Serotonin ndi Dopamine Kuchita Ntchito Zowonjezera pa Kutchova Juga kuti Zidzatha Kutaya (2010)

Neuropsychopharmacology. 2011 Januari; 36 (2): 402-410.

Wolemba pa intaneti 2010 October 27. doi:  10.1038 / npp.2010.170

PMCID: PMC3055672

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

Zolemba za Mlembi ► Article amanenanso ► Chidziwitso cha Copyright ndi License ►

Nkhaniyi yakhala wotchulidwa ndi nkhani zina mu PMC.

Pitani ku:

Kudalirika

Kupitiliza kutchova juga kuti upezenso zomwe zawonongedwa - 'kuthamangitsana' — ndichinthu chodziwika bwino pamasewera a juga. Komabe, ndizochepa zomwe zimadziwika za ma neuromodulators omwe amakhudza khalidweli. M'mayeso atatu osiyana, tidasanthula gawo la ntchito ya serotonin, D2/D3 zochitika za receptor, ndi ntchito ya beta-adrenoceptor pakutha kuthamangitsa zaka komanso ma IQ-ofanana omwe ali ndi thanzi labwino adasinthidwa mosasamala chithandizo kapena yoyenera / placebo. Mu Experiment 1, ophunzira adamwa zakumwa za amino-acid zomwe zinalibe kapena sizinali ndi serotonin precursor, tryptophan. Muyesera 2, ophunzira adalandira 176 imodziMlingo wa μg wa D2/D3 receptor agonist, pramipexole, kapena placebo. Muyesera 3, ophunzira adalandira 80 imodziMlingo wa beta-adrenoceptor blocker, propranolol, kapena placebo. Kutsatira chithandizo, ophunzira adamaliza masewera othamangitsa omwe adachita pakompyuta. Kusintha kwa mtima ndi mtima kumayesedwa poyambira ndikutsatira chithandizo. Kuchepetsa kwa Tryptophan kunachepetsa kwambiri kuchuluka kwa zisankho zomwe zimapangidwa pothamangitsa zomwe zawonongeka, komanso kuchuluka kwa zisankho motsatizana, kuthamangitsidwa kosintha kwamalingaliro. Mosiyana ndi izi, pramipexole idakulitsa kwambiri mtengo wazotayika zomwe zidathamangitsidwa ndikuchepetsa phindu lazopereka zomwe zaperekedwa. Propranolol idachepetsa kugunda kwa mtima, koma sizinasinthe kwenikweni pamachitidwe othamangitsa anthu. Kuthamangitsa kutayika kumatha kuganiziridwa ngati njira yothamangitsira yomwe ikulamulidwa, mwanjira ina, ndi kuchepa kwakanthawi kopitilira kutchova juga poyerekeza ndi phindu lazotayika kale. Serotonin ndi dopamine zimawoneka kuti zimagwira ntchito zosagwirizana ndi zomwe anthu amakonda kutchova juga kuti achire, kapena kufuna 'kuthawa' kutayika koyambirira. Zochita za Serotonergic zikuwoneka kuti zikulimbikitsa kupezeka kwa kuthamangitsidwa ngati njira yosankhira, pomwe D2/D3 ntchito ya receptor imabweretsa kusintha kosavuta mu mtengo wa zotayika zomwe zikuwoneka kuti zikuthamangitsidwa. Wosangalatsa wachifundo, osachepera monga wophatikiza ndi beta-adrenoceptors, satenga nawo mbali yayikulu pakusankha kuthamangitsidwa chifukwa cha ma labotale.

Keywords: serotonin, dopamine, kuthamangitsa, juga, kulimbikira, mtengo

Pitani ku:

MAU OYAMBA

Kutchova njuga kuti muchepetse zomwe zatayika, kapena kutayika kuthamangitsidwa (Lesieur, 1977,, ndi gawo lalikulu pakupanga zisankho za anthu (Kahneman ndi Tversky, 2000). Komabe, munthawi yazachipatala, kuthamangitsa anthu ambiri kumathandizanso kuwonetsa kuti ali ndi vuto la kuwonongeka kwakukulu mu gawo lalikulu la omwe akuti amapeza zovuta ndi njuga zawo (Corless ndi Dickerson, 1989; McBride Et al, 2010; Fodya Et al, 2010). Kusiyidwa, kuthamangitsidwa kumatha kubweretsa vuto lalikulu la kutchova njuga, kukulitsa ngongole zachuma koma kuchepa kwa zinthu, komanso, mavuto abanja lalikulu, zachikhalidwe, komanso ntchito pantchito yotchova njuga (Lesieur, 1979).

Panthawi yamaganizidwe, kuthamangitsa kumakhala kovuta ndipo nthawi zambiri kumakhudzana ndi zolinga zosokonekera, kugwetsa chikhumbo (kapena kufunika) kuti mupitirize kusewera motsutsana ndi mantha akuvutika kwambiri (Lesieur, 1977): Maiko amakhudzidwe amakhudzidwe omwe amagwiritsidwa ntchito pochita ndi zigawo zikuluzikulu zosagwirizana (Campbell-Meiklejohn Et al, 2008). Kutchova njuga kuti ubwezeretse zomwe zimawonongeka kumalumikizidwanso ndi mayiko omwe ali ndi chidwi chachikulu (onani pansipa) komanso chidwi chazambiri ndi zochitika zanjuga zomwe ndizodziwika bwino pazowonetsa zovuta zamatenda a njuga (Dickerson Et al, 1987; McBride Et al, 2010). Chifukwa chake, kuthamangitsidwa kumayimidwe kungayimire chandamale chothandizira kukhazikitsa chithandizo chamankhwala.

Ngakhale kuthana ndi vuto la kutchova juga, tikudziwa zochepa panjira yothamangitsa imayendetsedwa ndi machitidwe amachitidwe amagetsi. Umboni wochepa wazachipatala umawonetsa kuti kutchova juga kwa pathological kumalumikizidwa ndi kusokonekera kwa serotonergic monga momwe zikusonyezedwera (malipoti) zosonyeza kutsika kwa serotonin metabolite, 5-hydroxyindoleacetic acid mu madzi a cerebrospinal (Bergh Et al, 1997; Roy Et al, 1988) komanso ndi malipoti a kuchuluka kwa kutulutsa kwa prolactin (ndi malipoti a 'high' odzipereka) kutsatira zovuta zazikulu ndi 5-HT2c receptor agonist, meta-chlorophenylpiperazine (Pallanti Et al, 2006). Kusankha serotonin reuptake inhibitors kwawonetsanso lonjezo lina monga chithandizo cha juga ya pathological kudzera pazotsatira zawo zotsutsana ndi zovuta komanso nkhawa (Grant ndi Potenza, 2006; Pallesen Et al, 2007). Pomaliza, serotonin imakhala ndimakhalidwe oyenera - ngakhale, ovuta -Winstanley Et al, 2004), yomwe imalimbikitsa kuthamangitsa (Breen ndi Zuckerman, 1999,, ndipo ndizokweretsedwa m'mavuto otchova njuga (Blaszczynski Et al, 1997).

The pathophysiology yamavuto amatchova juga nawonso atha kukhudzana ndi kusokonezeka kwa ubongo wapakati pa dopaminergic, komanso masamba ake a mesolimbic ndi preferenceal projekiti (Hewig Et al, 2010; Potenza, 2008). Poyerekeza ndi zomwe zikuwoneka kuti ndizabwino, oyendetsa matendawa amawonetsa kuchepa kwa mayankho mkati mwa mesostriatal nuclei pomwe akuchita njuga yofananira yolipira mphoto ya ndalama (Zosintha Et al, 2005). Kupereka kwa psychostimulant, amphetamine, kwa otchova njuga kwa m'magazi kungathenso kuzindikira za njuga (Zack ndi Poulos, 2004), pomwe D2 receptor antagonist, haloperidol, imatha kukulitsa zabwino zopindulitsa motere (Zack ndi Poulos, 2007). Pomaliza, umboni wambiri ukusonyeza kuti mankhwala a dopaminergic amalumikizidwa ndi kutchova njuga (ndi zovuta zina zowongolera) mwa ochepa odwala omwe ali ndi matenda a Parkinson (Onani Et al, 2007), akuwonetsa kusokonekera kwa gawo lonse la dopamine pakupititsa patsogolo maphunziro ndi kuwerengera kwa ubale wamachitidwe (Dagher ndi Robbins, 2009; Onani Et al, 2010). Chifukwa chake, umboni womwe ulipo ukusonyeza kuti onse a serotonin ndi dopamine dysfunction mediate mbali pamavuto a juga (Zeeb Et al, 2009). Komabe, mpaka pano, udindo wawo wapakati pakukonda kuthamangitsa sunafufuzidwe koyesa.

Njira imodzi yoyambira kumvetsetsa magawo amomwe amachedwa kuthamangitsidwa nthawi zina omwe amawona m'mavuto otchova njuga ndikufufuza ntchito za ma neuromodulators osiyanasiyana pothamangitsa anthu akuluakulu athanzi omwe sakudziwa bwino njuga. Zambiri zomwe zapezedwa kuchokera ku zoyesazi zingathandize pakupanga malingaliro ofotokoza momwe zosokoneza mu ntchito za ma neuromodulators zimathandizira kutaya kuthamangitsa mu pathological state. Apa, pazoyesera zitatu zosiyana, tidagwiritsa ntchito mtundu wamalingaliro a kutaya kuthamangitsidwa opangidwa mu labotore yathu ndipo tidavomerezedwa kale ndi maginidwe oyenera a maginito (Campbell-Meiklejohn Et al, 2008) kuyerekezera kuthamangitsa kuthamangitsidwa kwa achikulire omwe samachita bwino kuchipatala (omwe anangonena zochepa zokhudzana ndi kutchova njuga) potsatira manambala a serotonergic, dopaminergic (D2/D3) ndi ntchito ya beta-adrenoceptor.

Mu Experiment 1, tidafufuza zotsatira za kutsika kwa tryptophan pa chizolowezi chofuna kupitiliza kutchova juga kuti mubwezeretse zowonongeka ndikuyesedwa pakati pa ma hypotheses awiri olosera mosiyanasiyana. Serotonin amadziwika kuti amachita mbali yayikulu pakuwongolera zinthu zomwe sizinalandilidwe mphotho komanso kuletsa kuchita zinthu kutsatira kupezeka kwa kulanga kapena zochitika zobwezera (Soubrie, 1986). Komanso, kuchepa kwakanthawi kwamkati mwa ntchito ya serotonin, komwe kumatheka kudzera mu tryptophan depletion, kumatha kuchepetsa kufatsa komwe kumapangitsa kuti azikhala ndi thanzi labwino kwa achikulire athanzi (Chingwe Et al, 2009). Pazifukwa izi, titha kuyembekeza kuti kuchepa kwa njira ya tryptophan kumakulitsa chizolowezi chofuna kupitiliza kutchova njuga kuti abwezeretse zomwe zidatayidwa kale chifukwa cholephera kuchita zosemphana ndi serotonin.

Komabe, serotonin imasinthananso ndi kuphunzira za zochitika zoyipa (Bari Et al, 2010; Daw Et al, 2002; Deakin ndi Graeff, 1991; Evers Et al, 2005). Dayan ndi Huys (2008) yalimbikitsa kuti kulephera kwa kayendetsedwe ka kayendedwe pambuyo pakuchepetsa mu ntchito ya serotonin (kuyesera kapena kwachipatala) kumatha kubweretsa kuwonjezeka kwakukulu mu kukula kwa zolakwitsa zolosera zomwe, zimapangitsa kubweretsa mabungwe osagwirizana ndi anthu osatetezeka (Dayan ndi Huys, 2008). Pafupifupi, tryptophan depletion imatha kupititsa patsogolo kulondola kwa zolosera za zotsatira zoyipa kapena kulanga anthu akuluakulu athanzi (Amazizira Et al, 2008). Komanso, Evers Et al (2005) idawonetsa kuti kutsitsa kwa tryptophan kumathandizira ntchito ya neural poyankha zolakwika pakumaphunzira kosinthika mkati mwa dera la cingulate lakunja, dera lomwe limayendetsedwa ndikupanga zisankho zosiya kuthamangitsa kuwonongeka (Campbell-Meiklejohn Et al, 2008). Chifukwa chake, titha kuneneranso kuti kuchepa kwatsoka kwa achikulire athanzi kumathandizira kutsika kwa zotsatira zoyipa mukamangotaya njuga, ndikuchepetsa mayendedwe obwezera.

Mu Experiment 2, tidafufuza za zotsatira za muyeso umodzi wa non-ergoline D2/D3 wolandila agonist, pramipexole (PPX). Pamodzi ndi mankhwala ena a dopaminergic, chithandizo cha PPX chakhala chikugwirizana ndi mavuto amtundu wa juga pagulu la odwala matenda a Parkinson (Onani Et al, 2007). Komabe, sikunayesedwe ngati chithandizo ndi D2/D3 ma receptors agonists amasintha kuthamangitsa chikhalidwe pa nthawi yomwe akutha kutchova njuga.

PPX ndiyosankha kwambiri D3 kuposa D2 ma receptors komanso kumangiriza ku dopamine (autoreceptor ndi post-synaptic) zolandilira mu mesolimbic mphoto njira (Camacho-Ochoa Et al, 1995) (Onani Zowonjezera). Mlingo wocheperako wa PPX (mwachitsanzo, 0.5mg) imatha kupewetsa kulimbitsa maphunziro mu akulu akulu (Pizzagalli Et al, 2008,, ndikuwonjezera zosankha zowopsa pamasewera amtundu wa lottery (Riba Et al, 2008), mwina kudzera muyezo wopindulitsa wa ma mesolimbic pathways (Riba Et al, 2008; Santesso Et al, 2009). Mwakuwona izi, ndikuwonetsa umboni kuti Mlingo wocheperako wa PPX, ndi othandizira ena akuchita D2 zolandilira, zosokoneza kuwonetsa zotsatira zoyipa ('zolosera zolakwika') (Frank ndi O'Reilly, 2006; Santesso Et al, 2009; van Eimeren Et al, 2009), tidayesa okokomeza kuti kuchuluka kwamtundu umodzi wa PPX kumawonjezera kuthamangitsa chikhalidwe ndipo mwina, kumapangitsa phindu la zotayika zomwe anthu athanzi okonzeka kuthamangitsa.

Ngakhale sizokayikitsa kuti zomwe tapeza mu Zoyeserera 1 ndi 2 zikuwonetsa kusintha kwakukulu pamayiko ogwirizana omwe amatsutsana ndi tryptophan depletion kapena chithandizo ndi PPX, ndizotheka kuti zomwe tikuwona zikugwirizana ndi kusintha pakudziwitsa kapena kukondweretsa, mwina kuwonetsa ndondomeko yayitali zamankhwala azamalonda. Mwachitsanzo, pamene tryptophan depletion mwanjira zambiri sizimasintha mkhalidwe mwa achikulire omwe awunika zovuta, angayankhe mayankho amthupi (mtima)van der Veen Et al, 2008). Kuphatikiza apo, kafukufuku wam'munda akuwonetsa kuti njuga zamalonda zimagwirizanitsidwa ndi kuchuluka kwa anthu omvera chisoni (Anderson ndi Brown, 1984; Meyer Et al, 2000). Chifukwa chake, sizikudziwika bwinobwino ngati kusintha kwadzuka kungakulitse kapena kuchepetsa chizolowezi chofuna kupitiliza kutchova juga kuti muthe kuyambiranso. M'mbuyomu, tapeza kuti mlingo umodzi wa beta-adrenoceptor antagonist, propranolol, umachepetsa chidwi cha omwe amapanga zisankho pamalingaliro okhudzana ndi zilango (Rogers Et al, 2004), kutha kumasula machitidwe othamangitsa kutayika. Mu Kafukufuku wa 3, tidayesa ngati kusinthaku kwamkomera, monga kuwonekera mwa mtundu wa kutsika kwa mtima (HR) wopangidwa mwa akulu wathanzi ndi muyezo umodzi wa beta-adrenoceptor antagonist propranolol ungathandizire kusiya kuthamangitsa.

Pitani ku:

ZIDA NDI NJIRA

Ophunzira ndi Zida

Ophunzira onse adapereka chidziwitso cholembedwa. Ophunzira adawunikiridwa ndi dokotala wazachipatala wodziwa zambiri, kuphatikiza kufunsa koyeserera kwa SCID-I kuti awonetsetse kuti palibe njira imodzi yoperekera yomwe idakwaniritsidwa: (i) matenda akuthupi; (ii) zamakono kapena zam'mbuyo za DSM-IV chachikulu kapena psychotic chisokonezo; ndi (iii) matenda osokoneza bongo amakono a DSM-IV. Ophunzira adayesedwa ndi South Oaks Gossip Screen (Lesieur ndi Blume, 1987); zonse zomwe zinali 0 kapena 1, zosawonetsa kuti pali vuto kapena njuga ya pathological.

Yesani 1

Akuluakulu makumi atatu mphambu anayi adachita nawo izi. Palibe amene anali ndi mbiri yovuta yamavuto; Panalibe choletsa pagawo la kusamba mwa azimayi omwe amatenga nawo mbali. Ophunzira khumi ndi asanu ndi awiri (amuna asanu ndi atatu) adamwa chakumwa cha amino-acid chomwe munalibe tryptophan (T−) ndipo otenga nawo mbali 17 (amuna asanu ndi atatu) adamwa chakumwa cha amino-acid chomwe chinali ndi tryptophan (T +). Omwe anali nawo T + ndi omwe anali nawo mu T− adafananizidwa malinga ndi jenda lawo (onani Supplementary Table S1), zaka (F <1.00), komanso luso lakuzindikira (khwangwala Et al, 1998) (F (1,30) <2.08).

Ophunzira adatsata zakudya zopanda protein (<2g) tsiku lisanafike phunzirolo, ndipo anasala kudya usiku umodzi asanapite ku labotale maola a 0830 patsiku loyesera. Njira zoyendetsera boma ndi zoyipa (Watson Et al, 1988) zidatengedwa panthawiyi limodzi ndi 15ml magazi zitsanzo kuti mupeze kuchuluka kwa plasma tryptophan. Ophunzirawo adamwa chakumwa cha amino-acid kwanthawi yayitali 60. Palibe aliyense mwa omwe adatenga nawo mbali omwe adanenapo zovuta zina kupyola mseru wakanthawi. Ophunzira adapatsidwa mapuloteni ochepa (<2g) nkhomaliro masana. Bwerezani zoyezera zoyipa za boma komanso zoyipa, ndi muyeso wachiwiri wamagazi, anasonkhanitsidwa + 5h atatha kumwa zakumwa za amino-acid, musanamalize kusewera kuthamangitsa.

Yesani 2

Akuluakulu azathanzi adasankhidwa kuti alandire 176μg ya PPX kapena placebo (placebo-PPX). Gulu lirilonse linali ndi amuna asanu ndi awiri. Panalibe kusiyana kwakukulu pakati pa omwe adalandira malowa ndi omwe adalandira PPX malinga ndi msinkhu wawo kapena kuthekera kwawo kuzindikira (Supplementary Table S2) (onse a F's <1.00).

The 176Mlingo wa μg wa PPX wogwiritsidwa ntchito ku experiment 2 ndi wofanana ndi mlingo womwe umawonetsedwa kuti ndiwothandiza pakubwezeretsa mwendo.Manconi Et al, 2007). Pali zifukwa zomveka zokhulupirira kuti wogonja (Hamidovic Et al, 2008) komanso mwamakhalidwe (Pizzagalli Et al, 2008; Riba Et al, 2008; Santesso Et al, 2009) zotsatira za otsika Mlingo wa dopaminergic wothandizira amawonetsa zochita za pre -aptaptic pa auto-receptors yomwe imayang'anira zochitika zapakati pa ubongo dopaminergic neurons (Frank ndi O'Reilly, 2006; Chisomo, 1995). Monga tafotokozera pansipa, timasinthanso zinthu zomwe tazipeza (1)mg) Mlingo wotsika wa PPX umachepetsa ma psychometric miyeso okhudzidwa ndi boma mwa anthu athanzi labwino ndipo amatengedwa kuti afotokozere njira ya pre-synaptic mode (Hamidovic Et al, 2008). Komabe, yathu 176Mlingo wa μg umakhalanso wofanana ndi omwe akuwonetsedwa kuti achepetse serum prolactin pamwamba pa 2h (Schilling Et al, 1992), osachepera kukweza mwayi woti zotsatira zathu zikuwonetsanso zochitika zina za post-synaptic receptor (Ben-Jonathan, 1985).

Ophunzira nawo adapita ku labotale maola a 0830 ndikumaliza kuyesa koyambira kwa zotsatira zabwino za boma komanso zoyipa (Watson Et al, 1988). Njira zoyambira za systolic / diastolic magazi (BP) ndi HR anasonkhana. Kutsatira izi, ophunzira adalandira 176 imodziMlingo wa μg wa PPX kapena kapisozi ya gelatine yokhala ndi lactose. Pambuyo pa 2h (+ 2h), miyeso yowonjezera ya systolic / diastolic BP ndi HR idatengedwa. Zotsatira zokomera boma komanso zoyipa zinasonkhanitsidwa panthawiyi, masewera asanathe.

Yesani 3

Omwe akutenga nawo gawo khumi ndi anayi (amuna asanu ndi awiri) adapatsidwa mwayi kuti alandire 80mg propranolol (placebo-PPL) ndi otenga nawo mbali 14 (amuna asanu ndi atatu) adapatsidwa mwayi kuti alandire lactose placebo (PLA-PPL). Magulu awiri omwe atenga nawo mbali anali ofanana mofanana ndi msinkhu wawo (onani Supplementary Table S4) (F <1) ndi kuthekera kwawo kuzindikira (F (1,24) = 1.87).

Ophunzira nawo adapita labotale m'mawa atasala kudya chifukwa cha 2h ndi wopanda khofi. Zotsatira zoyipa za boma ndi zovuta (PANAS) (Watson Et al, 1988), systolic BP, diastolic BP, ndi HR adayesedwa poyambira kenako 30 iliyonsemphindi pambuyo pake. Opanga nawo gawo adatsiriza masewera othamangitsa + 75mphindi kutsatira chithandizo.

Kutaya Kwambiri

Mtundu wa masewera athu othamangitsa omwe ali oyenera kuchitikira maginito ogwiritsidwira ntchito afotokozedwa mwatsatanetsatane kwina (Campbell-Meiklejohn Et al, 2008). Paseweredwe kalikonse, ophatikizidwa adayenera kusankha pakati pa kutchova juga kuti abwezeretse (pangozi yakuwonjezera kukula kwake) kapena kusiya (ndikusunga kutayika kwinakwake). Zovuta ngati izi zimabweretsa zisankho zowopsa pamagulu osiyanasiyana azachuma komanso azachuma (Shafir ndi Tversky, 1995). Malingaliro ofotokozera (osatsimikizika) amati izi zimachitika chifukwa chakuti zotayika zimagwera pa gawo la ntchito yama psychophysical yokhudzana ndi phindu lofananira (mwachitsanzo, zotsatira zachuma) pamtengo wokwanira kapena ntchito, kotero kuti amachepetsa othandizira ogwirizana ndi kuthamangitsa komanso kuwonongeka kwakukulu kumakhala kocheperako poyerekeza ndi kutsika kwazomwe zimachitika chifukwa chakuwonongeka kwinakuKahneman ndi Tversky, 2000). M'mbuyomu, tidapeza kuti kutchova juga kuti ubwezeretse kutaya pamasewera athu kumalumikizidwa ndi zochitika za psychometric zomwe zimakonda kuthamangitsa kuwonongeka muzochita zina zanjuga ((Campbell-Meiklejohn Et al, 2008).

Kumayambiriro kwamasewera, osewera adauzidwa kuti ali ndi ndalama zopeka za 20000 yosewera nayo, koma kuti yemwe akutenga nawo mbali kwambiri pamapeto pake akuyesa kupeza mphotho ya £ 70. Pazosewerera zilizonse zamasewera, £ 10, £ 20, £ 40, £ 80, kapena £ 160 adachotsedwa pamasewera awo onse. Ndalamayi idawonekera pansipa zosankha: 'Siya' ndi 'Sewani' (Chithunzi 1). Pakadali pano, ophunzira atha kusankha 'Kusiya', kupititsa patsogolo kutayika uku ndikumaliza kuzungulira nthawi yomweyo ('kusiya-kutaya' zotsatira), kapena atha kusankha 'Kusewera', ndiye kuti, kuthamangitsa zomwe zawonongeka. Chifukwa chake, amatha kutchova juga pakubwezeretsa ndalama zofananira ndi kutayika, koma pachiwopsezo chowonjezera zotayika zawo kuchuluka komweko. Ngati zotsatira zakusankha kutchova njuga zinali zabwino ('kuthamangitsa-kupambana'), kutayika kunapezedwanso ndipo kumapeto kwake kunatha. Ngati zotsatirazo zinali zoyipa ('kuthamangitsa-kutaya' zotsatira), zotayika zidachulukitsidwa ndipo omwe akutenga nawo mbali adapatsidwa mwayi wina wosiya kapena kuthamangitsa chisankho chotsatira. Zomwe mungasankhe - 'Play' kapena 'Siyani' - zimawoneka chimodzimodzi kumanzere ndi kumanja kwa makompyuta.

Chithunzi 1

Chithunzi 1

Wonetsani zotsatika zamasewera othamangitsa. Kumayambiriro kwamasewera aliwonse, kutayika kudayikidwa ndipo anaganiza zosewerera (kutchova njuga patsogolo) kapena kusiya (kuvomereza kutaya), ndikumaliza kuzungulira. Zotayika motsatizana komanso zosankha zidachitika ...

Zowonetsa pazotsatira (onani Chithunzi 1) adawonetsa ngati omwe atenga nawo mbali apambana pa juga ndikuti palibe ndalama yomwe yatayika ('chase-win'); ngati adataya njuga ndipo kuchuluka kutayika ('kuthamangitsa-kutaya'); kapena ndalama zomwe zidatayika ngati ophunzira atasankha kusiya ntchito ('kusiya-kutayika'). Kumapeto kwa kuzungulira kulikonse, ophunzira adadziwitsidwanso zakumapeto komaliza pakuwonetsera 'kotayika'. Chiwonetserochi chikuwonetsa kutaya konse kochulukirako, m'mawu ofiyira ngati zotayika zinali zazikulu kuposa 0, koma m'mawu obiriwira ngati 0. Miyezo yamasewera othamangitsayo adayamba ndi kutaya kwa $ 10, £ 20, £ 40, £ 80, kapena £ 160. Ngati ophunzira apitilizabe kutayika, zotayika zimachulukirachulukira mpaka zikafika pa $ 640, pomwe kumaliza kwake kumatha, kutayika kwakukulu.

Onse omwe adasewera adasewera 20 mozungulira pamasewera othamangitsa. Zotsatira zopambana-Chase zinayikidwa mosasinthika mozungulira kuzungulira kuti zotsatira zopambana zimachitika chimodzimodzi nthawi zambiri kutayika konse pakati (pakati pa 0 ndi 5) motayika. Zotsatira zamasewera othamangitsawa zidagawidwa kotero kuti zoyeserera za 14 zidabweza kutaya konse ngati otenga nawo mbali atasankha kusewera pamasewera aliwonse omwe angasankhe. Komabe, zoyambira zisanu ndi imodzi zinapangitsa kuti kutayika kwakukulu kwa £ 640.

Ophunzirawo sanauzidwe chilichonse chokhudza kutha kwa zabwino vs zotsatira zoyipa kotero kuti zisankho zawo zidapangidwa m'malo mwa 'kusamvetsetsa' (Camerer ndi Weber, 1992). Pofuna kuletsa omwe akutenga nawo mbali njira zosiyira pomwe adasiyira pomwepo kuti asunge ndalama zambiri momwe angathere, palibe zomwe zinanenedwa zokhudzana ndi masewera awo osewerera pamasewera. Ophunzirawo adadziwitsidwanso kuti sangathe kuchita bwino koposa kusewera kapena kusiya.

Mwachidule, ophunzirawo adakumana ndi zovuta zingapo zomwe zimakhudza chisankho pakati pa kutchova juga kuti awonongere mwayi wotayika kuwirikiza kukula kwake, kapena kupitiliza kutaya ndikumaliza kuthamangitsa, pomwe nthawi yomweyo amasunga zinthu zambiri momwe zingathere (Campbell-Meiklejohn Et al, 2008). Mtengo wazinthuzi (mfundo zodziyesa) zidaperekedwa ndi mutu wa mpikisano womwe ophunzira amatenga nawo mbali omwe amafunikira kuti ophunzira asunge mfundo zambiri momwe zingathere. Kuphatikiza komweku ndi mphotho zenizeni komanso ntchito zenizeni zakhala zikugwiritsidwa ntchito pazachuma pofuna kuwonetsa kuyenera ndi kakhalidwe kofanana ndendende ndi labotale (Cubitt Et al, 1998).

Chiwerengero cha Kusanthula

Njira zomwe zidatsalira zidaphatikizira gawo la zisankho kutchova njuga (kapena kuthamangitsa) zisankho zonse zomwe zidapangidwa pamasewera, ndi kuchuluka kwa kutayika kotsatizana kuthamangitsidwa kuzungulira. Tidasanthula kukula (kapena mtengo) wa zotayika zomwe zathamangitsidwa ndi kuchuluka (kapena mtengo) wa zotayika zomwe zidaperekedwa pamasewera. Izi zikuwonetsedwa monga zofunikira pazidziwitso zakutayika zonse zomwe zidakumana ndi masewerawa (onani Zowonjezera Zowonjezera kuti mumve zambiri).

Njira zowerengera, zogwirizanitsa, komanso kuthamangitsa zowunikira pazoyesazo zitatu zidayesedwa pogwiritsa ntchito njira imodzi yosanthula mosiyanasiyana (ANOVA) ndi zinthu zapakati pazinthu za chithandizo (T + vs T−, PPX vs placebo, kapena propranolol vs placebo) ndi jenda.

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ZINTHU

Kuyesa 1: Tryptophan Depletion

Zotsatira zathupi

Kutenga zakumwa za amino-acid popanda tryptophan (mankhwalawa T−) kunapangitsa kuchepetsa kwakukulu kwa ndende ya plasma + 5h pambuyo pake poyerekeza ndi chakumwa chowongolera (mu chithandizo cha T +) (onani Table Yowonjezera S1). Komabe, mankhwalawa a T− sanatulutse kusintha kwina kulikonse kapena koyenera poyerekeza ndi chithandizo cha T + (Supplementary Table S1) (onse F (1,30) 's <2.29).

Kutaya kuthamangitsa

Ophunzira omwe adalandira chithandizo cha T− adawonetsa kuwunika kwakukulu ndikuwongolera kwakukulu pakugamula zosankha poyerekeza ndi omwe adalandira chithandizo cha T + (Chithunzi 2a) (F (1,30) = 8.43, p<0.01). Chiwerengero cha zisankho motsatizana kuti athamangitse kutchova juga kunachepetsedwanso molondola kutsatira kuyesa kwa tryptophan (Chithunzi 2b) (F (1,30) = 8.06, p<0.01).

Chithunzi 2

Chithunzi 2

Kulimbikira kwathamangitsa machitidwe mu magawo atatu aanthu wathanzi, osachiritsika omwe ali ndi vuto lotsatira kutsika kwa matenda a tryptophan (vs chakumwa chowongolera amino-acid), 176 imodziμg wa D2/D3 receptor agonist, pramipexole (PPX vs placebo), ...

Mosiyana ndi zomwe zimachitika pachigawo chakutchova njuga kuti zithandizire kuwonongeka, palibe kusintha kwakukulu mu mtengo Zazotayika zomwe osewera omwe adadzazidwa ndi tryptophan adaganiza kuti azithamangitsa (zomwe zikuwonetsedwa monga kuchuluka kwa mathedwe onse omwe akumanidwa mu masewerawa; onani Zowonjezera Zowonjezera) (Chithunzi 3a) poyerekeza ndi omwe adalandira njira zowongolera (F's <1). Panalibe kusintha kulikonse mu mtengo za zotayika adadzipereka posankha kusiya (Chithunzi 3b(F's <1).

Chithunzi 3

Chithunzi 3

Kugwiritsa ntchito chidziwitso chamtengo wapatali pothamangitsa anthu omwe atayika mu magawo atatu aanthu wathanzi, omwe siachipatala omwe atenga nawo mbali potsatira kutsika kwa tryptophan (vs chakumwa chowongolera amino-acid), 176 imodziμg wa D2/D3 receptor agonist, pramipexole ...

Kuyesa 2: PPX

Zotsatira zathupi

Systolic BP, diastolic BP, ndi HR sizinasinthidwe motsatira kutsatira chithandizo ndi PPX poyerekeza ndi chithandizo ndi placebo (onani Zowonjezera Zowonjezera ndi Zowonjezera Tebulo S3) (zonse F (1,25) 's <1.86).

Chithandizo cha PPX chachepetsa kukhudzidwa kwabwino poyerekeza ndi placebo kudutsa + 2h kutsatira chithandizo (F (1,26) = 10.05, p<0.005) (Gulu lowonjezera S2). Makamaka, pomwe zabwino zimakhudzidwa ndikuwonjezera kutsatira mankhwala ndi placebo (F (1,13) = 3.53, p= 0.08), idachepetsedwa kwambiri kutsatira chithandizo ndi PPX (F (1,13) = 6.84, p<0.05). Pa +2h, akamaliza kusewera masewera othamangitsa, ochita nawo omwe adalandira PPX adanenanso zoyipa zochepa kuposa omwe adalandira placebo (F (1,26) = 8.34, p<0.01). PPX sinasinthe zovuta zoyipa poyerekeza ndi placebo (onse a F <1).

Kutaya kuthamangitsa

PPX idachepetsa pang'ono zosankha kuti zithamangitse, ndi kuchuluka kwa zosankha zotsatizana, pakutha kwa kutchova njuga poyerekeza ndi placebo (Chithunzi 2); komabe, zonsezi sizinachitike powerengera (F's <1). Mosiyana ndi izi, PPX kwambiri kuwonjezeka kufunika kwa zomwe otenga nawo mbali adaganiza kuti achite njuga kuti achire (Chithunzi 3a) (F (1,26) = 4.94, p<0.05), komanso kwambiri kuchepa phindu la otayika omwe adadzipereka (Chithunzi 3b) (F (1,26) = 5.87, p<0.05). Kusintha uku kwamtengo wotayika komwe kunathamangitsidwa ndikuperekedwa kumakhalabe kofunika pakakhala zabwino pa +2h idalowetsedwa ngati covariate (F (1,25) = 4.48, p<0.05 ndi F (1,25) = 4.39, p<0.05, motsatana). Sanasinthidwenso kwakukulu pomwe kusanthula kwa ziwerengero kunachitika pamtengo wosasinthidwa wazotayika zomwe zathamangitsidwa kapena zomwe zaperekedwa (onani Supplementary Information kuti mumve zonse).

Kuyesa 3: Propranolol

Zotsatira zathupi

Propranolol sinatulutse kusintha kwakukulu kapena kocheperako mu systolic kapena diastolic BP poyerekeza ndi placebo (onse F's <1). HR yachepa kuposa 75min kutsatira chithandizo (73.64 ± 10.82 vs 62.04 ± 7.68bpm) (F (1,24) = 60.30, p<0.0001). Komabe, kuchepa uku kunali kwakukulu kwambiri kutsatira propranolol poyerekeza ndi placebo (Supplementary Table S5) (F (1,24) = 4.98, p<0.05). Poyambira HR adakhala wamkulu mwa omwe amatenga nawo mankhwala a propranolol poyerekeza ndi omwe adachitidwa ndi placebo (F (1,24) = 2.64), tidawunikiranso zomwe zimachitika pakusintha kwa magawo a HR. Izi zidatsimikizira kuti propranolol idapangitsa kuchepa kwakukulu kwa HR poyerekeza ndi placebo (18.64 ± 8.45 vs 11.08 ± 11.38%) (F (1,24) = 4.64, p<0.05).

Zomwe boma limachita komanso zoyipa sizinali zosiyana kwenikweni pakutsata mankhwala ndi propranolol poyerekeza ndi chithandizo chokhala ndi placebo (onani Supplementary Information and Supplementary Table S4) (F <1.00 ndi F (1,24) = 1.61, motsatira). Panalibe kusiyana kwakukulu kokhudzana ndi chithandizo mwanjira iliyonse ku + 75min pomwe masewera othamangitsa atatha.

Kutaya kuthamangitsa

Panalibe kusiyana kwakukulu pakati pa propranolol ndi placebo malinga ndi kuchuluka kwa zosankha kuti azithamangitsa, kuchuluka kwa zosankha zotsatizana kuti azithamangitsa (Chithunzi 2,, kapena mtengo wotaika wothamangitsidwa ndi mtengo wa zotayika zinadzipereka (Chithunzi 3) (zonse za F <1).

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KUKANGANANI

Zomwe tapezazi zikuonetsa kuti serotonin ndi dopamine amasewera mbali zowonjezera pakulimbikitsa kutchova juga kuti ayambenso kutaya. Zochita za Serotonin zikuwoneka kuti zimathandizira kulimbikitsa kuthamangitsa, pomwe ntchito za dopamine, kuphatikizapo D2/D3 dongosolo receptor, limawoneka kuti limayang'anira kuchuluka kwa zotayika zomwe zimathamangitsidwa kapena kudzipereka. Mosiyana ndi izi, mbali zonsezi zakuthamangitsa ndizoyimiririka popanda kusintha kwachisoni, monganso momwe zimakhalira ndi beta-adrenoceptor. Tsamba lathu limatsindika zonena zatsopano za machitidwe a monoaminergic omwe amalimbikitsa kufotokozera kwa chapakati, koma osamvetsetsa bwino, mbali ya mchitidwe wa njuga.

Mu Experiment 1, tidafufuza zotsatira za kuchepa kwa tryptophan kuti tiwone ngati ntchito yapakati pa serotonin imatanthauzira ngati kuthamangitsa anthu. Izi zitha kuwonetsedwa m'njira ziwiri. Choyamba, maumboni angapo akusonyeza kuti serotonin imagwirizira zopinga zomwe sizinapindulidwe kapena kulangidwa (Chingwe Et al, 2009; Dayan ndi Huys, 2008; Soubrie, 1986). Chifukwa chake, tryptophan depletion, yomwe ikutsogolera kuchepetsedwa kwa ntchito ya serotonin, mwina ikuyembekezeredwa kuti iwonjezere kutchova juga kuti ayambenso kutaya mwa omwe akutenga nawo mbali wathanzi. Mosiyana ndi izi, ntchito ya serotonin imathandizanso kwambiri pophunzirapo, komanso kuthana ndi zochitika zomwe zimatsutsa (Bari Et al, 2010; Daw Et al, 2002; Deakin ndi Graeff, 1991; Evers Et al, 2005). Popeza kuti tryptophan depletion ikhozanso kusintha kuneneratu kwa kulanga zotsatira (Amazizira Et al, 2008,, ndikuthandizira mayankho a neural pakuwongolera zotsatira mkati mwa anterior cingrate cortex (Evers Et al, 2005), Tinkayembekezeranso kuti kuchepa kwa tryptophan kumatha kukulitsa chidwi cha zotsatira zoyipa ndikuchepetsa machitidwe othamangitsa ena. M'malo mwake, ngakhale kuti sizinasinthe kusintha kwa thanzi la achikulire athanzi, kuchepa kwa tryptophan kumachepetsa kwambiri kuchuluka kwa zisankho zomwe omwe akutenga nawo mbali kuti athamangitse zotayika, ndikuchepetsa kuchuluka kwa zisankho motsatizana, pakutha kwa kutchova juga. Izi zikusonyeza kuti, panthawiyi, ntchito ya serotonin imathandizira kupititsa patsogolo kuthamangitsidwa m'malo moyimitsa.

Malingaliro ofotokozera pamalingaliro osatsimikizika akuti kuthamangitsa mkhalidwe kumalingaliro akuti zomwe zingachepetsedwe pamtengo wothandizidwa kapena kuthana ndi kuthamangitsa ndikuwonongeka kwakukulu zikadali zocheperako kuposa zomwe zimagwiritsidwa ntchito ndi zomwe zawonongeka zazing'ono zomwe zawonongeka kale (Kahneman ndi Tversky, 2000). Pansi pa mikhalidwe iyi, ndizomveka kuti otchova juga apitilizabe kusewera, bola ngati zinthu zofunikira zilipo. Kuchokera pamalingaliro awa, kuthamangitsa kutayika kumatha kuonedwa ngati njira yongoyambira yolowerera, koma yoyendetsedwa, mwa gawo limodzi, mwa kupitilira kwakanthawi kwa kusewera komwe kumayenderana ndi kufafaniza. Kupeza kwathu kuti kuchepa kwa tryptophan kunachepetsa mayendedwe athu otayika kutanthauza kuti, munthawi iyi, kuchepa kwa ntchito pakati pa serotonin kunachepetsa kugwiritsidwa ntchito kwakanthawi kwakanthawi kosewerera mwakukulitsa zotsatira zoyipa zamtsogolo pazotsatira zamitengo zomwe zimakumana ndi masewerawa (Amazizira Et al, 2008; Deakin ndi Graeff, 1991).

Kuyesanso kwina kudzafunika kukhazikitsa ubale pakati pa ntchito ya serotonin ndi kutchova juga kuti mupeze zomwe mwataya. Komabe, titapatsidwa gawo lovuta la serotonin pakulamulira mopupuluma, sitiyenera kuganiza kuti ubalewu ungakhale wosavuta kapena wophatikizika (Winstanley Et al, 2004). Kupeza kwathu kuti tryptophan depletion yachepetsa kuthamangitsa ikugwirizana ndi zina zowunikira, zopezedwa pogwiritsa ntchito njira zosavuta kuyeza malingaliro omwe ali pachiwopsezo, chonyamula XXUMX STin2 jini (zomwe zimabweretsa Apamwamba mamvekedwe a serotonin) amawonetsa kusankha kosaka zowopsa chifukwa cha zotayika (Zhong Et al, 2009). Mosiyana ndi izi, zidziwitso zathu zikuwoneka kuti sizikugwirizana ndi zomwe anapeza kuti masabata a 2 amathandizidwa ndi tryptophan, monga gawo lodyera, adachepetsa zosankha pakati pa zosankha zowopsa popanga chisankho chimodzi pakati pa zopeza zina komanso phindu lalikulu kapena laling'ono, ndikusankha zomwe zingafunike pangozi popanga zosankha chimodzi pakati pa zotayika zina ndi kutaya kwakukulu kapena kochepa (Murphy Et al, 2009). Pamodzi, izi zikuwonetsa kuti zomwe serotonin imachita pakubetchera njuga kuti ibwezeretse zomwe zatayika zimatha kusiyanasiyana kutengera zochitika zingapo zamaganizidwe ndi zamankhwala, kuphatikiza ngati zoyeserera zikuphatikiza zisankho zingapo kapena zingapo zotsatizana kuti zithandizenso kutaya komanso ngati pali zina mwazosankha zina zomwe zikuphatikiza mfundo zabwino zoyembekezereka.

Zotsatira za 176 imodziMlingo wa μg wa PPX anali wosiyana kwambiri. Chithandizo ichi sichinachulukitse kuchuluka kwa zosankha kuti athamangitse kuwonongeka kapena kuchuluka kwa zosankha motsatizana kuthamangitsidwa kutchova njuga; Komabe, PPX idakulitsa kwambiri phindu la zomwe otaya nawo anali ofunitsitsa kuwathamangitsa, ndipo, nthawi yomweyo, amachepetsa phindu la zomwe otenga nawo mbali anali ofunitsitsa kudzipereka akasiya ntchito. Chifukwa chake, mlingo umodzi wa PPX unayambitsa chidwi chothamangitsa zowonongeka zazikulu popanda ndalama zochepa.

Tivomereza kuti machitidwe a 176 imodziMlingo wa μg wa PPX wogwiritsidwa ntchito ku experiment 2 ukadali wotsimikiza. Ngakhale zochita za zotsatira zochepa zamankhwala a dopaminergic zimatha kuwonetsa zochita za pre-synaptic pa auto-receptors ya dopamine neurones mkati mwa ubongo (Frank ndi O'Reilly, 2006; Santesso Et al, 2009), Mlingo umodzi wa 100 ndi 200μg PPX itha kuchepetsanso serum prolactin, ndikuwonetsa kuchitapo kwa-pambuyo -aptaptic wa mankhwala ku dopamine receptors mu anterior pituitary (Schilling Et al, 1992). Apa, tikubwereza zomwe tapeza m'mbuyomu, tikuwona kuti mlingo wa 176μg PPX inachepetsanso kwambiri zomwe ophunzira akuchita (Hamidovic Et al, 2008). Izi zikusonyeza kuti, pamayesowa osachepera, Mlingo wa PPX udapangitsa kuti masewerawa awonongeke kudzera pa D.2/D3 dopamine auto-receptors

D2 ndi D3 zolandila zimafotokozedweratu mkati mwa njira zolimbikitsira mu maukosi amsijeni ndi amygdala (Camacho-Ochoa Et al, 1995), pomwe onse akuwoneka kuti amathandizira pakulimbikitsa kwa mankhwala olimbikitsira monga cocaine (Caine Et al, 1997; Thiel Et al, 2010). Pakadali pano, tiribe njira yodziwira kuti ndi iti mwa izi zomwe zimapangitsa kuti kuthamangitsa kwawonedwe kuoneke. Kuyesa kwapakalepo kunanenanso kuti ntchito pa D2 zolandilira zitha kusokoneza kuphunzira kuchokera pazotsatira zoyipa zosankha zowopsa ('kuphunzira osaphunzira') posokoneza mawonedwe apakati paubongo wa dopamine zomwe zimawonetsa zolakwika zolosera (Frank ndi O'Reilly, 2006; Frank Et al, 2007a,2007b, 2009). Komabe, deta yathu ikusonyeza kuti izi zimapangitsa kuti kutaya zotsatira zoyenderana ndi D2/D3 Ntchito yolandirira imabweretsa kusintha kosavuta pamasankho owopsa kuposa kulephera kuphunzira pazinthu zoyipa. M'malo mwake, timaganizira kuti zovuta zomwe zimapezeka pakuzindikira kwa ntchito za dopamine kutsatira zotsatira zoyipa zidalephera kulembetsa kuwonongeka kwakung'ono, ndikuwonjezera kuchuluka kwa zisankho za omwe akutenga nawo mbali pa PPX kuti asiye ndalama zochepa. Komabe, kuchepa kwachidziwitso pakuchepa kwa zotsatira zokhudzana ndi D2/D3 ntchito idachepetsanso kusintha koyipa kwa phindu lokhudzana ndi kutayika kwakukulu, ndikuwonjezera phindu laling'ono lakumasewera; potero kulimbikitsa malingaliro kuthamangitsa kuwonongera kwakukulu pakuyerekeza ndi placebo.

Zosintha mu njira zophunzitsira zotsatirazi ndi PPX (Pizzagalli Et al, 2008) zimalumikizidwa ndi kusintha kosinthika mkati mwa chigawo cha cingate chotsatira zotsatira zoyipa (Santesso Et al, 2009) ndikuwonetsedwa ndikuwonetsa mkati mwa striatum kutsatira zotsatira zabwino (Riba Et al, 2008). M'mbuyomu, tawona kuti mayankho omwe amapezeka ndi zotsatira zabwino za kutchova juga mkati mwakapangidwe kanyumba kamatchulidwe kamalumikizidwe ndimayendedwe othamangitsa pamene tikuchita masewera athu othamangitsa (Campbell-Meiklejohn Et al, 2008). Izi ndizogwirizana ndi maumboni aposachedwa pamagetsi olemba kuti ntchito zokhudzana ndi mphotho za kanyumba kanyumba kapangidwe ka mzere wapakati zitha kusokonekera m'mitima yamagetsi (Hewig Et al, 2010). Chifukwa chake, zomwe zapezeka pa Experiment 2 zimakweza mwayi woti kuwonongera kamodzi kwa PPX kuonjezera phindu la zotayika zomwe zikuyenera kuthamangitsidwa ndikusintha kolowera ndikusinthidwa mkati mwa gawo lomwe limagawidwa ndi dera lozungulira lomwe limazungulira dera lakutali ndi magawo ake ogwirizanaNakano Et al, 2000).

Pomaliza, zotsatira za Experiment 3 zikuwonetsa kuti muyezo umodzi wa 80mg propranolol inachepetsa kwambiri HR poyerekeza ndi placebo, sizinasinthe kuchuluka kwa zosankha kuti kuthamangitse kutayika, phindu la zotayika limathamangitsidwa, kapena kuchuluka kwa zotayika zaperekedwa. Zotsatirazi zikuwonetsa kuti chidwi ndi kuthamangitsa kwakutaya kwakutaya komwe kumayesedwa ndi masewera athu - ngakhale zikuwonekeratu kuti sikuli kusangalala komwe kumachitika chifukwa chosewerera masewera (Anderson ndi Brown, 1984- - osapangidwa ndi machitidwe owonetsa beta-adrenoceptor. Zimaperekanso chitsimikizo kuti zotsatira za kuchepa kwa tryptophan ndi PPX zomwe tidaziwona mu Kafukufuku 1 ndi 2 sizingachitike chifukwa cha kusintha kosawoneka kwachisoni komanso / kapena kotumphukira. Komabe, machitidwe othamangitsa akhoza kuthekera kutengera zochita zina za noradrenaline, kuphatikiza zochitika za alpha2-adrenoceptors zomwe zimayambitsa zochitika zakukwera kosungidwa kwa locusuleus ndikuwongolera kukonza kwa zosankha zoyipa (kapena zolakwitsa zina) mu m'deraliRiba Et al, 2005).

Zovuta zingapo pazomwe tapeza zikufunika kuthana ndi kafukufuku wamtsogolo. Choyamba, pomwe masewera athu othamangitsa amatenga mawonekedwe ofunikira omwe amapitilira omwe amabweretsa zowonongeka, izi zimatilepheretsa kudzipatula yeniyeni njira zamaganizidwe zomwe zitha kutengeka ndi serotonin ndi D2/D3 ntchito yothandizira kutchova juga kuti ibwezeretse zomwe zatayika. Kuchepetsa kwa Tryptophan komanso kuchepa kwamtundu umodzi wa PPX kumapangitsa kusintha kwakutchova njuga kuti tipeze zomwe zawonongeka, koma kuyeserera kowonjezera kumafunikira kuti tipeze momwe zosinthazi zikugwirizirana ndi zomwe tikudziwa kale za gawo la serotonin popewa kapena kupewetsa chilango (Chingwe Et al, 2009; Soubrie, 1986) ndi zomwe tikudziwa pa udindo wa D2 zolandilira pophunzira kuchokera pazotsatira zoyipa (Frank, 2006). Chachiwiri, zovuta zakuchipatala pazomwe zapezazi zikufunika kuyang'aniridwa ndikuwona zotsatira za ma serotonergic ndi dopaminergic chithandizo pamachitidwe athu otayika-kuthamangitsa mu zitsanzo za otchova njuga. kuzolowera (Rogers Et al, 2010). Titha kuunikanso ntchito ya ma neurotransmitters ena, monga ma opiate ndi glutamate machitidwe, omwe angapangitse zovuta zamagetsi (Grant Et al, 2007, 2008).

Kutchova juga kwachidziwitso kumabweretsa mavuto akulu komanso mabanja ndipo imayimira nkhani yayikulu yathanzi (Shaffer ndi Korn, 2002). Komabe, tikudziwa zochepa chabe za zinthu zachilengedwe zomwe zimapereka chiopsezo pamavuto a juga, popanda chithandizo chamankhwala chomwe chilipo pano kuchipatala. Kuyesa komwe kwawonetsedwa pano kukuwonetsa njira imodzi yoyambira kuthana ndi mavutowa; kutanthauza mwa kufufuza za neural komanso pharmacological pazazidziwitso komanso zamakhalidwe zomwe zimawonekera mwa anthu omwe amapezeka pachipatalachi. Zotsatira izi zikuwonetsa kuti kulimbikira komwe otchova juga amasewera kuti abwezeretse ndalama kumawonongeka ndi ntchito ya serotonin, pomwe kuwunika kwa kutayika komwe otchova juga akuwathamangitsa kumayendetsedwa ndi zochitika za D.2/D3 dongosolo receptor.

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Kuvomereza

Kufufuzaku kunathandizidwa ndi ophunzira a Medical Research Council a Daniel Campbell-Meiklejohn komanso mphoto yodziyimira payokha kuchokera ku Biotechnology and Biological Sciences Research Council (BBSRC) kwa Robert Rogers. Tikuthokozanso kuthokoza a Michael Frank chifukwa cha malingaliro othandiza okhudza mtundu woyambirirawo.

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zolemba

Sitipereka lipoti lazachuma kapena kusokonekera kwa chiwongola dzanja.

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Mawu a M'munsi

Zowonjezera Zowerengera zimatsata pepala lomwe lili patsamba la Neuropsychopharmacology (http://www.nature.com/npp)

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Zowonjezera Zowonjezera

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Zothandizira

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