Serotonin iyo Dopamine Play Doorka Kala-duwan ee Khamaarka si Loona Helo Losses (2010)

Neuropsychopharmacology. 2011 Janaayo; 36 (2): 402 – 410.

Loo soo daabacay internetka 2010 Oktoobar 27. doi:  10.1038 / npp.2010.170

PMCID: PMC3055672

Daniel Campbell-Meiklejohn,1,2 Judi Wakeley,3 Vanessa Herbert,4 Jennifer Cook,4,5 Paolo Scollo,6 Manaan Kar Ray,3 Sudhakar Selvaraj,3 Richard E Passingham,2 Phillip Cowen,3 iyo Robert D Rogers2,3, *

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aan la taaban karin

Khamaarista sii socota si ay uga soo kabato khasaaraha - 'ceyrsashada' - waa astaamo caan ka ah khamaarka bulshada iyo cudurada. Si kastaba ha noqotee, wax yar ayaa laga ogyahay neuromodulators-ka saameeya habdhaqankan. Saddex tijaabo oo kala duwan, waxaan baarnay doorka waxqabadka serotonin, D2/D3 Waxqabadka soo dhoweynta, iyo howlaha beta-adrenoceptor ee ku saabsan raadinta luminta da'da iyo IQ-waafaqa dadka waaweyn ee caafimaad qabka ah ee loogu tala galay daaweynta ama xakameyn haboon / placebo. Tijaabada 1, kaqeybgalayaashu waxay cuneen cabitaanno amino-acid ah oo aan laheyn ama aan haynin hordhaca serotonin, tryptophan. Imtixaanka 2, kaqeybgalayaashu waxay heleen hal 176 ahdoseg qiyaasta daawada D2/D3 receptor agonist, pramipexole, ama placebo. Imtixaanka 3, kaqeybgalayaashu waxay heleen hal 80 ahmg mg ee beta-adrenoceptor xannibaadaha, propranolol, ama placebo. Daaweyn kadib, kaqeybgalayaashu waxay dhameystireen ciyaar kumbuyuutar ciyaar lagu baacsanayay. Xaaladda iyo garaaca wadnaha waxaa lagu cabiray aasaaska iyo daaweynta xigta. Xaalufinta 'Tryptophan' waxay si weyn hoos ugu dhigtay tirada go'aamada la gaadhay si loo cayrsho khasaaraha, iyo tirada go'aamada is xigxiga ee lagu ceyrsado, iyadoo aysan jirin isbeddello muuqda oo niyadda ku yimid. Taa bedelkeeda, pramipexole waxay si weyn u kordhisay qiimaha khasaarihii la ceyrsaday waxayna hoos u dhigtay qiimaha qasaaraha la soo gudbiyay. Propranolol wuxuu si muuqata hoos ugu dhigay garaaca wadnaha, laakiin ma uusan soo saarin isbeddello muhiim ah habdhaqanka-ceyrsashada luminta. Khasaarasho cayrsashada waxaa loo maleyn karaa inay tahay dabeecad baxsasho dhiirigalin ah oo la xakameynayo, qeyb ahaan, qiimaha yar ee sii socoshada khamaarka marka loo eego qiimaha khasaarihii horey u soo gaaray. Serotonin iyo dopamine waxay u muuqdaan inay ciyaarayaan doorar aan kala go 'lahayn oo u janjeera shakhsiyaadka inay khamaaraan inay soo kabtaan, ama inay raadiyaan inay' ka baxsadaan 'khasaarihii hore. Dhaqdhaqaaqa Serotonergic wuxuu umuuqdaa inuu sare uqaadayo helitaanka luminta cayrsashada oo ah ikhtiyaar ikhtiyaar ah, halka D2/D3 Waxqabadka receptor wuxuu soo saaraa isbeddelo adag oo ku saabsan qiimaha khasaaraha loo maleeyo inuu eryanayo. Kicinta dhibka leh, ugu yaraan sida uu u dhexdhexaadiyo beta-adrenoceptors, door weyn kama ciyaaro xulashooyinka ku saleysan luminta shaybaarka.

Keywords: serotonin, dopamine, eryanayo lumis, khamaar, adkeysi, qiimo

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HORDHAC

Khamaarista si loo soo celiyo khasaaraha, ama baacsi lumis (Lesieur, 1977), waa astaamaha udub dhexaadka go'aan gaarista aadanaha (Kahneman iyo Tversky, 2000). Si kastaba ha noqotee, xaalad ahaan, baadi-goobka khasaaraha xad-dhaafka ah sidoo kale wuxuu tilmaan caan ah u yahay xakameynta liidata ee saamiyada weyn ee shakhsiyaadka soo sheega dhibaatooyinka la xiriira habdhaqankooda khamaarka (Corless iyo Dickerson, 1989; McBride et al, 2010; Sacco et al, 2010). Bidixda aan la ilaalin, raadinta luminta waxay soo saari kartaa xaalad khatar ah ee ku lug lahaanshaha khamaarka, kordhinta deymaha maaliyadeed laakiin waxay yaraaneysaa ilaha, iyo, suurtagalnimada, qoyska xun ee daran, bulshada, iyo cawaaqib xumada shaqada ee khamaarka jirrada (Lesieur, 1979).

Heer maskaxeed, baacsashada lumintu waa mid adag oo inta badan ku lug leh dawlado dhiirigelin isku dhafan, iyada oo la tuurayo rabitaanka (ama baahida) si loo sii wado ka hortagga cabsida laga qabo silica xitaa khasaaraha weyn (Lesieur, 1977): dawlado shucuur xoog leh oo dhexdhexaadin ku samaynaya dhaqdhaqaaqyo ka dhex socda wareegga neural ee neecaw (Campbell-Meiklejohn et al, 2008). Khamaarka si loo soo ceshado khasaaraha sidoo kale waxaa lala xiriiriyaa dowladaha kacsan ee kacsanaanta (hoos ka fiiri) iyo mashquul aad u sarreeya oo ku saabsan howlaha khamaarka oo ah astaamaha ugu weyn ee lagu soo bandhigo dhibaatooyinka caafimaad ee khamaarka (Dickerson et al, 1987; McBride et al, 2010). Sidaas awgeed, eryashada luminta ayaa laga yaabaa inay matalaan bartilmaameed muuqda oo loogu talagalay horumarinta wax ka qabashada daaweynta.

In kasta oo ay udub dhexaad u tahay khamaarka dhibaatada, wax yar kama ogno sida loo eryanayo luminta ay saameyn ku leedahay dhaqdhaqaaqa nidaamyada neerfaha. Qaddar yar oo cadaymo caafimaad ah ayaa sheegaya in khamaarka cudurada faafa uu la xiriiro unugyada serotonergic sida tusaale ahaan loo soo qaatay (iskudhacaya) warbixinnada hoos udhaca saamiyada serotonin metabolite, 5-hydroxyindoleacetic acid ee dareeraha cerebrospinal (Bergh et al, 1997; Roy et al, 1988) iyo warbixinno ku saabsan sii-deynta prolactin sii kordheysa (iyo warbixinno 'heer sare ah') ka dib caqabadda ba'an ee 5-HT2c agonist receptor, meta-chlorophenylpiperazine (Pallanti et al, 2006). Xulashada 'Serotonin' reuptake inhibitors waxay sidoo kale muujiyeen xoogaa ballanqaad ah sida loo daweeyo khamaarka cudurada lagu daaweeyo ee loo adeegsado anticompulsive-ka iyo dhibaatooyinka anxiolytic (Grant iyo Potenza, 2006; Pallesen et al, 2007). Ugu dambayntiina, serotonin ayaa ku dhawaaqaya - in kasta oo ay adag tahay, oo cakiran - saamaynta ay ku yeelan karto dabeecad darrooyinka (Winstanley et al, 2004), oo labaduba dhiirrigeliya baacinta khasaaraha (Breen iyo Zuckerman, 1999), oo lagu buunbuuniyo khamaarlayaasha dhibaatada leh (Blaszczynski et al, 1997).

Cudurka loo yaqaan 'pathophysiology' ee khamaarka dhibaatada ayaa sidoo kale loo badinayaa inuu ku lug leeyahay nabaad-dhaafka maskaxda dhexe ee maskaxda, iyo bogagga saadaasha hore iyo tan hore (Hewig et al, 2010; Potenza, 2008). Marka la barbar dhigo maadooyinka kontoroolka caafimaadka leh, khamaarlayaasha cudurada faafa waxay muujinayaan hoos udhaca jawaabaha neuronal gudaha mesostriatal nuclei iyagoo ku howlan dhaqan khamaar la mid ah oo loogu talagalay abaalmarinta lacageed (Reuter et al, 2005). Maamulka cilmi nafsiga, amphetamine, ee qamaarayayaasha cudurada ku dhaca ayaa aqoon isweydaarsi ku saabsan khamaarka (Zack iyo Poulos, 2004), halka D2 antagonist reseptor, haloperidol, waxay kor u qaadi kartaa sifooyinka wanaagsan ee habdhaqanka noocan ah (Zack iyo Poulos, 2007). Ugu dambeyntiina, soo uruurinta caddaynta waxay muujineysaa in daaweynta dopaminergic ay la xiriirto khamaarka noolaha (iyo dhibaatooyinka kale ee xakameynta kicinta) ee tiro yar oo bukaan ah oo qaba cudurka Parkinson (Voon et al, 2007), oo loo maleynayo inay ka tarjumeyso khalkhalka doorka ballaaran ee dopamine ee xoojinta barashada iyo xisaabinta xiriirka iyo qiimaha xiriirkaDagbe iyo Robbins, 2009; Voon et al, 2010). Markaa, caddaynta dheeriga ahi waxay soo jeedinaysaa in labada serotonin iyo dpfunine labadaba ay dhexdhexaadinayaan dhinacyada khamaarka dhibaatada leh (Zeeb et al, 2009). Si kastaba ha noqotee, ilaa maanta, doorkooda udub dhexaadka u ah dhaqanka dabagalka ayaan wali sifiican looga baarin.

Hal hab oo lagu bilaabayo in la fahmo waxa ku saabsan ciribtirka luminta xad dhaafka ah ee mararka qaar lagu arko khamaarlayaasha dhibaatada waa in la baaro doorarka neuromodulators kaladuwan ee ku eryanaya dhaqanka dadka waaweyn ee caafimaad qaba ee qibrada khamaarka xaddidan leh. Macluumaadka laga helo tijaabooyinka noocan ah waxay gacan ka geysan doonaan samaynta fikradaha ku saabasan sida carqaladeynta howlaha neuromodulators ay u xallinayaan luminta baadi goobka cudurka. Halkan, sedex tijaabo oo kala duwan, waxaan adeegsanay qaab dabeecadeed oo ku saabsan ceyrsashada khasaaraha ee lagu sameeyay shaybaheena oo horeyba loogu ansaxiyay sawirka firfircoonaanta magnetic (Campbell-Meiklejohn et al, 2008) in la isbarbar dhigo dhaqanka baadi-goobka ah ee dadka waaweyn ee caafimaad-qabka ah (ee soo sheegay ku lug lahaanshaha khamaarka oo aad u kooban) ka dib markii la tacaaluqay cudurka serotonergic, dopaminergic (D)2/D3) iyo waxqabadka beta-adrenoceptor.

Imtixaannadii 1, waxaan baarnay saamaynta isku-dayga isku-dayga isku-dayga isku-darka ah ee isku-dayga ah inuu sii wado khamaarka si loo soo celiyo khasaaraha oo la tijaabiyo inta u dhaxaysa laba male-awaal oo leh saadaalinno kala-duwan oo si cad u muuqda. Serotonin waxaa lagu yaqaanaa inuu door muhiim ah ka ciyaaro xakameynta waxqabadka aan la abaalmarin iyo xakameynta anshaxa kadib dhacdada ciqaabta ama kahortagga dhacdooyinka (Soubrie, 1986). Intaas waxaa sii dheer, hoos u dhigista ku meel gaarka ah ee howlaha serotonin-ka, oo lagu gaaro isku dayga tijaabada ah ee loo yaqaan 'tryptophan', ayaa yareyn karta ciqaabta ay sababi karto ciqaabta dhaqangalka ah ee ku socota dadka waaweyn ee caafimaadka qaba (Crockett et al, 2009). Iyada oo ku saleysan aasaaska, waxaan filan karnaa in yaraanshaha isku dayga isku dayga ah inuu sii wadi doono khamaarka si uu uga soo kabto khasaarooyinkii hore ee soo foodsaaray fashilka dabeecada ku tiirsanaanta serotonin.

Dhanka kale, serotonin waxay kaloo dhexdhexaadineysaa barashada ku saabsan dhacdooyinka xun (Bari et al, 2010; Daw et al, 2002; Deakin iyo Graeff, 1991; Doomaha et al, 2005). Dayan iyo Huys (2008) waxay soo jeedisay in ku guuldareysiga xakameynta dabeecadda kadib hoos u dhaca howlaha serotonin (tijaabooyin ama caafimaad) ay soo saari karaan koror ballaaran oo baaxad weyn oo khaladaadka saadaalinta saadaalinta ah, taas oo kadhigeysa inay saameyn ku yeelato dowladaha saameynta xun ku leh shaqsiyaadka nugul (Dayan iyo Huys, 2008). Tijaabo ahaan, isku-darka 'tryptophan' wuxuu hagaajin karaa saxnaanta saadaalinnada xun ama ciqaab natiijooyinka dadka waaweyn ee caafimaad qaba (Cools et al, 2008). Intaa waxaa dheer, Doomaha et al (2005) Wuxuu muujiyey in yaraanta isku dayga 'pluptophan' ay xoojineyso waxqabadka neural-ka iyadoo laga jawaabayo qaladaadyada inta lagu gudajiro barashada dib-u-dhaca gudaha sagxadda murugsan, aagga la dhaqdhaqaaqayo iyadoo la sameynayo go'aammo lagu joojinayo eryada khasaaraha (Campbell-Meiklejohn et al, 2008). Markaa, waxaan sidoo kale saadaalin karnaa in isku dayga 'isku-dayga' isku-darka 'isku-darka dadka waaweyn ee caafimaadka qaba uu kor u qaadi doono cufnaanta natiijooyinka xun inta lagu jiro khamaarka luminta, iyo wuxuu yareyn doonaa dabeecadda daba-galka ah ee xigta.

Tijaabada 2, waxaan baarnay saameynta hal qadar oo ah nooca aan-ergoline D2/D3 agonist reseptor, pramipexole (PPX). Daaweynta dopaminergic ka sokow, daaweynta PPX waxay la xiriirtay dhibaatooyinka khamaarka qayb ka mid ah bukaannada cudurka Parkinson (Voon et al, 2007). Si kastaba ha noqotee, ma jirin tijaabooyin lagu ogaanayo in daaweynta D2/D3 soo-dhoweeyeyaasha ayaa ka hortagaya dhaqanka ceyrsiga inta lagu gudajiro qasaarooyinka.

PPX si weyn ayey xulasho u tahay D3 ka badan D2 Qaadashadayaasha iyo isku xidhka dawada loo yaqaan 'dopamine' (autoreceptor iyo post-synapti) dadka qaataha ku jira wadooyinka abaalmarintaCamacho-Ochoa et al, 1995) (eeg Macluumaadka Dheeriga ah). Qiyaasta yar ee PPX (tusaale ahaan, 0.5mg) waxay curyaamin kartaa barashada xoojinta barashada dadka waaweyn ee caafimaadka qaba (Pizzagalli et al, 2008), oo la kordhiyo xulashooyinka halista ah ee cayaaraha nooca natiimaadka ah (Riba et al, 2008), laga yaabee iyada oo loo marayo abaalmarinta abaalmarinta afka ah ee dariiqyada mesolimbic (Riba et al, 2008; Santesso et al, 2009). Marka la eego arrintan, iyo caddeyn muujineysa in qiyaasta hoose ee PPX, iyo wakiillo kale oo ku shaqeynaya D2 qabtayaasha, daciifiya calaamadaha natiijooyinka xun ('khaladaadka saadaasha xun') (Frank iyo O'Reilly, 2006; Santesso et al, 2009; van Eimeren et al, 2009), waxaan tijaabinay mala awaalka ah in qiyaasta kaliya ee PPX ay kordhiso dhaqan-raacdeynta luminta iyo, laga yaabee, inay saameyn ku yeelato qiimaha khasaaraha oo shakhsiyaadka caafimaad qaba ay diyaar u yihiin inay eryaan.

In kasta oo aynan suurtagal ahayn in natiijooyinka aan ka soo sheegno Tijaabooyinka 1 iyo 2 ay ka tarjumayaan isbeddello guud ee gobollada mawduucyada la xiriira midkoodna isku dayga isku-dayga daaweynta ama daaweynta PPX, waxaa suurtogal ah in indha indheynteena ay la xiriiraan isbeddelada feejignaanta ama dhiirrigelinta, laga yaabee inay ka tarjumayaan hab-nidaamyada xad-dhaafka ah. ee tijaabooyinka dawooyinka. Tusaale ahaan, halka yaraanta tryptophan sida caadiga ah aysan wax ka badalin saameynta gobolka ee dadka waaweyn ee laga baaray cudurada saameynta leh, waxay yareyn kartaa jawaabaha jir ahaaneed (wadnaha) jawaabaha waxqabadka xun (van der Veen et al, 2008). Waxaa intaa dheer, daraasadaha gudaha waxay muujinayaan in khamaarka ganacsiga uu la xiriiro kororka dareenka naxariista (Anderson iyo Brown, 1984; Meyer et al, 2000). Sidaa darteed, ma cadda in isbeddelada kacsiga ay kordhin karaan ama yareeyaan u janjeera inay khamaarka sii haysato si ay uga soo kabato khasaaraha. Markii hore, waxaan ogaanay in hal qiyaas oo ah beta-adrenoceptor antagonist, propranolol, ay yareeyeen feejignaanta go'aan qaadayaasha dhanka tilmaamaha ciqaabta la xiriira (Rogers et al, 2004), suuragalnimada sii deynta dabeecadda baacinta. Tijaabada 3, waxaan ku tijaabinay in isbedelada ay kacsan yihiin, sida ka muuqata nooca hoos u dhaca heerka garaaca wadnaha (HR) oo laga soosaaray dadka waaweyn ee caafimaad qaba hal xabbadood oo ah nooca loo yaqaan 'beta-adrenoceptor antagonist propranolol' ayaa saameyn ku yeelan doona dhaqanka luminta.

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MATERIALS AND METHODS

Kaqeybgalayaasha iyo Naqshadeeyayaasha

Dhamaan kaqeyb galayaasha waxay bixiyeen ogolaansho qoraal ah oo war bixin ah Kaqeybgaleyaasha waxaa lasiiyay baaritaan caafimaad oo ay kusameeyeen cilmi nafsi khibrad leh, ooy kujiraan wareysiga qaab dhismeedka qaabdhismeedka 'SCID-I' si loo hubiyo in midkoodna shuruudahan soosocda ee soosocda aan lasoo buuxin: (i) jirrooyinka jirka ee weyn; (ii) hadda jira ama xaaladdii hore ee DSM-IV niyadda weyn ama jahwareerka maskaxda; iyo (iii) ciladda daroogada DSM-IV ee hadda ama tii hore. Kaqeybgaleyaasha waxaa lagu qiimeeyay shaashada khamaarka South Oaks (Lesieur iyo Blume, 1987); dhibcaha oo dhan waxay ahaayeen midkood 0 ama 1, oo muujinaya inaysan jirin wax caddayn ah dhibaatada ama khamaarka cudurka.

tijaabi 1

Soddon iyo afar qof oo waaweyn oo caafimaad qaba ayaa kaqeyb qaatay Midkoodna ma lahayn taariikh cillad niyadda ah; Ma jirin wax xaddidan oo ku saabsan wajiga wareegga caadada ee ka qaybgalayaasha haweenka. Toddoba iyo toban kaqeybgalayaal (sideed rag ah) waxay cabeen cabitaan amino-acid ah oo aan kujirin tryptophan (T−) iyo 17 kaqeybgalayaasha (sideed rag ah) waxay cabeen cabitaanka amino-acid oo ay kujiraan tryptophan (T +). Kaqeybgaleyaasha T + iyo kaqeybgalayaasha T were waa lawaafajiyay marka la eego jinsigooda (eeg Jaantus Dheeraad ah S1), da'da (F <1.00), iyo awooda garashada (Raven et al, 1998) (F (1,30) <2.08).

Kaqeybgalayaashu waxay raaceen cunno yar oo borotiin ah (<2g) maalinta ka horeysa daraasada, oo sooman habeen ka hor intaysan tegin sheybaarka saacadaha 0830 maalinta tijaabada. Tallaabooyinka saameynta dowlad-wanaagga iyo is-il-gaarkaWatson et al, 1988) waxaa la qaatay waqtigan oo ay weheliso 15ml shaybaarka dhiigga si loo helo wadarta guud ee isku-uruurinta plasma tryptophan. Ka-qaybgalayaashu waxay markaa cabbeen cabitaan amino-acid ah muddo 60-daqiiqo ah. Midkoodna kaqeybgalayaashu mahelin waxyeellooyin ka baxsan lallabbada transitory. Ka-qaybgalayaasha waxaa la siiyay borotiin-hooseeya (<2g) qadada bartamihii maalinta. Ku soo celcelinta gobolka-togan-ka-soo-saarka cabbiraadda, iyo muunad dhiig oo labaad, ayaa la soo ururiyey + 5h ka dib isticmaalka cabitaanka amino-acid, ka hor intaadan dhameystirin ciyaarta luminta.

tijaabi 2

Soddon qof oo waaweyn oo caafimaad qaba ayaa si aan kala sooc lahayn loogu tala galay inay helaan 176ofg ee PPX ama placebo (placebo-PPX). Koox kastaa waxay ka koobnayd toddoba rag ah. Ma jirin farqi weyn oo u dhexeeya kaqeybgalayaasha qaatay placebo iyo kuwa helay PPX marka loo eego da'dooda ama awooddooda garasho (Jaantus Dheeraad ah S2) (labadaba F's <1.00).

176 TheQiyaasta ofg ee PPX ee loo adeegsado Tijaabada 2 waxay u dhigantaa qiyaasaha la muujiyey inay si wax ku ool ah u shaqeynayaan xanuunada lugta aan nasaneynin (Manconi et al, 2007). Waxaa jira asbaabo wanaagsan oo loo maleynayo in maadada (Hamidovic et al, 2008) iyo dhaqan (Pizzagalli et al, 2008; Riba et al, 2008; Santesso et al, 2009) saamaynta qiyaasta hoose ee wakiilada dopaminergic waxay ka tarjumayaan talaabooyinka pre-synaptik at the-auto-receptors kaas oo nidaamiya howlaha firfircoon ee maskaxda dopaminergic neurons.Frank iyo O'Reilly, 2006; Grace, 1995). Sida lagu sharaxay hoosta, waxaan ku celcelineynaa natiijooyinka midkaas (1)mg) qiyaasta hoose ee PPX waxay yareyneysaa cabirka nafsaaniga ah ee saameynta gobolka-kuyeelan ee dadka waaweyn ee caafimaadka leh waxaana loo qaatay inay soo jeediyaan qaab ficil pre-synaptic (ficil ahaan)Hamidovic et al, 2008). Si kastaba ha noqotee, 176keenaQiyaasta μg sidoo kale waa la barbar dhigi karaa kuwa la muujiyey si loo yareeyo proumctin serum ka sarreeya 2h (Schilling et al, 1992), uguyaraan kor u qaadista suurtagalnimada in natiijooyinkeenna sidoo kale ka tarjumaan qaar ka mid ah waxqabadka soo-dhaweynta synaptic-ka (Ben-Jonathan, 1985).

Kaqeybgalayaashu waxay kaqeybgaleen shaybaarka saacadaha 0830 iyo dhameystirka qiimeynta aasaasiga ah ee saameynta-gobolka iyo saameynta-cusubWatson et al, 1988). Qiyaasta aasaasiga ah ee dhiig karka (dhiig karka) (HRP) iyo HR ayaa la soo aruuriyay. Tan kadib, kaqeybgalayaashu waxay heleen hal 176 ahdoseg qiyaasta PPX ama kaabsoolka gelatin oo ay ku jirto laaktooska. Kadib 2h (+ 2h), cabirro dheeraad ah ee systolic / diastolic BP iyo HR ayaa la qaaday. Saameynta-gobolka iyo saameyn-ku-yeelashada ayaa sidoo kale la soo aruuriyey waqtigan, ka hor inta aan la dhameystirin ciyaarta eryada.

tijaabi 3

Afar iyo toban (toddobo rag ah) kaqeybgaleyaal ayaa si aan kala sooc lahayn loo xilsaaray inay helaan 80mg propranolol (placebo-PPL) iyo kaqeybgalayaasha 14 (sideed rag ah) ayaa si aan kala sooc lahayn loogu qoondeeyay inay helaan lactose placebo (PLA-PPL). Labada koox ee kaqeybgalayaasha ah ayaa sifiican iskuwaafajiyay da 'ahaan (eeg Jaantus Dheeraad ah S4) (F <1) iyo awooddooda garasho (F (1,24) = 1.87).

Kaqeybgalayaashu waxay kaqeybgaleen sheybaarka subaxa hore iyagoo sooman 2h iyo iyada oo aan lahayn kafeyn. Saameynta-gobolka iyo -ganeed (PANAS)Watson et al, 1988), systolic BP, diastolic BP, iyo HR ayaa lagu qiimeeyay aasaas ahaan ka dibna 30 kastadaqiiqo ka dib. Kaqeybgalayaashu waxay soo gabagabeeyeen ciyaarta luminta eryanaha + 75min daaweynta kadib.

Ciyaar luminta

Nooca ciyaartayaga luminta-ku-habboon ee sawirrada hal-ku-dhigga ee magnetic-ga ayaa si faahfaahsan loogu sharaxay meelo kale (Campbell-Meiklejohn et al, 2008). Ciyaar kasta, kaqeybgalayaasha waxaa laga rabey inay kala doortaan khamaarka si ay uga soo kabsadaan khasaaraha (qatarta ugu jira in ay laba jibaaraan cabirkooda) ama joojinta (iyo sii wadashada qasaaraha qaar). Dhibaatooyinka noocan oo kale ahi waxay horseedaan xulashooyinka khatarta leh duruufaha kala duwan ee bulshada iyo dhaqaalaha (Shafir iyo Tversky, 1995). Fikradaha sharraxa ee doorashada (shaki la’aan) ayaa u leh habdhaqankan xaqiiqada ah in khasaaraha uu ku dhaco qaybta isku-dhafka ah ee shaqada nafsiyeed ee la xiriirta qiimaha magaca (tusaale ahaan, natiijooyinka lacageed) qiimaha qiimaha ama adeegsiga, taas oo hoos udhacaysa adeegsiga la xidhiidha ceyrsashada iyo Dhibaatooyinka waaweyni aad bay uga yar yihiin kuwa hoos udhaca isticmaalka.Kahneman iyo Tversky, 2000). Markii hore, waxaan ogaanay in khamaarka si loo soo ceshado khasaaraha inta lagu jiro ciyaarteenna uu si togan ula xiriiro tillaabooyinka maskaxda ee u janjeedha in lagu eryo khasaaraha howlaha kale ee khamaarka (Campbell-Meiklejohn et al, 2008).

Bilowga ciyaarta, kaqeybgalayaasha waxaa loo sheegay inay leeyihiin khayaali ah £ 20000 si uu ula ciyaaro, laakiin kaqeybgaleha leh dhibcaha ugu badan dhamaadka tijaabada ayaa ku guuleysan doona abaalmarin dhab ah £ 70. 'Wareeg kasta' ee ciyaarta, bilow initial 10, £ 20, £ 40,, 80, ama £ 160 ayaa laga jaray wadar ahaan ciyaarta. Qaddarkani wuxuu ka muuqday hoos doorashooyinka: 'Jooji' iyo 'Ciyaar' (Jaantuska 1). Waqtigan xaadirka ah, kaqeybgalayaashu waxay dooran karaan 'Jooji', sii wadida khasaarahan isla markaana si dhakhso leh u soo afjaraya wareegga (natiijada 'joojinta-luminta'), ama waxay dooran karaan inay 'Ciyaaraan', taas oo ah, cayrsashada khasaaraha. Sidaa darteed, waxay ku qamaari karaan inay soo ceshadaan qaddar u dhigma khasaaraha, laakiin halista ah inay sii kordhiyaan khasaarahoodu isla qaddarka. Haddii natiijada go'aanka khamaarka ay ahayd mid wanaagsan (natiijada 'chase-win'), khasaarihii waa la soo ceshaday wareegiina wuu dhammaaday. Haddii natiijadu ay ahayd mid taban (natiijada 'baacsanaan-lumis'), khasaaruhu wuu labanlaabmay kaqeybgalayaashuna waxay heleen fursad kale oo ay ku joojiyaan ama ay ku eryan karaan doorashada xigta ee wareegga. Fursadaha xulasho kasta —'Play 'ama' Quit'-waxay u muuqdeen si isku mid ah had iyo jeer bidix iyo midig ee bandhigyada kumbuyuutarka.

Jaantuska 1

Jaantuska 1

Muuji taxanaha ciyaarta luminta. Bilowga wareeg kasta oo ciyaarta, khasaare ayaa lagu soo rogay oo go'aan ayaa lagu gaadhay midkood inuu ciyaaro (khamaar dheeri ah) ama joojiyo (inuu aqbalo khasaaraha), oo uu dhammaado wareegga. Khasaare isdaba-joog ah iyo go'aanno ayaa dhacay ...

Bandhigyada natiijada (eeg Jaantuska 1) wuxuu muujiyay haddii kaqeybgalayaashu ay guuleysteen qamaar iyo in lacagna aan lumin ('chase-win'); haddii ay lumeen khamaar iyo qadarka lumay ('chase-loss'); ama qaddarka lumay haddii kaqeybgalayaashu doorteen inay ka baxaan wareega ('Stop-loss'). Dhamaadka wareeg kasta, kaqeybgalayaasha waxaa sidoo kale lagu wargaliyay qasaarahoodii ugu dambeeyay ee bandhig 'wareega-lumis' ah. Bandhigani wuxuu muujiyey wadarta qasaaraha isugeynta wareeggaas, qoraalka guduudan haddii khasaaruhu ka weynaaday 0, laakiin qoraalka cagaaran haddii 0. Wareegyada ciyaarta luminta-ceyrsashada waxay ku bilaabatay khasaaro £ 10, £ 20, £ 40, £ 80, ama £ 160. Haddii kaqeybgalayaashu sii wadaan luminta, khasaaruhu wuu sii laba jibaaraa ilaa ay ka gaarayaan 640 XNUMX, xilligaas oo wareegga uu dhammaanayo, isagoo la kulmay khasaarihii ugu badnaa.

Dhammaan kaqeybgalayaasha waxay ciyaareen wareegyada 20 ee ciyaarta luminta. Natiijooyinka Chase-gu waxaa loogu meeleeyay si aan kala sooc lahayn wareeg kasta sida in natiijooyinka guuleysiga ay u dhacaan si isku mid ah had iyo jeer tiro kasta oo ah (inta u dhaxaysa 0 iyo 5) khasaare isdaba joog ah. Natiijooyinka ciyaarta baadi-goobka ayaa loo qaybiyey sidan oo kale wareegyada 14 ayaa soo celiyay dhammaan khasaaraha haddii kaqeybgalayaashu ay go'aansadeen inay ka ciyaaraan xulasho kasta oo ciyaarta ah. Si kastaba ha noqotee, lix wareeg ayaa sababay khasaaraha ugu badan ee £ 640.

Kaqeybgalayaasha looma sheegin wax kusaabsan itimaalka wanaag vs natiijooyin xun sidaa darteed go'aanadooda waxaa lagu gaadhay shuruudaha 'madmadowga' (Camerer iyo Weber, 1992). Si looga joojiyo kaqeybgalayaashu inay qaataan istiraatiijiyad muxaafidnimo oo ay horay uga joojiyaan si ay u ilaashadaan inta ugu badan ee lacagtooda ciyaarta intii suurtagal ah, wax macluumaad ah lagama bixin isugeynta wadarta guud ee lacagta ciyaarta inta lagu jiro ciyaarta. Kaqeybgaleyaasha waxaa sidoo kale lagu wargaliyay inaysan gaari doonin dhibcaha ugufiican ee suurta galka ah iyaga oo si gaar ah u ciyaaraya ama joojinaya.

Isku soo wada duuboo, kaqeybgalayaashu waxay la kulmayeen dhibaatooyin kaladuwan oo laxiriira xulasho udhaxeysa khamaar si aad uga soo kabato qasaarooyinka halista ah in aad labalaabto cabirkeeda, ama aad u sii wado khasaaraha oo aad kudhameyso fowdada, halka isla waqtiga la ilaaliyo ilaha badan ee suurta galka ahCampbell-Meiklejohn et al, 2008). Qiimaha agabyadan (qodobada tijaabada lagu qeexay) waxaa lagu bixiyay macnaha guud ee tartanka kaqeybgalayaasha ee u baahan kaqeybgalayaashu in ay ilaashadaan qodobbada ugu badan ee suuragalka ah. Isku-darka isku dhafan ee magac iyo abaalmarin dhab ah ayaa loo adeegsaday dhaqale ahaan dabeecadda si loo muujiyo hab dhaqan ahaan iyo tiro ahaanba la mid ah tan lagu arkay ka baxsan shaybaarka (Cubitt et al, 1998).

Falanqaynta tirakoobka

Tallaabooyinka ku-tiirsanaanta waxaa ka mid ahaa saamiga xulashooyinka khamaarka (ama eryada) dhammaan xulashooyinka la sameeyey intii lagu jiray ciyaarta, iyo tirada celceliska khasaaraha is daba jooga ah ee loo eryay wareeggiiba. Waxaan falanqeynay baaxadda (ama qiimaha) khasaaraha la eryay iyo baaxadda (ama qiimaha) khasaaraha la dhiibey intii lagu jiray ciyaarta. Qiimayaashan waxaa loo muujiyey inay yihiin saamiyo celceliska dhammaan wixii khasaare ah ee la kulantay intii lagu jiray ciyaarta (ka eeg Macluumaadka Dheeraadka ah faahfaahin dheeraad ah).

Tirakoobka dadka, ujeedka, iyo cillad-raacinta saddexda tijaabo ayaa la tijaabiyay iyadoo la adeegsanayo falanqaynta hal dhinac ah ee kala duwanaanshaha (ANOVA) iyada oo loo adeegsanayo qodobbada u dhexeeya-maaddooyinka daaweynta (T + vs T−, PPX vs placebo, ama propranolol vs placebo) iyo jinsi.

Tag:

Natiijooyinka

Tijaabada 1: Isku-darka Triptophan

Saameynta jirka iyo maaddada

Isticmaalka cabitaanka amino-acid ee aan lahayn tryptophan (daaweynta T−) waxay soo saartay hoos u dhac weyn oo ku yimid isku-darka guluubyada + 5h dambe markii la barbar dhigo cabitaanka xakamaynta (ee daaweynta T +) (eeg Shaxda Dheeriga ah S1). Si kastaba ha noqotee, daaweynta T− ma aysan soo saarin wax isbeddel ah oo calaamadeysan midkoodna xaalad-togan ama mid-ku-dhagane ah marka loo barbar dhigo daaweynta T + (Tababbarka dheeriga ah ee S1) (oo dhan F (1,30) 's <2.29).

Baxsashada

Kaqeybgalayaasha helay daaweynta T− waxay muujiyeen hoos u dhac weyn oo la taaban karo ee saamiga go'aanada si loo raacdeeyo khasaaraha marka la barbar dhigo kaqeybgalayaasha helay daaweynta T + (Jaantus 2a) (F (1,30) = 8.43, p<0.01). Tirada go'aamada isku xigxiga ee lagu ceyrsanayo qamaar luminta ayaa sidoo kale si kalsooni leh hoos loogu dhigay ka dib yaraynta tryptophan (Jaantus 2b) (F (1,30) = 8.06, p

Jaantuska 2

Jaantuska 2

Joogtada ah ee dabagalka dhaqanka ceyrsashada ee seddex muunad oo ka mid ah kaqeybgaleyaasha caafimaadka qaangaarka ah oo aan caafimaad ahaan la soconin ka dib markii ay yaraatey isku dayga 'tryptophan'vs xakamaynta cabitaanka amino-acid), hal xNUMX ahμg ee D2/D3 receptor agonist, pramipexole (PPX vs placebo), ...

Marka la barbardhigo saamaynta saamiga khamaarka si loo soo celiyo khasaaraha, ma jirin wax isbadal ah oo ku yimid qiimaha khasaaraha ay kaqeybgalayaashu iskuxiray iskudaygu waxay go aansadeen inay eryaan (loogu muujiyo saamiga ay uleeyihiin qiimayaasha dhamaan khasaaraha la soo kulmay intii ciyaarta lagu jiray; eeg Macluumaadka Dheeraadka ah) (Jaantus 3a) marka la barbardhigo kaqeybgalayaasha helay nidaamka xakamaynta (F's <1). Midkoodna ma jirin wax isbeddel ah oo ku yimid qiimaha khasaaraha ayaa isa soo dhiibay markii la go’aansaday inuu shaqada ka tago (Jaantus 3b) (F's <1).

Jaantuska 3

Jaantuska 3

Adeegsiga macluumaadka qiimaha ee dhaqanka luminta ee seddexda muunadood ee caafimaad, kaqeybgaleyaasha caafimaad oo aan la soconin ka dib isku-dayga 'gogoldtop' (vs xakamaynta cabitaanka amino-acid), hal xNUMX ahμg ee D2/D3 receptor agonist, pramipexole ...

Tijaabada 2: PPX

Saameynta jirka iyo maaddada

Systolic BP, diastolic BP, iyo HR si weyn looma beddelin daaweynta ka dib marka loo eego PPX marka loo eego daaweynta 'placebo' (eeg Macluumaadka Dheeriga ah iyo Tababbarka Dheeriga ah S3) (dhammaan F (1,25) 's <1.86).

Daaweynta PPX waxay si weyn hoos ugu dhigtay saameynta gobolka-wanaagsan marka la barbar dhigo placebo guud ahaan + 2h daaweynta ka dib (F (1,26) = 10.05, p<0.005) (Jaantus Dheeraad ah S2). Gaar ahaan, halka saameynta togan ay u muuqato inay sii kordheyso daaweynta ka dambeysa placebo (F (1,13) = 3.53, p= 0.08), waxaa si weyn hoos ugu dhacay ka dib daaweynta PPX (F (1,13) = 6.84, p<0.05). +2h, markii la dhammeystirayo ciyaarta baadi-goobka, kaqeybgalayaashii helay PPX waxay soo sheegeen saameyn hoose oo aan fiicneyn marka loo eego kuwa helay placebo (F (1,26) = 8.34, p<0.01). PPX ma aysan beddelin saameynta gobolka-taban ee la barbardhigo placebo (dhammaan F's <1).

Baxsashada

PPX waxay waxyar yareysay tirada go'aamada lagu eryo, iyo tirada go'aamada is daba jooga ah ee lagu eryo, inta lagu gudajiro khamaarayaasha marka loo barbar dhigo placebo (Jaantuska 2); si kastaba ha noqotee, midkoodna saameyntani ma ahan mid muhiim ah (F's <1). Taa bedelkeeda, PPX si weyn kordhay qiimaha khasaaraha ay kaqeybgalayaashu go’aansadeen inay khamaaraan si ay uga kabsadaan (Jaantus 3a) (F (1,26) = 4.94, p<0.05), iyo sidoo kale si weyn dhimay Qiimaha khasaaraha kaqeybgalayaashu is dhiibeen (Jaantus 3b) (F (1,26) = 5.87, p<0.05). Isbeddeladaan ku yimid qiimaha khasaarihii la ceyrsaday ee la dhiibtay ayaa wali muhiim ah markii ay saameyn togan ku yeelatay +2h waxaa loo galay sidii isuduwaha (F (1,25) = 4.48, p<0.05 iyo F (1,25) = 4.39, p<0.05, siday u kala horreeyaan). Sidoo kale si guud looma bedelin markii falanqaynta tirakoobka lagu sameeyay qiimaha aan hagaagsaneyn ee qasaaraha la ceyrsaday ama qiimaha la dhiibtay (eeg Macluumaad Dheeraad ah faahfaahin buuxda).

Tijaabada 3: Propranolol

Saameynta jirka iyo maaddada

Propranolol muu soo saarin isbeddello si weyn uga weyn ama ka yar systolic ama diastolic BP marka la barbar dhigo placebo (dhammaan F's <1). HR wuu yaraaday +75Daqiiqad kadib daaweynta (73.64 ± 10.82 vs 62.04 ± 7.68bpm) (F (1,24) = 60.30, p) Si kastaba ha noqotee, hoos-u-dhigani wuxuu ahaa mid aad u ballaadhan ka dib markii la barbardhigo placebo (Jaantus Dheeraad ah S0.0001) (F (5,24) = 4.98, p<0.05). Maaddaama aasaasiga HR ay u muuqatay inay ka weynaaneyso kaqeybgalayaasha lagu daaweeyay propranolol marka la barbar dhigo kaqeybgalayaasha lagu daaweeyay placebo (F (1,24) = 2.64), waxaan sidoo kale baarnay saameynta daaweynta ee isbeddelka saamiga ee kaqeybgalayaasha 'HR'. Tani waxay xaqiijisay in propranolol ay soo saartay hoos u dhac weyn oo HR ah marka loo eego placebo (18.64 ± 8.45 vs 11.08 ± 11.38%) (F (1,24) = 4.64, p

Saameynta gobolka ee wanaagsan iyo-daweynta ayaa ah mid aan si weyn u kala duwaneyn daaweynta ka dib marka la barbar dhigo daaweynta marka loo eego daaweynta placebo (eeg Macluumaadka Dheeraadka ah iyo Jaantus Dheeraad ah S4) (F <1.00 iyo F (1,24) = 1.61, siday u kala horreeyaan). Ma jirin kala duwanaansho la xiriira daaweynta oo muhiim ah ama midkood cabbir ahaan ah + 75min markii ciyaarta luminta eryana la dhammeeyo.

Baxsashada

Ma jirin farqi weyn oo u dhexeeya propranolol iyo placebo marka loo eego tirada go'aamada la eryanayo, tirada go'aamada is daba jooga ah ee la eryanayo (Jaantuska 2), ama qiimaha khasaaraha la eryay iyo qiimaha khasaaraha la dhiibo (Jaantuska 3) (dhammaan F's <1).

Tag:

DHIBAATOOYINKA

Waxyaabaha aan helnay waxay soo jeedinayaan in serotonin iyo dopamine ay ka ciyaaraan door isugeyn ah iyagoo u janjeera inay khamaarka sii hayaan si ay uga soo kabsadaan khasaaraha. Waxqabadka Serotonin wuxuu u muuqdaa inuu door ka ciyaarayo sii wadashada dhaqan-ceyrsashada, halka nashaada dopamine, ay kujirto ugu yaraan D2/D3 Nidaamka soo dhoweynta, wuxuu u muuqdaa inuu nidaaminayo baaxadda khasaaraha la eryay ama la dhiibtay. Marka la barbardhigo, labada dhinacba ee baacsiga luminta ayaa si weyn uga madax bannaan isbadallada ku dhaca dhiirigelinta naxdinta leh, ugu yaraan sida ay u dhexdhexaadinayaan waxqabadka beta-adrenoceptor. Xogteenna ayaa muujineysa male-awaal ku saabsan hababka loo yaqaan 'monaminaminergic system' ee dhiirrigeliya muujinta xaruntan, laakiin si liidata loo fahmay, hab dhaqanka khamaarka.

Tijaabada 1, waxaan baarnay saamaynta isku dayga iskudhafka tijaabada si loo tijaabiyo bal in waxqabadka bartamaha serotonin uu dhexdhexaadinaayo dhaqanka luminta. Tan waxaa laga yaabaa in lagu muujiyo ugu yaraan laba siyaabood. Marka hore, dhowr khadad oo caddeyn ah ayaa sheegaya in serotonin-ka uu dhexdhexaadinaayo xakameynta dabeecad aan la abaalmarin ama la ciqaabo (Crockett et al, 2009; Dayan iyo Huys, 2008; Soubrie, 1986). Marka, isku-darka 'tryptophan', oo horseedaysa hoos u dhaca waxqabadka serotonin, ayaa laga yaabaa in la filayay inuu kordhiyo khamaarka si uu uga soo kabsado luminta kaqeyb galayaashayada caafimaad qabka ah. Marka la barbardhigo, waxqabadka serotonin wuxuu sidoo kale ka ciyaaraa door muhiim ah barashada, iyo la qabsiga, dhacdooyinka kahortaga (Bari et al, 2010; Daw et al, 2002; Deakin iyo Graeff, 1991; Doomaha et al, 2005). Marka la eego isku-dayga 'isku-darka' isku-darka 'tryptophan' wuxuu sidoo kale hagaajin karaa saadaalinta ciqaabta natiijooyinka (Cools et al, 2008), iyo kor u qaadista jawaabaha habdhiska ee ciqaabida natiijooyinka gudaha xuubka hoose ee afka kore (Doomaha et al, 2005), Waxaan sidoo kale fileynay in yaraanshaha 'tryptophan' uu kordhin karo saliida natiijooyinka xun iyo inuu yareeyo dabeecada ceyrsashada. Xaqiiqdii, iyada oo aan la soo saarin wax isbeddel ah oo muuqda oo ku saabsan gobolka dadka waaweyn ee caafimaadka qaba, saamaynta yaraanta 'tryptophan' ayaa si weyn hoos ugu dhigtay saamiga go'aannada ka-qaybgalayaashu gaadheen inay ceyrsadaan khasaaraha, waxayna yareeyeen tirada go'aannada isku xigxiga ee ceyrsanaya, inta lagu guda jiro orodka luminta khamaarista. Tani waxay soo jeedinaysaa, markan uguyaraan, waxqabadka serotonin wuxuu caawiyaa joogtaynta cayrsashada luminta halkii laga celin lahaa.

Fikradaha sharraxa ee doorashada ee hubinta aan loo meel dayin ayaa dabeecad u-eryanaya fikirka fikirka ah in hoos udhaca ku yimid qiimaha maaddada ama tasiilaadka la xiriira daba-galka iyo silica khasaaraha badan uu weli si aad ah uga yar yahay hoos udhaca isticmaalka.Kahneman iyo Tversky, 2000). Xaaladahan, macno ayey u leedahay khamaarayaashu inay sii wadaan ciyaarta, illaa inta laga helayo kheyraadka lagama maarmaanka ah. Marka loo eego aragtidan, baacsiga luminta waxaa loo arki karaa dabeecad ka baxsad kacsanaan ah, laakiin mid la xakameeyay, ugu yaraan qayb ahaan, adeegsiga marginal ee sii wadista ciyaarta marka loo eego joojinta. Soo helitaankeenii isku dayga isku-darka ee isku-darka 'isku-darka' ee loo yaqaan 'tryptophan' ayaa hoos u dhigay qaab dhaqankeena ah ee baacsashada dadka waxay sheegaysaa in, tusaale ahaan ugu yaraan, waxqabadka serotonin-ka wax u dhimaya faa iidada yareynta ciyaarta sii kordheysa iyadoo la kordhinayo cabashada natiijooyinka xun ee mustaqbalka guud ahaan qiyamka la soo gudboonaaday intii lagu jiray ciyaarta (Cools et al, 2008; Deakin iyo Graeff, 1991).

Tijaabooyin dheeri ah ayaa loo baahan doonaa si loo dhiso xiriirka ka dhexeeya waxqabadka serotonin iyo khamaarka si looga soo kabto khasaaraha. Si kastaba ha noqotee, marka la eego serotonin-ka wax ku oolka ah ee xakamaynta kicinta, ma aha inaan u maleyno in xiriirkani uu noqon doono mid fudud ama toosan (Winstanley et al, 2004). Raadinteena ah in isku dayga yaraynta isku dayga guuldarrooyinka ee loo yaqaan 'tryptophan' uu hoos u dhigay raadinta luminta ayaa la jaan qaadaya aragtida kale, waxaa lagu helay iyada oo la adeegsanayo habab fudud oo lagu cabbiro dabeecadaha halista ah, kuwa xambaaraya 10-ku celcelis dhantaalka ah STin2 hiddo-wadaha (taasi waxay keenaysaa in sare serotonin tone) waxay muujisaa kordhinta xulashooyinka halista raadinta ee khasaaraha (Zhong et al, 2009). Taa bedelkeeda, xogteenna ayaa si muuqata u waafajineysa natiijooyinka la helay ee ah in toddobaadyo 2 toddobaad ah oo lagu daaweeyo tryptophan, ay tahay cunno cunno, yareyso isbeddelada u dhexeeya xulashooyinka halista ah marka la sameynayo go'aammo keli ah inta u dhexeysa faa'iidooyinka qaarkood iyo faa'iidooyinka waaweyn ama aan la hubin, iyo xulashooyinka halista raadinta markii la sameynayo. go'aano keli ah oo u dhexeeya khasaaraha qaar iyo khasaaraha aan la hubin ama ka yar.Murphy et al, 2009). Isku soo wada duuboo, xogtaani waxay muujineysaa in saameynta serotonin ee khamaarka si looga soo kabsado qasaaraha ay ku kala duwanaan karto iyadoo ku xiran dhowr arrimood oo cilmi nafsi iyo daawooyin ah, oo ay ku jiraan in xaalada tijaabada ay ku lug leedahay hal ama dhowr doorasho oo isku xigta oo lagu soo kabanayo qasaaraha iyo haddii ay jirto xaalad kale oo xulashooyin kale oo ku lug leh qiyamka wanaagsan ee laga filayo.

Saameynta hal xNUMXdoseg ee PPX aad bay u kala duwanaayeen. Daaweyntani ma kordhinin saamiga go'aanada ee lagu baadi goobayo khasaaraha ama tirada go'aanada isku xigxiga ee lagu eryanayo inta lagu gudajiro khamaarayaasha luminta; si kastaba ha noqotee, PPX waxay si weyn u kordhisay qiimaha khasaaraha ee ay kaqeybgalayaashu rabeen inay eryaan oo isla waqtigaasna ay yareeyaan qiimaha khasaaraha ay kaqeybgalayaashu diyaar u yihiin inay dhiibaan markii ay joojiyeen. Sidaa darteed, hal cabir oo ah PPX ayaa horseed u ah doorashada daba-galka khasaaraha ballaaran iyadoo laga baxsanayo khasaaraha yaryar.

Waxaan qiraynaa in habka ficil ee hal xNUMXQiyaasta ofg ee PPX ee loo adeegsado Tijaabada 2 wali lama hubo. In kasta oo saameynta dabeecadda ee qiyaasta hoose ee daawooyinka dopaminergic laga yaabo inay muujiso ficil pre-synaptic at auto-receptors of dopamine neurones gudaha maskaxda-dhexe (Frank iyo O'Reilly, 2006; Santesso et al, 2009), hal qaadasho oo ah 100 iyo 200μg PPX wuxuu kaloo yareyn karaa qulqulka 'serum prolactin', isagoo soojeedinaya tallaabada ka dambeysa synaptik-ka ee daroogada qaadata daawada dopamine ee ku taal gudaha hore ee wadnaha (Schilling et al, 1992). Halkan, dib-u-soocelinta natiijooyinka hore, waxaan ogaan karnaa in qiyaastayada 176μg PPX sidoo kale waxay si weyn hoos ugu dhigtay saamaynta xaalada wanaagsan ee kaqeybgalayaasha (Hamidovic et al, 2008). Tani waxay soo jeedinaysaa, in tijaabadan ugu yaraan, qiyaaso ah PPX ay saameyn ku yeelatay waxqabadka ciyaarteenna eryanaya iyada oo loo sii marayo waxqabadka D2/D3 dopamine auto-receptors

D2 iyo D3 Soo-dhoweeyeyaasha waxaa inta badan lagu muujiyaa dariiqooyin xoojin ah oo ku yaal sanbabada Nuclearka iyo amygdala (Camacho-Ochoa et al, 1995), taas oo labaduba u muuqda inay saameyn ku leeyihiin xoojinta qiimaha dawooyinka kicinta sida kokain (Caine et al, 1997; Thiel et al, 2010). Waqtigan xaadirka ah, ma hayno qaab aan ku ogaan karno nooca qaababka soo dhaweynaya ee doorka weyn ka qaata dabagalka luminta ee la arkay. Tijaabooyin hore waxay soo jeediyeen nashaadaadka D2 soo-dhoweeyayaasha ayaa wax u dhimi kara barashada natiijooyinka xun ee go'aannada halista ah ('no-go learning') adoo wax u dhimaya muujinta dips-ka ee dhaqdhaqaaqa dopamine-ka ee maskaxda bartamaha kaas oo muujinaya khaladaadka saadaasha xun (Frank iyo O'Reilly, 2006; Frank et al, 2007a,2007b, 2009). Si kastaba ha noqotee, xogteenna ayaa soo jeedineysa in daneyntan ay u tahay natiijooyinka luminta natiijooyinka la xiriira D2/D3 Waxqabadka soo-dhoweynta wuxuu soo saaraa isbeddelo aad u adag oo ku saabsan xulashooyinka halista ah marka loo eego guuldarada fudud ee laga barto dhacdooyinka xun. Saas ma aha, waxaan qiyaaseynaa in cilladaha soo ogaanshaha dheecaannada dhaqdhaqaaqa dopamine ka dib natiijooyin xun ay soo saartay guuldaradii tooska ahayd ee diiwaangelinta khasaarooyinka yar yar, sidaas darteedna la kordhiyay tirada kaqeybgalayaasha PPX ee lagu daweeyay go'aannada ay uga tagayaan saamiyada yar. Si kastaba ha noqotee, dareenka xasaasiga ah ee luminta natiijooyinka la xiriira D.2/D3 nashaada ayaa sidoo kale sii yareysay isbeddelka xun ee qiimaha maaddada la xiriirta ee lasaarayo khasaaraha ballaaran, iyadoo la kordhinayo qiimaha yaraanta ee ciyaarta sii socota; sidaas darteed kor u qaadista go'aannada si loo eryo khasaaraha qiimaha weyn marka loo eego placebo.

Isbeddelada ku saabsan xoojinta barashada kadib daaweynta PPX (Pizzagalli et al, 2008) waxaa lala xiriiriyaa calaamadaha wax laga beddelo gudaha gobolka murugada leh kadib natiijooyin xun (Santesso et al, 2009) iyo calaamad aan qarsooneyn marka loo eego duruufaha ka dambeeya natiijooyinka wanaagsan (Riba et al, 2008). Markii hore, waxaan soo aragnay in jawaabaha dareenka ah ee natiijooyinka khamaarka xun ee gudaha murugada ciriiriga ah ay sidoo kale la xiriirto sii socoshada dabeecadda inta lagu gudajiro waxqabadka ciyaarteenna khasaaraynta ah (Campbell-Meiklejohn et al, 2008). Tani waxay la jaanqaadeysaa cadaymihii elektiroonigga ah ee dhowaaq ee ahaa in shaqooyinka la xiriira abaalmarinta ee dibedda murqaha iyo qaab-dhismeedka khadka dhexe laga yaabo in lagu carqaladeeyo khamaarlayaasha cudurada ku dhaca.Hewig et al, 2010). Sidaa darteed, natiijooyinka Tijaabinta 2 waxay sare u qaadeysaa suurtagalnimada in qaadasho keli ah oo loo yaqaan 'PPX' ay kordhiso qiimaha khasaaraha ee loo maleynayo in lagu eryanayo calaamadaha xoojinta isbedelka ah ee loo yaqaan 'wareegga neural' ee ka kooban gobolka dillaaca gudaha iyo bartilmaameedyada marinka hawo-mareenka ee xiisaha leh.Nakano et al, 2000).

Ugu dambeyntii, natiijooyinka Tijaabinta 3 waxay muujineysaa in halka hal cabir oo ah 80mg propranolol wuxuu si weyn hoos ugu dhigay HR marka loo barbar dhigo placebo, si weyn ugama badalin tirada go'aamada lagu eryanayo khasaaraha, qiimaha khasaaraha la eryay, ama qiimaha khasaaraha la dhiibo. Natiijooyinkaani waxay soo jeedinayaan in fahamka iyo wajiyada shucuur ahaanta ee raadinta ergo qaabeeysa ciyaarteena — in kasta oo sida muuqata aysan aheyn xiisaha la xiriira howlaha ciyaarta ganacsiga (Anderson iyo Brown, 1984) - oo aan saameyn ku lahayn khalkhalgelinta waxqabadka beta-adrenoceptor. Waxay sidoo kale bixiyaan xoogaa dammaanad ah in saamaynta isku dayga iskudhafka iyo PPX ee aan ku aragnay Tijaabooyinka 1 iyo 2 aan loo aanayn karin isbeddellada aan la ogaan ee isbeddelada naxariista iyo / ama dareenka durugsan. Si kastaba ha noqotee, dhaqanka dabagalka ayaa sifiican saameyn ugu yeelan kara dhinacyo kale oo ah shaqo noradrenaline ah, oo ay kujirto waxqabadka alpha2-adrenoceptors kaas oo saameyn ku leh waxqabadka koritaanka gudaha ee deegaanka coeruleus isla markaana wanaajinaya socodsiinta natiijooyinka go'aan diidmo ah (ama khaladaadka ficilka) ee aagga murugsan (Riba et al, 2005).

Dhowr xadidan oo ah natiijooyinkayaga ayaa u baahan in wax looga qabto baaritaannada mustaqbalka. Marka hore, in kasta oo ciyaarteenna khasaaradu ay qabsato dabeecadda lama huraanka u ah ciyaarta sii wadata ee keenta khasaaraha sii kordha, tani waxay daruuri u tahay inay xadiddo awooddeena aan ku go'doomin karno gaar ah habab cilmi nafsi oo laga yaabo inay saameyn ku yeeshaan serotonin iyo D2/D3 firfircoonida si ay u saameyso khamaarka si ay uga soo kabato khasaaraha Qiyaasta 'Tryptophan' iyo hal qiyaas oo yar oo ah PPX waxay soo saartay isbeddel dhaqameed oo khaas ah oo khamaarka si looga soo kabsado khasaarihii, laakiin tijaabooyin dheeri ah ayaa loo baahan yahay si loo dejiyo sida isbeddeladani ula xiriiraan waxa aan horay uga ogaanay doorka serotonin ee ka-hortagga ama ciqaabta la ciqaabayo (Crockett et al, 2009; Soubrie, 1986) iyo waxaan ka ognahay doorka D2 qaabilaadaha wax barashada marka laga yimaado natiijooyinka taban (Frank, 2006). Marka labaad, saamaynta caafimaad ee natiijooyinkaan ayaa loo baahan yahay in la baaro iyadoo la baarayo saameynta daaweynta 'serotonergic iyo dopaminergic' ee ku saabsan waxqabadka ciyaarteenna-eryanaya ee muunadaha qamaarka cudurada, iyo sidoo kale tijaabinta luminta baadi-goobka tusaale ahaan xakameyn liita ee kale. qabatinka (Rogers et al, 2010). Waxaa kale oo aan baari karnaa doorka kuwa kale ee maskaxda ka shaqeeya, sida nidaamka opiate iyo glutamate, kuwaas oo sii wadi kara dhibaatooyinka khamaarka (Grant et al, 2007, 2008).

Khamaarka jirku waa il aad u weyn oo dhibaato qoys iyo mid qoys leh waxayna matalaysaa arrimo caafimaad oo weyn oo dadweynaha ah (Shaffer iyo Korn, 2002). Si kastaba ha noqotee, wax yar baynu ka og nahay arrimaha noolaha ee keenaya u nuglaanta dhibaatooyinka khamaarka, iyada oo aan lahayn daaweyn shatiyootis oo shati leh oo ay hadda heli karaan dhakhaatiirta. Tijaabooyinka lagu soo bandhigay halkan waxay muujinayaan hal hab oo lagu bilaabi karo in arrimahan wax looga qabto; taas oo ah, iyada oo la baadho aasaaska iyo dawada asaasiga ah ee garashada iyo dabeecadda dabeecadda ee ka muuqata shakhsiyaadka jooga rugta caafimaad. Natiijooyinkaas waxay soo jeedinayaan in dulqaadka guud ee khamaarayaashu ay u ciyaarayaan si ay uga soo kabsadaan khasaaraha waxaa lagu habeeyay waxqabadka serotonin, halka qiimeynta khasaaraha ay kuwa khamaaradu u xukumaan inay eryaan ay dhexdhexaadinayso waxqabadka D2/D3 nidaamka receptor.

Tag:

Mahadnaq

Daraasaddan waxaa lagu maalgeliyey xubinnimada Golaha Cilmi-baarista Caafimaadka si ay u helaan Daniel Campbell-Meiklejohn iyo abaalmarin madax-bannaan oo laga soo qaatay Golaha Cilmi-baarista Bayoolajiga iyo Bayoolajiga (BBSRC) Robert Rogers. Waxaan sidoo kale jeclaan lahayn inaan uga mahadcelino Michael Frank talooyinkii caawinta badnaa ee ku saabsan nooc hore ee qoraal gacmeedkan.

Tag:

Notes

Waxaan soo sheegin wax dano dhaqaale ah oo biomedical ah ama khilaafaadka ka dhalan kara xiisaha.

Tag:

Qoraalada

Macluumaadka Dheeraadka ah ayaa la socda waraaqda websaydhka 'Neuropsychopharmacology' (http://www.nature.com/npp)

Tag:

Qalabka Dheeraadka ah

Macluumaadka Dheeraadka ah

Halkan riix halkan si aad u heshid xog dheeri ah.(81K, doc)

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tixraacyada

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