Mesebetsi ea Serotonin le Dopamine Play Complementary ho Papali ea chelete ho khutlisa ho lahleha (2010)

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

E phatlalalitsoe marang-rang 2010 Mphalane 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 Motsamaisi Kar Ray,3 Sudhakar Selvaraj,3 Richard E Passingham,2 Phillip Cowen,3 'me Robert D Rogers2,3, *

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Eya ho:

inahaneloang

Ho becha ho tsoelang pele ho khutlisa tahlehelo - 'ho lelekisa papali' ke karolo e hlahelletseng ea papali ea chelete le papali ea chelete. Leha ho le joalo, ha ho tsejoe hanyane ka li-neuromodulators tse susumetsang boitšoaro bona. Litekong tse tharo tse arohaneng, re batlisitse karolo ea ts'ebetso ea serotonin, D2/D3 ts'ebetso ea li-receptor, le ts'ebetso ea beta-adrenoceptor mabapi le tahlehelo ea ho lahleheloa ke botsofali le batho ba baholo ba phetseng hantle ba IQ ba rutehileng ka mokhoa oa kalafo kapa taolo e loketseng. Boitekong ba 1, barupeluoa ba ile ba sebelisa lino tse tahang tsa amino-acid tse neng li se na kapa li se na protocol ea serotonin, tryptophan. Boitekong ba 2, barupeluoa ba amohetse 176 e le 'ngoeTekanyetso ea μg ea D2/D3 agonist agonist, pramipexole, kapa placebo. Thutong ea boraro, barupeluoa ba amohetse e le 'ngoetekanyo ea mg ea beta-adrenoceptor blocker, propranolol, kapa placebo. Kamora kalafo, bankakarolo ba phethile papali ea ho lelekisa tahlehelo ka likhomphutha. Boemo ba maikutlo le pelo bo ne bo lekantsoe motheong oa mantlha mme ho latela kalafo. Ho fokotseha ha Tryptophan ho fokolitse haholo palo ea liqeto tse entsoeng ho lelekisa tahlehelo, le palo ea liqeto tse latellanang tsa ho lelekisa, ka lebaka la ho ba le liphetoho tse hlakileng tsa maikutlo. Ka lehlakoreng le leng, pramipexole e ekelitse boleng ba tahlehelo haholo 'me ea fokotsa boleng ba tahlehelo e nehetsoeng. Propranolol e fokotsehile haholo ka lebelo la pelo, empa ha ea hlahisa liphetoho tse kholo mokhoeng oa ho lelekisa tahlehelo. Ho lelekisa tahlehelo ho ka nkuoa e le mokhoa oa ho phonyoha o susumetsoang ka mokhoa o khelohileng o laoloang, karolo e 'ngoe, ke boleng bo nyane ba ho tsoela pele ho becha ho bapisoa le boleng ba tahlehelo e seng e bokelletsoe. Serotonin le dopamine li bonahala li bapala likarolo tse sa arohaneng moetlong oa batho oa ho becha ho hlaphoheloa, kapa ho batla ho 'baleha' tahlehelo ea pele. Mosebetsi oa Serotonergic o bonahala o khothaletsa ho fumaneha ha tahlehelo e le mokhoa oa boits'oaro, athe D2/D3 ts'ebetso ea li-receptor e hlahisa liphetoho tse thata boleng ba tahlehelo e nkoang e le bohlokoa ho lelekisoa. Mosali ea nang le kutloelo-bohloko, bonyane joalo ka ha a kopantsoe ke beta-adrenoceptors, ha a phethe karolo ea bohlokoa likhethong tse thehiloeng ho tahlehelo ea laboratori.

Keywords: serotonin, dopamine, ho lelekisa tahlehelo, papali ea chelete, ho phehella, boleng

Eya ho:

SELELEKELA

Ho becha ho khutlisa tahlehelo, kapa ho lahleheloa ke tahlehelo (Lesieur, 1977), ke karolo ea mantlha ea ho etsa liqeto tsa motho (Kahneman le Tversky, 2000). Leha ho le joalo, tikolohong ea bongaka, ho lelekisa tahlehelo e feteletseng ke sesupo se totobetseng sa taolo e sa sebetseng hantleng karolong e kholo ea batho ba tlalehang mathata ka boits'oaro ba bona ba papali ea chelete (Corless le Dickerson, 1989; McBride et al a, 2010; Khauta et al a, 2010). Ha e sa laoloe, ho lelekisa tahlehelo ho ka hlahisa sebaka se kotsi sa ho kenella papaling ea papali ea chelete, ho eketsa likoloto tsa lichelete empa ho fokotsa lits'ebeletso, mme ho ka ba le mathata a tebileng a lelapa, sechabeng le litlamorao tsa mosebetsi oa papali ea papali ea chelete (Lesieur, 1979).

Boemong ba kelello, ho lelekisa tahlehelo ho rarahane ebile khafetsa ho kenyelletsa maikutlo a phehisanong, ho beha takatso (kapa tlhoko) ea ho lula u bapala khahlanong le tšabo ea tahlehelo e kholo le ho feta (Lesieur, 1977): Maemo a matla a maikutlo a kopantsoeng ke ts'ebetso kahare ho lipotoloho tse fapaneng tsa neural (Campbell-Meiklejohn et al a, 2008). Papali ea chelete ea ho becha e boetse e amana le linaha tse tsosang takatso (bona ka tlase) le ho tšoarella ka mesebetsi e metle ea papali ea chelete eo e leng tšobotsi e hlahelletseng ea kliniki ea mathata a papali ea chelete.Dickerson et al a, 1987; McBride et al a, 2010). Ka lebaka leo, ho lelekisa tahlehelo ho ka emela sepheo sa mantlha sa ntlafatso ea mekhoa ea phekolo.

Leha e le bohare ba eona bothateng ba ho becha, ha re tsebe letho ka tsela eo ho lelekisa tahlehelo ho susumetsoang ke ts'ebetso ea methapo ea methapo. Palo e fokolang ea bopaki ba kliniki e fana ka maikutlo a hore ho becha ha li-pathological ho tsamaisana le ho se sebetse hantle ha serotonergic joalo ka mohlala oa (litheolelo) tsa litekanyetso tse fokotsehileng tsa serotonin metabolite, 5-hydroxyindoleacetic acid ho mokelikeli oa k'holeseterole (Bergh et al a, 1997; Roy et al a, 1988) le ka litlaleho tsa tokollo e eketsehang ea prolactin (le litlaleho tsa 'high' tse ikhethileng) kamora phephetso e matla le 5-HT2c agonist ea ho amohela, meta-chlorophenylpiperazine (Pallanti et al a, 2006). Li-inhibitors tse khethiloeng tsa serotonin li boetse li bontsitse tšepiso e itseng e le kalafo ea papali ea papali ea methapo ea methapo ka litlamorao tsa bona tse bakang mathata le ho tšoenyeha (Grant le Potenza, 2006; Pallesen et al a, 2007). Kamora nako, serotonin e na le tšusumetso e nang le tšusumetso boits'oarong bo sa susumetseng (Winstanley et al a, 2004), tseo ka bobeli li khothaletsang ho lelekisa tahlehelo (Breen le Zuckerman, 1999), ebile li fetelletse mathateng a papali ea chelete (Blaszczynski et al a, 1997).

The pathophysiology ea mathata a ho becha le eona e na le monyetla oa ho kenyelletsa ho se sebetse hantle ha bokopa bo bohareng ba dopaminergic, le libaka tsa polokelo ea mesolimbic le tsa pele (Hewig et al a, 2010; Potenza, 2008). Ha ho bapisoa le lithuto tse lumellanang le taolo e phetseng hantle, basomi ba masapo a methapo a bontša likarabo tse fokotsang tsa "neuronal" ka har'a mesostriatal nuclei ha ba ntse ba etsa mokhoa o ts'oanang oa papali ea chelete bakeng sa moputso oa chelete (Reuter et al a, 2005). Tsamaiso ea psychostimulant, amphetamine, ho basomi ba methapo ea methapo ea mafu a marang-rang e ka u lematsa haholo ka papali ea chelete (Zack le Poulos, 2004), athe D2 receptor antagonist, haloperidol, e ka ntlafatsa thepa e ruisang ea boitšoaro bo joalo (Zack le Poulos, 2007). Kamora nako, bopaki bo bokellanang bo supa hore kalafo ea dopaminergic e amahanngoa le papali ea chelete ea mafu (le mathata a mang a taolo ea maikutlo) ho bakuli ba fokolang ba nang le lefu la Parkinson (Bona et al a, 2007), mohlomong ho bonts'a pherekano ea karolo e pharalletseng ea dopamine ho matlafatseng ho ithuta le palo ea likamano tsa boleng le liketso (Dagher le Robbins, 2009; Bona et al a, 2010). Kahoo, bopaki bo atileng bo fana ka maikutlo a hore serotonin le dopamine dysfunction mediate likarolo tsa ho becha ka mathata (Zeeb et al a, 2009). Leha ho le joalo, ho fihlela joale, karolo ea bona ea karolo e bohareng ea boitšoaro ba ho lelekisa tahlehelo ha e so fumanoe ka liteko.

Mokhoa o mong oa ho qala ho utloisisa likarolo tse nyane tsa tahlehelo e fetelletseng eo ka linako tse ling e shejoang ho ba bechang, ke ho etsa lipatlisiso mabapi le karolo ea li-neuromodulator tsa ho lelekisa boitšoaro ba batho ba baholo ba phetseng hantle ba nang le boiphihlelo bo fokolang ba ho becha. Tlhahisoleseling e fumanoeng litekong tse joalo e tla thusa ho theheng maikutlo a mabapi le ho ferekanya hoa tšebetso ea li-neuromodulators mediate lahleheloang ho lelekisa maemong a methapo. Mona, litekong tse tharo tse arohaneng, re sebelisitse mofuta oa boitšoaro oa tahlehelo o lelekiloeng ka laboratoring ea rona mme o se o ntse o netefalitsoe ka monahano o sebetsang oa matla a matla a khoheli (Campbell-Meiklejohn et al a, 2008) ho bapisa boitšoaro ba tahlehelo ea batho ba baholo ba sa pheleng tleleniki (ba tlalehileng karolo e fokolang feela ea papali ea papali ea chelete) kamora ho fetoloa ha serotonergic, dopaminergic (D2/D3) le mosebetsi oa beta-adrenoceptor.

Boitekong ba 1, re fuputse litlamorao tsa ho tepella ho hoholo ha tryptophan tšekamelong ea ho tsoela pele ho becha ho fumana tahlehelo le ho lekoa lipakeng tsa li-hypothes tse peli tse nang le likhakanyo tse hlakileng tsa ho se sebetse. Serotonin e tsejoa e bapala karolo e hlahelletseng taolong ea ts'ebetso e seng moputso le thibelo ea boitšoaro kamora ketsahalo ea kotlo kapa liketsahalo tse nyarosang (Soubrie, 1986). Ho feta moo, phokotso ea nakoana mesebetsing ea serotonin e bohareng, e fihletsoeng ka ho fokotsoa ha tryptophan, e ka fokotsa tšenyo e bakiloeng ke kotlo ea boitšoaro bo tsoelang pele ho batho ba baholo ba phetseng hantle (Holckett et al a, 2009). Motheong ona, re ka lebella hore ho fokotsoa ha tryptophan ho tla eketsa tšekamelo ea ho tsoela pele ho becha e le hore o ka fumana tahlehelo ea nakong e fetileng ka ho sitisoa ke boitšoaro bo itšetlehileng ka boitšoaro ba serotonin.

Ka lehlakoreng le leng, serotonin e boetse e sebelisana le ho ithuta ka liketsahalo tse mpe (Bari et al a, 2010; Tlo et al a, 2002; Deakin le Graeff, 1991; Evers et al a, 2005). Dayan le Huys (2008) e hlahisitse hore liphoso tsa taolo ea boits'oaro ka mora ho fokotseha hoa ts'ebetso ea serotonin (liteko kapa tsa bongaka) li ka hlahisa keketseho e kholo ka boholo ba liphoso tse mpe tse boletsoeng esale pele tseo ka nako e 'ngoe li ka hlahisang libaka tse mpe tse amanang le batho ba tlokotsing (Dayan le Huys, 2008). Ka mokhoa o hlakileng, ho hloka matla ha tryptophan ho ka ntlafatsa ho nepahala ha ha likhakanyo tsa sephetho se fosahetseng kapa sa kotlo ho batho ba baholo ba phetseng hantle (Ho fola et al a, 2008). Ho feta moo, Evers et al a (2005) e bonts'itse hore tryptophan depletion e ntlafatsa ts'ebetso ea neural ha e araba liphoso nakong ea ho ithuta hape ka hare ho sebaka sa kantle sa cingulate, sebaka se qalang se ntse se etsa liqeto tsa ho khaotsa ho lelekisa tahlehelo (Campbell-Meiklejohn et al a, 2008). Kahoo, re kanna ra bolela esale pele hore ho fokola ha bophelo ba tryptophan ho batho ba baholo ba phetseng hantle ho tla ntlafatsa sepheo sa liphetho tse mpe nakong ea ho lahla ho becha, le ho fokotsa boitšoaro bo latelang ba ho lelekisa tahlehelo.

Boitekong ba 2, re fuputse litlamorao tsa tekanyetso e le 'ngoe ea non-ergoline D2/D3 receptor agonist, pramipexole (PPX). Hammoho le mefuta e meng ea kalafo ea dopaminergic, kalafo ea PPX e amahanngoa le mathata a papali ea chelete setulong sa bakuli ba lefu la Parkinson (Bona et al a, 2007). Leha ho le joalo, ha ho e-so be le tlhahlobo ea hore na kalafo e nang le D2/D3 li-receptors agonists li fetola boitšoaro ba ho lelekisa nakong ea ho lahla ho becha.

PPX e khetha D haholo3 ho feta D2 li-receptors hape li tlama ho dopamine (autoreceptor le post-synaptic) li-receptor tsa mesolimbic mopalamo oa litsela (Camacho-Ochoa et al a, 1995) (Bona Tlhahisoleseling ea Tlatsetso). Litekanyetso tse fokolang tsa PPX (mohlala, 0.5mg) e ka sitisa ho matlafatsa ho ithuta ho batho ba baholo ba phetseng hantle (Pizzagalli et al a, 2008), le ho eketsa likhetho tse kotsi lipapaling tsa mofuta oa lothari (Tsoala et al a, 2008), mohlomong ka ho supa moputso o sa bonahaleng oa litselana tsa mesolimbic (Tsoala et al a, 2008; Santesso et al a, 2009). Ka lebaka la sena, le bopaki ba hore tekanyetso e tlase ea PPX, le basebeletsi ba bang ba sebetsang ho D2 li-receptors, li sitisa ho tšoaea liphetho tse mpe ('liphoso tse fosahetseng tsa ho bolela esale pele') (Frank le O'Reilly, 2006; Santesso et al a, 2009; van Eimeren et al a, 2009), re lekile maikutlo a hore tekanyetso e le 'ngoe ea PPX e eketsa ho lelekisa boitšoaro mme mohlomong, e bile le tšusumetso ea boleng ba tahlehelo eo batho ba phetseng hantle ba ikemiselitseng ho e lelekisa.

Leha ho ka se be bonolo hore seo re se fumaneng ho Thutong ea 1 le ea 2 se bonts'a liphetoho tse kholo literekeng tse ikamahantseng le ho theoha ha kalafo kapa kalafo ka PPX, ho ka etsahala hore lipatlisiso tsa rona li amanang le liphetoho mabapi le ho lemosa kapa ho tsosa, mohlomong ho bonts'a protocol ea nako e telele. tsa liteko tsa meriana. Mohlala, le ha tryptophan depletion hangata e sa fetole boemo ba boemo ho batho ba baholo ba hlahlobiloeng bakeng sa mathata a amanang le mathata, e ka fumana likarabo tsa 'mele (pelo) le karabelo e mpe ea ts'ebetso (van der Veen et al a, 2008). Ho feta moo, lithuto tsa masimong li bonts'a hore papali ea chelete ea khoebo e amahanngoa le keketseho ea mohono oa kutloelo-bohloko (Anderson le Brown, 1984; Meyer et al a, 2000). Ka hona, ha ho hlake hore na liphetoho tsa ho tsosa takatso li ka eketsa kapa tsa fokotsa tloaelo ea ho boloka papali ea chelete e le hore e hlaphoheloe hape. Pejana, re fumane hore tekanyetso e le 'ngoe ea mohanyetsi oa beta-adrenoceptor, propranolol, e fokotsa tlhokomelo ea ba nkang liqeto mabapi le lintlha tse amanang le kotlo (Rogers et al a, 2004), e ka lokollang mokhoa oa ho lelekisa tahlehelo. Boitekong ba boraro, re ile ra hlahloba hore na liphetoho tse nyarosang, joalo ka ha li bontšoa ke mofuta oa "pelo" e fokotsoang ea HR e hlahisoang ke batho ba baholo ba phetseng hantle ka tekanyo e le 'ngoe ea beta-adrenoceptor antagonist propranolol.

Eya ho:

LISEBELISOA LE MEKHOA

Barupeluoa le meralo

Barupeluoa bohle ba fane ka tumello e ngotsoeng e ngotsoeng. Barupeluoa ba ile ba fuoa tlhahlobo ea bongaka ke ngaka e nang le boiphihlelo ea kelello, ho kenyelletsoa le tlhahlobo ea tlhahlobo ea SCID-I ho netefatsa hore ha ho le e 'ngoe ea mekhoa e latelang ea ho kenyelletsa e fihletsoeng: (i) bokuli bo boholo ba' mele; (ii) DSM-IV ea maikutlo a maholo kapa a kelello kapa khatello ea kelello; le (iii) bokuli ba tlhekefetso ea lithethefatsi tsa hona joale kapa tsa nakong e fetileng tsa DSM-IV. Barupeluoa ba ile ba hlahlojoa ka Screen Oaks Gurb Screen (Lesieur le Blume, 1987); lintlha kaofela e ne e le 0 kapa 1, ho bonts'a ha ho na bopaki ba bothata kapa papali ea chelete ea ho becha.

Leka 1

Batho ba baholo ba mashome a mararo a metso e mene ba phetseng hantle ba nkile karolo. Ha ho le ea mong ea neng a e-na le nalane ea lefu la maikutlo; ho ne ho se na thibelo mohatong oa ho ilela khoeli ho barupeluoa ba basali. Barupeluoa ba leshome le metso e supileng (banna ba robeli) ba noetse seno sa amino-acid se neng se se na tryptophan (T−) le barupeluoa ba 17 (banna ba robeli) ba noa seno sa amino-acid se neng se na le tryptophan (T +). Barupeluoa ba T + le barupeluoa ba T− ba ne ba bapisoa ho latela bong ba bona (bona Lethathamo la Tlatsetso S1), lilemo (F <1.00), le bokhoni ba ho tseba (lekhoaba et al a, 1998) (F (1,30) <2.08).

Barupeluoa ba ile ba latela lijo tse nang le protheine e tlase (<2g) letsatsi pele ho thuto, 'me a itima lijo bosiu bo bong le bo bong pele a ea laboratoring ka lihora tse 0830 ka letsatsi la tlhahlobo. Mehato ea maemo a amang boemo bo botle le maemo a amang (Watson et al a, 1988) li nkuoe ka nako ena le 15li-sampuli tsa mali tsa ml ho fumana likhakanyo tse felletseng tsa plasma tryptophan. Barupeluoa ba ile ba noa seno sa amino-asiti nakong ea metsotso e 60. Ha ho le ea mong oa barupeluoa ea tlalehileng litla-morao ho feta ho nyekeloa ke pelo nakoana. Barupeluoa ba fuoe protheine e tlase (<2g) lijo tsa motšehare har'a motšehare. Pheta litekanyetso tse amang maemo a amang boemo bo botle le tse mpe tsa 'mele, le sampole ea bobeli ea mali, li ile tsa bokelloa +5h kamora ho nwa seno sa amino-acid, pele a qeta papali ea tahlehelo ea tahlehelo.

Leka 2

Batho ba baholo ba mashome a mararo a bophelo bo botle ba ile ba abeloa hore ba fuoe ba 176μg ea PPX kapa placebo (placebo-PPX). Sehlopha ka seng se ne se na le banna ba supileng. Ho ne ho se na phapang e kholo lipakeng tsa bankakarolo ba fumaneng placebo le ba fumaneng PPX ho latela lilemo tsa bona kapa bokhoni ba bona ba ho tseba (Supplementary Table S2) (bobeli ba F's <1.00).

The 176Tekanyetso ea μg ea PPX e sebelisitsoeng ho liteko tsa 2 e ka bapisoa le litekanyetso tse bontšitsoeng li sebetsa hantle tleleniking ea boloetse ba leoto bo sa foleng.Manconi et al a, 2007). Ho na le mabaka a utloahalang a ho nahana hore subjential (Hamidovic et al a, 2008) le boits'oaro (Pizzagalli et al a, 2008; Tsoala et al a, 2008; Santesso et al a, 2009) litlamorao tsa litekanyetso tse tlase tsa li-dopaminergic agents li bonts'a liketso tsa pre-synaptic ho li-auto-receptors tse laolang tšebetso ea li-neurop tsa dopaminergic neurons tsa bohareng.Frank le O'Reilly, 2006; Mosa, 1995). Joalokaha ho hlalositsoe ka tlase, re pheta lipatlisiso tse fumanehang (1mg) litekanyetso tse tlase tsa PPX li fokotsa litekanyo tsa psychometric tsa tse amang maemo a nepahetseng ho batho ba phetseng hantle le tse nkiloeng ho fana ka maikutlo a mofuta oa ketso ea pre-synaptic (Hamidovic et al a, 2008). Leha ho le joalo, ba rona ba 176Tekanyetso ea μg e boetse e bapisoa le e bontšitsoeng ho fokotsa serum prolactin e fetang 2h (Ho fepa et al a, 1992), bonyane ho phahamisa monyetla oa hore liphetho tsa rona li bonts'a mosebetsi o mong oa post-synaptic receptor (Ben-Jonathan, 1985).

Barupeluoa ba ile laboratoring ka lihora tse 0830 mme ba qetile litlhahlobo tsa motheo tsa tse amang boemo bo botle ba 'muso le tse matla (Watson et al a, 1988). Mehato ea motheo ea methapo ea mali ea systolic / diastolic (BP) le HR e ile ea bokelloa. Kamora sena, barupeluoa ba amohetse 176 e le 'ngoeTekanyetso ea μg ea PPX kapa "capsule" ea gelatine e nang le lactose. Kamora 2h (+2h), ho ile ha nkuoa mehato e meng ea systolic / diastolic BP le HR. Maikutlo a amang boemo ba naha le a mabe a ne a bokelloa ka nako ena, pele ho phethoa papali ea tahlehelo ea tahlehelo.

Leka 3

Barupeluoa ba 80 (ba batona ba supileng) ba ile ba abeloa ho amohela ba XNUMXmg propranolol (placebo-PPL) le barupeluoa ba 14 (banna ba robeli) ba ile ba abeloa ho fumana sebaka sa lactose placebo (PLA-PPL). Lihlopha tse peli tsa bankakarolo li ne li lekana hantle ho latela lilemo tsa bona (bona Letlapa la Tlatsetso S4) (F <1) le bokhoni ba bona ba ho tseba (F (1,24) = 1.87).

Barupeluoa ba ile ba ea laboratoring hoseng ba itime lijo ka 2h le ntle le ho ja koae. Tšusumetso e ntle le e mpe ea naha (PANAS) (Watson et al a, 1988), systolic BP, diastolic BP, le HR ba ile ba hlahlojoa motheong oa pele ebe ba bang le ba bang ba 30mets kamora moo. Barupeluoa ba phethile papali ea ho lelekisa tahlehelo +75mets e latelang kalafo.

Tahlehelo ea tahlehelo

Mofuta oa papali ea tahlehelo ea tahlehelo e ka hlalosoang ka mokhoa o hlakileng o hlalositsoeng ka mokhoa o qaqileng sebakeng se seng (Campbell-Meiklejohn et al a, 2008). Papaling e 'ngoe le e' ngoe, barupeluoa ba ne ba kopuoa ho khetha pakeng tsa papali ea chelete hore ba boele ba lahleheloe (kotsing ea ho e eketsa habeli) kapa ba tlohele (le ho boloka tahlehelo e itseng). Mathata a joalo a kenya likhetho tse kotsi maemong a fapaneng a bophelo le moruo (Shafir le Tversky, 1995). Litlhaloso tse hlalosang tsa boikhethelo (tlasa botsitso) li supa boits'oaro bona ke hore tahlehelo e oela karolong ea ts'ebetso ea kelello e amanang le boleng ba lebitso (mohlala, liphetho tsa lichelete) ho boleng ba ts'ebeliso kapa ts'ebeliso, e le hore ts'ebeliso e fokotsehang ts'ebelisong e amanang le ho lelekisa le tahlehelo e kholo ea tahlehelo e nyane ka tekanyo ho fokotseha hoa ts'ebeliso e amanang le tahlehelo e itseng empa e nyane (Kahneman le Tversky, 2000). Pele re ne re fumana hore papali ea chelete ea ho becha e ka khutlisa nakong ea papali e tsamaisana le mekhoa ea maikutlo ea ho lelekisa tahlehelo mesebetsing e meng ea ho becha (Campbell-Meiklejohn et al a, 2008).

Qalong ea papali, barupeluoa ba ile ba bolelloa hore ba na le £ 20 ea tšōmo000 eo ba ka bapalang le eona, empa hore monkakarolo ea nang le lintlha tse ngata qetellong ea teko o tla hapa moputso oa $ 70. Ho 'potoloho' ka 'ngoe ea papali, £ 10, £ 20, £ 40, £ 80, kapa £ 160 li ile tsa ntšoa palong eohle ea papali. Chelete ena e hlahile ka tlase ho likhetho: 'Tlohela' le 'Bapala' (Setšoantšo sa 1). Mothating ona, barupeluoa ba ka khetha ho 'Tlohela', ba ts'ehetsa tahlehelo ena mme ba qetelle ho potoloha hanghang (sephetho sa 'tlohela-tahlehelo'), kapa ba ka khetha ho 'Bapala', ke hore, ho lelekisa tahlehelo. Kahoo, ba ne ba ka becha ka ho fumana chelete e lekanang le tahlehelo, empa ba le kotsing ea ho eketsa tahlehelo ea bona ka chelete e lekanang. Haeba sephetho sa qeto ea papali ea chelete se ne se le setle (sephetho sa 'chase-win'), tahlehelo e ile ea fumanoa hape 'me papali eo ea fela. Haeba sephetho se ne se le mpe ('ho lelekisa tahlehelo'), tahlehelo e ile ea imena habeli mme bankakarolo ba fuoa monyetla o mong oa ho tlohela kapa ho lelekisa khetho e latelang ea potoloho. Likhetho tsa khetho ka 'ngoe-'Play' kapa 'Tlohela' -e hlahile ka ho lekana khafetsa le ka ho le letona la likarolo tsa komporo.

Setšoantšo sa 1

Setšoantšo sa 1

Bonts'a tatelano ea papali ea tahlehelo ea tahlehelo. Qalong ea papali e 'ngoe le e' ngoe ea papali, ho ne ho lahleloa tahlehelo ebe ho etsoa qeto ea ho bapala (ho becha ho ea pele) kapa ho tlohela (ho amohela tahlehelo), le ho emisa. Tahlehelo e ileng ea latela le liqeto li ile tsa latela ...

Lipontšo tsa sephetho (bona Setšoantšo sa 1) e bontšitse hore na bankakarolo ba hapile papali ea chelete le hore ha ho na chelete e lahlehileng ('chase-win'); hore na ba lahlile papali ea chelete le chelete e lahlehileng ('chase-loss'); kapa chelete e lahlehileng haeba barupeluoa ba khethile ho tlohela mosebetsi ('tlohela-tahlehelo'). Qetellong ea potoloho ka 'ngoe, barupeluoa le bona ba ile ba tsebisoa ka tahlehelo ea bona ea hoqetela pontsong ea' tahlehelo ea ho potoloha '. Pontšo ena e bonts'a tahlehelo e akaretsang ea kakaretso ea potoloho eo, ka mongolo o mofubelu haeba tahlehelo e ne e le kholo ho feta 0, empa ka mongolo o motala haeba 0. 10, kapa £ 20. Haeba barupeluoa ba ntse ba tsoela pele ho lahleheloa, tahlehelo e ile ea lula e imena habeli ho fihlela ba fihla ho $ 40, ka nako eo potoloho e ile ea fela, hobane e bakile tahlehelo e kholo.

Barupeluoa bohle ba ile ba bapala liranta tse 20 tsa papali ea tahlehelo ea tahlehelo. Liphetho tsa katleho ea Chase li ne li behiloe ka mokhoa o sa reroang ho potoloha e 'ngoe le e' ngoe e le hore liphetho tsa howina li etsahetse ka tsela e tšoanang khafetsa kamora palo efe kapa efe ea (pakeng tsa 0 le 5) tahlehelo e latellanang. Liphetho tsa papali ea tahlehelo ea tahlehelo li ile tsa ajoa hoo e neng e le lipotoloho tse 14 li khutliselitseng tahlehelo eohle haeba barupeluoa ba entse qeto ea ho bapala papaling e 'ngoe le e' ngoe e khethiloeng. Leha ho le joalo, liranta tse tšeletseng li felletse ka tahlehelo e phahameng ea £ 640.

Barupeluoa ha baa ka ba bolelloa letho ka menyetla ea botle vs diphetho tse mpe e le hore diqeto tsa bona di etswe tlasa maemo a 'hlakang' (Camerer le Weber, 1992). Bakeng sa ho nyahamisa barupeluoa ho amohela maano a tloaelo a ho tlohela chelete ho boloka chelete ea bona e ngata kamoo ho ka khonehang, ha ho tlhahiso-leseling e fanoeng mabapi le kakaretso ea chelete ea bona ea papali nakong ea papali. Barupeluoa ba ile ba tsebisoa hape hore ba ke ke ba fumana lintlha tse ntle ka ho bapala kapa ho tlohela.

Ho akaretsa, barupeluoa ba ile ba tobana le letoto la mathata a amanang le khetho ea papali ea chelete hore ba ka lahleheloa ke kotsi ea ho eketsa makhetlo a mabeli, kapa ba boloka tahlehelo le ho phethela ho lelekisa, athe ka nako e tšoanang ba boloka lisebelisoa tse ngata kamoo ho ka khonehang (Campbell-Meiklejohn et al a, 2008). Boleng ba lisebelisoa tsena (lintlha tse hlalosoang ke liteko) li fanoe ke moelelo oa tlholisano e arolelanang karolo e hlokang hore litho tsa sehlopha li boloke lintlha tse ngata kamoo ho ka khonehang. Motsoako ona oa moputso oa 'nete le oa sebele o sebelisitsoe ho moruo oa boitšoaro ho bontša boitšoaro ka mokhoa o lekanang le o lekanang hantle le o bonts'itsoeng ka ntle ho laboratori (Cubitt et al a, 1998).

Tlhahlobo ea Litekanyetso

Mehato ea boiketlo e kenyelletsa karolo ea likhetho tsa ho becha (kapa ho lelekisa) likhethong tsohle tse entsoeng nakong ea papali, le palo e boletsoeng ea tahlehelo e latellanang motsotsoana. Re ile ra sekaseka boholo (kapa boleng) ba tahlehelo e lelekiloeng le boholo (kapa boleng) ba tahlehelo e fanoeng nakong ea papali. Lits'ebetso tsena li ile tsa hlahisoa e le karolelano ea boleng ba boleng ba tahlehelo eohle e fumanoeng nakong ea papali (sheba Tlhahisoleseling ea lintlha tse ling).

Mehato ea demographic, subjential, le ho lelekisa tahlehelo bakeng sa liteko tse tharo li ile tsa lekoa ho sebelisoa tlhahlobo e le 'ngoe ea phapang (ANOVA) ka lintlha tsa kalafo lipakeng (T + vs T−, PPX vs placebo, kapa propranolol vs placebo) le bong.

Eya ho:

LIPOTSO

Teko ea 1: Ho akheha ha Tryptophan

Litla-morao tsa 'mele le tse ling

Tšebeliso ea seno sa amino-acid ntle le tryptophan (kalafo ea T−) se hlahisitse phokotso e kholo ea kakaretso ea plasma ea mahlakoreng + 5h kamora nako ha e bapisoa le seno se laoloang (ka kalafo ea T +) (bona Lethathamo la S1 la tlatsetso). Leha ho le joalo, kalafo ea T− ha ea ka ea hlahisa liphetoho leha e le life tse amehang maemong a amang boemo ba naha kapa tse mpe ha li bapisoa le kalafo ea T + (Supplementary Table S1) (kaofela F (1,30) 's <2.29).

Tahlehelo e lelekisa

Barupeluoa ba fumaneng kalafo ea T− ba bontšitse phokotso e tšoaeang le e kholo ea karolo ea liqeto tsa ho lelekisa tahlehelo ha ho bapisoa le barupeluoa ba fumaneng kalafo ea T + (Setšoantšo sa 2a) (F (1,30) = 8.43, p<0.01). Palo ea liqeto tse latellanang tsa ho lelekisa papali ea papali ea chelete e lahlehileng e ile ea fokotsoa ka ts'epahalo kamora ho felloa ke tryptophan (Setšoantšo sa 2b) (F (1,30) = 8.06, p

Setšoantšo sa 2

Setšoantšo sa 2

Phehello ea boitšoaro ba ho lelekisa tahlehelo mehatong e meraro ea batho ba baholo ba se nang kalafo ba se nang tleleniki kamora ho putlama ha tryptophan (vs seno se laolang amino-acid), e leng 176μg ea D2/D3 agonist ea li-receptor, pramipexole (PPX vs sebaka), ...

Ha a bapisoa le litlamorao tsa karolo ea papali ea chelete, hore ho hlaphoheloe tahlehelo, ho ne ho se na phetoho e kholo ho boleng mabapi le tahlehelo eo barupeluoa ba felletseng ba sehlopha sa tryptophan ba nkile qeto ea ho e lelekisa (e hlahisitsoeng e le litekanyetso tsa boleng ba tahlehelo eohle e fumanoeng nakong ea papali; bona Tlhahisoleseling ea Tlatsetso) (Setšoantšo sa 3a) ha e bapisoa le bankakarolo ba fumaneng ts'ebetso ea taolo (F's <1). Hape ha ho na phetoho ea bohlokoa ho boleng ea tahlehelo e ileng ea etsoa ha a etsa qeto ea ho tlohela (Setšoantšo sa 3b(F's <1).

Setšoantšo sa 3

Setšoantšo sa 3

Ts'ebeliso ea tlhaiso-leseling ea boleng boits'ebetsong ba ho lelekisa tahlehelo mehatong e meraro ea barupeluoa ba phetseng hantle, bao e seng ba kliniki ka mor'a ho theoha ha tryptophan (vs seno se laolang amino-acid), e leng 176μg ea D2/D3 agonist ea agonist ...

Teko ea 2: PPX

Litla-morao tsa 'mele le tse ling

Systolic BP, diastolic BP, le HR ha lia ka tsa fetoloa haholo kalafo e latelang le PPX ha e bapisoa le kalafo ka placebo (bona Tlhahisoleseling ea Tlatsetso le Tafole ea Tlatsetso S3) (kaofela F (1,25) 's <1.86).

Phekolo e nang le PPX e fokolitse litšusumetso tse ntle tsa 'muso haholo ha li bapisoa le placebo ho pholletsa le +2H ho latela kalafo (F (1,26) = 10.05, p<0.005) (Letlapa la Tlatsetso S2). Ka ho khetheha, ha tšusumetso e ntle e ne e atisa ho eketsa kalafo e latelang ka placebo (F (1,13) = 3.53, p= 0.08), e fokotsehile haholo kalafo e latelang ka PPX (F (1,13) = 6.84, p<0.05). Ka +2h, ha ba phethela papali ea ho lelekisa tahlehelo, barupeluoa ba fumaneng PPX ba tlaleha litlamorao tse tlase ho feta ba amohetseng placebo (F (1,26) = 8.34, p<0.01). PPX ha ea ka ea fetola tšusumetso e mpe ea mmuso ha e bapisoa le placebo (kaofela F's <1).

Tahlehelo e lelekisa

PPX e fokolitse palo ea liqeto ho li lelekisa, le palo ea liqeto tse latellanang ho lelekisa, nakong ea ho lahla ho becha ha ho bapisoa le placebo (Setšoantšo sa 2); leha ho le joalo, ha ho le e 'ngoe ea litlamorao tse neng li le bohlokoa lipalo-palo (F's <1). Ka lehlakoreng le leng, PPX haholo e eketsehile boleng ba tahlehelo eo barupeluoa ba nkile qeto ea ho becha ho fola (Setšoantšo sa 3a) (F (1,26) = 4.94, p<0.05), hape haholo e fokotsehile boleng ba tahlehelo eo litho tsa sehlopha li ileng tsa fana ka tsona (Setšoantšo sa 3b) (F (1,26) = 5.87, p<0.05). Liphetoho tsena tsa boleng ba tahlehelo li lelekiloe le ho nehelanoa li lula li le bohlokoa ha phello e ntle ho +2h e kenelletse joalo ka covariate (F (1,25) = 4.48, p<0.05 le F (1,25) = 4.39, p<0.05, ka ho latellana). Li ile tsa boela tsa fetoha ka mokhoa o pharalletseng ha lipalo-palo li ne li etsoa ka boleng bo sa fetoloang ba tahlehelo e lelekiloe kapa litekanyetso tse nehetsoeng (bona Tlhahisoleseling ea Tlatsetso bakeng sa lintlha tse felletseng).

Teko ea 3: Propranolol

Litla-morao tsa 'mele le tse ling

Propranolol ha ea hlahisa liphetoho tse kholo kapa tse nyane haholo ho systolic kapa diastolic BP ha e bapisoa le placebo (kaofela F's <1). HR e fokotsehile ho feta + 75metsotso e latelang kalafo (73.64 ± 10.82 vs 62.04 ± 7.68bpm) (F (1,24) = 60.30, p<0.0001). Leha ho le joalo, phokotso ena e ne e le kholo haholo ho latela propranolol ha e bapisoa le placebo (Letlapa la Tlatsetso S5) (F (1,24) = 4.98, p<0.05). Ha mantlha HR e ne e tloaetse ho ba kholo ho bankakarolo ba tšoaroang ka propranolol ha e bapisoa le bankakarolo ba alafiloeng ka placebo (F (1,24) = 2.64), re boetse re hlahlobile litlamorao tsa kalafo phetohong e lekanang ho HR ea bankakarolo. Sena se netefalitse hore propranolol e hlahisitse phokotso e kholo ho HR ha e bapisoa le placebo (18.64 ± 8.45 vs 11.08 ± 11.38%) (F (1,24) = 4.64, p

Litla-morao tsa boemo bo botle ba naha le tse mpe li ne li sa fapana haholo kamora kalafo ka propranolol ha e bapisoa le kalafo ea placebo (bona Tlhahisoleseling ea Tlatsetso le Letlapa la Tlatsetso S4) (F <1.00 le F (1,24) = 1.61, ka ho latellana). Ha ho na liphapang tse amanang le kalafo ka tekanyo efe kapa efe ho +75mets ha papali ea ho lelekisa taolo e phetheloa.

Tahlehelo e lelekisa

Ha ho na phapang e kholo lipakeng tsa propranolol le placebo ho latela palo ea liqeto tsa ho lelekisa, palo ea liqeto tse latellanang ho lelekisa (Setšoantšo sa 2), kapa boleng ba tahlehelo bo lelekiloe le boleng ba tahlehelo bo nehelanoang (Setšoantšo sa 3) (tsohle tsa F <1).

Eya ho:

TŠOHLOA

Seo re se fumaneng se fana ka maikutlo a hore serotonin le dopamine li bapala karolo e tlatselletsang molemong oa ho boloka papali ea chelete ho fumana tahlehelo. Ts'ebetso ea Serotonin e bonahala e bapala karolo ea ho ntlafatsa boikoetliso ba tahlehelo ea tahlehelo, athe ts'ebetso ea dopamine e kenyelletsa bonyane D2/D3 sisteme ea receptor, e bonahala e laola boholo ba tahlehelo e lelekiloeng kapa e inehelitsoeng. Ka lehlakoreng le leng, likarolo tsena ka bobeli tsa ho lelekisa tahlehelo li ikemetse ka mokhoa o pharalletseng oa liphetoho lipuisanong tsa kutloelo-bohloko, bonyane joalo ka ha li kopantsoe ke tšebetso ea beta-adrenoceptor Lintlha tsa rona li totobatsa likhopolo-taba tsa lipale mabapi le mekhoa ea monoaminergic e khothalletsang polelo ea karolo ena ea mantlha, empa e sa utloisisoe hantle.

Boitekong ba 1, re fuputse litlamorao tsa ho theoha ha tryptophan ho lekola hore na ts'ebetso ea serotonin e bohareng e sebetsana le boitšoaro ba ho lelekisa tahlehelo. Sena se kanna sa bonts'a bonyane ka mekhoa e 'meli. Taba ea pele, lintlha tse 'maloa tsa bopaki li fana ka maikutlo a hore serotonin e loants'oa thibelo ea boitšoaro bo sa fuoeng moputso kapa kotlo (Holckett et al a, 2009; Dayan le Huys, 2008; Soubrie, 1986). Kahoo, ho fokotsoa ha tryptophan, ho lebisang ho fokotseheng ha ts'ebetso ea serotonin, ho ka be ho lebelletsoe ho eketsa papali ea chelete ho khutlisa tahlehelo ho barupeluoa ba rona ba phetseng hantle. Ka lehlakoreng le leng, ts'ebetso ea serotonin e boetse e bapala karolo ea bohlokoa ho ithuta ho, le ho sebetsana ka katleho le liketsahalo tse khopisang (Bari et al a, 2010; Tlo et al a, 2002; Deakin le Graeff, 1991; Evers et al a, 2005). Ho latela hore ho theoha ha tryptophan ho ka ntlafatsa le ponelopele ea sephetho sa kotlo (Ho fola et al a, 2008), le ho ntlafatsa likarabo tsa neural bakeng sa likotlo tsa kotlo e kahare ho cortex ea anterior (Evers et al a, 2005), Re boetse re lebelletse hore ho felloa ke matla ha tryptophan ho ka eketsa botsitso ba liphetho tse mpe le ho fokotsa boits'oaro ba ho lelekisa. Ebile, leha e sa hlahise liphetoho tse hlakileng maemong a batho ba baholo ba phetseng hantle, tryptophan depleting e fokolitse haholo karolo ea liqeto tseo bankakarolo ba li nkileng ho lelekisa tahlehelo, mme ea fokotsa palo ea liqeto tse latellanang tsa ho lelekisa, nakong ea papali ea papali ea chelete. Sena se fana ka maikutlo a hore, ketsahalong ena bonyane, ts'ebetso ea serotonin e thusa ho boloka tahlehelo e lelekisa ho fapana le ho e thibela.

Likhopolo tse hlalosang tsa boikhethelo tlasa mokhoa o sa tsitsang oa ho lelekisa boitšoaro ba ho lahleheloa ke mohopolo oa hore phokotso e tla ba teng ka boleng bo ikhethileng kapa ts'ebelisano e amanang le ho lelekisa le ho lahleheloa ke tahlehelo e kholo e ntse e le nyane ho feta litšenyehelo ts'ebelisong e amanang le tahlehelo e nyane e seng e entsoe (Kahneman le Tversky, 2000). Tlas'a maemo ana, hoa utloahala ho barekisi ho tsoela pele ho bapala, ha feela lisebelisoa tse hlokahalang li fumaneha. Ho tloha ka pono ena, ho lelekisa tahlehelo ho ka talingoa e le mokhoa oa ho pholoha o susumetsang, empa o mong o laoloang, bonyane ka ts'ebeliso ea ts'ebeliso ea papali ea papali e sa khaotseng e amanang le ho felisoa ha eona. Ho fumana ha rona hore tryptophan depletion ho fokolitse mokhoa oa rona oa ho lahleheloa ke tahlehelo ho fana ka maikutlo a hore, ketsahalong ena bonyane, ts'ebetso ea serotonin e fokotsehileng e fokolitse ts'ebetso ea morao-rao ea papali ka ho eketsa lits'oants'o tsa liphetho tse mpe tsa nakong e tlang lipakeng tsa boleng bo kopaneng le nakong ea papali (Ho fola et al a, 2008; Deakin le Graeff, 1991).

Ho tla hlokahala liteko tse ling ho theha kamano lipakeng tsa tšebetso ea serotonin le papali ea chelete ho fumana tahlehelo. Leha ho le joalo, ha re fuoa tlatsetso e rarahaneng ea serotonin ho laola maikutlo, ha rea ​​lokela ho nahana hore kamano ena e tla ba bonolo kapa e otlolohe (Winstanley et al a, 2004). Ho fumana ha rona hore tryptophan depletion e fokotseng ho lahleheloa ke tahlehelo ho lelekisa ho tsamaellana le liphuputso tse ling, tse fumanoeng li sebelisoa ka mokhoa o bonolo oa ho lekanya ho lekola maemo a kotsi, a hore batho ba jereng allele ea 10 ba sa phetse. STin2 gene (seo se fella ka e phahameng serotonin tone) bontša likhetho tse eketsehileng tsa ho batla likotsi bakeng sa tahlehelo (Zhong et al a, 2009). Ka lehlakoreng le leng, datha ea rona e bonahala e sa lumellane le ho fumana hore kalafo ea libeke tse peli le tryptophan, e le mokhoa oa ho ja, e fokotsang liphetoho lipakeng tsa likhetho tse fapaneng ha u etsa liqeto tse le 'ngoe lipakeng tsa phaello e itseng le meputso e meholo kapa e nyane, le likhetho tse batlang kotsi ha u etsa liqeto liqeto tse le 'ngoe lipakeng tsa tahlehelo e itseng le tahlehelo e kholo kapa e nyane (Murphy et al a, 2009). Ka kakaretso, tlhaiso-leseling ena e bontša hore tšusumetso ea serotonin ho papali ea chelete ho fumana tahlehelo e ka fapana ho latela maemo a 'maloa a kelello le litlhare, ho kenyeletsoa hore na boemo ba liteko bo na le khetho e le' ngoe kapa tse ngata tse latellanang ho khutlisa tahlehelo le hore na ho na le moelelo oa likhetho tse ling tse kenyeletsang. makgabane a lebelletsweng a nepahetseng

Litlamorao tsa 176 e le 'ngoeTekanyetso ea μg ea PPX e ne e fapane haholo. Phekolo ena ha ea ka ea eketsa palo ea liqeto tsa ho lelekisa tahlehelo kapa palo ea liqeto tse latellanang ho lelekisa nakong ea ho lahleheloa ke ho becha; Leha ho le joalo, PPX e ile ea eketsa boleng ba tahlehelo eo barupeluoa ba neng ba ikemiselitse ho e lelekisa mme ka nako e ts'oanang, ba fokotsa boleng ba tahlehelo eo barupeluoa ba neng ba ikemiselitse ho inehela ha ba tlohela. Kahoo, tekanyetso e le 'ngoe ea PPX e bakile khetho ea ho lelekisa tahlehelo e kholo ka litšenyehelo tsa tahlehelo e nyane.

Rea amohela hore mokhoa oa ketso ea 176 e le 'ngoeTekanyetso ea μg ea PPX e sebelisitsoeng ho liteko tsa 2 e lula e sa tsejoe. Le ha litlamorao tsa boits'oaro ba litekanyetso tse tlase tsa lithethefatsi tsa dopaminergic li ka bonts'a ts'ebetso ea pre-synaptic ho li-auto-receptors tsa dopamine neurones kahare ho mokokotlo.Frank le O'Reilly, 2006; Santesso et al a, 2009), tekanyetso e le 'ngoe ea 100 le 200μg PPX e kanna ea fokotsa serum prolactin, e fana ka tlhahiso ea ts'ebetso ea post-synaptic ea lithethefatsi ho li-dopamine receptors ho peterase ea ka ntle (Ho fepa et al a, 1992). Mona, re pheta liphumano tse fetileng, rea hlokomela hore lethal dose la rona la 176μg PPX e boetse e fokolitse haholo boemo bo botle ba barupeluoa (Hamidovic et al a, 2008). Sena se fana ka maikutlo a hore tekong ena, bonyane litekanyetso tsa PPX li bile le tšusumetso ts'ebetsong ea papali ea tahlehelo ea tahlehelo ea rona ka ts'ebetso ho D.2/D3 Li-auto-receptors tsa dopamine

D2 le D3 li-receptors li hlahisoa haholo kahare ho litsela tse matlafatsang ka har'a li-nucleus accumbens le amygdala (Camacho-Ochoa et al a, 1995), tseo ho tsona ka bobeli li hlahang li susumetsa boleng bo matlafatsang ba lithethefatsi tse matlafatsang tse kang cocaine (Caine et al a, 1997; Thiel et al a, 2010). Nakong ea hajoale, ha re na mokhoa oa ho tseba hore na ke efe ea li-subtypes tsena tse amohelang karolo e kholo molemong oa boitšoaro ba ho lelekisa ba lahlehileng. Liteko tsa pejana li khothalelitse ketsahalo eo ho D2 li-receptors li ka sitisa ho ithuta ho tsoa liphellong tse mpe tsa liqeto tse kotsi ('no-go learning') ka ho senya polelo ea li-dips bohareng ba boko ts'ebetso ea dopamine e bonts'ang liphoso tse fosahetseng tsa ho noha (Frank le O'Reilly, 2006; Frank et al a, 2007a,2007b, 2009). Leha ho le joalo, data ea rona e fana ka maikutlo a hore ho hloka kutloelo-bohloko ho lahleheloang ke liphetho ho amanang le D2/D3 Ketsahalo ea receptor e hlahisa liphetoho tse rarahaneng likhethong tse kotsi ho feta ho hloleha ho bonolo ho ithuta liketsahalong tse mpe. Sebakeng seo, re nahana hore ho senyeha ha phumano ea li-dips ts'ebetsong ea dopamine kamora sephetho se sebe ho hlahisitse ho hloleha ho otlolohileng ho ngolisa tahlehelo e nyane, ka hona ho eketsa palo ea liqeto tsa bankakarolo ba tšoaroang ke PPX ba ho tlohela litheko tse nyane. Leha ho le joalo, kutloisiso e fokotsehileng ea ho lahleheloa ke litholoana e amanang le D2/D3 Ketsahalo e boetse e fokotsa phetoho e mpe ea boleng bo ikhethileng bo amanang le tahlehelo e kholo, e eketsa boleng bo tlase ba papali e tsoelang pele; ka hona ho khothaletsa liqeto tsa ho lelekisa tahlehelo e kholo ea boleng ha e bapisoa le placebo.

Liphetoho ntlafatsong ea ho ithuta ho latela kalafo le PPX (Pizzagalli et al a, 2008) li amahanngoa le ho tšoaea ho fetotsoeng kahare ho sebaka sa kantle sa cingrate ho latela liphetho tse mpe (Santesso et al a, 2009) le ho tšoaea liphoso ka har'a striatum e latelang liphetho tse ntle (Tsoala et al a, 2008). Pejana, re hlokometse hore likarabo tsa neural tse fumanehang liphethong tse mpe tsa papali ea chelete kahare ho siling ea cylateus e boetse e amana le boitšoaro bo tsoelang pele ba ho lelekisa nakong ea papali ea tahlehelo ea rona ea tahlehelo (Campbell-Meiklejohn et al a, 2008). Sena se lumellana le bopaki ba morao-rao ba motlakase oa hore mesebetsi e amanang le moputso ea likarolo tsa methapo ea methapo le methapo ea methapo ea methapo e kanna ea sitisoa ho becha ha basekaseki (Hewig et al a, 2010). Ka hona, liphetho tsa Teko ea Bobeli li phahamisa monyetla oa hore tekanyetso e le 'ngoe ea PPX e eketse boleng ba tahlehelo e lekantsoeng e lelekisoa ka mokhoa o fetotsoeng oa ts'ebetso ea potoloho e kenyelletsang sebaka sa anterior cingrate le lipehelo tsa karolo ea sona ea boemo ba morao (Nakano et al a, 2000).

Kamora nako, litholoana tsa liteko tsa 3 li bonts'a ha e le tekanyetso e le 'ngoe ea 80mg propranolol e fokolitse HR haholo ha e bapisoa le placebo, ha e fetole haholo lipalo tsa liqeto ho lelekisa tahlehelo, boleng ba tahlehelo bo lelekiloe, kapa boleng ba tahlehelo bo inehetseng. Liphumano tsena li fana ka maikutlo a hore karolo ea kelello le ea maikutlo ea ho lelekisa tahlehelo e etsisoang ke papali ea rona-le ha ho hlakile hore e ne e se thabo e tlisoang ke mesebetsi ea papali ea papali (Anderson le Brown, 1984) - ha e susumetsoe ke mananeo a beta-adrenoceptor. E boetse e fana ka tiiso ea hore litlamorao tsa ho theoha ha tryptophan le PPX eo re e boneng ho liteko tsa 1 le 2 li ke ke tsa nkuoa e le liphetoho tse sa lebelloang ho kutloelo-bohloko le / kapa pherekano ea pherekano. Leha ho le joalo, boits'oaro ba tahlehelo ea tahlehelo bo kanna ba susumetsoa ke likarolo tse ling tsa ts'ebetso ea noradrenaline, ho kenyelletsa ts'ebetso ea alpha2-adrenoceptors e susumetsang ts'ebetso ea ts'ebetso e nyolohang ea ts'oaetso ea locus le ho fetolela ts'ebetso ea sephetho se fosahetseng (kapa liphoso tsa ketso) ho sebakeng se kopaneng (Tsoala et al a, 2005).

Liphetoho tse 'maloa ho seo re se fumaneng li hloka ho rarolloa lipatlisisong tse tlang. Taba ea mantlha, ha papali ea rona ea ho lelekisa tahlehelo e tlisa boitšoaro ba bohlokoa ba papali e tsoelang pele e tlisa tahlehelo e ntseng e eketseha, sena se tiisa bokhoni ba rona ba ho khetholla itseng mekhoa ea kelello e ka 'nang ea susumetsoa ke serotonin le D2/D3 Ketsahalo ea ho susumetsa papali ea chelete ho fumana tahlehelo. Ho felloa ke matla ha Tryptophan le tekanyetso e le 'ngoe e tlase ea PPX ho hlahisitse liphetoho tse fapaneng tsa boits'oaro ho becha ho khutlisa tahlehelo, empa liteko tse ling lia hlokahala ho fumana hore na liphetoho tsena li amana joang le seo re seng re ntse re se tseba ka karolo ea serotonin ho qoba kapa ho thibela kotlo (Holckett et al a, 2009; Soubrie, 1986) le seo re se tsebang ka karolo ea D2 li-receptors ka ho ithuta ho tsoa liphellong tse mpe (Frank, 2006). Taba ea bobeli, litlamorao tsa bongaka tsa liphumano tsena li hloka ho hlahlojoa ka ho hlahloba litlamorao tsa kalafo ea serotonergic le dopaminergic mabapi le ts'ebetso ea papali ea tahlehelo ea rona ea tahlehelo lipapaling tsa papali ea papali ea papali ea chelete, hammoho le tlhahlobo ea tahlehelo ea ho lelekisoa e le mohlala oa taolo e senyehileng ho tse ling. bokhoba (Rogers et al a, 2010). Re ka boela ra hlahloba karolo ea li-neurotransmitter tse ling, joalo ka lits'ebetso tsa opiate le glutamate, tse ka bolokang mathata a ho becha (Grant et al a, 2007, 2008).

Ho becha ka tsela ea tlhaho ke mohloli oa mahlomola a maholo a botho le a lelapa mme ho bontša taba ea bohlokoa ea bophelo bo botle ba sechaba (Shaffer le Korn, 2002). Leha ho le joalo, re tseba hanyane ka mabaka a tlhaho a fanang ka tlokotsi bakeng sa mathata a papali ea chelete, ka ho se na mangolo a tumello ea kalafo ea meriana ea meriana e fumanehang ho lingaka. Liteko tse hlahisitsoeng mona li bonts'a mokhoa o le mong oa ho qala ho sebetsana le litaba tsena ka matla; e leng, ka ho etsa lipatlisiso tsa motheo oa neural le oa bongaka oa khethollo le boits'oaro bo hlahang bathong ba hlahisang tleliniking. Liphumano tsena li fana ka maikutlo a hore ho phehella ho akaretsang ha batho ba bapalang papali ea chelete ho bapala chelete e lahlehileng ho fetotsoe ke ts'ebetso ea serotonin, athe tlhahlobo ea tahlehelo eo batseteli ba ahlolang hore e lokela ho ba lelekisa e kenella mesebetsing ea D.2/D3 sistimi ea receptor.

Eya ho:

lumela hore baa fokola

Patlisiso ena e tšehelitsoe ke boithuti ba Council of Medical Research Council ho Daniel Campbell-Meiklejohn le ka moputso o ikemetseng o tsoang ho Biotechnology and Biological Science Science Council Council (BBSRC) ho Robert Rogers. Re tla rata hape ho leboha Michael Frank ka litlhahiso tse ka re thusang mabapi le mofuta oa pejana oa buka ena e ngotsoeng ka letsoho.

Eya ho:

Notes

Ha re bue ka lithahasello tse mpe tsa lichelete kapa likhohlano tse ka bang teng.

Eya ho:

Mongolo o botlaaseng ba leqephe

Tlhahisoleseling ea tlatsetso e tsamaea le pampiri ho websaeteng ea Neuropsychopharmacology (http://www.nature.com/npp)

Eya ho:

Boitsebiso bo Eketsehileng

Boitsebiso bo Eketsehileng

Tlanya mona bakeng sa faele e eketsehileng ea data.(81K, doc)

Eya ho:

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