Dopamine Modulates Kotsi-Ho nka e le Mosebetsi oa Mokhoa oa ho Batla Boikutlo ba Baseline (2013)

J Neurosci. 2013 August 7; 33 (32): 12982-12986.

doi:  10.1523 / JNEUROSCI.5587-12.2013

PMCID: PMC3735881

inahaneloang

Takatso ea maikutlo, e hlalosoang e le tlhoko ea maikutlo a fapaneng, a rarahaneng, le a tebileng, e emetse drive e fokolang ea patlisiso ea boitšoaro ba methapo ea motho. E amana le kotsi e eketsehang bakeng sa boits'oaro bo fapaneng ho kenyelletsa ts'ebeliso ea lithethefatsi, papali ea chelete le mekhoa e kotsi ea thobalano. Phapang e fapaneng le e 'ngoe ea ho ipatlela maikutlo a boithati e hokahane le ts'ebetso ea dopamine ea boko, haholo ho li-receptor tse kang D2, empa ho fihlela joale ha ho na bopaki ba mabaka a hore karolo ea dopamine ketsahalong ea ho batla maikutlo ho batho. Mona, re fuputse litlamorao tsa kabon ea agonist e ikhethileng ea D2 / D3 mabapi le ts'ebetso ea khetho e kotsi ea kotsi ho batho ba phetseng hantle ba sebelisang moralo o laoloang ke "placebo".

Cabergoline e bile le tšusumetso haholo tsela eo barupeluoa ba kopaneng matšoao a fapaneng a hlakileng mabapi le menyetla le tahlehelo ha a khetha pakeng tsa likhetho tsa karabelo tse amanang le liphetho tse sa tsejoeng. Habohlokoa, litlamorao tsena li ne li its'etleha ka matla ho sekhutlong sa ho batla maikutlo. Ka kakaretso, cabergoline e ile ea eketsa tlhalohanyo ea khetho ho fana ka tlhahisoleseling mabapi le monyetla oa ho hapa; ha e ntse e fokotsa khethollo ho latela boholo ba tahlehelo e ka bang teng e amanang le likhetho tse fapaneng. Tlitlamorao tse kholo tsa lithethefatsi li ile tsa bonoa ho barupeluoa ba nang le lintlha tse fokolang tse batlang maikutlo. Liphumano tsena li fana ka bopaki ba hore boitšoaro bo nkang batho kotsing bo ka fetisoa ka kotlollo ke sethethefatsi sa dopaminergic, empa hore katleho ea thetso e joalo e ipapisitse le phapang ea motheo mokhoeng oa ho batla maikutlot. Sena se totobatsa bohlokoa ba ho nahana ka liphapang tsa batho ka bomong ha ho etsoa lipatlisiso tsa ho etsa liqeto tse kotsi, 'me ho ka ba le bohlokoa ba nts'etsopele ea litlhare tsa mafu a amanang le likotsi tse amanang le ho bea batho kotsing, joalo ka ho becha ho tsa mafu.

Selelekela

Ho na le likheo tse khahlehang lipakeng tsa litlaleho tse tloaelehileng tsa ho etsa liqeto le boitšoaro ba motho ba letsatsi le letsatsi.Kahneman le Tversky, 1984). Mohlala, ke eng e susumetsang batho hore ba qoelise marang-rang, ho ja lijo tse nokiloeng ka linoko, kapa ho tsitsisa lihora tse ngata bakeng sa ho palama rollercoaster ho nka metsotso e seng mekae? Mohopolo oa mantlha thutong ea botho ke ho ba teng ha sebopeho se amehang ka maikutlo a hedonic ho batla "maikutlo" a matla, le ho mamella menyetla ea ho ba le sepheo sa ho ba le monyetla (oa ho beha kotsing) molemong oa liphihlelo tse joalo tsa maikutlo (Zuckerman, 1974).

Ts'ehetso ea mohopolo oa tšobotsi e le 'ngoe e amanang le tšusumetso ea boiphihlelo ba boiphihlelo maikutlong a maholohali e nkiloe ke ho bonoa ha cigariance ea koae, joala le ts'ebeliso ea koae; ts'ebeliso ea lithethefatsi; le boits'oaro bo kotsing ba ho ba le thobalano ho batho ba baholo le ba lilemong tsa bocha.Carmody et al., 1985; Gillespie et al., 2012; King et al., 2012). Bopaki ba phetoho e tšoanang mabapi le mamello ea likotsi bo fanoa ke mokhatlo pakeng tsa ho itšireletsa ha maikutlo a phahameng ka ho fetisisa (SS) le litekanyetso tse eketsehang tsa tšebeliso e mpe ea lithethefatsi, papali ea chelete e ngata le litloaelo tse ling tse mpe (Coventry le Brown, 1993; Roberti, 2004; Ersche et al., 2010).

Phapang e fapaneng le e 'ngoe ea ho batlana le maikutlo e' nile ea hokahanngoa le tšebetso ea boko dopamine (DA), haholo ho li-receptors tsa D2-like (D2 / D3 / D4). Bathong, trait SS e amahanngoa le phapang ea liphatsa tsa lefutso ho D2 le D4 receptor loci (Ratsma et al., 2001; Hamidovic et al., 2009; Derringer et al., 2010), le "stumanor" ea "striatal D2 / 3" joalo ka ha ho hakantsoe ka 11C-raclopride PET (Gjedde et al., 2010). Litonong, mosebeletsi ea matla ea arabelang meputso ea maikutlo a sa hlalosoang o bontšitsoe hore o ela hloko li-antipsychotic flupenthixol (D1-D5 receptor antagonist) le amphetamine (Olsen le Winder, 2009; Shin et al., 2010). Leha ho le joalo, hajoale ha ho na bopaki ba ho qhekella ho batho bakeng sa karolo ea DA ho feto-fetoleng boitšoaro e le ts'ebetso ea mokhoa oa SS.

Thutong ena, re sebelisitse k'habergoline — setlhare se nang le kamano e haufi haholo le li-receptors tse kang D2 joaloka liemeli tse sebelisitsoeng lithutong tsa pele (Kvernmo et al., 2006) - Ho hlahisa diphetho tse neng li sa lebelloe ho thetso ea litekanyetso tsa boits'oaro bo nkang kotsi ka DonNUMX agonists (Hamidovic et al., 2008; Riba et al., 2008). Habohlokoa hape, re ile ra boela ra nahana ka monyetla oa ho fetoha hoa litlamorao tsa lithethefatsi ka tšibollo ea SS e tlalehiloeng.

E ipapisitse le bopaki ba ts'ebetso ba ho nahanisisa bo tsoang ho batho ba mamello ba ntseng ba phekoloa ka mokhoa o sa feleng oa dopamine agonist (Abler et al., 2009), re boletse esale pele hore k'habeche e tla eketsa tšusumetso ea tlhahisoleseling mabapi le menyetla ea meputso, leha e le hore e ka fokotsa le phello ea litlamorao tse mpe, nakong ea khetho e kotsi kapa e sa tsejoeng. Leha lithuto tsa pejana li tlalehile likarabo tse kholo ho lithethefatsi tse susumetsang tsa DAergic ho baithaopi ba phahameng ba SS (HSS), ho boetse ho khothalelitsoe hore batho ba batlang maikutlo a tlase ba ka ba le mokhoa o phahameng oa ho fumana striatal DA (Gjedde et al., 2010; bona le Puisano), e ka bolelang karabelo e kholo ho li-agonists tse ikhethang lithutong tse tlase tsa SS (LSS). Re fumane hore cabergoline e susumetse haholo kutloisiso ea khetho mabapi le tlhaiso le tahlehelo e ka bang teng, le hore, ka mokhoa o makatsang, boholo ba litlamorao tsena bo ne bo its'epahalla ka ho fapana ha motheo ho SS e itlalehileng.

Lisebelisoa le mekhoa

Barupeluoa.

Barupeluoa e ne e le banna ba phetseng hantle ba 20 (bolelele ba lilemo, lilemo tsa 26.7; SD, lilemo tsa 5.67). Litekanyetso tsa ho lelekoa li ne li kenyelletsa bokuli bofe kapa bofe ba hona joale, ketsahalo ea hajoale kapa ea nalane ea bokuli ba kelello, le / kapa tšebeliso ea lithethefatsi boithabisong tse fetang e le 'ngoe likhoeling tse fetileng tsa 6. Lithuto tsohle li fane ka tumello e ngotsoeng e fanoeng mme thuto e amohetsoe ke komiti ea melao ea University College London.

Moqapi.

Boithuto bona bo ile ba etsoa ho latela sebopeho se laoloang ke mahlo a bohareng ba lithuto. Sebokeng sa pele, barupeluoa ba ile ba hlahlojoa bakeng sa litlolo tsa lithethefatsi, ba fuoa tumello e nang le tsebo, 'me ba tsebisoa ke paradigm e kotsi ea ho etsa liqeto. Lihlooho li boetse li tlatsitse Barratt Impulsivity Scale (BIS-11) le UPPS (ho potlaka; (ho hloka) boiketlo; (ho hloka) tiisetso; ho batla maikutlo) mehato ea ho itlaleha (Patton et al., 1995; Whiteside le Lynam, 2001), tekanyo ea bokhoni ba ho sebetsa ba memori (sebaka se fetisang pele ho latela Wechsler Adult Intelligence Scale-III; The Psychological Corporation, 1997), le litekanyo tse sa lekanyetsoang tsa bokhoni ba kelello (Raven's 12-item Advanced Progressive Matrices; Pearson Education, 2010 ). Kopanong ea bobeli le ea boraro (ea liteko), barupeluoa ba fihlile hoseng mme ba fuoa letlapa le nang le 20 mg ea domperidone (antiemetic), e lateloe metsotso e 20 hamorao ke 1.5 mg ea cabergoline kapa placebo (matlapa a litlhare le a placebo a ne a sa bonahale. ). Tekanyo ena e khethiloe hore e be kholo ho feta e fanoeng thutong e fetileng moo ho bonoeng litlamorao tse sa lumellaneng tsa boits'oaro (1.25 mg; Frank le O'Reilly, 2006), ka kenyelletso ea mask ea domperidone ho fokotsa khahlano le litlamorao tse ka bang teng 'meleng.

Ho lumella maemo a plasma ea lithethefatsi hore a fihle maemong a phahameng, ho etsa liteko ho qalile 2 h kamora ho kenella letlapeng la bobeli (Andreotti et al., 1995). Sebokeng se seng le se seng sa tlhahlobo, barupeluoa ba ile ba qeta mehato ea pono ea analog, ho ama, litlamorao tsa mmele le tsebo ea taolo ea lithethefatsi / placebo. Taelo ea lithethefatsi / placebo e ile ea hanyetsoa ho lithuto tsohle, ka nako ea ho hlatsoa libeke tsa 2 lipakeng tsa lithuto tse peli tsa liteko.

Parisigm ea ho etsa liqeto.

Ho etsa liqeto ka kotsi ho ile ha botsoa ho sebelisoa mosebetsi oa khetho oa bo-maiketsetso o hlalositsoeng pele ke Roger le basebetsi mmoho (Roger et al., 2003; Murphy et al., 2008). Ka bokhutšoanyane, tekong e 'ngoe le e' ngoe, lithuto li ne li lokela ho khetha pakeng tsa libapali tse peli tse hlahisitsoeng ka nako e le 'ngoe. Papali e 'ngoe le e' ngoe e ne e emeloa ka pono ke histogram, eo bophahamo ba eona bo neng bo bontša monyetla oa ho hapa lintlha tse itseng. Bokete ba menyetla e neng e ka ba teng bo ne bo bontšoa ka botala ka holimo ho histogram e 'ngoe le e ngoe, ka boholo ba tahlehelo e ka bang teng ka tlase ho bofubelu.

Teko e 'ngoe le e' ngoe, papali ea chelete e le 'ngoe e ne e lula e na le 50: monyetla oa 50 oa ho hapa kapa ho lahleheloa ke lintlha tsa 10 ("papali ea" taolo ea "papali ea chelete, e lebelletsoeng boleng ba 0). Mokhoa o mong oa ho becha ("liteko") o fapa-fapaneng oa (1) oa ho hapa (0.6 kapa 0.4), (2) oa menyetla (30 kapa lintlha tsa 70), le (3) tsa tahlehelo e ka bang teng (30 kapa 70) .

Thepa ena ea papali ea chelete e ile ea tšela ka botlalo, ea hlahisa mefuta e robeli ea liteko. Ho ile ha fanoa ka maikutlo a pono (win / lahleha) ka mor'a khetho e 'ngoe le e' ngoe, 'me lintlha tse ntlafalitsoeng li ile tsa hlahisoa pele ho nyeoe e latelang.

Baithuto ba ile ba qeta liteko tse 'ne tsa liteko tsa 20,' me ba laetsoe hore palo e phahameng ka ho fetisisa eo ba e fumaneng e tla fetoloa e le pence ebe e lefshoa qetellong ea mosebetsi joalo ka bonase ea chelete. Linako tsa Deliberation (Karabelo) le tsona li tlalehiloe.

Tlhahlobo ea tlhaiso-leseling.

Lintlha li ile tsa hlahlojoa e le khetho e lekantsoeng ea papali ea "liteko" e le ts'ebetso ea ho hapa, boholo ba menyetla e ka bang teng, le boholo ba tahlehelo e ka bang teng. Haholo-holo, lintlha tsa khetho e lekantsoeng li kentsoe ANOVA e lekantsoeng hangata e nang le lintlha tsa lithethefatsi, monyetla oa ho hapa, boholo ba meputso e lebelletsoeng, le boholo ba tahlehelo e lebelletsoeng. Taelo ea kalafo e kenyellelitsoe joalo ka karolo ea lithuto lipapaling. Ho ile ha etsoa tlhahlobo e tšoanang bakeng sa data ea nako ea karabelo. Likhetho li ile tsa boela tsa hlahlojoa ho latela boleng bo lebelletsoeng le "ho ba kotsing ea" makhopho a khethiloeng, 'me a morao a hlalosoa e le SD ea liphetho tse ka bang tsa papali e' ngoe le e 'ngoe e khethiloeng. Litlhahlobo tsohle tse boletsoeng esale pele tse bonolo li ne li bapisoa le ba babeli ba sebelisang phetoho ea Bonferroni bakeng sa lipapiso tse ngata. Lintlha tse tsoang nthong e le 'ngoe li ne li senyehile mme ka hona li ne li sa kenyelletsoe tlhahlobisong.

Results

Lintlha tse ikhethileng tsa khetho

Ha ho na phello e kholo ea taelo ea lithethefatsi, kapa tšebelisano pakeng tsa lintlha tsa taelo ea lithethefatsi le lithethefatsi, tse fumanoeng (ka bobeli p > 0.09). Ho eketsa matla, taelo ea lithethefatsi ka hona e ile ea lahloa ho tsoa mefuteng bakeng sa litlhahlobo tse latelang. Ka kakaretso, bankakarolo ba khethile papali ea "liteko" khafetsa khafetsa ha monyetla oa eona oa ho hapa o ne o le moholo ha o bapisoa le ha o ne o le tlase (F(1,18) = 40.305, p <0.001, ηp2 = 0.691). Mokhoa ona oa ho etsa liqeto o ne o eketsoa haholo tlasa k'habeche e amanang le placebo (lithethefatsi * monyetla oa ho hapa; F(1,18) = 6.733, p = 0.018, Studp2 = 0.272).

Baithuto le bona ba khethile papali ea "liteko" hangata haholo ha menyetla e lebelletsoeng e le kholo ho feta nakong eo moputso o neng o lebelletsoe o le nyane (F(1,18) = 50.522, p <0.001, ηp2 = 0.736). Leha ho le joalo, ho ne ho se na bopaki bo tiileng ba hore mokhoa ona oa khetho o ne o fapane ka tlasa cabergoline (boholo ba lithethefatsi * tsa menyetla e neng e ka ba teng, F(1,18) = 3.615, p = 0.074).

Kamora nako, baithaopi ba khethile papali ea "liteko" hangata haholo ha tahlehelo ea eona e ne e le kholo ho feta ha tahlehelo ea eona e le nyane (F(1,18) = 56.486, p = 0.001, Studp2 = 0.758). Mokhoa ona oa ho etsa liqeto o ile oa totobatsoa haholo tlasa k'habeche ea hae (boholo ba lithethefatsi * tsa tahlehelo e ka ba teng, F(1,18) = 6.773, p = 0.018, Studp2 = 0.273). Bakeng sa kakaretso ea litlamorao tsena Setšoantšo sa 1.

Setšoantšo sa 1.  

Khetho ea karolo ea "papali" ea "liteko" ho latela thepa ea ho becha, ka tlas'a placebo le cabergoline. **p <0.001, *p <0.05.

Ha ho na phello ea k'hothokhoe ka kakaretso ea likhetho tsa "liteko" tsa papali ea "liteko" (p = 0.480), mme ha ho na litšebelisano tse kholo tsa taelo e phahameng e kenyelletsang sesosa sa lithethefatsi (kaofela p > 0.2).

Puisano le phapang e fapaneng le motho ka mong

SubPS SS e ile ea fumanoa e sebelisana haholo le litlamorao ka bobeli tsa lithethefatsi ka boitšoaro bo ikhethileng [lithethefatsi * monyetla oa ho hapa (pwin) * lintlha tsa SS, F(1,17) = 6.331, p = 0.022, Studp2 = 0.271; tahlehelo * ea lithethefatsi * Sekole sa SS, F(1,17) = 11.501, p = 0.003, Studp2 = 0.404; ha ho bapisoa, lilemo, khakanyo ea IQ, mohopolo oa ho sebetsa, le ho se itlalehe ka botlalo ho teng kaofela p > 0.3].

Ka sebele, tšebelisano ea lithethefatsi le mabaka le pwin le boholo ba tahlehelo e lebelletsoeng e bonahala e tsamaisoa haholo ke lithuto tse nang le lintlha tse tlase tsa SS (Feie. 2A). Tlhahlobo e bonolo ea litlamorao e senoletse hore, ha a hlalosa lihlopha tsa LSS le HSS ka karohano e akaretsang ea lintlha tsa SS, li-LSS li ile tsa khetha ho becha ho feta "liteko" ha pwin e ne e phahame (F(1,17) = 5.996, p = 0.025) le tse fokolang ha pwin e ne e le tlase (F(1,17) = 7.808, p = 0.012) ho lithethefatsi tse amanang le placebo. Ka lehlakoreng le leng, sehlopha sa HSS se ne se sa fapana ka khetho ea bona ea likhetho tse tlase kapa tse phahameng lipakeng tsa lithethefatsi le placebo (p > 0.2).

Setšoantšo sa 2.  

A, Liphello tsa cabergoline lithutong tse khethiloeng ke lihlooho, tse arotsoeng ka lihlopha tsa HSS le LSS ka karohano e bohareng ea likolo tse tlase tsa UPPS SS. Bakeng sa lithuto tsa LSS feela, ho feto-fetoha ha boitšoaro ba khetho ho ile ha feteletsoa haholo ho latela tlhaiso-leseling e mabapi le ...

Li-LSS li boetse li bonts'itse mokhoa o senang mohopolo oa ho khetha lits'ebetso tse fokolang ha tahlehelo e ka ba nyane (F(1,17) = 4.262, p = 0.0546), le metjeko e mengata ha tahlehelo e ka ba teng e ne e le kholo (F(1,17) = 3.052, p = 0.090; Feie. 2A), k'habeche e bapisoa le placebo. Ha ho litla-morao tsena tse ileng tsa latela bohlokoa ho sehlopha sa HSS (p > 0.2). Lihlopha tsa HSS le LSS ha lia ka tsa fapana haholo ho latela lipalo tse ling tsa boipheliso tse ikhethileng, lilemo, palo ea linomoro, kapa IQ e hakantsoeng (kaofela p > 0.3).

Ho lekola litlamorao tsena ka kotloloho, lintlha tse peli tsa boholo ba phello ea lithethefatsi ka khetho li ile tsa baloa bakeng sa thuto ka 'ngoe (phapang e kholo ea phello ea phetoho ea monyetla oa ho hapa, kapa boholo ba tahlehelo e ka bang teng ka khetho e lekantsoeng ea tlhahlobo ho becha pakeng tsa maemo a lithethefatsi le a placebo). Chelete ea SS e fumanoe e le moetapele oa bohlokoa oa lits'ebetso tsena ka bobeli (r2adj = 0.229, p = 0.022; r2adj = 0.336, p = 0.005; tlhahlobo ea morao-rao ea khatello ea maikutlo), empa ha e hakanyetse IQ, bolelele ba linomoro, kapa lintlha tse ling tse ipolelang tsa ho itlhahisa (kaofela p > 0.1). Maemong ka bobeli, bankakarolo ba nang le lintlha tse tlase tsa ho batla maikutlo ba ile ba susumetsoa haholo ke boits'oaro ba bona ka cabergoline (Feie. 2B). Lintlha tse peli ka botsona li ne li sa amanang haholo (p = 0.117).

Linako tsa boikhopotso

Ho ne ho se na litlamorao tse kholo tsa monyetla oa ho hapa, boholo ba meputso e ka bang teng, kapa boholo ba tahlehelo e ka bang teng linakong tsa lipuisano tsa bankakarolo (kaofela F <1), mme ha ho na phello ea bohlokoa ea cabergoline ka nako ea karabelo (p = 0.204). Ha ho na litlamorao tse kholo tsa tšebelisano ea lithethefatsi, thepa ea papali ea chelete, le boemo ba SS ka linako tsa boikoetliso (kaofela p > 0.3).

Boleng bo lebelletsoeng le kotsi

Boleng bo lebelletsoeng ba marang-rang bo ne bo amana haholo le khetho e lekantsoeng ka tlasa mofuta oa placebo le cabergoline (r2adj = 0.890, p <0.001; r2adj = 0.737, p = 0.004; li-coefficients tse sa fapane haholo, p = 0.924). Kotsi ea kotsi ea "Gamble" (SD) e ne e sa amane haholo le khetho e lekantsoeng tlas'a maemo a lithethefatsi (p > 0.5). Ho ne ho se na phello ea bohlokoa ea lithethefatsi ho boleng bo lebelletsoeng bo bolelang (p = 0.582) kapa ho bolela ho beha menyetla ea ho becha ho khethiloeng (p = 0.376). Hape ha ho na tšebelisano e kholo ea lithethefatsi le lintlha tsa SS ka mehato ena (p > 0.2).

Phapang e fapaneng le motho ka mong

Ha re nahana ka datha ho tsoa lenaneong la placebo feela, ho ne ho se na tšebelisano e kholo lipakeng tsa lintlha tsa SS le litlamorao tsa thepa ea papali ea chelete (pwin, boholo ba meputso le tahlehelo e lebelletsoeng) ka khetho (tsohle p > 0.1). Hape ho ne ho se na likamano tsa bohlokoa lipakeng tsa mekhahlelo efe kapa efe ea khetho (ke hore, ho bolela kotsi ea papali ea chelete e khethiloeng, ho bolela papali ea chelete e khethiloeng e lebelletsoeng, le lintlha tse hapiloeng kaofela) le lintlha tsa SS (tsohle p > 0.1). Leha ho le joalo, ho ne ho na le kamano e mpe e mpe lipakeng tsa lintlha tsa SS le nako ea lipuisano sebakeng sa placebo (r = -0.479, p = 0.038; Feie. 3A), e neng e sa bonahale tlasa k'habeche (p > 0.5). Mehato e phetoang ea ANOVA ea nako ea lipuisano e bolelang le lintlha tse lipakeng tsa sehlopha sa SS e senotse hore lithuto tse tlase tsa SS li bonts'itse tloaelo ea ho arabela butle haholo nakong ea seboka sa placebo feela (tšebelisano-'moho ea sehlopha sa SS, F(1,17) = 4.404, p = 0.0511; Feie. 3B).

Setšoantšo sa 3.  

ANako ea khetho ea ho nahana ka boleng ba sebaka sa placebo e hokahane hampe le lintlha tsa UPPS SS (r = -0.479, p = 0.038). B, Lithuto tsa LSS li bonts'itse linako tsa ho nahana butle butle ho feta lithuto tsa HSS ka lithuto tsa placebo feela. **p <0.001, *p = 0.023. ...

Liphetho tse ka u amang

Boemong bo sa hlophisehileng, barupeluoa ba ne ba khutsitse haholo (p = 0.033) le ho otsela (p = 0.017), hape e tlalehiloe hlooho e bohloko ho feta (p = 0.020), k'habeche e amanang le placebo. Leha ho le joalo, phetoho ho e 'ngoe ea mehato ena e ne e sa amane haholo le e' ngoe ea litheko tsa litlamorao tsa lithethefatsi, kapa lintlha tse tlalehiloeng tsa SS (kaofela p > 0.4), ho fana ka maikutlo a hore sena ha se tlatsetse ho litlamorao tse kholo tsa cabergoline kapa liphapang tsa motho ka mong ka phello ea cabergoline. Ha ho litlamorao tse matla tsa lithethefatsi tse fumanoeng ho litla-morao tse ling tse ka bang teng mmeleng (p > 0.25), maikutlo, kapa ho ama sekala (p > 0.16; Mehato e 26 ka botlalo) le tsebo ea ts'ebeliso ea lithethefatsi / placebo ha ea fumanoa e fapane haholo lipakeng tsa linako tsa liteko (t1,18 = 1.681, p = 0.110).

Puisano

In thuto ena, re fumane litlamorao tse kholo tsa tekanyetso e le 'ngoe ea cabon ea agonist ea D2 / D3 mabapi le ho etsa liqeto tlasa maemo a sa tsitsang kapa a kotsi, eo, ka bomalimabe, e neng e itšetleha ka phapang ea motheo mokhoeng oa ho itlaleha oa SS. Ka kakaretso, sephetho sa "cabergoline" e ne e le ho fetisa modumo ea boits'oaro ba khetho ho latela matšoao a hlakileng mabapi le monyetla oa ho hapa, mme ka nako e ts'oanang ho fumana phetisetso ea khetho ho latela tlhaiso-leseling ka boholo ba tahlehelo e ka bang teng (Feie. 1). Habohlokoa le ho feta, boholo ba phello ea lithethefatsi bo ile ba ntlafatsoa haholo ke lintlha tsa motheo tsa UPPS tsa SS ((Feie. 2) - re ikarabella bakeng sa karolo e kholo ea phapang e kholo litlamong tsa bobeli ba k'habergoline ka ho etsa liqeto tse kotsi (∼23- 34%). Maemong ana ka bobeli, batho ba tlalehileng maemo a tlase a mofuta oa SS ba bonts'itse tšusumetso e matla ea khabergoline ka boitšoaro ba bona ba khetho.

'Mele oa bopaki bo tsoang ho lithuto tsa batho le tsa liphoofolo o hlahisa phapang lipakeng tsa li-neurotransmission tsa D2R-mediated ho phapang e le' ngoe ea boitšoaro ba SS (Ratsma et al., 2001; Blanchard et al., 2009; Hamidovic et al., 2009; Gjedde et al., 2010). Leha ho le joalo, liteko tsa pejana tsa ho sebelisa khetho e kotsi ka kotloloho ho liphoofolo le batho ba sebelisang lithethefatsi tsa D2ergic li hlahisitse litholoana tse sa lumellaneng (Hamidovic et al., 2008; Riba et al., 2008; St. Onge le Floresco, 2009; Simone et al., 2011). Sena se ka 'na sa bakoa ke ho se tšoane ka litlhaloso tsa kotsi (mohlala, ho fapana hoa menyetla e kholo ea meputso vs monyetla oa sephetho se phetlelang), kapa ka lebaka la litlamorao tse tlisoang ke tekanyetso ketsong ea lithethefatsi.

Ho ba teng ha li-receptors tsa presynaptic le tsa postynaptic D2 ho bolela hore tlatsetso ea lithethefatsi e ka ba le litlamorao tse hanyetsanang phetisong ea dopaminergic (Usiello et al., 2000). Le ha li-presynaptic D2 autoreceptors li beha hampe likarabo tsa DA tsa phasic, li-D2R tsa li-postynaptic li laola lipalo tsa DA tsa tonic tse amehang ponts'ong ea kotsi (Mosa, 1991; Fiorillo et al., 2003; Schmitz et al., 2003; Schultz, 2010). Sena se lebisa mathateng a ho toloka litlamorao tsa lithethefatsi, haholo-holo ka litekanyetso tse tlase moo ho ka khothalletsoang feela li-inhibitory autoreceptors tse phahameng. Re lekile ho netefatsa ts'usumetso ea li-DynNUMXR tsa postynaptic ka ho sebelisa D2 / D2 agonist agonist cabergoline (Kvernmo et al., 2006), ka tekanyetso e phahameng ho feta thuto e fetileng ha ho ne ho bonoa litlamorao tse sa lumellaneng tsa lithethefatsi (Frank le O'Reilly, 2006). Ho sebelisa mask ho Domperidone ho ne ho sebelisetsoa ho fokotsa litlamorao tse ka bang kotsi tse kang ho nyekeloa ke pelo, 'me lithuto ka kakaretso li ne li sa tsebe tšebeliso ea lithethefatsi / placebo. Ha rea ​​ka ra fumana bopaki ba tšusumetso e mpe ea lithethefatsi, eo pele e neng e nkuoa e le sesupo sa ts'ebetso ea lithethefatsi pele ho nako (mohlala, Hamidovic et al., 2008).

Ho fumana ha rona phello e kholo ea k'habeche ho LSSs ho ka utloahala ho makatsa ha ho fanoa ka litlaleho tse fetileng tsa hore li-HSS li bonts'a likarabo tse eketsehileng tsa mmele le subjective ho li-dopaminergic tse matlafatsang, joalo ka amphetamine (Kelly et al., 2006; Stoops et al., 2007), le hore lintlha tsa SS li lumellana hantle le tokollo ea DA ea amphetamine e hlahisitseng striatum (Riccardi et al., 2006). Leha ho le joalo, Gjedde le basebetsi-mmoho ba sa tsoa ngangisana motheong oa bopaki ba PET ba hore li-LSS li na le maemo a tlase a D2 / D3 receptor density le litekanyetso tse tlase tsa DA ho feta balekane ba bona ba HSS, hore "phaello" ea tsamaiso ea DA (reacaction to dopamine) in striatum e amana ka kotloloho le lintlha tsa SS (Gjedde et al., 2010). Kahoo barupeli ba LSS ba ka ba le phaello e phahameng ea DA. Li-agonists tsa Direct D2, joalo ka ha li sebelisitsoe thutong ea rona, ka hona li ka lebelloa ho fana ka litlamorao tse kholo ho batho bana.

Ho ts'ehetsa maikutlo ana, ho na le bopaki bo bong ba hore li-LSS li ka ba le maemo a tlase a mokha oa DA ho feta li-HSS. Li-LSS li bonts'a maemo a phahameng a liplatele tsa monoamine oxidase (catabolist ea DA; Zuckerman, 1985; Carrasco et al., 1999), le boemo ba LSS bo amahantsoe le tšebetso e fokolang ea dopa decarboxylase (DDC; enzymme e fokotsa tekanyetso bakeng sa synthesis ea DA) ho striatum; ka ho fapana ka bobeli ho CDD gene ka boeona (Derringer et al., 2010) le polymorphism ea Taq1a (Ratsma et al., 2001; Laakso et al., 2005; Eisenberg et al., 2007). Leha ho le joalo, hajoale ha ho na bopaki ba "phaello" e eketsehileng (mohlala, ka li-receptor hypersensitivity) ho li-neurotransmission tsa DA ho batho ba LSS ka lebaka la sena.

Lithuto tsa rona li na le meeli. Taba ea pele, cabergoline ha e na taba e tobileng tumellanong ea eona ea D2R. E boetse e na le ts'ebetso e fokolang ea agonist ho 5-HT2A, 5-HT2B, le li-receptor tsa D1 (Kvernmo et al., 2006). Ka hona ha ho khonehe ho ba le bonnete bo felletseng ka mochine o kenyang litlamorao tsa boitšoaro ba oona. Taba ea bobeli, leha re sa ka ra fumana bopaki ba ho tšehetsa phello ea ho se tšoane hoa mantlha kapa ho eketseha hoa maemo a amanang le D2 mabapi le "menyetla" mabapi le phapang lipakeng tsa liphetho tse ka bang teng, maemong ana a mane ha ho bapisoa ho ne ho kentsoe ts'ebetso, ka hona sephetho sena ha sea lokela ho nkuoa joalo ka sephetho. . Liteko tsa nako e tlang li sebelisa likotsi tse ngata tsa papali ea chelete li ka mphenya sena ka ho eketsehileng. Ntle le moo, ha re fuoa mohlala oa lithuto tsa 20, thuto e kanna ea se be le sephetho se nepahetseng mme sephetho sa eona se ka una molemo ho phetolelong e tlang.

Leha e le bohlokoa bo hlakileng ba tleliniki, ho laola lintho tse entsoeng tlasa kotsi e fumanehang maemong a kotsing ha e sa qaptjoa ho batho le liphoofolo (Winstanley, 2011). Thutong ena, re fana ka lekhetlo la pele leo ka lona tsebo ea rona ea mantlha ea motheo ea tsebo ea mantlha ea SS e amang tsela eo manolo a meriana a fetotseng boitšoaro ba hae bo behang kotsing. Liphumano tsena li hatisa bohlokoa ba ho nahana ka liphapang tsa batho ka bomong, joalo ka SS, ha ba etsa lipatlisiso tsa ho etsa liqeto tse kotsi, 'me ba ka ba le bohlokoa ba nts'etsopele ea litlhare tsa meriana bakeng sa mafu a kenyelletsang ho nka kotsi e ngata, joalo ka ho becha ha methapo ea kutlo.

Mongolo o botlaaseng ba leqephe

Mosebetsi ona o tšehelitsoe ke Wellcome Trust le Lekhotla la United Kingdom Medical Research Council.

Bangoli ha ba phatlalatse lithahasello tsa lichelete.

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