 2013). Leha ho le joalo, lithutong tsena, ho tlalehiloe likamano tse amanang le ho feto-fetoha ha maikutlo kapa maikutlo a akaretsang, ho etsa liqeto tse mpe kapa ho ts'oaroa ka thata ke papali ea chelete, ho fana ka maikutlo a hore ts'ebetso ea dopamine e ka amana le likarolo tse ikhethang tsa PG (Potenza le Brody, 2013). Liphumano tsena li tsamaellana le mohopolo oa hore PG e emela boemo bo boholo le hore ho khetholla liphapang tse amanang le baeloji kapa li-subgroups ho ka thusa ho nts'etsapele nts'etsopele ea kalafo kapa sepheo se nepahetseng sa ho kenella ha kalafo.

Mokhatlo o seng o ngotsoe hantle o pakeng tsa dopamine le PG o teng ho lefu la Parkinson (PD) (Leeman le Potenza, 2011). Ka ho khetheha, dopamine agonists (mohlala, pramipexole, ropinirole) e 'nile ea amahanngoa le PG le boits'oaro bo feteletseng kapa bo nang le mathata libakeng tse ling (tse amanang le thobalano, ho ja le ho ea mabenkeleng) ho batho ba nang le PD (Weintraub et al., 2010). Ho feta moo, levodopa dosing e boetse e amahantsoe le maemo ana ho PD (Weintraub et al., 2010). Leha ho le joalo, mabaka a neng a bonahala a sa kopane le dopamine (mohlala, lilemo tsa ho qala ha PD, boemo ba lenyalo le sebaka seo a leng ho sona) le tsona li amanang le maemo ana ho PD (Voon et al., 2006; Weintraub et al., 2006, 2010; Potenza et al., 2007), ho totobatsa li-etiologies tse rarahaneng tsa mafu ana. Le ha ho le joalo, lithutong tse sebelisoang [11C] raclopride, batho ka bomong ba nang le PD le PG ha ba bapisoa le ba nang le PD feela ba bonts'itsoeng ho "ventral" (empa eseng dorsal) striatum e fokotsehile joalo ka ho tlama-D2-as binding ho feta le tse ling tse kholo [11C] sebaka sa boikhathollo sa marang-rang nakong ea ts'ebetso ea papali ea papali ea chelete / ho etsa liqeto (ho fana ka tlhahiso ea dopamine e kholo sehlopheng sa PG nakong ea ts'ebetso ea mosebetsi) (Steeves et al., 2009). Liphumano tsena li re hopotsa tse khothatsang levodopa e kentsoeng ke levodopa e kentsoeng sebakeng sa nakoana ea [11C] raclopride ka har'a ventral empa eseng dorsal striatum lithutong tsa PD tse ikatisang tse sebelisang mekhoa ea phekolo ea dopamine-ho fetelletsa (ho bapisoa le ba sa etseng) (Evans et al., 2006). Joalokaha liphuputso tse ling li bonts'itse ha li kopana le litekanyetso tsa boits'oaro ho PD (le ba nang le PD feela) lets'oao le fokotsitsoeng ho "ventral striatum" ka motheo le nakong ea ho nka kotsi (Rao et al., 2010), ho hlaha potso ea hore na dopamine e ka amana le lits'ebetso tsena ho PD. Ho na le lipotso tse tšoanang ka ts'ebetso e batlang e sa sebetsane ea "potral striatal" e bonoang ho non-PD PG litšoantšong tse se nang ligand nakong ea papali ea chelete (Reuter et al., 2005) le ts'ebetso ea moputso oa chelete (Balodis et al., 2012a; Choi et al., 2012). Leha lithuto tse ngata li fumane ho kenella ha ts'ebetso nakong ea ts'ebetso ea tefello ea moputso (haholo nakong ea ts'ebetso ea mesebetsi ea ho lieha ho senya chelete) maemong a mangata a tlhekefetso [mohlala, tšebeliso ea joala (Wrase et al., 2007; Beck et al., 2009) le ts'ebeliso ea koae (Peters et al., 2011) likotsi] le maemo a mang a tšoauoa ke taolo e nang le tšusumetso ea tšohanyetso [mohlala, ho itlopa lijo ho jang (Balodis et al., 2013, mochine oa khatiso)], lithuto tse ling li fumane tšebetso e matla ea ho kenella ka hare nakong ea ts'ebetso ea moputso ho batho ba nang le PG le ba nang le litlolo tse ling (Hommer et al., 2011; van Holst et al., 2012a), ho botsa lipotso tse eketsehileng mabapi le hore na tšebetso ea striatal e kenya letsoho joang ho PG le litumelong le hore na dopamine e ka kenya letsoho joang lits'ebetsong tsena (Balodis et al., 2012b; Leyton le Vezina, 2012; van Holst et al., 2012b).

Leha boholo ba datha tse amanang le radioligand tse hlalositsoeng ka holimo li etsa lipatlisiso ka ts'ebetso ea li-receptor tsa D2 / D3, tse ling tsa dopamine receptors waranti li hlahlojoa ka PG. Mohlala, mosebetsing oa mochini oa "grent slot", "D2-receptor agonist quinpirole e ntlafalitsoeng le tebello e fosahetseng ea moputso litekong tse haufi tsa ho hloloheloa, 'me phello ena e fumanoe ke D4 e khethiloeng (empa eseng D3 kapa D2) dopamine receptor antagonist (Cocker et al., 2013). Liphumano tsena tsa preclinical li tlatselletsa lithuto tsa batho tse fanang ka maikutlo a karolo bakeng sa D4 dopamine receptor ka boitšoaro ba papali ea chelete. Mohlala, phapang ea motsoako ho mofuta oa coding bakeng sa D4 dopamine receptor e amahantsoe le likarabo tse fapaneng tsa keketseho e amanang le levodopa ea boits'oaro ba papali ea chelete (Eisenegger et al., 2010). Liphumano tsena li tlatsana le lingoliloeng tse kholo tse hokahanyang D4 dopamine receptor le li-impruivity tse amanang le ho qobelloa le mathata a joalo ka tlhokomelo-deficit / hyperactivity disorder, leha ho le joalo ka mokhoa o sa lumellaneng (Ebstein et al., 1996; Gelernter et al., 1997; DiMaio et al., 2003). E le preclinical (Fairbanks et al., 2012) le motho (Sheese et al., 2012) ya data e fana ka maikutlo a lipuisano tse amanang le tikoloho tse kenyeletsang gene e kenyellelitseng D4 dopamine receptor le likarolo tsa boitšoaro bo sa tsotelleng kapa bo sa laoloang hantle, lipatlisiso tse ling li lokela ho nka karolo bakeng sa D4 dopamine receptor ho PG, haholo-holo lithutong tse sebelisang liteko tse hlokolosi tsa tikoloho le liphatsa tsa lefutso. mabaka. Le ha li-complex tsa D4 tse khethollang / tse khethang agonist (mohlala, PD-168,077 le CP-226,269) li sebelisitsoe lithutong tsa preclinical ho ithuta li-receptors tsa D4, lipatlisiso tse eketsehileng li hlokahala ho ithuta li-receptor tsa D4 tsa dopamine ka ha ho ka etsoa ka positron-emission- lithuto tsa Tomography - sena se bontša letoto la bohlokoa la lipatlisiso tsa nako e tlang (Bernaert le Tylli, 2003; Tarazi et al., 2004; Basso et al., 2005). Ho feta moo, ha D1 dopamine receptor e se e kentsoe litlatsetsong tse joalo ka ho ts'epa koae (Martinez et al., 2009), karolo ea D1 dopaminergic system ho lihloela tsa moferefere oa PG.

Liphumano tse ka holimo li bonts'a hore na ts'ebetso ea dopaminergic e ka kenya letsoho joang ho PG le litlatsetso tse ling hajoale e sa le qalong ea kutloisiso. Boitsebiso ba hajoale bo fana ka maikutlo a hore ho fapana hoa ts'ebetso ea dopamine ho ka fifatsa liphapang lipakeng tsa batho ba PG le bao e seng ba PG, ka khang e matla e pakeng tsa sehlopha sa batho ho fihlela kajeno e nkuoeng sehlopheng se nang le dopaminergic pathology (PD). Litšobotsi tse ikhethileng (mohlala, ho susumetsa, ho etsa liqeto le boitšoaro bo amanang le papali ea chelete) tse hokahantsoeng le tšebetso ea dopamine lithutong tsa PG le tseo eseng tsa PG le tsona li tiisa hore ho nahanoa ka pono ea bongaka mme li fana ka maikutlo a hore lintlha tsena li ka supa lipheo tsa kalafo tse amanang tse amanang haufi haholo le tlhaho. ts'ebetso [e phahamisa monyetla oa hore ba ka natefeloa ka ho khetheha mabapi le meriana (Berlin et al., 2013)]. Ho feta moo, li-endophenotypes tse ling tse ka bang le ho qobelloa (Fineberg et al., 2010, mochine oa khatiso) ho nahanoa ka tumello e fuoeng lihokelo tsa bona tsa pele ho sephetho sa kalafo ho PG (Grant et al., 2010). Ntle le moo, lits'ebetso tse ka laolang tšebetso ea dopamine li tiisa ho nahanisisa ka ho eketsehileng ntlafatsong ea kalafo. Mohlala, litekong tsa bongaka tse sa sebetseng, bahanyetsi ba opioid ba kang nalmefene le naltrexone ba fumanoe ba phahame ho feta placebo ho phekola PG (Grant et al., 2006, 2008b), haholo-holo hara batho ba nang le litabatabelo tse matla tsa papali ea chelete kapa nalane ea malapa ea joala (Grant et al., 2008a). Ka mokhoa o ts'oanang, lits'ebetso tsa glutamatergic li tiisa ho nahanisisa ka taba ena (Kalivas le Volkow, 2005), ka data ea pele e hokahanyang neutraceutical n-acetyl cysteine ​​le sephetho se nepahetseng sa kalafo ho PG (Grant et al., 2007). Joalokaha ho khetholla sisteme ea dopamine e fana ka leseli mabapi le PG, mekhoa e tšoanang e lokela ho sebelisoa ho etsa lipatlisiso ts'ebetsong ea serotonin ho PG (Potenza et al., 2013), haholo-holo e fumanoeng e fumanoeng e sa lumellaneng le meriana ea serotonergic kalafo ea PG (Bullock le Potenza, 2012). Mokhoa o hlophisehileng oa ho etsa lipatlisiso ka li-neurobiology le litšobotsi tsa kliniki tsa PG li lokela ho thusa ho ntšetsa pele maano a thibelo le kalafo bakeng sa PG.

Litlhaloso

Dr. Marc N. Potenza ha a na likhohlano tsa lichelete tsa lithahasello mabapi le litaba tsa buka ena e ngotsoeng ka letsoho mme o fumane tšehetso ea lichelete kapa matšeliso bakeng sa ba latelang: Dr. Marc N. Potenza o buisane le ho eletsa Boehringer Ingelheim, Ironwood le Lundbeck; e rerile ebile e na le lithahasello tsa lichelete Somaxon; e fumane ts'ehetso ea lipatlisiso ho tsoa Mohegan Sun Casino, Setsi sa Naha sa Lipapali tse Ikarabellang, Forest Laboratories, Ortho-McNeil, Oy-Control / Biotie, Psyadon, Glaxo-SmithKline, Mekhatlo ea Naha ea Bophelo le Tsamaiso ea Veteran; o nkile karolo lipatlisisong, posong kapa lipuisanong tsa mohala tse amanang le bokhoba ba lithethefatsi, mathata a taolo ea tšusumetso kapa lihlooho tse ling tsa bophelo bo botle; e rerile liofisi tsa molao le ofisi ea mosireletsi oa sechaba litabeng tse amanang le mathata a ho laola maikutlo; e fana ka tlhokomelo ea bongaka Lefapheng la Connecticut la Bophelo bo Botle ba kelello le Litšebeletso tsa Lithethefatsi Lits'ebeletso Lenaneo la Litšebeletso tsa Ho becha; e phethile litlhahlobo tsa lithuso bakeng sa Mekhatlo ea Naha ea Bophelo le mekhatlo e meng; e na le likarolo tsa likoranta tse hlophisitsoeng ke baeti; o fane ka lipuo tsa thuto lipapaling tse kholo, liketsahalo tsa CME le libaka tse ling tsa bongaka kapa tsa mahlale; hape e hlahisitse libuka kapa likhaolo tsa libuka bakeng sa baphatlalatsi ba litemana tsa bophelo bo botle ba kelello.

lumela hore baa fokola

Phuputso ena e ne e tšehelitsoe ke Setsi sa Naha sa Tlhekefetso ea Lithethefatsi (NIDA) P20 DA027844, Setsi sa Naha sa Tlhekefetso ea Joala le Tlhekefetso ea joala RL1 AA017539, Lefapha la Bophelo bo Botle ba Kelello le Lithethefatsi, Connecticut Mental Health Center, le Setsi sa Naha sa Boikarabello Setsi sa Boipheliso sa Lipapali Phuputsong ea Papali ea chelete Univesithing ea Yale.

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