Maseŵera a juga ndi Kutchova njuga Chizolowezi: Kuyanjanitsa udindo wa Dopamine mu Irrationality (2013)

Kutchova juga kwachikhalidwe ndi chizolowezi chomwe chimadziwika ndi zochuluka (ndalama) zomwe zimayambitsa mavuto poyang'ana zotsatilapo zoipa, monga kufooka kapena mavuto abwenzi. Dopamine ya ubongo akuti idatenga gawo lofunikira kwambiri pamakhalidwe oyipa ndi chizolowezi chanjuga. Komabe, tikudziwa zochepa pokhudzana ndi njira zomwe zimayendetsa magawano osiyanasiyana m'njira zomwe zimayambitsa ngozi, kapena zinthu zomwe zimapangitsa munthu kukhala wosuta njuga. Kafukufuku waposachedwa wama makoswe (Cocker et al., 2012) adafufuza ubale womwe ulipo pakati pa dopamine ndi zisankho zowopsa, pogwiritsa ntchito njira zowunikira, kuphatikiza mankhwala, ndi kulingalira kwa ubongo. Olembawa akuwonetsa mgwirizano pakati pa kufalikira kwa driatal dopaminergic komanso chidwi ndi kukula kwamitengo, zomwe zimapangitsa kuti zizigwirizana ndi njuga ya anthu. Mukuwunikaku, timayang'ana mozama umboni womwe ukugwirizana ndi ulalo uno. Tikuti kuyika machitidwe oika pachiwopsezo kuchokera ku makoswe kupita kwa anthu akuyenera kuchitidwa mosamala kwambiri komanso kuti chidwi chathu chikhale chakuzidwa Cocker et al. (2012) ndizosiyana ndi tsankho lotayirira lomwe limawonedwa mu kutchova juga kwa anthu.

M'maphunziro awo, Cocker et al. (2012) adayesa kutenga chiwopsezo pagulu la makoswe a 32 pogwiritsa ntchito njuga yamwano. Pazoyesera zilizonse, makoswe amasankha pakati pa cholembera "chotetezeka" chomwe chimapereka chiwongola dzanja chambiri (masanjidwe 1-3), motsutsana ndi wopereka "osatsimikizika" wopereka 50 / 50 mwayi wowonjezera kuchuluka kapena kulandira chilichonse. Chifukwa chake, mwanjira iliyonse yotetezeka ya x ma pellets, njira ina yotchera njuga ingapangitsenso 0.5 * 2x = x ma pellets, kulola olemba kuti athe kuwunika momwe angayikidwire popanda kusiyana pamiyezo yomwe akuyembekezerayo. Khoswe yemwe angayankhe mwapang'onopang'ono mphotho yaying'onoyo adawerengedwa kuti "wodziika pachiwopsezo," pomwe lingaliro "lofuna" Pafupipafupi, makoswe adawonetsa mkhalidwe wofuna chiopsezo, kusankha wosatsimikizika pa ∼60% mayesero.

Olembawo adafufuza momwe kuwopseza kunasinthidwira pakati pa mayesero omwe anali osiyana kukula, monga, mu kuchuluka kwa omwe amapezeka pa shuga. Ngakhale kutenga chiopsezo kudakhala kosadukiza pamiyala itatu pafupifupi ya magawo awiri a atatu, makoswe "oopsa"Cocker et al., 2012, mkuyu wawo. 2A,B). Olembawo amatanthauzira makoswe owoneka ngati abwinobwino ngati zopanda pake, chifukwa kuchuluka kwa mitengo sikunasinthe phindu lomwe likuyembekezeredwa ndi njira ina yosatsutsika.

Kenako, olemba adawerengera zotsatira za nonspecific dopamine enhancer amphetamine ndi dopamine D_2/3 receptor antagonist eticlopride pa kutenga chiopsezo. Amphetamine adakulitsa chiwopsezo chonse kutenga makoswe omwe amayang'anira ma wager, pomwe eticlopride adachepetsa kutenga ngozi mu makoswe a wager-osasamala (Cocker et al., 2012, mkuyu wawo. 2C-F). Makamaka, a D₁ wotsutsa sanatulutse zinthu zowoneka. Pomaliza, olemba adayeza striatal dopamine D_2/3 makulidwe a receptor mu gawo lama makoswe (n = 9) pogwiritsa [¹¹C] raclopride PET ndi autoradiography. Adapeza kulumikizana koyipa pakati pa zomverera za wager ndi D_2/3 kuchuluka kwa receptor mu dorsal striatum (Cocker et al., 2012, mkuyu wawo. 4). Pokambirana, olemba akuganiza kuti kukhudzidwa kwa ma wager kumakhala kofanana ndi njuga zamatenda, ndikuti amalumikizana ndi striatal D_2/3 Mlingo wa receptor ukugwirizana ndi zotsatira zomwe zimawoneka pakukonda mankhwala osokoneza bongo.

Olembawo adalumikiza kukhudzidwa kwa wager ndi dopamine activation ya striatal D_2/3 ma receptor ogwiritsa ntchito njira zingapo zophatikiza, kuphatikiza pamankhwala, ndi kuyerekezera kwa PET. Kudziwika kwa zotsatira za neurobiological kumapangitsa chidwi chambiri chakuzisiyanitsa pakupanga zisankho zowoneka bwino m makoswe. Komabe, kuwonjezera zomwe apezazo ku njuga zomwe zimayambitsa chiopsezo cha anthu komanso njuga ndizovuta. Choyamba, mosiyana kwambiri ndi anthu, makoswe mu phunziroli adakondwera ndi njira yosatsimikizika muzoposa theka la zomwe adasankha. M'mikhalidwe yofananayo, anthu amakonda kukhala osakhala pachiwopsezo, amakonda kusankha ndalama zowonjezera pamitengo yoopsa ya mtengo wofanana woyembekezeka. Khalidweli lamasuliridwa kukhala ntchito yothandiza pamalingaliro amakono opanga zisankho zowopsa, kuwonetsa lingaliro loti kubwereza kukula kwa mphotho sikuwonjezere kuwirikiza kwa chinthu chofunikira (Fox ndi Poldrack, 2008). Ngakhale kusinthaku kukuwonetsa kusiyana pakati pa mitundu kapena chifukwa cha kusiyana kwa machitidwe, mwachitsanzo, mphotho zoyambilira zofanana ndi kuwunika koyamba kapena kuwomberedwa motsutsana ndi zosankha zobwereza, ndi funso lotseguka (pokambirana, onani. Hayden ndi Plt, 2009). Ngakhale zili choncho, zopezeka zingapo zosiyanazi zikutsindika kufunikira kwa kusamala tikamasulira zotsatira kuchokera ku nyama kupita kwa anthu.

Chachiwiri, lingaliro la kusakhazikika pansi momwe limagwiritsidwira ntchito ndi Cocker et al., 2012, ndi kulumikizana kwake ndi matenda azachipatala, ndizotsimikizirika. Olembawo akuti mchitidwe wama makoswe owoneka ngati abwinobwino ndiwopanda pake, chifukwa kusintha kwawo kuchoka pachiwopsezo kufuna kuyika ngozi poti mitengo ikukwera sikupereka phindu lililonse. Kenako amalumikizitsa izi zopanda pake ndi njuga zamatenda mwa anthu, poganiza kuti kusakondera kopanda tanthauzo pakupanga zisankho kumayambitsa otchova njuga kupatula malamulo oyenera. Tikuganiza kuti uku ndi kulumpha kolimba mtima. Khalidwe limafotokozedwa ngati losamveka malinga ndi kupatuka panjira yokhazikika yomwe imatanthauzira kumasulira kwa cholinga chamtengo wapatali kukhala chinthu chogwirizana. Makoswe oopsa kwambiri amatha kuwoneka ngati achabechabe ngati chinthu chofunikira chikufanana ndi mtengo womwe ukuyembekezeredwa, womwe umayimira zokonda zodziwika pachiwopsezo chonse. Komabe, njira zawo zowonera zangozi zitha kutsatiridwa kuchokera ku ntchito ina, mwachitsanzo, yomwe imapereka phindu ndi chiopsezo. M'malo mwake, chiwopsezo chowonjezereka ndi mitengo ikubwera chimalembedwa bwino mwa anthu (Holt ndi Laury, 2002). Khalidweli, lomwe nthawi zina limatchedwa kuti "chiponde," lingawonedwe kukhala lofananira, popeza munthu alibe zambiri zomwe angataye akamachita juga pa chiponde, koma mwina ayenera kuganizira kawiri akatchova njuga nyumba yake. Kuchokera pamalingaliro awa, machitidwe a makoswe osakhudzidwa ndi ngongole amafanana ndi zomwe zimawonedwa mwa anthu athanzi ndipo mwina siziyenera kuwonedwa ngati zamatenda.

Kuphatikiza apo, ngakhale titha kuona kukomoka uku kukhala kopanda tanthauzo, ndizosiyana ndi mtundu wa chikhalidwe chopanda tanthauzo chomwe chikuwoneka pamavuto opanga zisankho zowopsa. Mu njuga zamatenda mwachitsanzo, kuchepa kwa mawuwa kumatanthauza kukondera kwachidziwitso monga kulowetsedwa kwa kuwongolera ndi zikhulupiriro mu mwayi (Fortune ndi Goodie, 2012). Kusankhana uku kumafanana ndi malingaliro olakwika a momwe zinthu zinapangidwira, mosiyana ndi njira yodalira ngozi. Chifukwa cha kusazindikira kwatsoka kotereku, otchova njuga amakonda kuwonetsa chiopsezo chowopsa, chomwe chiri chosiyana kwambiri ndi chikhalidwe chomwe chimawoneka m'miyendo yovuta kwambiri. Mwachitsanzo, pulojekiti yochepetsera kuchotsera, yomwe imapanga chisankho chofananira popanga chiopsezo monga momwe zimakhalira ndi Cocker et al. kuphunzira, otchova njuga amawonetsa kusintha kosasunthika pazosankha zowopsa (Ligneul et al., 2012). Monga zowonjezera pazowonera izi, titha kunena kuti makoswe omwe ali pachiwopsezo chofuna kutchova juga mu Cocker et al. Kafukufukuyu ndiomwe saganizira kukula kwa wager, kapena amawonetsa kutenga zowopsa pamitengo yowonjezereka (Cocker et al., 2012, mkuyu wawo. 2B). Kulekerera koteroko pachiwopsezo chachikulu kumafanana ndi chimodzi mwazizindikiro zazikulu za kutchova juga kwazomwe zikufotokozedwa mu DSM-IV, kutanthauza "kufunikira kutchova njuga ndi ndalama zowonjezereka kuti akwaniritse chisangalalo chomwe mukufuna."

Kuwona kwina kumeneku kungayike dopamine yomwe idawonedwa kumabweretsa kuwala kwina. Cocker et al. fotokozani za ubale wosagwirizana pakati pa dopamine D_2/3 kutalika kwa receptor ndi chidwi chager, chomwe amagwiritsa ntchito pofotokozera kusiyanasiyana kwakumachitika kwa ma dopaminergic pamankhwala pakati pa makoswe aukali komanso oopsa. Kuchepetsa kwa D_2/3 kachulukidwe ka receptor kumawoneka ngati kovuta kuti tigwirizane ndi lingaliro lathu kuti makoswe osagwirizana ndi omwe ali pachiwopsezo cha kusuta kwa juga, chifukwa kuchepetsedwa kotereku kumagwirizanitsidwa nthawi zonse ndi chizolowezi cha mankhwala osokoneza bongo mwa anthu (Volkow et al., 2010). Komabe, ndikofunikira kuzindikira kuti maphunziro a PET aumunthu mpaka pano alephera kufotokoza kusiyana kulikonse mu D_2/3 kupezeka kwa ma receptor pakati pa otchova njuga ndi kuwongolera (Boileau et al., 2012; Clark et al., 2012). Izi zikusonyeza kuti njira zamitundu mitundu zomwe zimayambira njuga zitha kukhala zosiyana pang'ono ndi zomwe zadziwika kuti zimagwiritsa ntchito mankhwala osokoneza bongo.

Kapenanso, kutchova njuga kwa m'magazi kumatha kutengedwa ndi kuchuluka kwa ma dopamine, mogwirizana ndi mtundu wa psychostimulant-mimeticZack ndi Poulos, 2009). Thandizo la mtunduwu limachokera ku kafukufuku waposachedwa yemwe amayang'ana kuthamangitsidwa kwa kutaya, chikhalidwe china chodziwika kwambiri cha kutchova juga komwe otchova njuga amapitiliza kuwonjezera ndalama zawo kuti abwezeretse zomwe adataya kale. Pomwe ochita nawo zathanzi adawonetsa kuwonjezeka kwa ngozi zomwe zikuwoneka kuti zikuwonjezereka pamiyala ya placebo, adawonetsa kuwonongeka kosalekeza kuthamangitsa pamtengo pambuyo pothandizidwa ndi dopamine enhancer methylphenidate (Campbell-Meiklejohn et al., 2012). Pogwirizana ndi izi, makoswe okhala ndi chidwi cha Cocker et al. (2012) Kufufuza kunawonetsa kuchuluka kofunafuna zoopsa pothandizidwa ndi amphetamine, pomwe makoswe a wager-osaganizira (omwe tikuwauza kuti atha kukhala pachiwopsezo cha kutchova juga) adakhala osafunikira kwenikweni potsatira zomwe D_2/3 receptor antagonist eticlopride. Kuyankha kosiyaniratu pakati pa magulu awiriwa kumapitilizanso kuyenderana ndi zomwe zapezedwa kale kuti zotsatira za mankhwala a dopaminergic zimatengera kusiyana pamiyeso ya dopamine yofunikiraCools et al., 2009).

Mwachidule, kafukufuku wo Cocker et al. (2012) imapereka chithandiziro chambiri pamabuku othandiza popanga zisankho zowopsa, kuwonetsera kulumikizana kowoneka bwino pakati pa kusiyana pakati pa kuthekera kwa mphamvu ya wager ndi kufalikira kwa driometri kudzera pa D_2/3 zolandila. Cholinga cha ndemanga iyi chinali kukambirana kufanana komwe olemba adachita pokhudzana ndi kuthekera kwa nthabwala, ndikuwona mafotokozedwe ena pazotsatira zamakhalidwe ndi mankhwala. Tikuti kudziwa kukopa kwa ming'alu mu makoswe mpaka kutchova juga kwa anthu sikungakhale kolunjika, ndipo tikuti "vuto lililonse" kwa otchova juga lingakhale losiyana ndi zomwe olemba amapereka. Osatikhumudwitsa njira zotanthauzira, tikuyembekeza kuti zonena zathu zimayambitsa kukambirana ndikulimbikitsa kufufuza kwamtsogolo zomwe zikuyang'ana kwambiri pakuchepetsa kusiyana pakati pa kutchova juga kwa nyama ndi anthu.

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Nkhani Yogwirizana

• Zolemba - Khalidwe / Machitidwe / Kuzindikira: Kusankha Mwanzeru Pazokayikitsa Kulumikizana ndi Lower Striatal D_2/3 Kulandila Kumangilira mu Makoswe 

  • Paul J. Cocker,
  • Katherine Dinelle,
  • Rick Kornelson,
  • Vesna Sossi,
  • ndi Catharine A. Winstanley

  The Journal of Neuroscience, 31 October 2012, 32 (44): 15450-15457; doi: 10.1523 / JNEUROSCI.0626-12.2012

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  • Malembo Okwanira (PDF)

Nkhani zomwe zikufotokoza izi

• Kusayenerera pakumvetsetsa mitundu yosiyanasiyana ya malipiro mu kutchova njuga Ubongo, 1 August 2013, 136 (8): 2527-2538
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