Dopamine Modulates-Kutenga Kugwiritsa Ntchito Monga Mchitidwe Wofuna Kulimbana Ndi Zowona (2013)

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

do:  10.1523 / JNEUROSCI.5587-12.2013

PMCID: PMC3735881

Kudalirika

Kufunafuna kwamtundu, kumawonetsedwa ngati kufunika kwa mitundu yosiyanasiyana, yovuta, komanso kumvetsetsa kwakukulu, kumayimira kuyendetsa kosagwirizana kwa hedonic pakufufuza kwamakhalidwe a anthu. Zimakhudzana ndi chiwopsezo chowonjezeka chamakhalidwe osiyanasiyana kuphatikiza kugwiritsa ntchito mankhwala osokoneza bongo, kutchova juga, komanso kuchita chiwerewere. Kusiyana kwapadera pakudziwona komwe kumakhala komwe kumapangitsa kuti pakhale chidwi chaphatikizidwa ndi ntchito ya dopamine ya ubongo, makamaka ku D2-ngati ma receptors, koma pakadali pano palibe umboni wotsimikizira kuti gawo la dopamine limapangitsa chidwi mwa anthu. Apa, tafufuza zotsatira za kabati ya agonist yosankhidwa ya D2 / D3 pakugwiritsa ntchito ntchito yowoneka bwino yoopsa mwa anthu athanzi pogwiritsa ntchito kapangidwe kake kamene kali m'manja mwa placebo.

Cabergoline anathandizira kwambiri momwe ophunzira anaphatikizira mawu omasulira osiyanasiyana okhudza kuthekera ndi kutayika posankha pakati pazosankha zoyenderana ndi zotsatira zosatsimikizika. Zofunikira, zotsatirazi zinali zodalira kwambiri pazomwe zimafunikira. Pazonse, kabergoline anawonjezera chidwi cha kusankha kudziwa zambiri zakupambana; ndikumachepetsa kusankhana malinga ndi kuchuluka kwa zotayika zomwe zimayenderana ndi zosankha zosiyanasiyana. Tiye amene anali ndi zotsatira zazikulu za mankhwalawo adawonedwa mwa omwe ali ndi chidwi chofuna kudziwa zambiri. Zotsatira izi zimapereka umboni kuti njira zoika anthu pachiwopsezo zitha kupezedwa mwachindunji ndi dopaminergic mankhwala, koma kuti kutha kwa kunyengerera koteroko kumadalira pakusiyana kwenikweni pakukonda kotenga chidwi.t. Izi zikutsindika kufunika koganizira kusiyana komwe munthu akusankha popanga njira zowopsa, ndipo zingakhale zofunikira pakukula kwa mankhwala opatsirana pamatenda omwe amayambitsa kutenga chiopsezo kwambiri mwa anthu, monga njuga zamatenda.

Introduction

Pali mipata yochititsa chidwi pakati pa nkhani zopanga zisankho komanso zochita za anthu tsiku ndi tsiku (Kahneman ndi Tversky, 1984). Mwachitsanzo, nchiyani chomwe chimalimbikitsa anthu kuti ayambe kukwera m'mwamba, kudya zakudya zonunkhira, kapena mzere kwa maola ambiri kuti akwere ma rollercoaster omwe amakhala mphindi? Lingaliro lalikulu pakuphunzira za umunthu kwakhala kukhalapo kwa chikhalidwe chokhudzidwa ndi hedonic drive yofunafuna "zomverera" zazikulu, komanso kulekerera kuthekera kwa zotsatira zomwe zingakhalepo (pachiwopsezo) chifukwa cha zochitika zamtunduwu (Zuckerman, 1974).

Kuthandizira lingaliro lamtundu umodzi wokhudzana ndi kusunthika kwa chidwi cha zochitika pamalingaliro am'malingaliro amachokera pakupenyerera kwa kusuta kwa ndudu, mowa, ndi kumwa khofi; kugwiritsa ntchito mankhwala; ndi mchitidwe oopsa wogonana mwa akulu ndi achinyamata.Carmody et al., 1985; Gillespie et al., 2012; Mfumu ndi al., 2012). Umboni wosinthika mosalekeza pachiwopsezo choperekedwa umaperekedwa ndi mgwirizano pakati pa anthu omwe amadziona kuti ali ndi chidwi chofuna kudzimva (SS) komanso kuchuluka kwazomwe zimatha kugwiritsa ntchito mankhwala osokoneza bongo, kuchita juga kwambiri, komanso zizolowezi zina zoyipa (Coventry ndi Brown, 1993; Roberti, 2004; Ersche et al., 2010).

Kusiyana kwapadera pakusaka kotengeka kwalumikizidwa ndi ubongo dopamine (DA) ntchito, makamaka pa D2-like (D2 / D3 / D4) receptors. Mwa anthu, mtundu wa SS umalumikizidwa ndi kusintha kwa majini ku D2 ndi D4 receptor loci (Ratsma et al., 2001; Hamidovic et al., 2009; Derringer et al., 2010), ndi striatal D2 / 3 receptor "kupezeka," monga akuyerekezera kudzera 11C-raclopride PET (Gjedde et al., 2010). M'makola, wogwira ntchito mwamphamvu poyankha mphotho zopanda malingaliro zawonetsedwa kuti akumvera zonse za antipsychotic flupenthixol (a D1-D5 receptor antagonist) ndi amphetamine (Olsen ndi Winder, 2009; Shin et al., 2010). Komabe, pakalibe umboni wopatsa chidwi mwa anthu pa udindo wa DA pakusintha machitidwe ngati gawo la ntchito ya SS.

Phunziroli, tinagwiritsa ntchito kabulogoline - mankhwala omwe ali ndi ubale wofanana komanso wogwirizana kwambiri ndi ma D2 ngati receptors kuposa othandizira kale m'maphunziro akale (Kvernmo et al., 2006) - kuti athandize zotsatira zomwe sizinawonekere pamankhwala omwe amachititsa kuti D2 agonists iwonongeke pachiwopsezo.Hamidovic et al., 2008; Riba et al., 2008). Zofunikanso, tidaganiziranso kuthekera kwakusintha kwa zotsatira za mankhwala ndikudziuza wekha SS.

Kutengera luso lolingalira logwira ntchito kuchokera kwa anthu odwala omwe akupatsidwa chithandizo cha dopamine agonist (Abler et al., 2009), tidaneneratu kuti kabulogoline ikhoza kukulitsa chidwi chazambiri zokhudzana ndi mphotho, ngakhale kuti ikuchepetsa zotsatira za zotsatirapo zoyipa, munthawi yazovuta kapena posankha. Ngakhale maphunziro am'mbuyomu adanenapo zambiri pakuyankha kwa a DAergic othandizira omwe ali odzipereka odzipereka a SS (HSS), akuti nawonso anthu omwe akufuna kudziwa zambiri atha kukhala ndi njira yayikulu yolemerera DA (Gjedde et al., 2010; wonaninso Zokambirana), yomwe ikanalosera kuyankha kwakukulu kwa agonists apadera m'mitu yotsika ya SS (LSS). Tidapeza kuti kabergoline adakhudzika kwambiri pakumvetsetsa kwakasankhidwa kudziwa zambiri zokhuza kuthekera ndi kutayika, ndikuti, modabwitsa, kukula kwa zotsatirazi kudalira mwamphamvu kusiyana komwe kumayambira mu SS yomwe inadziwuza.

Zida ndi njira

Ophunzira.

Omwe anali nawo anali amuna achikulire a 20 (zaka zoyenera, zaka za 26.7; SD, zaka za 5.67). Njira zochotsedwera zinali ndi matenda ena aliwonse, pakachitika pano kapena mbiri yakale ya matenda amisala, komanso / kapena kugwiritsa ntchito mankhwala osokoneza bongo kangapo kamodzi m'miyezi yapitayi ya 6. Maphunziro onse adapereka chilolezo chodzilemba ndipo kafukufukuyu adavomerezedwa ndi komiti ya University College London.

Kupanga.

Kafukufukuyu adachitika molingana ndi kapangidwe ka kaimidwe kawiri-kochita khungu. Pa gawo loyamba, ophunzira adayang'aniridwa chifukwa chophwanya malamulo, adalandira chilolezo, ndipo adazolowera Paradigm yowopsa yochita kusankha. Omasulira adamaliziranso Barratt Impulsivity Scale (BIS-11) ndi UPPS (kufulumizitsa; (kusowa) kukonzekereratu; (kusowa) chipiriro; kusaka chidwiPatton et al., 1995; Whiteside ndi Lynam, 2001), kuchuluka kwa kukumbukira kukumbukira (kupitilira manambala molingana ndi Wechsler Adult Intelligence Scale-III; The Psychological Corporation, 1997), ndi muyeso wokhazikika wosagwiritsa ntchito mawu (Raven's 12-item Advanced Progressive Matrices; Pearson Education, 2010 ). Pa gawo lachiwiri ndi lachitatu (mayeso), ophunzira adafika m'mawa ndipo adapatsidwa piritsi lokhala ndi 20 mg ya domperidone (antiemetic), yotsatiridwa mphindi 20 pambuyo pake ndi 1.5 mg wa cabergoline kapena placebo (mapiritsi a mankhwala ndi placebo anali osadziwika ). Mlingowu udasankhidwa kuti ukhale woposa womwe udaperekedwa mu kafukufuku wakale pomwe zotsatira zosagwirizana pamakhalidwe zimawonedwa (1.25 mg; Frank ndi O'Reilly, 2006,, ndi kuphatikiza kwa domperidone maski kuti tithane ndi zotsatira zoyipa za thupi.

Kulola kuchuluka kwa plasma ya mankhwala kufikira kwambiri, kuyezetsa kunayamba 2 h pambuyo pakumeza piritsi lachiwiri (Andreotti et al., 1995). Pa gawo lililonse lazoyeserera, ophunzira adamaliza mawonekedwe a kusintha kwa machitidwe, kukhudza, zolakwika, ndi chidziwitso cha mankhwalawa / placebo. Dongosolo la mankhwala / placebo linali lololekana pamaphunziro onse, ndipo inali ndi nthawi yochepa yosamba ya masabata a 2 pakati pa magawo awiri oyeserera.

Parisigm yopanga zisankho.

Kupanga chisankho mwachisawawa kunayesedwa pogwiritsa ntchito chisankho chogwirizana ndi Roger ndi anzawo kale (Rogers et al., 2003; Murphy et al., 2008). Pang'onopang'ono, pamayeso aliwonse, mitu yomwe amafunika kuti azisankha pakati pa njuga ziwiri zomwe zimaperekedwa nthawi yomweyo. Kutchova njuga kulikonse kunayimiriridwa ndi histogram, kutalika kwake komwe kunkawonetsa kuthekera kopambana kwa mfundo zingapo. Kukula kwa zotheka kunawonetsedwa pamtunda pamwamba pa histogram iliyonse, ndikukula kwa zotayika zomwe zikuwonetsedwa pansi pazofiyira.

Pamayeso aliwonse, kutchova njuga kamodzi kumakhala ndi 50: 50 mwayi wopambana kapena wotaya 10 mfundo (kutchova "chiwongolero"), kuyembekezera phindu la 0). Kutchova njuga kwa njira ina ("kuyesera") kosiyanasiyana (1) yopambana .

Izi kutchova njuga zidawoloka kwathunthu, ndikupereka mitundu isanu ndi itatu ya mayesero. Maganizo owoneka (kupambana / kutaya) adaperekedwa pambuyo kusankha kulikonse, ndipo mfundo zowunikiridwa zidaperekedwa pamlandu wotsatira.

Omasulira adamaliza kuyesa magawo anayi a mayeso a 20, ndipo adalangizidwa kuti kuchuluka kwakukulu komwe adakwanitsa kusinthidwa kudzasinthidwa kukhala pence ndikulipidwa kumapeto kwa ntchitoyi ngati bonasi ya ndalama. Nthawi zokumbukira (mayankho) zinajambulidwa.

Kusanthula deta.

Zomwe adasanthula zidafotokozedwa ngati gawo la mtundu wa "zoyeserera" monga ntchito yopambana, kukula kwa phindu, ndi kukula kwa zotayika. Makamaka, zosankha zolingana zinalowetsedwa mu ANOVA yochitira zinthu mobwerezabwereza zinthu zomwe zingapangidwe ndi mankhwala, kuthekera kopambana, kukula kwa zopambana zomwe zikuyembekezeredwa, ndi kukula kwa zotayika. Chithandizo cha mankhwalawa chidaphatikizidwa ngati chinthu chapakati pazophunzirazo. Kusanthula kofananako kunachitidwa kwa yankho la nthawi yanthawi. Zisankho zidawunikiranso mogwirizana ndi kuchuluka kwa magwiritsidwe ake oyenera komanso "kuwopsa" kwa njuga zomwe zidasankhidwa, zomalizirazo zimafotokozedwa kuti ndi SD ya zothekera zilizonse zomwe zasankhidwa. Zofufuza zosavuta zomwe zidafotokozedwa zidali kudzera m'mafanizo awiriwa pogwiritsa ntchito kusintha kwa Bonferroni pakuyerekeza kambiri. Zambiri kuchokera pamutu umodzi zidawonongeka motero sizimaphatikizidwa pakuwunika.

Results

Gawo losankha

Palibe zotsatira zazikulu zamalamulo azakumwa, kapena kuyanjana pakati pazinthu zamtundu wa mankhwala ndi mankhwala, zidapezeka (zonse ziwiri p > 0.09). Kuti mukulitse mphamvu, mankhwala osokoneza bongo adatayidwa kuchokera pachitsanzo posanthula pambuyo pake. Mwambiri, omwe adatenga nawo mbali adasankha juga ya "zoyeserera" pafupipafupi pomwe mwayi wopambana unali wapamwamba poyerekeza ndi pomwe unali wotsika (F(1,18) = 40.305, p <0.001, ηp2 = 0.691). Njira iyi popangira zisankho idakokedwa kwambiri pansi pa kabergoline wokhudzana ndi placebo (mankhwala * omwe angathe kupambana; F(1,18) = 6.733, p = 0.018, ηp2 = 0.272).

Omasulira adasankhanso kutchova juga "koyesera" nthawi zambiri pomwe phindu limakhala lalikulu kuposa momwe phindu limayembekezera linali laling'ono (F(1,18) = 50.522, p <0.001, ηp2 = 0.736). Komabe, panalibe umboni wamphamvu wosonyeza kuti kusankha kumeneku kunali kosiyana ndi kabulogoline (kukula * kwa mankhwala * omwe amapezeka, F(1,18) = 3.615, p = 0.074).

Pomaliza, odzipereka adasankha kutchova juga "koyesera" nthawi zambiri pomwe kutayika kwake kunali kwakukulu kuposa momwe kutayika kwake kunali kochepa (F(1,18) = 56.486, p = 0.001, ηp2 = 0.758). Njira iyi popangira zisankho idakonzedwa kwambiri ndi kabergoline (kukula * kwa mankhwala * F(1,18) = 6.773, p = 0.018, ηp2 = 0.273). Mwachidule pazotsatira izi Chithunzi 1.

Chithunzi 1.  

Sankhani kuchuluka kwa kutchova njuga "zoyeserera" molingana ndi kutchova njuga, pansi pa placebo ndi kabergoline. **p <0.001, *p <0.05.

Panalibe zotsatira za kabergoline paliponse pazosankha zamasewera "oyeserera" (p = 0.480), ndipo palibe machitidwe apamwamba apadongosolo okhudzana ndi zomwe zimapangitsa mankhwala (onse p > 0.2).

Kuchita ndi kusiyana kwa anthu

UPPS SS yothandizira idapezeka ikulumikizana kwambiri ndi zotsatirapo zonse za mankhwala pazisankho [mankhwala * kuthekera kopambana (pwin) * mphambu wa SS, F(1,17) = 6.331, p = 0.022, ηp2 = 0.271; kutayika kwa * mankhwala * SS score, F(1,17) = 11.501, p = 0.003, ηp2 = 0.404; poyerekeza, zaka, IQ yowerengeka, kuchuluka kwa kukumbukira, ndi kudziwonetsa kwathunthu zonse zinali zonse p > 0.3].

Zowonadi, kuyanjana kwa mankhwala ndi zinthu zomwe zimayambitsa ndi kukula kwake ndikuwoneka kuti zimayendetsedwa makamaka zimayendetsedwa ndi maphunziro omwe ali ndi zambiri zotsikira za SS (Chith. 2A). Kupenda kosavuta kunavumbula kuti, pofotokozera magulu a LSS ndi HSS ndi kugawanika kwapakati pa masitepe a SS, a LSSs adasankha njira zowonera "zowunika" nthawi yayitali ngati (F(1,17) = 5.996, p = 0.025) ndi ocheperako pomwe chidutswa chidali chochepa (F(1,17) = 7.808, p = 0.012) pa mankhwala okhudzana ndi placebo. Mosiyana ndi izi, gulu la HSS silinasiyane posankha mitundu ing'ono kapena yayikulu pwinoko pakati pa mankhwala ndi placebo (p > 0.2).

Chithunzi 2.  

A, Zotsatira za kabergoline pamachitidwe omwe amasankhidwa, agawika m'magulu a HSS ndi LSS kudzera pagawidwe lapakatikati la UPPS SS subscale scores. Kwa maphunziro a LSS okha, kusinthasintha kwamakhalidwe osankhika adakokomezedwa kwambiri kutengera chidziwitso chokhudza ...

Ma LSS adawonetseranso njira zosasankha pakusankha njuga zochepa pomwe kutayika kungakhale kochepa (F(1,17) = 4.262, p = 0.0546), ndi kutchova njuga zambiri pamene kuthekera kotayika kungakhale kwakukulu (F(1,17) = 3.052, p = 0.090; Chith. 2A), pa kabergoline poyerekeza ndi placebo. Palibe chilichonse mwazotsatira izi zomwe sizinafanane ndi gulu la HSS (p > 0.2). Magulu a HSS ndi LSS sanasiyane kwambiri potengera zina zilizonse zomwe anthu amadzinenera kuti ali ndi chidwi, zaka, kuchuluka kwa manambala, kapena IQ yoyerekeza (yonse p > 0.3).

Kuti muthane ndi zotsatirazi pamlingo wokhawokha, magawo awiri a mphamvu zamankhwala pamasankho amawerengedwa pamutu uliwonse (kusiyanasiyana kwakukulu kwa kusintha kwa kuthekera kopambana, kapena kukula kwa kutayika, pamalingaliro osankha oyeserera kutchova njuga pakati pa mankhwala ndi malo a placebo. Kulemba kwa SS kunapezeka kuti kukuwonetseratu zofunikira zonse izi (r2adj = 0.229, p = 0.022; r2adj = 0.336, p = 0.005; kusanthula kwakanthawi), koma osaganizira IQ, kuchuluka kwa manambala, kapena mtundu wina wazodzilengeza (zonse p > 0.1). Pazochitika zonsezi, ophunzira omwe anali ndi chidwi chotsata chidwi adakhudzidwa kwambiri ndi machitidwe awo ndi cabergoline (Chith. 2B). Zinthu ziwiri zomwezo sizinali zofanana kwambiri (p = 0.117).

Nthawi zokumbukira

Panalibe zovuta zazikulu zakupambana, kukula kwa zopindulitsa, kapena kukula kwa zotayika munthawi yolingalira za ophunzira (zonse F <1), ndipo palibe phindu lililonse la kabergoline munthawi yoyankha (p = 0.204). Panalibe kuyanjana kwakukulu kwa mankhwala, kutchova njuga, ndi kuyesa kwa SS pazowongolera nthawi (onse p > 0.3).

Mtengo woyembekezeredwa ndi chiwopsezo

Mtengo woyembekezeredwa wa njuga unali wofanana ndendende ndi kusankhidwa kwa mitundu yonse ya placebo ndi kabergoline (r2adj = 0.890, p <0.001; r2adj = 0.737, p = 0.004; ma coefficients osiyana kwambiri, p = 0.924). Kuchepetsa chiopsezo cha jekete (SD) sikunali kogwirizana kwambiri ndi kusankha kwa mitundu yonse ya mankhwala (p > 0.5). Panalibe zotsatira zofunikira za mankhwala pamtengo woyembekezereka (p = 0.582) kapena kutanthauza chiopsezo cha njuga zosankhidwa (p = 0.376). Panalibe kuyanjananso kwakukulu kwa mankhwala ndi SS alama pazinthu izi (p > 0.2).

Kusiyana kwa anthu payokha

Mukamaganizira za gawo la placebo lokha, panalibe kuyanjana kwakukulu pakati pa gawo la SS ndi zotsatira za kutchova njuga (malamba, kukula kwa ziyembekezo ndi kutayika) posankha (zonse p > 0.1). Panalibe ubale wofunikira pakati pa magawo aliwonse osankha (mwachitsanzo, kutanthauza kukhala pachiwopsezo cha kutchova juga, kutanthauza kutchova juga komwe kwasankhidwa, ndi mfundo zonse zomwe zapambana) ndi ziwonetsero za SS (zonse p > 0.1). Panali kulumikizana kwakukulu pakati pa kuchuluka kwa SS ndikutanthauza nthawi yolingalira pa placebo (r = -0.479, p = 0.038; Chith. 3A), yomwe sizinkawoneka pansi pa kabergoline (p > 0.5). ANOVA yowunika mobwerezabwereza yamkati yolingalira mozama pakati pa maphunziro a gulu la SS idawulula kuti maphunziro otsika a SS adawonetsa njira yoyankhira pang'onopang'ono pagawo la placebo kokha (kulumikizana ndi gulu la SS, F(1,17) = 4.404, p = 0.0511; Chith. 3B).

Chithunzi 3.  

A, Kutanthauza kusinkhasinkha nthawi yomwe ili pa placebo sikugwirizana bwino ndi UPPS SS score (r = -0.479, p = 0.038). B, Maphunziro a LSS adawonetsa kuwongolera kosankha pang'onopang'ono kuposa maphunziro a HSS pamagawo a placebo okha. **p <0.001, *p = 0.023. ...

Zotsatira zake

Atafika pamalo osalongosoka, otenga nawo mbali anali odekha (p = 0.033) ndi kugona (p = 0.017), ndipo adanenanso zowonjezera mutu (p = 0.020), pa kabergogine wachibale ndi placebo. Komabe, kusintha pa chilichonse mwanjira izi sikunali kogwirizana kwambiri ndi mankhwala amtundu wa mankhwala, kapena chodzilemba cha SS (zonse p > 0.4), ndikuwonetsa kuti izi sizinapangitse zotsatira zoyipa za cabergoline kapena kusiyanasiyana komwe kumachitika chifukwa cha kabergoline. Palibe zovuta zomwe mankhwalawa adapeza pazovuta zina zilizonse (p > 0.25), kusangalala, kapena kukhudza masikelop > 0.16; Miyezo ya 26 yathunthu) komanso kudziwa kwamankhwala osokoneza bongo / placebo sikunapezeke mosiyana kwambiri pakati pa magawo oyeserera (t1,18 = 1.681, p = 0.110).

Kukambirana

In Phunziroli, tapeza zotsatira zoyipa za kaboni imodzi ya D2 / D3 agonist pa kupanga zisankho pamikhalidwe yosatsimikiza kapena yowopsa, yomwe, mwankhanza, zimadalira pazosiyana koyambira podziuza za SS. Pazonse, mphamvu ya kabergoline inali yowonjezera kusintha kwa zosankha malinga ndi kutanthauzira kotsimikizika kopambana, komanso munthawi yomweyo kutsata kusinthaku malinga ndi chidziwitso cha kukula kwa kutayika (Chith. 1). Makamaka, kukula kwa mankhwalawa kunakonzedwa kwakukulu ndi baseline UPPS SS score (Chith. 2, - takhala ndikuwerengera kwakukulu pakusintha kwazotsatira zonse ziwiri za kabergogine pa kupanga zisankho zowopsa (∼23-34%). M'magawo onse awiriwa, anthu omwe adafotokoza za SS omwe ali otsika kwambiri adawonetsa mphamvu yamachitidwe awo.

Umboni wokwanira kuchokera ku maphunziro a anthu ndi zinyama umayambitsa kusinthika kwa ma DotNUMXR-mediated neurotransication mukusiyanasiyana kwa chikhalidwe cha SS (Ratsma et al., 2001; Blanchard et al., 2009; Hamidovic et al., 2009; Gjedde et al., 2010). Komabe, kuyesa kwapakalepo kuwongolera chisankho chowopsa mwachindunji mu nyama zonse komanso anthu omwe amagwiritsa ntchito mankhwala a D2ergic atulutsa zotsatira zosagwirizana (Hamidovic et al., 2008; Riba et al., 2008; St. Onge ndi Floresco, 2009; Simon et al., 2011). Izi mwina zitha kuchitika chifukwa cha kusiyanasiyana kwa matanthauzidwe a chiopsezo (mwachitsanzo, kusinthika mu kuthekera kwa mphotho yayikulu motsutsana ndi chotulukapo chotsatira), kapena chifukwa cha zotsatira zomwe zimadalira mankhwala.

Kukhalapo kwa onse a presynaptic ndi postynaptic D2 receptors kumatanthauza kuti kuwonjezera kwa mankhwala kungakhale ndi zotsutsana ndi kufalikira kwa dopaminergic (Usiello et al., 2000). Pomwe presynaptic D2 autoreceptors imayendetsa molakwika mayankho apasic DA, ma postynaptic D2Rs amawongolera tonic DA kuwonetsa omwe akuwonetsa zoopsa (Chisomo, 1991; Fiorillo et al., 2003; Schmitz et al., 2003; Schultz, 2010). Izi zimabweretsa zovuta pakutanthauzira mankhwalawa, makamaka pa Mlingo wocheperako komwe okhawo omwe ali ndi mphamvu zapamwamba kwambiri omwe angalimbikitsidwe. Tinayesa kuwonetsetsa kukhudzidwa kwa postynaptic D2Rs pogwiritsa ntchito D2 / D3 agonist agonist kabergoline (Kvernmo et al., 2006), pa mlingo wapamwamba kuposa kafukufuku wam'mbuyomu pomwe zotsatira zosagwirizana ndi mankhwala zimawonedwa (Frank ndi O'Reilly, 2006). Domperidone maski idagwiritsidwa ntchito kuchepetsa zotsatira zoyipa zomwe sizingachitike, monga nseru, ndipo maphunziro onse sanadziwe za mankhwalawa / mankhwalawa. Sitinapezenso umboni wakukhudzidwa kwa mankhwalawa, komwe kale kumatengedwa ngati chisonyezo cha precomaptic drug action (mwachitsanzo, Hamidovic et al., 2008).

Kupeza kwathu kwamphamvu kwambiri kwa kabergoline mu LSSs zitha kuwoneka kukhala zosadabwitsa kutanenedwa m'mbuyomu kuti HSSs ikuwonetsa kuyankha kwakuthupi komanso kogwirizana ndi zomwe zimapangitsa dopaminergic, monga amphetamine (Kelly et al., 2006; Stoops et al., 2007), ndikuti kuchuluka kwa SS kumakwaniritsa bwino ndi kumasulidwa kwa DA komwe kumapangitsa amphetamine ku striatum (Riccardi et al., 2006). Komabe, Gjedde ndi anzawo adangotsutsana pamwambapa chifukwa cha umboni wa PET kuti ma LSS onse ali ndi ma D2 / D3 receptor kachulukidwe komanso otsika amkati mwa DA kuposa anzawo a HSS, kuti "phindu" la dongosolo la DA (reaciture to dopamine) mu striatum ndiolumikizana kwambiri ndi SS lintlha (Gjedde et al., 2010). Chifukwa chake otenga nawo mbali pa LSS atha kukhala ndi phindu lalikulu la DA. Achinyamata a D2 agonists, monga momwe amagwiritsidwira ntchito phunziroli, amayembekezeredwa kukhala ndi zotsatira zabwino mwa anthu awa.

Pothandizira lingaliro ili, pali umboni wina woti ma LSS atha kukhala ndi magulu otsika a DA kuposa ma HSS. Ma LSS akuwonetsa kuchuluka kwa mapulogalamu a monoamine oxidase (wothandizira wa DA; Zuckerman, 1985; Carrasco et al., 1999), ndipo mawonekedwe a LSS adalumikizidwa ndi ntchito yochepera dopa decarboxylase (DDC; kuchuluka kwa malire a synthesis wa DA) mu striatum; kudzera onse kusiyanasiyana mu DDC majini enieni (Derringer et al., 2010) ndi ma polymorphism a Taq1a (Ratsma et al., 2001; Laakso et al., 2005; Eisenberg et al., 2007). Komabe, pakalibe umboni wowonjezera "phindu" (mwachitsanzo, kudzera pa receptor hypersensitivity) mu DA neurotransication mwa anthu a LSS chifukwa cha izi.

Phunziro lathu lili ndi malire. Choyamba, kabergoline sichiri mwachindunji mu mgwirizano wake wa D2R. Ilinso ndi zochitika zochepa za agonist ku 5-HT2A, 5-HT2B, ndi D1 receptors (Kvernmo et al., 2006). Chifukwa chake sikothekanso kutsimikiza zenizeni za momwe limagwirira ntchito zake zimakhalira. Chachiwiri, ngakhale sitinapeze umboni wothandizirana pakusiyana kwa anthu wamba kapena kuwonjezeka kwa kukhudzika kwa D2 pakusankha "zoopsa" pazosintha pazotsatira zomwe zingatheke, pamigawo inayi kufananizaku kunayenera kuperekedwa, chifukwa chake izi sizoyenera kutsimikiziridwa kuti sizotsimikizika . Kuyesa kwamtsogolo pogwiritsa ntchito ngozi zochulukirapo kungafufuzenso izi. Kuphatikiza apo, titapatsidwa zitsanzo za maphunziro a 20, kafukufukuyu sangakhale wopatsa chidwi ndipo zomaliza zake zingapindule ndi kubwereza kwamtsogolo.

Ngakhale chiwonetsero chake chachipatala, kuphatikiza kwachuma pamachitidwe osankha omwe ali pachiwopsezo pakadali pano sichikuphatikizidwa mwa anthu ndi nyama (Winstanley, 2011). Phunziroli, tikupereka koyamba koyamba kusiyanitsa umboni wa momwe zimakhalira zimasiyana mu njira ya SS zomwe zimakhudzira njira zomwe zimapangitsa kuti mankhwalawo asinthe. Zotsatirazi zikutsindika kufunika koganizira kusiyana komwe kungakhalepo, monga SS, pakufufuza popanga zisankho zowopsa, ndipo kungakhale ndi mwayi wokhudzana ndi chitukuko cha mankhwala opatsirana pamatenda omwe amayambitsa kutenga chiopsezo kwambiri, monga njuga ya pathological.

Mawu a M'munsi

Ntchitoyi idathandizidwa ndi Wellcome Trust ndi United Kingdom Medical Research Council.

Olembawo salengeza kuti palibe mpikisano wa ndalama.

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