Dopamine Modulates Risk-Takooridda sida shaqeynaya dareemida asaasiga ah-raadinta tayada (2013)

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

doi:  10.1523 / JNEUROSCI.5587-12.2013

PMCID: PMC3735881

aan la taaban karin

Dareenka dabeecada-raadinta, oo lagu qeexay baahi loo qabo kala duwanaansho kala duwan, dareen adag, iyo dareen xoog leh, waxay ka dhigan tahay daraasad riwaayadeed oo aan fiicnayn oo ku salaysan cilmi-baarista nöroscience ee bini-aadannimada. Waxay la xiriirtaa khatarta sii kordheysa ee dabeecadaha kala duwan oo ay ku jiraan isticmaalka walxaha, khamaarka, iyo dhaqanka galmada khatarta ah. Farogelinta shakhsiyeed ee isdifaac-raadinta isdaba-joogga ah ayaa lala xiriiriyay hawlaha dopamine ee maskaxda, gaar ahaan duubayaasha D2, laakiin illaa iyo hadda ma jirto caddayn aan sabab lahayn oo ah doorka dopamine ee dabeecadda dareen-raadinta ee dadka. Halkaan, waxaan baarnay saameyntii D2 / D3 cabirka agonist-ka ah ee ku saabsan waxqabadka xulashada khatarta leh ee bini'aadamka caafimaad qaba adigoo isticmaalaya maaddo xasaasi ah mawduucyo gudahood, boodbood-lagu xakameeyo.

Cabergolol waxay si aad ah u saameysay sida ka qaybgalayaashu ay isugu dhejiyeen calaamado cad oo kala duwan oo ku saabsan suurtagalnimada iyo khasaaridda markaad dooranayso doorashooyinka jawaabta ee la xidhiidha natiijooyinka aan la hubin. Muhiimad ahaan, saameyntani waxay si xoog leh ugu tiirsanayd dareenka aasaasiga ah ee raadinta-raadinta. Guud ahaan, cabergool waxay kordhiyeen dareenka doorashada ee ku saabsan macluumaadka ku saabsan suurtogalnimada guuleysta; iyadoo hoos u dhigaysa midabtakoorka iyada oo la eegayo baaxadda lumitaanka dhici karta ee la xidhiidha fursadaha kala duwan. Twaxa uu saameyn ugu yeeshay daroogada ayaa lagu arkay kaqeybgalayaasha oo leh dhibco hoose ee dareen-raadinta. Natiijooyinkaas waxay cadeynayaan in dabeecadaha khatarta ah ee bini-aadamka ay si toos ah u maamuli karaan daroogooyinka dopaminergic, laakiin in waxtarka noocan ahi uu ku xiran yahay farqiga asaasiga ah ee dareen-raadinta trait. Tani waxay xoojineysaa muhiimada ay leedahay in la tixgeliyo kala duwanaanshaha shakhsiyadeed marka baaritaan lagu sameeyo khalkhalka go'aan qaadashada khatarta leh, waxaana laga yaabaa in ay ku haboon tahay horumarinta daawooyinka dawooyinka ee ku lugta leh khatarta khatarta badan ee dadka, sida khamaarka noolaha.

Hordhac

Kala duwanaanshaha xiisaha leh ee u dhaxeeya xisaabaadka caadiga ah ee go'aan qaadashada iyo habdhaqanka bini-aadanka maalin kasta (Kahneman iyo Tversky, 1984). Tusaale ahaan, waxa dadka ku dhiirrigeliya in ay tagaan cirifka, u cunaan cuntooyinka basbaaska leh, ama safka saacadaha loogu talagalay safarka raajada ah ee soconaya daqiiqado? Fikradda muhiimka ah ee daraasadda shakhsi ahaaneed ayaa jirey jiritaanka khatarta ah ee hedon-ga si loo raadiyo "dareemo", oo loo dulqaadan karo suurtagalnimada natiijooyinka ka soo horjeeda (khatarta) waayo aragnimada dareenka (Zuckerman, 1974).

Taageerida fikradda hal arin oo la xidhiidha dhiirrigelinta xoojinta khibradda guud ee habdhiska dareenka ayaa laga soo qaatay kormeerka khariidada sigaarka, khamriga, iyo kafeega; isticmaalka daroogada; iyo dabeecad galmo qatar ah ee dadka waaweyn iyo qaangaarka (Carmody et al., 1985; Gillespie et al., 2012; King et al., 2012). Caddaynta isbeddel ku yimaada is-waafajinta halista ah waxaa bixiya ururo u dhexeeya iskudhufsasho-is-daba-dheer-is-sheegid (SS) iyo heerarka kordhaya ee isticmaalka walxaha waxyeelada leh, khamaarka xad dhaafka ah, iyo dabeecadaha kale ee aan macquul ahayn (Coventry iyo Brown, 1993; Roberti, 2004; Ersche et al., 2010).

Kala duwanaanshaha shakhsi ahaaneed ee dareenka-raadinta ayaa lala xiriiriyay shaqooyinka dopamine (DA) ee maskaxda, gaar ahaan kuwa soo-saarka D2-sida (D2 / D3 / D4). Bini'aadamka, sifaha SS waxaa lala xiriiriyaa kala duwanaanta hidde-wade ee D2 iyo D4 reseptor loci (Ratsma et al., 2001; Hamidovic et al., 2009; Derringer et al., 2010), iyo qiyaasta "D2 / 3" helitaanka "helitaanka," sida lagu qiyaasay 11C-raclopride PET (Gjedde et al., 2010). Jiirka, shaqeeyaha xooggan ee ka jawaabaya abaalmarinta dareenka aan shuruudda lahayn ayaa lagu muujiyay inuu yahay mid xasaasi ah labada lafdhabarta antipsychotic flupenthixol (D1-D5 antagonist) iyo amphetamine (Olsen iyo Winder, 2009; Shin et al., 2010). Si kastaba ha ahaatee, ma jiraan wax caddayn ah oo aadanaha ah oo loogu talagalay doorka DA ee habdhaqanka habdhaqanka sida shaqo SS ah.

Daraasaddan, waxaan isticmaalnay cabergoole-daroogo oo leh labadaba tiiraanyo badan iyo qaasatan qaasatan qiyamka D2-da oo ka badan kuwa loo isticmaalo daraasadaha hore (Kvernmo et al., 2006) -Waxaad ku kordhisaan natiijooyin aan hore loo arag oo ku saabsan fara-saarka daaweynta daaweynta khatarta qaadista by D2 agonists (Hamidovic et al., 2008; Riba et al., 2008). Muhiimad ahaan, waxaan sidoo kale tixgelinay suurtogalnimada isbeddel ku yimaadda saamaynta daroogada iyada oo la adeegsanayo sifooyinka SS-ga.

Iyadoo lagu saleynayo caddaynta sawirrada muuqaalka ah ee laga helay bukaannada bukaanka ah ee lagu daweeyo dopamine agonist daaweyn joogto ah (Abler et al., 2009), waxaan saadaalinnay in cabergoladu kordhin doonto saameynta macluumaadka ku saabsan suurtagalnimada abaalmarinta, iyadoo laga yaabo in ay sidoo kale hoos u dhigto saameeynta cawaaqib xumada iman karta, inta lagu jiro doorashada halista ama aan la hubin. Inkastoo daraasadihii hore ay soo tebiyeen jawaabaha badan ee daawooyinka loo yaqaan 'DAergic drug stimulant' ee SS SS (HSS), waxaa sidoo kale la soo jeediyay in dadka dareen-celiyeyaasha hooseeya ay yeelan karaan nidaam aad u sarreeya oo lagu iibsado DA-daGjedde et al., 2010; eeg sidoo kale Doodsi), taas oo saadaalin doonta jawaab weyn oo loogu talagalay agonayaasha gaarka ah ee hooseeya (SSL) maadooyinka. Waxaan ogaanay in cabergoolnadu si aad ah u saameeyeen dareenka doorasho ee ku saabsan macluumaadka ku saabsan suurtogalnimada iyo lumitaanka suurto galka ah, iyo, si feejignaan ah, baaxadda saameyntani waxay si xoog leh ugu tiirsanayd kala-duwanaanta asaasiga ah ee is-sheegista SS.

Qalabka iyo Dariiqooyinka

Ka qaybgalayaasha.

Ka qaybgalayaashu waxay ahaayeen 20 ragga ragga (da'da da'da, sanadaha 26.7, sanadaha SD, 5.67). Shuruudaha ka-saariddu waxay ka kooban tahay cudur kasta oo hadda jira, dhacdooyinka iminka taagan ama taariikhda cudurada maskaxda, iyo / ama isticmaalka daroogada xilliga firaaqada wax ka badan hal munaasabood intii lagu jiray bilihii 6 ee hore. Dhammaan maadooyinka waxay bixiyeen oggolaansho qoraal ah oo daraasaddana waxaa ansixiyay guddiga anshaxa jaamacada London.

Naqshad.

Daraasada waxaa lagu fuliyay maaddooyinka maadooyinka indhoolayaasha ah ee indhoolayaasha ah. Casharka kowaad, ka qaybgalayaasha ayaa lagu baaray khilaafka daroogada, waxay bixiyeen oggolaansho la wargeliyey, waxaana la baray barashada barashada khatarta ah. Mawduucyada waxaa kale oo ay dhammeystireen cabirka Barratt Impulsivity Scale (BIS-11) iyo UPPS (deg-deg ah (la'aan), (la'aanta) feejignaan, dareemid-raadin)Patton et al., 1995; Whiteside iyo Lynam, 2001), cabbiraadda awoodda xasuusta shaqada (jihada hore ee lambar sida ku xusan Wechsler Qiyaasta Sirdoonka Qaangaarka-III; Shirkadda Cilmi-nafsiga, 1997), iyo cabbiraad aan caadi aheyn oo karti maskaxeed ah (Raven's 12-item Advanced Advanced Matrices; Pearson Education, 2010) ). Kalfadhiyadii labaad iyo saddexaad (tijaabinta), kaqeybgalayaashu waxay yimaadeen subaxnimadii waxaana lasiiyay kiniin ay kujiraan 20 mg oo ah domperidone (antiemetic), kadib 20 daqiiqo kadib midkood 1.5 mg ah cabergoline ama a placebo (daroogada iyo kiniinada placebo lama kala saari karin) ). Qiyaastan ayaa loo doortay inay ka weynaato tii lagu bixiyay daraasad hore halkaasoo saamaynno aan is-waafaqsanayn oo ku saabsan dabeecadda lagu arkay (1.25 mg; Frank iyo O'Reilly, 2006), oo ay weheliso maadada domperidone oo lagu yareeyo waxyeelooyinka jirka ee dhici kara.

Si loogu oggolaado heerarka qiyaasta daawada ee udubdhexaadka si ay u gaaraan xoojinta ugu saraysa, tijaabinta waxay bilaabatay 2 ka dib markii la qaato kiniinka labaad (Andreotti et al., 1995). Cashar kasta oo tijaabo ah, kaqeybgalayaashu waxay dhammaystireen cabbirro isku mid ah oo muuqaal ah oo ku saabsan niyadda, saameynta, saameynta jirka, iyo aqoonta ku saabsan maaraynta daroogada / xeegada. Amarka daroogada / placebo ayaa miisaaniyadii miisaankoodu ahaa miisaan ahaan, iyada oo la isticmaalayo muddadii ugu yarayd ee isbuucyada 2 inta u dhaxaysa labada kulan ee imtixaanka.

Qalabaynta go'aaminta qatarta.

Go'aan qaadashada halista ah ayaa la tijaabiyey iyadoo la adeegsanayo hawlihii doorashadii la doortay ee lagu sharraxay Rogers iyo asxaabtoodii (Rogers et al., 2003; Murphy et al., 2008). Si kooban, tijaabo kasta, maadooyin ayaa looga baahan yahay in ay doortaan inta u dhaxeysa laba khamaar oo isku mar la soo bandhigay. Khamaar kastaa wuxuu u muuqdaa mid muuqaal ahaan u taagan iyadoo loo eegayo histogaraam, dhererka kaas oo tilmaamaya suurto-galnimada qaraabada ee ku guulaysata tiro dhibco ah. Baaxadda waxqabadka suurtagalka ah waxaa lagu muujiyay cagaaran ka sarreeya histogaraam kasta, iyada oo miisaanka weyn ee suurta galka ah ee lagu tilmaamayo guduudan guduudan.

Hal tijaabo kasta, hal khamaar markasta wuxuu ka koobnaa 50: 50 fursada ah inuu ku guuleysto ama lumiyo dhibcaha 10 ("xakamaynta" khamaarka, qiimaha la filayo 0). Badanka kale ("tijaabo") khamaar ayaa ku kala duwan (1) inta ay ku guuleysan karto (0.6 ama 0.4), (2) weynaanta guulaha suurtagalka ah (30 ama 70 dhibcaha), iyo (3) weynaanta dhibcaha suuragalka ah (30 ama 70 dhibco) .

Guryaha khamaarka ah ayaa si buuxda loo soo gooyay, iyagoo soo saaray siddeed nooc oo tijaabo ah. Jawaab celin muuqaal ah (guul / guul darro) ayaa la bixiyay ka dib markii doorasho kasta la sameeyay, wadarta guud ee dib loo eegay ayaa la soo bandhigay ka hor dacwadda xigta.

Mawduucyada waxay dhameeyeen afar qaybood oo ka mid ah tijaabooyinka 20, waxaana la baray in dhibcaha wadarta ugu sarreeya ee ay ku guuleysteen in la gaaro lagu beddeli doono miisaanka oo la bixiyo dhamaadka hawsha oo ah gunno lacag ah. Xilliga la qabsashada (jawaabaha) ayaa sidoo kale la duubay.

Falanqaynta xogta xulashada.

Xogta ayaa lagu falanqeeyay sida xulasho dhexdhexaad ah ee "khibrad" khamaaraya iyada oo la adeegsanayo suurtogalnimada guuleysiga, xajmiga faa'iidooyinka suurtagalka ah, iyo xajmiga dhibaatooyinka suurtogalka ah. Gaar ahaan, xogta doorashooyinka saamiga ah ayaa lagu soo gaabiyey ANOVA oo lagu celceliyo qiyaasaha maadooyinka daroogada, macquulnimada guuleysiga, xajmiga guusha la filayo iyo qiyaasta lumiska la filayo. Amarka daweynta waxaa lagu daray maaddooyinka u dhexeeya maadooyinka dhexdooda. Daraasad la mid ah ayaa loo sameeyey xogta waqtiga jawaabta. Doorashooyinka ayaa sidoo kale lagu qiimeeyay qiimaha la filayo iyo "riskiness" ee khamaarka la doortay, iyada oo tan dambe lagu qeexay inay tahay SD ee natiijooyinka suurtagalka ah ee khamaar kastoo dooratay. Dhammaantood waxay ku warbixiyeen falanqaynta waxyeellooyinka sahlan ee la adeegsaday iyada oo la isbarbardhigayo labadaba iyadoo la adeegsanayo Bonfarroni isku-hagaajin is-barbardhig badan. Xogta mawduuc ka mid ah ayaa la jabiyay oo sidaas darteed laga saaray falanqaynta.

Natiijooyinka

Macluumaadka doorashada ee kordha

Wax saameyn ah kuma leh amarka daroogada, ama isdhexgalka ka dhexeeya arrimo daroogada iyo daroogada, ayaa la helay (labadaba p > 0.09). Si kor loogu qaado awoodda, amarka daroogada ayaa sidaas darteed laga tuuray tusaalaha falanqaynta dambe. Guud ahaan, kaqeybgalayaashu waxay doorteen khamaarista "tijaabada ah" si aad ah marar badan marka ay u badan tahay suurtagalnimada guuleysiga marka la barbar dhigo markii ay hooseysay (F(1,18) = 40.305, p <0.001, ηp2 = 0.691). Nidaamkan go'aan qaadashada si wayn ayaa loogu sii kordhiyay iyada oo la tixraacayo qaamuuska qaamuuska ah ee loo yaqaan 'placebo' (daroogada * macquulnimada guusha; F(1,18) = 6.733, p = 0.018, ηp2 = 0.272).

Mawduucyada sidoo kale waxay doorteen "khibrad" khamaar si aad ah inta badan marka laga filayo guulaha la filayo inay ka badan yihiin marka laga filayo guulaha laga filayey (F(1,18) = 50.522, p <0.001, ηp2 = 0.736). Si kastaba ha ahaatee, ma jirin wax caddayn ah oo muujinaya in qaabkan doorashadu uu ka duwan yahay cabergool (daroogo * cabbirka guulaha suurtogalka ah, F(1,18) = 3.615, p = 0.074).

Ugu dambeyntii, mutadawiciintu waxay door bideen "khibrad" khamaarka si aad u yar marka la filayo in khasaaraha la filayay uu ka weynaa markii ay khasaaruhu yaraa (F(1,18) = 56.486, p = 0.001, ηp2 = 0.758). Qaabkan go'aan-qaadashada si weyn ayaa loo xakameeyey kaameradda (daroogada * cabbirka khasaare badan, F(1,18) = 6.773, p = 0.018, ηp2 = 0.273). Wixii soo koobaya saameynahan soo arag Jaantuska 1.

Jaantus 1.  

Kala doorashada qiimaha "khibradda" khamaarka sida waafaqsan guryaha khamaarka, kaarka iyo cabbergoolka. **p <0.001, *p <0.05.

Wax saameyn ah kuma yeelanin cabergoolka qaybta guud ee doorashooyinka "khibradda" khamaarka (p = 0.480), iyo ma jiro isdhexgal sare oo sarreeya oo isdhexgalka oo ku lug leh qodobka daroogada (dhammaan p > 0.2).

Isdhexgalka shakhsiyaadka kala duwan

UPPS SS subscore waxaa lagu ogaadey inuu si weyn u dhexgalo saameynta daroogada ee habdhaqanka doorashada [daroogada * macquulnimada guulaysiga (sleepin) * SS score, F(1,17) = 6.331, p = 0.022, ηp2 = 0.271; daroogada * khasaaraha * dhibcaha SS, F(1,17) = 11.501, p = 0.003, ηp2 = 0.404; marka la barbardhigo, da'da, qiyaastii IQ, awoodda xusuusta shaqada, iyo guud ahaan is-dareen-celinta oo dhan p > 0.3].

Xaqiiqda, isdhexgalka daroogada ee arrimaha isweydaarsiga iyo xajmiga dhibaatooyinka la filayo waxay u muuqdaan in badanaa lagu riixo maadooyinka leh dhibcaha hoose ee HS (Berdihii. 2A). Falanqaynta saameynaha sahlan ayaa shaaca ka qaaday, marka la qeexayo kooxaha LSS iyo kooxaha HSS by dhexdhexaadinta kala duwan ee SS, LSSs waxay doorteen khamaarro badan "tijaabo" khamaar markii ay jiiftay (F(1,17) = 5.996, p = 0.025) iyo wax yar ka yar markii uu uurku hooseeyo (F(1,17) = 7.808, p = 0.012) oo ku saabsan daroogada ku xiran xuddunta. Taas bedelkeeda, kooxda HSS kuma aysan kala duwanayn doorashadooda ikhtiyaarrada jiitameysa ama sareeya ee u dhaxeeya xaaladaha daroogada iyo xayawaanka (p > 0.2).

Jaantus 2.  

A, Saamaynta cabergoline ee ku saabsan dabeecadaha xulashada maadooyinka, oo loo qaybiyay kooxaha HSS iyo LSS iyada oo loo marayo kala qaybsanaanta dhexdhexaadka ah ee dhibcaha hoose ee UPPS SS. Maaddooyinka LSS oo keliya, wax ka beddelka habdhaqanka xulashada ayaa si weyn loo buunbuuniyey iyadoo la raacayo macluumaadka ku saabsan ...

LSSs waxay sidoo kale muujiyeen isbeddellada aan fiicnayn ee doorashada khamaarka yar marka dhibaatooyinka yar yar ay yaryihiin (F(1,17) = 4.262, p = 0.0546), iyo khamaar dheeraad ah markii khasaarihii uu jirey uu weynaa (F(1,17) = 3.052, p = 0.090; Berdihii. 2A), cabirkada marka la barbar dhigo cirbadda. Midkoodna saameyntani lama soo koobi jirin kooxda HSS (p > 0.2) Kooxaha HSS iyo LSS si weyn ugama duwaneyn dhanka dhibcaha hoose ee is-sheegashada kale ee is-sheegista, da'da, tirade lambar, ama qiyaasta IQ (dhammaantood) p > 0.3).

Si loo qiyaaso saameynta heerarka shakhsiyeed, labo calaamadood oo ah saameynta daroogada ee saamaynta daroogada ayaa loo xisaabiyey maaddo kasta (farqiga u dhaxeeya saameynta isbeddelka ah ee suurogalnimada guuleysi, ama baaxad ahaan lumitaanka suurtogalka ah, xulasho dhexdhexaad ah ee tijaabinta khamaarka inta u dhexeysa xaaladaha daroogada iyo xayawaanka). Dhibcaha SS waxaa lagu ogaadey inuu yahay saadaalin weyn oo labadaba labadaba (r2ku dheji = 0.229, p = 0.022; r2ku dheji = 0.336, p = 0.005; falanqaynta qadarin la'aanta), laakiin aan lagu qiyaasi karin IQ, tirada wareega, ama dhibcaha kale ee isdabajoogga ah (dhammaantood p > 0.1). Labada xaaladoodba, kaqeybgalayaasha leh dhibcaha raadinta dareenka hoose ayaa saameyn badan ku yeeshay dhaqankooda cabergoline (Berdihii. 2B). Labada indheysood ee ismaandhaafka ah lalama xiriirin (p = 0.117).

Waqtiyada wadahadalka

Ma jirin wax saameyn ah oo weyn oo ku saabsan suurtagalnimada guuleysiga, cabirka faa'iidooyinka suurtagalka ah, ama cabirka khasaaraha suurtagalka ah ee waqtiyada wada hadalka kaqeybgalayaasha (dhammaantood) F <1), oo aan saameyn weyn ku yeelanaynin cabergoline waqtiga jawaabta (p = 0.204). Ma jirin wax saameyn ah oo saameyn ku yeeshay daroogada, guryaha khamaarka, iyo dhibcaha SS ee wakhtiyada la isku afgarto (dhammaan p > 0.3).

Qiyaasta la filayo iyo khatarta

Qiimaha la filayay ee khamaarka wuxuu ahaa mid si qoto dheer loola xiriiriyay xulashada dhexdhexaadinta ee labadaba loo yaqaan 'placebo and cabergoline'r2ku dheji = 0.890, p <0.001; r2ku dheji = 0.737, p = 0.004; Coefficients regression si aan kala duwaneyn, p = 0.924). Khamaarista khamaarka (SD) si aad ah uguma xirnayn doorasho saami ah oo hoos timaad xaalad daroogo (p > 0.5). Ma jirin saameyn weyn oo daroogada ah oo ku timid qiimaha la filayo (p = 0.582) ama macnaheedu yahay khamaarista khamaarka la doortay (p = 0.376). Waxaa sidoo kale jirin isdhexgalin muhiim ah ee daroogada iyo dhibcaha SS ee ku saabsan tallaabooyinkan (p > 0.2).

Khilaafka shakhsi ahaaneed ee aasaasiga ah

Markaad tixgelinayso xogta ka soo baxday casharka aan keli ahayn, ma jirin wax isdhexgal ah oo dhexdhexaad ah oo ka dhexeeya dhibcaha SS iyo saamaynta guryaha hantida khamaarka (jiinka, xajmiga guusha laga filayo iyo khasaaraha) doorashada p > 0.1). Sidoo kale ma jirin cilaaqaad muhiim ah oo udhaxeeya halbeegyada hal xulasho oo keliya (ie, macnaha khatarta khamaarka la doortay, celceliska qiimaha khamaarka la doortay ee la filayo, iyo wadarta dhibcaha lagu guuleystay) iyo dhibcaha SS (dhammaantood) p > 0.1). Si kastaba ha noqotee, waxaa jiray xiriir aan fiicnayn oo udhaxeeya dhibcaha SS iyo waqtiga wadahadalka ee placebo (r = -0.479, p = 0.038; Berdihii. 3A), oo aan ka muuqanin hoos cabergool (p > 0.5). Tallaabooyin soo noqnoqday oo ANOVA ah oo ah celcelis ahaan wadahadal lala yeesho maaddooyinka u dhexeeya kooxda SS ayaa shaaca ka qaaday in maadooyinka SS ee hooseeya ay muujiyeen isbeddel xagga jawaab celinta si gaabis ah oo ku saabsan kalfadhiga placebo kaliya (daroogada * Isdhexgalka kooxda SS, F(1,17) = 4.404, p = 0.0511; Berdihii. 3B).

Jaantus 3.  

A, Waqtiga xallinta doorashada caadiga ah ee kuxusta placebo ayaa si xun ula xiriirta dhibcaha UPPS SS (r = -0.479, p = 0.038). B, Maadooyinka LSS waxay muujiyeen waqtiyada qadarinta doorashooyinka tartiib tartiib ah marka loo eego maaddooyinka HSS oo keliya fadhiyada munaasabadda. **p <0.001, *p = 0.023. ...

Dhibaatooyinka dabiiciga ah

Marka la eego xadka aan qarsooneyn, kaqeybgalayaashu waxay si aad ah u degganayeen (p = 0.033) iyo lumid (p = 0.017), waxaana sidoo kale soo sheegey wax yar oo madax xanuun ah (p = 0.020), oo ku saabsan cabergoolka kuxirsan xudunta. Si kastaba ha noqotee, isbedel kasta oo ka mid ah tallaabooyinkan si aad ah uguma xirna mid ka mid ah saameynta daawada daroogada, ama dhibcaha SS-ga oo dhan (dhammaan p > 0.4), oo soo jeedinaysa inay taasi wax ku biirinaynin saamaynta ugu weyn ee cabergoline ama kala duwanaanshaha shaqsiyeed ee saamaynta cabergoline. Wax saameyn ah oo weyn oo daroogada ah lagama helin waxyeellooyin kale oo jidheed oo suuragal ah (p > 0.25), niyadda, ama saamaynta miisaanka (p > 0.16; 26 qiyaasta wadarta) iyo aqoonta daroogada / maareynta placebo lama helin inay si weyn ugu kala duwan yihiin kalfadhiyada imtixaanka (t1,18 = 1.681, p = 0.110).

Dood

In Daraasaddaan, waxaan aragnaa saameyn weyn oo ah hal dose oo ah D2 / D3 Cabonolon agonist ee go'aan qaadashada iyadoo shuruudo aan hubin lahayn ama khatar ah, taas oo, ugu muhiimsan, ku xiran tahay kala-duwanaanta asaasiga ah ee isku-dhafka SS. Guud ahaan, saamaynta cabergololku waxay ahayd in la baddalo habdhaqanka doorashooyinka doorashada si waafaqsan calaamadaha cad ee ku saabsan suurtogalnimada guusha, iyo isla mar ahaanteed si loo yareeyo xakamaynta xulashada sida waafaqsan macluumaadka ku saabsan xajmiga dhibaatooyinka suurtogalka ah (Berdihii. 1). Muhiimad ahaan, baaxadda saameynta daroogada ayaa si weyn u dhexdhexaadinaysay dhibcaha aasaaska UPPS SS (Berdihii. 2) Oo lagu xisaabtamayo qayb weyn oo kala duwanaansho ah oo ku saabsan baaxadda saamiga cabirka ee qamriga go'aan qaadashada khatarta ah (~ 23-34%). Labada xaaladood, shakhsiyaadka soo sheegey heerar hoose oo SS ah waxay muujiyeen saameyn xooggan oo cabirkol ah oo ku saabsan habdhaqankooda doorashada.

Jidhka caddaynta ee daraasaddaha bani'aadamka iyo xayawaanka labadaba waxay ka tarjumeysaa kala duwanaanshaha D2R-dhexdhexaadinta neurotransmission ee kala duwanaanshaha shakhsiyadeed ee SS habdhaqanka (Ratsma et al., 2001; Blanchard et al., 2009; Hamidovic et al., 2009; Gjedde et al., 2010). Si kastaba ha ahaatee, isku daygii hore ee lagu xakameyn lahaa doorashada khatarta ah ee xayawaanka iyo bini-aadanba ayadoo la isticmaalayo daroogooyinka D2ergic ayaa soo saaray natiijooyin aan khilaaf ahayn (Hamidovic et al., 2008; Riba et al., 2008; St. Onge iyo Floresco, 2009; Simon et al., 2011). Tani waxaa laga yaabaa in qayb ahaan loo xaddido khilaafaadka qeexida khatarta (tusaale ahaan, isbeddel ku yimaada jaangoynta suuro galka ah ee fursada ah natiijada ka soo horjeeda), ama sababo tallaal ah oo saameyn ku leh dawada daroogada.

Jiritaanka xayawaanka D2 ee presynaptic iyo Postynaptic labadaba waxaa loola jeedaa in daroogada lagu daro saameyn ku yeelan karto gudbinta dopaminergic (Usiello et al., 2000). Inkasta oo mishiinka D2 Daawooyinka D2 ay si xun u xakameeyaan jawaabaha DH ee jawaabaha, DXNUMXRs ayaa xakameynaya taariiqda DA ee tayada leh ee ka muuqda khatarta khatarta (Grace, 1991; Fiorillo et al., 2003; Schmitz et al., 2003; Schultz, 2010). Tani waxay keenaysaa dhibaatooyinka turjumidda saameynta maandooriyaha, gaar ahaan qiyaasaha hooseeya oo kaliya meelaha kor u kaca ah ee koronto-ilaaliyaha ah ee laga yaabo in la kiciyo. Waxaan isku dayeynay inaan hubinno dhiirigelinta postsynaptic D2Rs adigoo isticmaalaya cabirka sare D2 / D3 cabon agonist (Kvernmo et al., 2006), qadar sarreeya oo ka badan daraasad hore oo aan waxyeelleyn daroogooyinka aan la socon (Frank iyo O'Reilly, 2006). Maaskarada Domperidone ayaa loo adeegsaday si loo yareeyo waxyeelada aan la isku haleyn karin, sida lallabbada, maadooyinka guudna kama warqabin wax-qabadka daroogada / xeegada. Waxa kale oo aan helnay caddaymo muujinaya in saameyn xun oo daroogo ah ay saameyn ku yeesheen daroogada, taas oo horay loo qaaday si loo muujiyo waxqabadka daroogada badan ee loo yaqaan 'presynaptic action' (tusaale ahaan, Hamidovic et al., 2008).

Natiijadayada saameynta weyn ee cabergololeedka ee LSSs waxay u muuqan kartaa waxoogaa la yaab leh oo la siiyay warbixino hore oo ay HSSs muujisay jawaabaha nafsaaniga ah iyo shakhsiyadeed ee kicinta dopaminergic, sida amphetamine (Kelly et al., 2006; Stoops et al., 2007), iyo in buundada SS ay si fiican ugu xiran tahay sii-deynta DA amphetamine-ku-soo-saarka ku jirta striatum (Riccardi et al., 2006). Si kastaba ha noqotee, Gjedde iyo asxaabtiisu waxay dhawaan ku doodeen caddaynta PET ee ah in LSSs ay labaduba hoos u dhacaan D2 / D3 Cunto-qaadashada iyo hoos-u-dhaafka DA-da oo ka hooseeya heerka HSS, sida "helitaanka" nidaamka DA (reactive to dopamine) gawaarida waxay ku xiran tahay dhibcaha SS (Gjedde et al., 2010). Sidaas awgeed kaqaybgalayaasha LSS waxay yeelan karaan faa'iidada sare ee DA. Doonyaha D2 ee tooska ah, sida loo isticmaalo daraasaddeena, ayaa la filayaa in ay saameyn weyn ku yeeshaan shaqsiyaadkaas.

Taageerada sharaftan, waxaa jira caddayn ah in LSSs ay yeelan karaan heerarka DA ee ka hooseeya HSSs. LSS-yada waxay muujiyaan heerarka qumman ee sare ee oksaydh (monoamine oxidase) (tusaaleyaal DA; Zuckerman, 1985; Carrasco iyo al., 1999), iyo Xaaladda LSS waxay la xiriirtay dopa decarboxylase (DDC), enzymes-limiting enzyme for DA synthesis) ee kudhaca qaybta 'striatum'; iyada oo loo eegayo labadaba DDC gene laftiisa (Derringer et al., 2010) iyo TaqXnUMXa polymorphism (Ratsma et al., 2001; Laakso et al., 2005; Eisenberg et al., 2007). Hase yeeshee, ma jiraan wax caddayn ah oo lagu kobcinayo "korodh" (tusaale ahaan, iyada oo la adeegsanayo maqnaashaha xasaasiyadeed) ee DA neurotransmission ee dadka shakhsiyaadka LSS taas oo ka dhalatay arrintan.

Daraasaddeena waxay leedahay waxoogaa xaddidan. Ugu horeyn, cabergoloolka ma aha mid gaar ah oo ka mid ah D2R. Waxa kale oo uu leeyahay xaddidaad agonist oo ku taal 5-HT2A, 5-HT2B, iyo dukaamada D1 (Kvernmo et al., 2006). Sidaa darteed suurtogal ma ahan in si buuxda loo hubiyo oo ku saabsan nidaamka hoos yimaada saameynta dabeecadeed. Marka labaad, inkasta oo aynaan helin wax caddeymo ah oo ku saabsan taageerada asaasiga ah ee shakhsiyaadka asaasiga ah ama kor u qaadista Doontada D2 ee ku salaysan doorka "khatarta" marka la eego kala duwanaanta natiijooyinka suurtagalka ah, afartan heerba waa isbarbardhig, sidaas darteed natiijadan ma aha in la qaado . Imtixaannada mustaqbalka ee isticmaalaya khataro badan oo khamaaraya ayaa laga yaabaa inay baaritaan dheeraad ah sameeyaan. Intaa waxaa dheer, marka la eego maaddada 20, daraasadda waxaa laga yaabaa inaysan si fiican u shaqeynin, natiijooyinkuna waxay ka faa'iideysan doonaan mustaqbalka.

Inkasta oo ay muhiim tahay in daaweynta faraha badan ee daaweynta, farsamoyinka cilmi-baarista ee khatarta ah ee halista ah ay hadda halis ku yihiin labada qof iyo xayawaanka (Winstanley, 2011). Daraasaddan, waxaan ku siineynaa markii ugu horeysay ee caddaynta aqooneed ee caddaynta dhabta ah ee muuqaalka SS waxay saameynaysaa habka faragelinta daawada ee wax ka beddelaysa dabeecadaha halista ah. Natiijooyinkaasi waxay xoojinayaan muhiimada ay leedahay in la tixgeliyo kala duwanaanshaha shakhsi ahaaneed, sida SS, marka baadhitaan lagu sameeyo go'aan qaadashada khatarta ah, waxaana laga yaabaa inay ku haboonaato horumarinta daawooyinka dawooyinka loogu talagalay cudurada khatarta badan, sida khamaarka cudurada.

Qoraalada

Shaqadani waxaa taageeray Guddiga Cilmi-baarista Caafimaadka ee Boqortooyada Ingiriiska iyo Wellcome Trust.

Qorayaashu ma sheegaan danaha maaliyadeed ee tartanka.

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