Dopamine e Laola ho Atamela-Ho Qoba ho Batla Batho (2015)

Int J Neuropsychopharmacol. 2015 Apr 9. pii: pyv041. doi: 10.1093 / ijnp / pyv041.

Norbury A1, Kurth-Nelson Z2, Winston JS2, Roiser JP2, Husain M2.

inahaneloang

Background: Ho batla letsoalo ke tšobotsi e bakang karolo ea bohlokoa ea ho ba tlokotsing ea mafu a fapaneng a kelello ka theko e phahameng sechabeng. Leha ho le joalo, ha ho utloisisoe hanyane ka methapo e susumetsang ea boiphihlelo bo matla ba maikutlo kapa ho feto-fetoha ha maikutlo hoa bona ho batho.

Mekhoa: Mona, re qala re sekaseka paradigm e ncha ho fuputsa takatso ea maikutlo ho batho. Teko ena e lekola hore na barupeluoa ba khetha ho qoba kapa ho itšireletsa ka mokhoa o matla oa tactile (tšusumetso e nyane ea motlakase) ho sebetsa mesebetsing e bonolo ea ho etsa liqeto tsa moruo. Ka mor'a moo re etsa lipatlisiso ka karolo e fapaneng ea bankakarolo hore na boitšoaro bona bo nahanela ho qhekella ha li-receptor tsa DopNUMX tsa dopamine li sebelisa moralo o ka hare ho lithuto, sebopeho se laoloang ke placebo, se nang le mahlo a mabeli.

Results: Ka har'a mehlala ena ka bobeli, batho ba nang le maikutlo a phahameng ka ho fetisisa ba ipolelang ba ikhethile ba khethile karolo e kholo ea tšusumetso e nyane e amanang le motlakase, leha e ne e le sehlabelo sa phaello ea chelete. Tlhahlobo ea mohlala oa Computational e fumane hore batho ba faneng ka boleng bo eketsehileng ba moruo ho khothaletso e nyane e amanang le motlakase ba bonts'a likarabo tse potlakileng ha ba khetha lintlha tsena. Ho fapana le hoo, ba abetseng boleng bo seng bobebe ba bonts'a likarabo tse liehang. Liphumano tsena li tsamaisana le ho nka karolo ha maemo a tlase, mekhoa ea ho qoba mekhoa. Ntle le moo, halcoidol ea hanyetsanang le D2 e theoletse tlase boleng bo eketsehileng ba moruo bo fuoeng tšusumetso e nyane e amanang le ts'usumetso ea motlakase ho batho ba bonts'itseng karabelo ea lintho tsena tse susumetsang tlasa maemo a tloaelehileng (ba batlang boits'oaro bo phahameng ba boitšoaro).

Qeto: Liphumano tsena li fana ka bopaki ba pele bo hlakileng ba boits'oaro ba maikutlo a ho susumetsoa ke mokhoa oa ho qoba lintho, o fetisoang ke dopamine bathong. Li fana ka moralo oa ho etsa lipatlisiso tsa li-psychopathologies tseo ho tsona takatso ea maikutlo e feteletseng e leng sesosa sa ho ba kotsing.

Keywords:

  • batlang maikutlo
  • ho se tsotelle
  • dopamine
  • D2 antagonist
  • lemalla ntho

Selelekela

Ho batlana le maikutlo ke tšobotsi eo motho a nang le eona ea ho susumetsa maikutlo a "matla, a sa tloaelehang le a ke keng a hlalosoa" (Zuckerman, 1994) e bopang phapang ea bohlokoa le e hlalositsoeng hantle e le motho ka mongRoberti, 2004). Ho kenya letsoho liketsong tse fapaneng tsa ho batla maikutlo (mohlala, tšebeliso ea lithethefatsi, boithabiso bo kotsi le boits'oaro), ho batho ba baholo le ba lilemong tsa bocha.Carmody et al., 1985; King et al., 2012). Ntle le moo, mehato e thehiloeng ho lipotso ea botho bo batlang maikutlo a nang le maikutlo e na le litekanyetso tse phahameng tsa heritability (40-60%; Koopmans et al., 1995; Stoel et al., 2006) le maemo a tatellano ea boemoTerracciano et al., 2011).

Ho batla maikutlo ka mokhoa o feteletseng ho bile le tšusumetso ho li-psychopathologies tse fapaneng ka litšenyehelo tse phahameng tsa sechaba, ho kenyelletsa lithethefatsi le lithethefatsi tsa papali ea chelete (Zuckerman, 1994; Roberti, 2004; Perry et al., 2011). Har'a batho ba nang le bothata ba tšebeliso ea lithethefatsi, lintlha tse phahameng tse batloang ke maikutlo a amanang le lilemo tsa pejana, ts'ebeliso e matla ea polysubstance, ts'ebetso e mpe haholo ea ts'ebetso, le sephetho se futsanehileng sa kalafo (Ball et al., 1994; Staiger et al., 2007; Lackner et al., 2013). Ho tsejoa ka mekhoa e ka sehloohong e batlang maikutlo a batho ka hona ho ka ba le bohlokoa bo phahameng ba kliniki.

Patlisiso ea mehlala ea liphoofolo tse batloang ke takatso ea maikutlo e hlahisitse phapang e fapaneng mosebetsing oa dopamine, haholo-holo ka mefuta ea D2 (D2 / D3 / D4) dopamine receptors, ka ho khetha likhetho tsa motho ka mong bakeng sa likhetho tsa ho hlahisa kapa ho susumetsa maikutlo.Bardo et al., 1996; Blanchard et al., 2009; Shin et al., 2010). Ha ts'ebetso ea ts'ebetso ea phetisetso ea drietal dopaminergic e nkoa e nka karolo karolo ea matla a boits'oaro ba karabelo ho latela tšusumetso e kholo (Kemoto, 2007; Robbins le Everitt, 2007), ak'haonte e le 'ngoe e fana ka maikutlo a hore motheo oa liphapang tsa motho ka mong mabapi le takatso ea maikutlo ke ts'ebetsong e fapaneng ea ts'ebetso ea ho tlosa mekhoa ea ho amohela dopaminergic ha e araba rialo le tšusumetso e matla (Zuckerman, 1990).

Tumellanong le pono ena, bopaki ba liphatsa tsa lefutso le PET bo hlahisitse phapang e teng tšebetsong ho li-receptors tsa mofuta oa D2 phapusing e le 'ngoe ea ho batla ha batho maikutlo (mohlala, Hamidovic et al., 2009; Gjedde et al., 2010). Ka bomalimabe, leha ho le joalo, khaello ea litakatso tsa boitšoaro bo bobe ho ba lengolong le pele e bolela hore ha ho na monyetla oa ho leka tšibollo ea maikutlo ea ho qoba mekhoa ka kotloloho ho batho. Mokhoa o joalo pejana o ipakile o beha litholoana haholo mabapi le likarolo tse ling tsa ho potlaka (Winstanley, 2011; Jupp le Dalley, 2014).

Mona, re qalile ra leka mofuta oa bohlokoa oa boits'oaro ba batho ba batlang boits'oaro bo kenyelletsang monyetla oa ho iketsetsa tšebetso ea motlakase (empa e sa fumanehe) nakong ea ts'ebetso ea ho etsa liqeto tsa moruo. Mosebetsi ona o ne o reretsoe hore e be o khahlisang ho paradigm ea morao-rao e sebelisang maikutlo bakeng sa litakatso (e entsoeng bakeng sa litoeba)Olsen le Winder, 2009). Ka mor'a moo re ile ra sebelisa moralo oa lithuto tsa ka hare ho etsa lipatlisiso ka litlamorao tsa D2 dopamine receptor antagonist haloperidol mabapi le ts'ebetso ea mosebetsi ka sampole e fapaneng ea baithaopi ba phetseng hantle. Re ne re boletse esale pele hore: (1) batho ba phahameng ka ho feteletseng ba batlang mekhoa e metle ba tla fana ka boleng bo nepahetseng ba moruo monyetla oa ho ba le tšusumetso ea maikutlo a "matla le a sa tloaelehang"; (2) khetho ena e ka bonts'oa nako ea karabelo e potlakileng joalo ka lebelo bakeng sa lintho tsena tse susumetsang; le (3) "boits'oaro ba maikutlo" bo ka sitisoa ke ho qhekella ho li-receptors tsa D2, ho latela ts'ebetso e batlang ts'ebetso ea maikutlo (Norbury et al., 2013).

Ithute 1

mekhoa

barupeluoa ba

Barupeluoa ba mashome a mane a metso e mehlano ba phetseng hantle (28 basali), ba bolelang lilemo tsa 24.3 (SD 3.55), ba hapuoe ka lipapatso tsa marang-rang (bakeng sa tlhaiso-leseling ea demographic, bona Lethathamo 1). Boholo ba sampole ena bo ile ba khethoa ho re lumella ho bona kamano e matla pakeng tsa ts'ebetso ea mosebetsi le mokhoa o ipatileng oa ho batla maikutlo motheong oa liphumano tse fetileng tsa hore likamano lipakeng tsa mekhoa ea boits'oaro le lipotso tsa likarolo tse ling tsa boits'oaro bo sa tsitsang li na le boikokobetso bo matla. li-coefficients tsa khokahano ho fihlela 0.40; mohlala, Helmers et al., 1995; Mitchell, 1999). Palo ea matla a priori a khethileng hore boholo ba sampole ea 44 bo ka hlokahala ho fumana khokahano ea 0.40 ea khokahano ka matla a tloaelehileng a 80% le alpha ea 0.05. Litekanyetso tsa ho lelekoa li ne li kenyelletsa bokuli bofe kapa bofe ba morao-rao ba kelello kapa ba kelello, kapa ba hlooho ea hlooho. Barupeluoa bohle ba ile ba fana ka tumello e ngotsoeng e nang le tsebo mme thuto e amohetsoe ke Komiti ea Boitšoaro ea London College London.

Tafole 1. 

Tlhahisoleseling ea palo ea batho ho nka karolo

 Ithute 1Ithute 2
n (mosali)45 (28)28 (0)
Lilemo (lilemo)24.3 (3.55)22.3 (2.74)
Lilemo tsa thuto16.1 (3.1) -
Raven's 12-APM lintlha -9.1 (2.5)
Kakaretso ea kakaretso ea SSS-VR261 (46) (162-352) -
UPPS SS lintlha (mefuta) -23.2 (5.8) (18-47)
Joala (lino ka beke)3.7 (4.5)5.9 (8.7)
Ho tsuba (koae ka beke)4.1 (10.2)8.4 (18.3)
Ts'ebeliso e 'ngoe ea lithethefatsi (n)
 None3018
 Matekoane (kamehla)85
 Matekoane (khafetsa)51
 Tšebeliso e khothatsang (e kileng ea ba teng)24
Boitšoaro ba papali ea chelete (n)
 Le ka mohla3917
 Makhetlo a 'maloa ka selemo53
 Makhetlo a 'maloa ka khoeli17
 Beke le beke kapa ho feta01
  • Kakaretso: Raven's 12-APM = Teko e tsoetseng pele ea Raven ea Tsoelo-pele ea Raven e tsoetseng pele (mofuta oa 12-ente); SSS-VR, mofuta oa Selling-Searching Scale Vale (e ntlafalitsoeng); UPPS SS, UPPS sekhahla sa ho hlasimolla se batlang sepheo sa ho batla.

  • Likolo tse ling tsa palo ea batho li bua ka boitšoaro nakong ea likhoeli tsa 12 tsa ho qetela. Ntle le ha ho boletsoe ka tsela e 'ngoe, lipalo li emela (SD) bakeng sa sehlopha ka seng.

Mosebetsi oa ho Batla Tsoala

Barupeluoa ba phethile mohopolo o batloang ke sepheo sa ho fumana boleng bo hlakileng ba moruo (o motle kapa o mobe) oo ba o fileng monyetla oa ho fumana matla a matla a ho hlasimolla (MES). Karolong ea pele ea mosebetsi (karolo ea phihlello), ba ithutile feela lintlha tsa bohlokoa tse amanang le tšusumetso e fapaneng ea tšusumetso e sa bonahaleng (maemo a hlohlelletsoang [CSs]). Likarolo tse robeli tse fapaneng li ile tsa sebelisoa e le li-CS, 2 ea tsona e abetsoe e 'ngoe ea li-point tsa 4 tse ka khonehang (25, 50, 75, kapa 100 lintlha. Tekong e 'ngoe le e' ngoe, likhechana li ne li hlahisoa e le babedi, tse thibelitsoeng ho ba le mofuta o haufi kapa oa boleng bo lekanang ba lintlha, tse fanang ka mefuta e fapaneng ea liteko tsa 10 (Setšoantšo sa 1).

Setšoantšo sa 1. 

Mosebetsi oa ho batla ho sesa. Karolong ea pele ea mosebetsi (karolo ea phihlello), barupeluoa ba ile ba hlahisoa ka letoto la liqeto tse qobelloang pakeng tsa litšoantšo tse sa hlaka. Ho ne ho na le 8 e fapaneng e bakang tšusumetso (maemo a ts'oaroang [CSs]) le li-CSNUMX tse fapaneng tsa 2 tse abetsoeng e 'ngoe le e' ngoe ea lintlha tsa 4 tsa lintlha tse ka khonehang (25, 50, 75, kapa 100 lintlha; ka khetho ea mofuta o itseng fractal e emeloe ka mokhoa o ikhethileng bakeng sa karolo e 'ngoe le e' ngoe). Likara tse ikhethileng li ne li thibetsoe ho kenyeletsa lintlha tse haufi le tsona kapa tsa boleng bo lekanang, li hlahise mefuta ea liteko tsa 10. Karolo ea phihlello ea mosebetsi e tsoetse pele bonyane ba liteko tsa 80 ho fihlela barupeluoa ba fihlela boemo ba ts'ebetso, ≥80% lintlha tse phahameng tsa khetho ho feta litekong tsa 10 tsa ho qetela moo khetho ea lintlha tse phahameng e neng e khonahala. Kamora hore mohato ona oa ho ithuta o phethe, litho tsa sehlopha li ile tsa ea pele ho karolo ea bobeli ea mosebetsi (karolo ea liteko). Bakeng sa mohato oa liteko, barupeluoa ba ile ba laeloa hore lintho tsohle tse susumetsang li ne li amana le boleng ba lintlha tse tšoanang le tsa pele empa tse ling tsa tse susumetsang li se li amana le monyetla oa ho fumana matla a motlakase a matla a motlakase (boholo ba MES ka boeona e ile ea fuoa mokhoa oa ho "susumetsa empa o se utloise bohloko" pele a qala mosebetsi). Ka ho khetheha, halofo e le 'ngoe ea mehopolo e ile ea khethoa e le CS + s (monyetla oa MES) le halofo e' ngoe ea CS-s (ha ho na monyetla oa MES) ka tsela eo liteko li ileng tsa oela ho 1 ea mefuta ea 3: tseo CS + e neng e le ho tsona likhetho tsa lintlha tse tlase, moo CS + e neng e le khetho ea lintlha tse holimo, hape, ka bomalimabe, moo CS + le CS-stimuli li neng li le lintlha tse lekanang. Ho eketsa boteng ba tšusumetso e matla, ho amoheloa ha matla a motlakase ho ne ho etsahala ka linako tsohle le ka nako. Monyetla oa ho amohela MES o khethiloeng oa khothatso ea CS + e ne e le 0.75, ha ho qaleha ha MES ho etsahala ka mokhoa o sa reroang nakong ea 2500-ms inter-stimulus interval (ISI), eo ho eona barupeluoa ba ileng ba hlahisoa ba e-na le skrini se se nang letho.

Karolo ea phihlello e tsoetse pele bonyane ba liteko tsa 80 ho fihlela barupeluoa ba fihlela boemo ba ts'ebetso (ba khetha fractal e amanang le boleng ba lintlha tse holimo ho 80% kapa liteko tse kholo moo sena se neng se ka khonahala, holim'a liteko tse leshome tse fetileng). Kamora hore mohato ona oa ho ithuta o phethe, litho tsa sehlopha li ile tsa ea pele ho karolo ea bobeli ea mosebetsi (karolo ea liteko).

Boemong ba liteko, halofo e le ngoe ea liqeto tse ikhethileng e ile ea amahanngoa le monyetla oa ho amohela MES e seng e matla letsohong. Liqabang tsena li tla tloha joale li bitsoa CS + s (bakeng sa lintlha tse felletseng, bona Setšoantšo sa 1). Likarolo tse ling li ne li sa amane le tšusumetso ea motlakase kahoo ho thoe ke CS-. Bakeng sa boleng bo bong le bo bong, e 'ngoe ea likhathatso tse amanang e ile ea fetoha CS + (monyetla oa MES), ha e' ngoe e le CS- (ha ho na monyetla oa MES). Sena se hlahisitse mefuta ea teko ea 3: tseo CS + e neng e le khetho ea lintlha tse tlase, moo CS + e neng e le khetho ea lintlha tse phahameng, hape, ka bomalimabe, ke moo CS + le CS-stimuli li neng li le lintlha tse lekanang.

Barupeluoa ba ile ba tsoela pele ho etsa liqeto lipakeng tsa karohano, 'me phapang e le teng feela ke hore halofo ea likhetho li ile tsa amahanngoa le monyetla oa ho fumana MES, ho kenyeletsoa, ​​ho bohlokoa litekong moo likamano li neng li le bohlokoa ka bobeli. Potso ea bohlokoa ea liteko e ne e le hore na likhetho tsa barupeluoa ba bang li ka khethoa ha ho khethoa CS + stimuli ha e na le lintlha tse lekanang ho CS-. Tekanyo ea khethollo ea barupeluoa ho khetha kapa ho ba hole le CS + tlhoko, mabapi le boleng bo lekanyelitsoeng ba khetho ea CS +, ka hona e ile ea lumella ho baloa ka nepo boleng ba moruo (o motle kapa o mobe) morupeluoa e mong le e mong ea abetsoeng monyetla oa ho fumana tse ling tshusumetso e matla ea maikutlo (sheba tlhahlobo ea mohlala ea Computational).

Barupeluoa ba ile ba qeta liteko tsa tekolo ea 100 (10 ka mofuta oa teko) mme ba bolelloa hore ba tla lefuoa bonase qetellong ho latela palo eohle ea lintlha tse hapiloeng. Ho eketsa boteng ba tšusumetso e matla, ho amoheloa ha MES ho ne ho etsahala ka linako tsohle le ka nako. Monyetla oa ho fumana khetho ea MES e fanoeng ea khothaletso ea CS + e ne e le 0.75, ka ho qaleha ha MES ho etsahala ka mokhoa o sa reroang nakong ea nako ea ho hlohlelletsa ea 2500-ms.

Pele ba qala mosebetsi, barupeluoa ba ile ba lekanya hore na ba batla ho sebelisoa leqhetsoana le leng le le leng ho sebelisoa paradigm sekhoneng sa analogue (VAS) sa k'homphieutha (ho tloha ho “ho rata”). Mohato ona o ile oa phetoa ka lekhetlo la bobeli kamora ho phethoa ha karolo ea phihlello (ke hore, kamora ho ithuta boleng ba lintlha tse amanang le CS e ngoe le e ngoe), le lekhetlo la boraro qetellong ea tlhahlobo (ke hore, ho latela tlhahiso ea MESs). Bakeng sa lintlha tsa lisebelisoa le likarolo tsa ts'usumetso tse sebelisetsoang ho tsamaisa MES, bona Boitsebiso bo Eketsehileng.

Design

Ka mor'a tumello le litaelo tsa mosebetsi, bophahamo ba matlafatso ea motlakase bo ne bo lekantsoe ka bonngoe bakeng sa karolo e 'ngoe le e' ngoe ka sebapali se ts'oanang. Ka ho khetheha, barupeluoa ba ile ba fumana letoto la li-stimulation tse le 'ngoe tse qalileng, ho qala sebakeng se tlase haholo (0.5 mA; ka kakaretso se tlalehiloe ke barupeluoa e le ba sa bonahaleng) mme hanyane ka hanyane ba eketseha ka matla a hona joale ho fihlela pherekano e lekantsoe e le 6 kantle ho 10 ho VAS Ho tloha ho 0 (e sa tsoa bonoa) ho ea ho 10 (e bohloko kapa e sa thabiseng), boemo boo barupeluoa ba ileng ba tiisa tlhaloso ea maikutlo e le "ea hlasimollang empa e seng e utloisang bohloko." Ts'ebetso ena e ile ea phetoa habeli bakeng sa karolo e 'ngoe le e' ngoe ho netefatsa ho ba le botsitso.

Barupeluoa le bona ba phethile mehato e 'maloa ea ho itlaleha: tekanyetso e ntlafalitsoeng ea mofuta oa Selling-Searching Scale VZuckerman, 1994; Grey le Wilson, 2007); tekanyo ea molumo oa hedonic, Snaith-Hamilton Anhedonia Scale (Snaith et al., 1995); le sekhahla sa tšibollo ea mmuso oa tikoloho ea mmuso.Spielberger et al., 1970). Mehato ea 2 ea morao-rao e kentsoe ho leka tlhahlobo ea hore na liphapang tsa motho ka mong tsa MES li ka amana le ho tšoenyeha ka tšobotsi kapa boemo ba hona joale (a) hedonia ho fapana le ho tsamaisoa ke botho bo batlang maikutlo ka bonngoe. Tlhahisoleseling ea batho mabapi le lilemo tsa thuto, koae le tšebeliso ea joala, ts'ebeliso ea lithethefatsi tsa boithabiso le khafetsa ho etsa lintho tse amanang le ho becha le tsona li ile tsa bokelloa.

Tlhahlobo ea Mochini oa Computational

Bakeng sa data ea mekhahlelo ea liteko, ho ne ho nahanoa hore khetho pakeng tsa 2 CSs, A le B (moo A e leng tlhoko ea CS + le B ke CS-), e ka emeloa e le:

VA= RA+ θ
VB= RB,

moo RX ke boleng ba ntlha ea khothalletso X, θ ke boleng bo eketsehileng (ka lintlha) bo fuoeng monyetla oa ho fumana MES (e ntle kapa e seng ntle), le VX e emela boleng ba kakaretso ea khetho ka 'ngoe.

Moetso ona o ile oa kenngoa data yohle ea khetho ea liteko bakeng sa morupeluoa e mong le e mong ka ts'ebetso ea khetho ea sigmoidal (softmax):

P(khetha A) = / (1 + khulan(-β*(VA-VB)))

Melao ea liparamente tsa mahala θ le β (paramethara ea mocheso oa softmax, tekanyo ea boits'oaro bo ikhethileng) e ne e kengolelitsoe ho data motheong oa taba ka ho sebelisa menyetla ea log log.

Results

Phapang ea motho ka mong molemong oa ho ikhahla ka matla

Ka kakaretso, barupeluoa ba ile ba khetha tlhahiso-leseling e amanang le MES (CS +) ho 20.4% (SD 17.6) ea liteko moo li bonts'a khetho ea lintlha tse tlase, 68.9% (24.8) ea liteko moo e neng e le likhetho tsa lintlha tse phahameng, le 45.2% ( 19.9) ea liteko moo CS + le CS- stimuli li neng li lekana boleng ba lintlha. Ho bile le phello e kholo ea mofuta oa teko mabapi le khetho ea CS + stimuli (F 2,88= 157.29, P<0.001). Posthoc t Liteko li senotse hore barupeluoa ka kakaretso ba khethile khetho ea CS + haholo hangata litekong tse tlase ho feta liteko tse lekanang, mme hangata haholo litekong tse phahameng ho feta liteko tse lekanang (t 44= -11.997, P<.001; t 44= -8.102, P<.001, ka ho latellana).

Habohlokoa ho ne ho na le phapang e batsi molemong oa khetho e amanang le MES litekong moo CS + le likhetho tsa CS- li neng li lekana boleng ba lintlha. Ho bolela khetho e lekantsoeng ea CS + stimuli e tlohang ho 7.5% ho 92.5% (Setšoantšo sa 2A; boleng ba CS + ba 0). Khakanyo ea khetho e khethiloeng haholo litekong tsena e ka etsoa ka sampole ea phepelo ea binomial; bakeng sa liteko tsa 40 le alpha ea 0.05, monyako ona o batla o le 26 / 40 (0.65) bakeng sa khetho e phahameng haholo le 13 / 40 (0.35) bakeng sa khetho e tlase haholo. Ho ipapisitsoe le likotlo tsena, 8 / 45 (kapa 18%) ea barupeluoa ba khethile karolo e phahameng haholo ea CS + stimuli, ka mantsoe a mang, ba batlana le MES haholo, mme 13 / 45 (29%) ea barupeluoa ba ile ba qoba likhetho tsa CS + haholo.

Setšoantšo sa 2. 

Phapang e fapaneng pakeng tsa tšebetso ea mosebetsi. (A) Ts'ebetso ea psychometric ea motho ka mong bakeng sa monyetla oa ho khetha khetho ea motlakase e bonolo (MES; CS + kapa MES-e amanang le eona) e le ts'ebetso ea lintlha tsa eona tse amanang (chelete), e hlahisoang bakeng sa karolo e 'ngoe le e' ngoe ho tsoa ho data le khetho ho mefuta eohle ea liteko (mekoloko e metšo e bonts'a 'nete Khetho ea tekanyo ea mofuta o mong le o mong oa teko). Phetolelo ea letsoho le leng le le leng le letšehali e emela tšusumetso ea boleng ba MES (kapa θ) ka khetho, ka botaki ba ts'ebetso e khethiloeng ke paramente ea mocheso oa softmax β (tekanyo ea boits'oaro ba khetho ea bankakarolo). Ho fetohela ka lehlakoreng le leng ts'ebetsong ho bonts'a phello e ntle ea menyetla ea tatso e matla holima khetho, ke hore, khetho e kholo ea likhetho tse amanang le MES ho feta kamoo ho neng ho ka lebelloa ho tsoa ho khetho e thehiloeng ho lintlha feela. (B) Boleng boo motho ka mong a abetsoeng monyetla oa ho fumana MES (θ) a boletseng esale pele phapang ea bona ka linako tsa khetho (RTs) ho CS + vs CS- stimuli (median RTCS + - mohareng RTCS-; r = -0.690, P<.001). Monyetla oa ho hlohlelletsa maikutlo a eketsehileng o liehisitse khetho ea likhetho tsena ho barupeluoa bao e neng e le boiphetetso (khetho e fokolang ea CS +; quadrant e tlase), empa e ile ea phahamisa khetho ho barupeluoa bao e neng e le takatso ea bona (khetho e phahameng ea CS +; holimo). quadrant ea leqele, shading ea lamunu). Mehala e sohlokehileng e ntšo e bonts'a linako tsa ts'epo ea 95%. n = 45.

Khetho e phahameng e atisang ho ba le tšusumetso e amanang le MES e ile ea bonoa sehlopheng sa barupeluoa esita le mefuta ea teko moo CS + e neng e le khetho ea lintlha tse tlase, ke hore, ho kenyelletsa boitelo ba boleng ba moruo (Setšoantšo sa 2A, boleng ba CS + ba 25).

Ho lekola hore na khetho ea barupeluoa ea susumetso e amanang le MES e fapane hofeta nakong ea mosebetsi (ke hore, haeba khetho e fetotsoe ka ho fokola ha maikutlo), liteko tsa karolo ea liteko li ile tsa kenngoa ka likarolo tsa 4. ANOVA e lekantsoeng khafetsa e nang le lintlha tse kahare tsa nako (mekhahlelo ea 4) ha e fumane bopaki ba phello e kholo ea mosebetsi mosebetsing mabapi le khetho ea CS + e susumetsang lithutong tsohle (p> .1). Khetho e akaretsang ea litlhahiso tsa CS + le eona e ne e sa tsamaellane le palo ea liteko tse nkuoeng ho fihlela ts'ebetso ea litekanyetso kapa karolo ea likarabo tse nepahetseng (khetho ea boleng bo holimo litekong moo sena se neng se khonahala) nakong ea mohato oa ho fumana (P> .1), ho fana ka maikutlo a hore khetho ea tšusumetso e amanang le MES e ne e sa amanngoe le ho ithuta litekanyetso tsa lintlha nakong ea karolo ea pele ea mosebetsi. Khetho ea MES le eona e ne e sa amane le bophahamo ba hona joale (P> .1).

Tlhatlhobo ea mohlala oa computational e hlalosang boleng (ka lintlha) tseo ba nkang karolo ho fumana monyetla oa ho fumana MES (θ) ba fane ka tlaleho e ntle ea ts'ebetso ea mosebetsi (bakeng sa lintlha, bona Boitsebiso bo Eketsehileng). Setšoantšo sa 2B e bonts'a li-curometric curves tsa motho ka mong tsa monyetla oa ho khetha khetho e amanang le MES (CS +) e le ts'ebetso ea lintlha tsa eona tse lekanang (chelete), e hlahisoang ke mokhoa o nepahetseng oa ho khetha data ho mefuta eohle ea liteko bakeng sa motho e mong le e mong ea nkang karolo.

Kamano lipakeng tsa boleng ba moruo e abetsoeng monyetla oa ho fumana nako ea ho tsitsipana le maikutlo ka nako ea MES vs Non-MES-Associated Stimuli

Lits'oants'o tsa motho ka mong li ne li hokahane hampe ka ho fapana ha nako ea khetho (RT) bakeng sa CS + vs CS- stimuli (r= -0.690, P<.001) (Setšoantšo sa 2B). Haholo-holo, barupeluoa ba khethileng karolo e kholo ea tšusumetso e amanang le MES ba ne ba potlakela ho khetha lintho tsena tse khothalletsoang (tse khothalletsang mokhoa o hlakileng). Ka lehlakoreng le leng, barupeluoa ba neng ba tloaetse ho qoba ho susumetsoa ke CS + ba ne ba lieha ho ba khetha (boits'oaro ba khatello ea maemo) (Pearce, 1997). Sena e ne e se phello ea nako mesebetsing (mohlala, ka lebaka la tloaelo ea ho fokotseha ka bobeli e bolela RT le khetho ea CS + nakong ea mosebetsi), kaha kamano ena e ile ea lula e bohlokoa haholo ha ho nahanoa liteko tse tsoang halofo e qetellang ea karolo ea liteko (halofo ea pele ea liteko r= -0.692, halofo ea bobeli ea liteko r= -0.625, ka bobeli P<.001).

Kamano lipakeng tsa mosebetsi oa mosebetsi le litekanyetso tsa ho itlaleha

Litholoana tsa motho ka mong li ne li amana hantle le sekhahla se ipatileng sa maikutlo a ho itlhahisa, hoo barupeluoa ba tlalehileng litekanyetso tse phahameng tsa maikutlo ba fuoeng boleng bo boholo ho fumana monyetla oa ho fumana MES (r= 0.325, P= .043) (Setšoantšo sa 3A).

Setšoantšo sa 3. 

Kamano pakeng tsa ts'ebetso ea mosebetsi le mehato ea ho itlaleha. (A) Lenaneo le ipatileng la litakatso tsa boithati le tlalehiloeng ka botlalo le ne le amana hantle le boleng ba ba arolelanoeng monyetla oa ho fumana mofuthu oa motlakase (MES) (r= 0.325, P<.05). (B) Ho ne ho na le kamano e ntle lipakeng tsa boleng bo abetsoeng ho fumana mohopolo o matla oa maikutlo (θ) le ho bolela phetoho ea sekhahla sa analogue (VAS) "ho rata" tekanyetso ea khothalletso e amanang le MES kamora ho kenngoa ha ts'usumetso ea motlakase o eketsehileng (r= 0.368, P<.05). Mehala e senyehileng e bonts'a linako tsa ts'epo tsa 95%. n = 45.

Boleng ba Theta bo ne bo sa amanngoe le ho tšoenyeha ka tšebeliso ea maikutlo, molumo o ikemetseng oa hedonic, boemo bo phahameng ba hona joale, kapa lilemo tsa thuto (kaofela P> .1). Liteko tsa nonparametric li sebelisitsoe ho amahanya ts'ebetso ea ts'ebetso le ho itlaleha ha joala le ts'ebeliso ea koae, kaha lintlha tsena li ne li khelositsoe haholo. Liteko tsa boipheliso tse ikemetseng li senotse hore batho ba faneng ka boleng bo nepahetseng ho monyetla oa ho amohela MES (ke hore, θ> 0, n = 17) ba tsuba lisakerete tse ngata haholo ka beke (Fisher's P= .006) mme e bonts'itse mokhoa o se nang bohlokoa ho isa lino tse tahang ka joala ka beke (P= .098) ho feta batho ba neng ba tloaetse ho qoba MES (ke hore, θ <0, n = 28) (lisakere tse bolelang ka beke 6.7 ± 10.4 vs 2.5 ± 9.9; ho bolela lino tse tahang ka beke 4.2 ± 3.9 vs 3.4 ± 4.9). Ho ne ho se na phapang e kholo pakeng tsa boleng bo bolelang lipakeng tsa batho ba entseng khahlanong le (n = 15 vs n = 30) ba tlaleha tšebeliso efe kapa efe ea boithabiso ntle le joala kapa koae likhoeling tse 12 tse fetileng (mehlala e ikemetseng t teko, P> .1) (Lethathamo 1). Ho ne ho se na phapano ea bohlokoa ba boleng ba boleng pakeng tsa barupeluoa ba banna le basali (disampole tse ikemetseng t teko, P> .1).

Boleng ba MES (θ) le bona bo ne bo amana hantle le phetoho ho VAS "rata" litekanyetso tsa CS + stimuli kamora ho kenyelletsoa hoa MES (ke hore, lipakeng tsa li-2 tsa tekanyetso le 3; r= 0.368, P=.013) (Setšoantšo sa 3B). Barupeluoa ba faneng ka litekanyetso tse ntle tsa MES ba ikemiselitse ho eketsa litekanyetso tsa bona tse amanang le MES, athe barupeluoa ba nang le litekanyetso tse mpe ba ikemiselitse ho theola litekanyetso tsa bona.

Lintlha tsa boleng ba mofuta oa tlhahiso ea li-paramente indexing khetho stochasticity (choice; tekanyo ea hore na khetho ea bankakarolo e ne e susumetsoa ke phapang pakeng tsa likhetho tsa 2) e ne e sa amanngoe le litšobotsi tsa ho ipatlela maikutlo le litekanyetso tsa θ (P> .1), e fana ka maikutlo a hore batho ba batlang maikutlo a phahameng kapa batho ba batlang MES ba ne ba sa susumetsoe ke boleng ba boits'oaro ba bona ho feta balekane ba bona ba tlase ba batlang maikutlo.

Ithute 2

mekhoa

barupeluoa ba

Barupeluoa e ne e le banna ba phetseng hantle ba 30, ho bolelang lilemo tsa 22.3 (SD 2.74) (Lethathamo 1). Litlamorao tse ka bakoang ke haloperidol ho baithaopi ba basali ba kanna ba emara ts'ebeliso ea litlhare ho basali thutong ena. Boholo ba mohlala (n = 30) bo ne bo thehiloe holim'a matla a kamano ea MES boleng / RT eo re e boneng ho Study 1. Ho ile ha baloa hore sampuli ea barupeluoa ba 29 e lokela ho re lumella ho pheta (le ho bona litlamorao tsa haloperidol ho) boholo ba phello ea r= 0.50 ka matla a 80% le alpha ea 0.05. Litekanyetso tsa ho lelekoa li ne li kenyelletsa bokuli bofe kapa bofe ba hona joale, ketsahalo ea hona joale kapa ea nalane ea bokuli ba kelello, le / kapa nalane ea ho lemala hloohong. Lithuto tsohle li fane ka tumello e ngotsoeng e felletseng mme thuto e amohetsoe ke Komiti ea Litloaelo tsa London College London.

Design

Phuputso e entsoe ho latela moralo o ka hare ho lithuto, o sa boneng mahlo hape o laoloa ke placebo. Sebokeng sa pele, barupeluoa ba ile ba fana ka tumello mme ba qeta mosebetsi oa ho batla maikutlo e le ho fokotsa phello ea litlamorao tsa ts'ebetso nakong eohle ea 2 e latelang (tlasa placebo kapa lithethefatsi). Eaba ba qeta ho botsa lipotso tsa UPPS tsa ho itlhahisa.Whiteside le Lynam, 2001), e nang le litlatsetso tsa ho batla maikutlo, le 3 lintlha tse ling tse hlahisoang ke tšusumetso. Mohato ona o ile oa khethoa ho lekola khetho ea kamano pakeng tsa ts'ebetso ea mosebetsi le ho batla-maikutlo ha o bapisoa le mefuta e meng ea ho se ts'oanelehe. Subscale e batlang maikutlo a UPPS e nkuoe haholo ho tsoa linthong tsa SSS-V, ka hona lintlha ho mehato ea 2 li hokahana haholo (Whiteside le Lynam, 2001). Tekanyetso e sa lekanyetsoang, e sa amaneng le bokhoni ba kelello e ile ea boela ea tsamaisoa (Raven's 12-item Advanced Progressive Matrices; Pearson Education, 2010).

Sebokeng sa bobeli le sa boraro, barupeluoa ba ile ba fihla hoseng 'me ba fuoa 2.5mg haloperidol kapa placebo (lithethefatsi le placebo li ne li sa hlalosehe). Tekanyetso ea 2.5mg haloperidol e ile ea khethoa e le hore e be kholo ho feta e fanoeng thutong e fetileng moo litlamorao tse sa lumellaneng tsa lithethefatsi li ileng tsa bonoa (2mg; Frank le O'Reilly, 2006), empa e le tlase ho e sebelisitsoeng lithutong tse ling tsa boits'oaro moo ho fumanoeng litlamorao tse mpe tsa haloperidol holima mohono kapa ama (3mg; Zack le Poulos, 2007; Liem-Moolenaar et al., 2010). Ho etsa liteko ho qalile lihora tsa 2.5 kamora ho kenella letlapeng bakeng sa ho lumella maemo a plasma ea lithethefatsi hore a fihle sehlohlolong se phahameng (Midha et al., 1989; Nordström et al., 1992).

Kamora nako ena e nkileng nako, barupeluoa ba ile ba qeta mehato ea VAS ea ho ferekana, ho ama, litlamorao tse mpe tsa 'mele, le tsebo ea taolo ea lithethefatsi / placebo. Setsi sa Lipatlisiso sa Bokhoba ba Tlatsetso ea litlamorao tsa lithethefatsi tsa psychoactive (ARCI; Martin et al., 1971) e ile ea boela ea tsamaisoa, kaha sena se kile sa bontšoa se ameha ka haloperidol (Ramaekers et al., 1999). Barupeluoa ba ile ba boela ba tlatsa 1 ea 2 liforomo tse lekanang tsa tlhahlobo ea mangolo-lengolo (LDST; van der Elst et al., 2006), tlhahlobo e bonolo ea pentšele le pampiri ea psychomotor e akaretsang le ts'ebetso ea kelello. Tekanyo ea pelo ea Arterial le khatello ea mali li ile tsa beoa leihlo pele ho nako le ka mor'a lithethefatsi.

Mosebetsi oa ho batla maikutlo o bile joalokaha o hlalositsoe ho Study 1. Bakeng sa thuto ena, barupeluoa ba ile ba tlatsa letoto la litekanyetso tsa VAS qetellong ea mosebetsi ho etsa liteko tsa ho ithuta tsa CS + / CS- (MES-Associated vs non-MES- amanang). Bakeng sa CS e 'ngoe le e' ngoe, barupeluoa ba ile ba lekanya hore na ba lumela ka matla hakae hore ba khetha boikhathollo bo amanang le monyetla oa ho susumetsoa ke motlakase ("ha ho na monyetla oa ho makala" le "monyetla oa ho makala"). Ts'ebetso ea ho ikakhela ka setotsoana e ile ea phetoa thutong e 'ngoe le e' ngoe ho netefatsa hore botebo ba boikemelo (ho fapana le bophahamo ba hona joale) bo tsamaisoa ka linako tsohle. Taelo ea lithethefatsi / placebo e ne e hanyetsanoa ho lithuto tsohle, ka nako ea ho hlatsoa libeke tsa 1-beke lipakeng tsa liteko tsa 2 (nako e bolelang lipakeng tsa ketelo e ne e le matsatsi a 18).

Analysis

Tlhahlobo ea mohlala ea computational ea mosebetsi o batloang ke maikutlo e bile joalo ka ha ho hlalositsoe ho Study 1. ANOVA e lekantsoeng khafetsa e nang le lintlha tse kahare tsa lithethefatsi (haloperidol vs placebo), le sepheo sa lipakeng tsa taelo ea lithethefatsi (karolo ea pele ea tlhahlobo ea bobeli) e sebelisitsoe ho hlahlobisisa liphapang tsa bohlokoa tse tsoang ho tlhaiso-leseling ea liteko. Haholo-holo tsena e ne e le tšebeliso ea sethala ea hajoale e nkang karolo, mehlala ea mohlala e hlalosang boleng ba MES (θ) le khetho ea methapo (β), khetho ea khetho ea RT, le phello ea RT ka bonngoe (median RTCS + - mohareng RTCS-). Litlhahlobo tsohle tse boletsoeng esale pele tse bonolo li bapisoa ka bobeli le phetoho ea Bonferroni bakeng sa lipapiso tse ngata.

Mehato ea litla-morao tsa lithethefatsi tse akaretsang le tse latelang (VAS, ARCI, lintlha tsa LDST, le methapo ea pelo) li ile tsa bapisoa lipakeng tsa liteko tsa liteko ka sampole ea li-paired t liteko. Morupeluoa a le mong o ne a sitoa ho ea sebokeng sa tlhahlobo ea ho qetela kahoo tlhaiso-leseling ea hae ha ea kengoa tlhahlobisong. Morupeluoa e mong o ile a hloleha ho fihlella tšebetso ea boemo ba tlhahlobo sethaleng sa ho fumana mosebetsi ka linako tsohle tsa tlhahlobo, ka hona, tlhaiso-leseling ea hae e ile ea qheleloa ka thoko, ea hlahisa n ea ho qetela ea 28.

Litlhahlobo tsohle tsa lipalo-palo li ile tsa etsoa ho SPSS 19.0 (IBM Corp., Armonk, NY), ntle le tlhahlobo ea mohlala ea computational, e sebelisitsoeng ho Matlab R2011b (Mathworks, Inc., Sherborn, MA).

LIPOTSO

Litlamorao tsa ho its'epahalla ha Basline ka ho latela ts'ebetso ea ho ts'oara

Liphetho tsa mantlha tsa Study 1 li bile teng phetong ea motheo ea barupeluoa (likamano tsa bohlokoa melaong e lebelletsoeng lipakeng tsa boleng ba θ le sephetho sa RT ka bomong le ho ipatlela maikutlo ka boithatelo) (Setšoantšo sa tlatsetso 1). Tlhahlobo ea concordance lipakeng tsa data ho tloha metheong ea motheo le likarolo tsa placebo le eona e bontšitse ho ts'epahala ho lekantsoeng ha litekanyetso tsa boleng ba "boleng" (bona Boitsebiso bo Eketsehileng), ho ts'ehetsa bonnete ba ts'ebeliso ea rona ea moralo oa mehato e phetoang.

Ha u nahana ka lintlha tsa tlhahlobo ea 2 (lithethefatsi / placebo), ka kakaretso, barupeluoa ba boetse ba khetha tlhahiso-leseling e amanang le ts'oabo (CS +) khafetsa haholo lintlheng tse phahameng ho feta liteko tsa lintlha tse lekanang, 'me ka ho tšoana ha ba bapisoa le liteko tse tlase, ho placebo ka bobeli le likarolo tsa lithethefatsi (phello e ka sehloohong ea mofuta oa teko; F 2,54= 138.54, ƞ p 2 = 0.837, P < .001; phapang lipakeng tsa mefuta kaofela P<.001; Khetho ea (± SD) ho placebo e ne e le 0.806 ± 0.19, 0.398 ± 0.17, and 0.126 ± 0.13, ka ho latellana, ka mefuta ena ea liteko, ha haloperidol e ne e le 0.744 ± 0.19, 0.399 ± 0.15.

Ho ne ho se na litlamorao tse akaretsang tsa kalafo ea haloperidol ho amplitude ea hona joale, lintlha tsa boleng tse abetsoeng MES (choice), khetho stochasticity (β), ho bolela RT, kapa RT e amanang le tšusumetso e amanang le MES vs non-MES-all P> .1). Taelo ea lithethefatsi (boitokiso bo sebetsang lenaneong la pele la teko ea bobeli le la bobeli) e ne e se ntho ea bohlokoa lipakeng tsa-lithuto bakeng sa mefuta efe kapa efe e itšetlehileng ka eona (P> .1), 'me ho ne ho se na tšebelisano-mmoho ea lithethefatsi *P> .1). Ka hona, taelo ea lithethefatsi e lahliloe ho tsoa ho mohlala bakeng sa litlhahlobo tse latelang ho eketsa kutloisiso.

Kamano e matla lipakeng tsa lintlha e nka karolo barupeluoa ba abetsoeng ho fumana MES le khetho ea RT bakeng sa tšusumetso e amanang le MES e amanang le MES e qotsitsoeng ho Study 1 e ile ea phetoa sampole ea bobeli tlasa maemo a placebo (r= -0.602, P=.001), empa, ka mokhoa o makatsang, eseng tlasa haloperidol (r= -0.199, P> .1) (Setšoantšo sa 4A).

Setšoantšo sa 4. 

Litlamorao tsa haloperidol ka boleng bo abetsoeng ho tsosa maikutlo a matla. (A) Mohlaleng oa bobeli oa baithaopi ba phetseng hantle, boleng bo abetsoeng ho susumetsa maikutlo bo matla (maikutlo a bonolo a motlakase [MES]) bo ne bo amana haholo le nako ea khetho (RT) bakeng sa tšusumetso e amanang le MES vs non-MES- e amanang le sebaka sa placebo (r= -0.602, P=.001), empa eseng tlasa haloperidol (P> .1; ho fokotseha ho hoholo ha coefficient ea khatello, P<.05). Mehala e senyehileng e bonts'a linako tsa ts'epo tsa 95%. (B) Haeba lithuto li ne li arotsoe ka ba atamelang (ba bonts'itse RTS e potlakileng ho leba, n = 8) le ba neng ba qoba (ba bonts'a lietsahala RT ho ea, n = 20) monyetla oa tšusumetso e matla ea maikutlo tlasa placebo, ho bile le tšebelisano ea bohlokoa pakeng tsa sehlopha se batlang maikutloP<.01). Haloperidol e fokotse boleng ba moruo bo fuoeng MES feela ho barupeluoa ba bonts'itseng karabelo mabapi le tšusumetso e amanang le MES tlasa maemo a tloaelehileng (batho ba batlang maikutlo a phahameng [HSS]; cf batho ba batlang maikutlo a tlase [LSS]). Liphoso tsa liphoso li emela SEM. **P=.01, ns P> .10, lithethefatsi vs placebo. n = 28.

Tlhahlobo ea posthoc e senotse hore kannete ho bile le khakanyo ea bohlokoa ea kamano ena tlasa haloperidol (Fisher r-to-Z tlhahlobo e fetotsoeng ea Pearson-Filon bakeng sa ho fokotseha ha komporo ea khokahano; Z= -1.735, P=.041, 1-tailed; Raghunathan et al., 1996). Kahoo, kalafo ea haloperidol e ile ea bonahala e felisa sephetho sa ho qoba mokhoa ona mabapi le khetho eo motho a e khethang bakeng sa tšusumetso e matla ea maikutlo. Ka mokhoa o ts'oanang, leha lintlha tsa ho ipata tsa boithati li ne li hokahane haholo le ka mokhoa o khethiloeng ka boleng ba MES (θ) ho placebo (r= 0.391, P=.040; lintlha tsohle tse ling tsa subscale tsa UPPS tse sa amaneng le likhetho tsa MES, P> .1), ho ne ho se joalo tlasa haloperidol (r= -0.127, P> .1; La Steiger Z bakeng sa phapano ea bohlokoa khokahanong ea khokahano pakeng tsa maemo a lithethefatsi = 2.25, P=.024; Steiger, 1980).

Re ipapisitse le seo re se fumaneng holimo, kopantsoeng le seo re se boneng pejana hore litlamorao tsa lithethefatsi tse mpe tsa D2 li ka ipapisa le ho batla maikutlo a mantlha (Norbury et al., 2013), Tlhatlhobo e ngoe e ile ea etsoa ho lekola litlamorao tsa lithethefatsi tse itšetlehileng ka mantlha tse kanna tsa patoa tlhahlobisong ea boemo ba sehlopha. Ho fumana hore na ke eng e neng e khannela phello ea phello ea RT tlasa lithethefatsi, barupeluoa ba ile ba aroloa ka lihlopha ho latela hore na ba bonts'a mokhoa o nepahetseng (RT ea CS + vs CS- stimuli, ke hore, motho ka mong RT effect <0, N = 8) kapa khatello ea maemo ( liehisa RT ho CS + vs CS- stimuli, ke hore, motho ka mong RT effect> 0, n = 20) ea likarabo tsa bona mabapi le ts'usumetso e matla ea maikutlo tlasa maemo a placebo.

Ha mokhoa ona kapa oa ho qoba sehlopha o kenyelletsoa mohlaleng oa lithuto tsa pakeng tsa lithuto, ho bile le tšebelisano e kholo lipakeng tsa kalafo ea lithethefatsi le sehlopha ka boleng bo fuoeng MES (tšebelisano ea bohlokoa ea sehlopha sa lithethefatsi * ka boleng ba θ; F 1,26= 10.64, ƞ p 2= 0.290, P=.003; tšebelisano ka boleng ba β P> .1). Liphuputso tse bonolo tsa litlamorao li senotse phokotso e kholo ea boleng ba MES sehlopheng se atamelaneng ho haloperidol vs placebo (F 1,26= 7.97, ƞ p 2 = 0.235, P=.009). Ka lehlakoreng le leng, ha ho na phello ea lithethefatsi ka boleng ba MES sehlopheng sa qoba (P> .1) (Setšoantšo sa 4B). Kahoo, haloperidol e ile ea bonahala e amohela boleng ba MES ka mokhoa o ikhethileng ho batho ka bomong ba bonts'ang boitšoaro ba mokhoa o lebisang ho matlafatso e matla ea maikutlo tlasa maemo a motheo.

Lihlopha tse atamelang le ho qoba li ne li sa tšoane ka lilemo, boima, khakanyo ea IQ, kapa boits'oaro bo ikemetseng (disampuli tse ikemetseng t liteko, kaofela P> .1), empa e fapane lipakeng tsa ho batla maikutlo a UPPS (t 26= 2.261, P=.032, e phahameng haholo e bolela lintlha sehlopheng sa mekhoa; 40.9 ± 8.1 vs 32.9 ± 8.5). Ka mokhoa o ts'oanang ho Study 1, liteko tsa bo-'mampuli tse ikemetseng li senotse hore batho ka sehlopheng se atamelang ba tsube lisakerete tse ngata ka beke ho feta sehlopha sa Fisher's P=.022) mme e bonts'itse mokhoa o sa natefeloang bakeng sa ts'ebeliso e kholo ea joala beke le beke (P=.096; bolela lisakerete ka beke 20 ± 25 vs 3.9 ± 13; ho bolela lino-mapholi ka beke 12 ± 13 vs 3.5 ± 3.9).

Matla a haloperidol ho boleng ba θ (phapang ea boleng pakeng tsa lithethefatsi le likarolo tsa placebo) e ne e sa amanngoe le lilemo, boima, tekanyetso ea IQ, litlamorao tsa lithethefatsi maemong a kakaretso kapa tlhokomeliso ea litekanyetso tsa VAS, litlamorao tsa lithethefatsi ho sedation kapa dysphoria sekaleng sa ARCI, kapa phello ea lithethefatsi mosebetsing o akaretsang oa psychomotor (lintlha tsa LDST; kaofela P> .1). Ho ne ho boetse ho se na kamano ea bohlokoa lipakeng tsa litlamorao tsa boleng ba boleng le palo ea lino tse tahang tse nooang kapa lisakerete tse tsubang ka karolelano bekeng (Spearman's ρ <0.25, P> .1). Lihlooho tse neng li se na / li se na (n = 10 vs n = 18) (Lethathamo 1) ea sebelisitseng lithethefatsi tse ling ntle le joala kapa koae nakong ea likhoeli tsa 12 tse fetileng ha a fapana ka phello ea haloperidol ka boleng ba θ (disampuli tse ikemetseng t teko, P> .1).

Liphetho tsa lithethefatsi tsa Subjective le General Psychomotor

Se fumanoeng ka holimo se ne se ke ke sa hlalosoa ke litlamorao tsa mofuta oa kalafo ea lithethefatsi. Ka kakaretso, ho ne ho se na litlamorao tse kholo tsa haloperidol ho litekanyetso tsa VAS tsa ho feto-fetoha ha maikutlo, tšusumetso, kapa litlamorao tse ka bang 'meleng (likala tsa 16, kaofela P> .1) (bakeng sa lintlha, bona Letlapa le tlatsetsang 1). Hape ha ho na phello ea haloperidol ho palo efe kapa efe ea subscale ea ARCI (MBG euphoria, sedation ea PCAG, litekanyetso tsa LSD dysphoric le psychotomimetic, BG le A sekhahla se ts'oanang le litekanyo tse kang litlamorao, kaofela P> .1) kapa mehato ea pelo (khatello ea mali le lebelo la pelo, P> .1). Ho ne ho se na tšusumetso ea kalafo ea lithethefatsi holima litekanyetso tsa bankakarolo ba hore na ba lumela hore ba sethaleng sa lithethefatsi kapa sa placebo (P> .1). Kamora nako, ho ne ho se na phello ea haloperidol ts'ebetsong e akaretsang ea psychomotor joalo ka ha e entsoe ke ts'ebetso ea LDST (P> .1).

Litlamorao tsa lithethefatsi ho Ithuta

Kamora nako, re ile ra hlahloba khopolo-taba ea hore litlamorao tse bonojoang tsa haloperidol li ka bakoa ke liphapang tsa ho ithuta lipakeng tsa lithethefatsi le li-placebo. Ha rea ​​fumana phello ea haloperidol palong ea liteko tse hlokahalang ho fihlella tšebetso ea boemo mohatong oa pele oa mosebetsi (P> .1). Lintlha tsa "karolo ea" tsebo "ea barupeluoa bakeng sa CS + le CS- stimuli (lintlha tsa VAS ho tloha ka monyetla oa ho tsosoa [+ 300] ho se na monyetla oa ho tsosoa [-300] li kentsoe mefuteng ea mehato e phetoang le e kahare- lintlha tsa litaba tsa lithethefatsi (haloperidol vs placebo) le mofuta oa CS (CS + vs CS-), e senolang phello e kholo ea mofuta oa CS (F1,27= 74.56, ƞ p 2= 0.734, P<.001; ho bolela [± SEM] tekanyetso ea CS + stimuli 146 ± 18.2, ho bolela tekanyetso ea CS- stimuli -150 ± 19.1), empa ha ho na phello ea kalafo ea lithethefatsi (P> .1) kapa ts'ebeliso ea mofuta oa CS * (P> .1) ka tsebo e hlakileng ea mekhatlo ea MES. Ha mokhoa oa ho atamela khahlanong le ho qoba sehlopha o kenyellelitsoe ho mohlala e le ntho e pakeng tsa-lihlooho, ho ne ho se na phapang lipakeng tsa lihlopha ka lebaka la lithethefatsi ho litekanyetso tsa tsebo ea ts'oaetso (sehlopha sa lithethefatsi *, P> .1), kapa litlamorao tsa sethethefatsi ho latela mofuta oa CS (sethethefatsi sa * mofuta oa CS *, P=.09).

Puisano

Re ile ra hlahloba kamoo monyetla oa ho ba le tšusumetso e matla ea maikutlo (MES) e ileng ea ama boitšoaro nakong ea mosebetsi o bonolo oa ho etsa liqeto tsa moruo, mme kamora moo, hore na index ena ea boits'oaro ea maikutlo e ne e anngoe joang ke D2 dopamine receptor antagonist haloperidol. Ka holimo khetho ea mofufutso e amanang le ts'usumetso e matla ea tactile e etsahetse ka mokhoa o ts'epahalang ho barupeluoa ba bang, leha khetho ena e ne e kenyelletsa boitelo ba phaello ea chelete. Ho fumana hona ho tsamaellana le maikutlo a matla a susumetsang a nkoang a le monate ho batho bana. Ho ts'ehetsa phetolelo ena, barupeluoa ba khethileng karolo e kholo ea sepheo se amanang le MES ba bile le lintlha tse phahameng tse ipolelang tse ipatileng, ba eketsa litekanyetso tsa bona tsa "ho rata" ka mora ho hlahisoa ha MESs, mme ba abela boleng bo botle ba moruo ho le monyetla oa ho fumana matla a eketsehileng a ho susumetsa molemong oa ho sebetsa ka mokhoa o loketseng.

Habohlokoa, ho ne ho na le kamano ea bohlokoa haholo lipakeng tsa khetho ea ts'usumetso e matla ea maikutlo le li-RTs tse ikhethileng, tse lumellanang le maikutlo a hore MES e na le bohlokoa bo susumetsang ho barupeluoa. Mehlaleng ka bobeli, barupeluoa ba khethileng karolo e kholo ea tšusumetso e amanang le MES ba bonts'a karabelo e potlakileng ea likarabo tsa bona ha ba khetha lintlha tsena, ka sephetho se fapaneng se bonngoe ho batho ba neng ba ikemiselitse ho li qoba. Ka kopanelo le lipatlisiso tse fetileng tsa hore batho ka kakaretso ba bonts'a linako tse potlakileng tsa karabelo molemong oa takatso ea lijo empa ba lieha ho atamela ho susumetsa ka mokhoa o phollatsi (Crockett et al., 2009; Wright et al., 2012), sena se fana ka maikutlo a hore monyetla oa ho susumetsa maikutlo haholo o ile oa susumetsa khetho ea barupeluoa ka mokhoa oa ho qoba lintho joaloka bona.

Ka bomalimabe, phello ena e ne e sa bonahale tlas'a tšusumetso ea mohanyetsi oa D2 receptor antagonist. Sena se ne se bakoa ke ho fokotseha hoa boleng ba moruo bo abetsoeng ho amohela matlafatso a matla a maikutlo ho batho ba nkang karolo ba bonts'itseng ba fokotsehile RTs mabapi (kapa ba bonts'a mokhoa oa ho arabela) MES tlasa maemo a placebo (ba batlang boits'oaro bo phahameng).

Liphetho tse hlahisitsoeng mona li tsamaisana le nalane e pharaletseng ea bopaki bo tsoang ho batho le liphoofolo tse amanang le tšekamelo ea maikutlo ea ho batla phetoho ho dopaminergic neurotransmission, haholoholo libakeng tsa striatal (Hamidovic et al., 2009; Olsen le Winder, 2009; Shin et al., 2010; Gjedde et al., 2010; Norbury et al., 2013). Motsoako o kopaneng oa bopaki bo tsoang lipatlisisong tsa lefutso la radiology le PET tsa radiology tsa PET li bontša hore batho ba phahameng ka ho feteletseng ba batlang botho ba ka ba le maemo a phahameng a dopamine le likarabo tse kholo tsa dopaminergic litabeng tsa moputso o tlang striatum (Riccardi et al., 2006; Gjedde et al., 2010; O'Sullivan et al., 2011). Ho latela mohlala o mong o nang le tšusumetso ea karolo ea dopamine ts'ebetsong ea striatal (Frank, 2005), maemong a tloaelehileng sena se ka tlatsetsa ho eketseheng hoa thibelo ea "NoGo" (ts'ebetso ea thibelo) ea tsela ea methapo ea kutlo ka ho phahamisa ho eketsehileng ha li-receptor tsa inhibitory tsa postynaptic D2. Sena se tla fella ka ts'ebeliso e kholo ea thalamic disinhibition kapa "E ea" khethollo ea polelo) ho batho ba batlang maikutlo a phahameng, haholoholo moo ho nang le meputso e ntle.

Haloperidol ke mohanyetsi ea khutsitseng oa D2 receptor (li-block endo native dopamine signing ka D2 receptors; Cosi et al., 2006), mme bahanyetsi ba D2 ba kile ba bonts'oa pele ho ama ts'ebetso ea ts'ebetso ea striatal (Kuroki et al., 1999; Mahe a linotsi et al., 2003). Ka hona, ho a khonahala hore tlasa haloperidol, likarabo tsa ba batlang maikutlo a phahameng li ka fetoloa (ho eketseha ho tšoana le ba batlang maikutlo a tlase) ka ho lumella tlhahiso ea NoGo e eketsehang. Sena se ka hlalosa ho fumanela ha rona phokotso ea karabelo ea maikutlo le maikutlo a matla ho batho ba phahameng ba batlang maikutlo.

Ho fumana ha rona phello e kholo ea haloperidol ka khetho, ho se na tšusumetso leha e le efe ea ho ithuta, ho tsamaisana le mosebetsi oa morao-rao o bonts'ang hore bahanyetsi ba D2 ba ka ba le litlamorao tse matla mabapi le khetho ea ho khothaletsa moroalo-ho bolela esale pele ha ba tlohela ho ithuta ba sa tsitsa (Eisenegger et al., 2014). Leha ho le joalo, ho bohlokoa ho hlokomela hore mochine o behang litlhahiso tse kaholimo o nka phello ea posynaptic haholo ea haloperidol (Frank le O'Reilly, 2006). Leha re leka ho netefatsa li-receptor tsa bohlokoa tsa postynaptic tse tlamang ka tšebeliso ea litekanyetso tse kholo ho feta thuto e kileng ea bontšoa (moo ho neng ho nahanoa hore litlamorao tse mpe le tsa postynaptic D2-ha li na bopaki bo tobileng ba sena. Ho feta moo, litlatsetso mabapi le likarolo tsa boko tse kenyelletsoeng liphumatsong tsa rona li hakantsoe mme li ka hloka ho lekoa mosebetsing o mong, mohlala, o kenyelletsang monahano o sebetsang.

Lithuto tse fanoeng mona li na le meeli. Taba ea mantlha, ha boits'oaro bo batlang bo le teng lefatšeng la 'nete bo ka nka mefuta e mengata e fapaneng, ho ka bonahala ho makatsa hore ts'ebeliso ea "mES" e le' ngoe e matla e khona ho hapa mokhoa o lekaneng oa ho batla maikutlo ho batho bohle. Leha ho le joalo, seo re se fumaneng se lumellana le phuputso e fetileng e tlalehang liphihlelo tse fapaneng tsa karabelo ea 'mele ho tsitsipano ea motlakase ho batho ba batlang maikutlo a tlase le ba iphahamisang (De Pascalis et al., 2007). Ha re na ho batla ho fana ka ts'ebetso ea hore mosebetsi oa rona o ama botho ba ho batla maikutlo, kaha ona ke tšobotsi e rarahaneng ea mefuta e mengata, empa e ka ts'oara ts'ebetso e ts'oanang ea ho batla maikutlo a kang bonyane ba batho ba batlang maikutlo a phahameng. , ka tsela eo e re lumella ho etsa metheo ea methapo ea methapo ka laboratoring (mohlala, ka ho qhekella). Ka mokhoa o makatsang, ho na le bopaki bo bonts'ang hore ts'ebetso e sa lumellaneng le phoofolo ea boitšoaro bo batlang takatso ea ho tsilatsila e ka hula bonyane karolo e itseng ea sepakapaka sa neural (mohlala, Parkitna et al., 2013).

Ka mokhoa o makatsang, lithutong tsa rona ka bobeli, ho ile ha fumanoa khetho ea MES e amanang le MES e ikhethileng ka litekanyetso tse ngata tse ipatileng tsa maikutlo a ho itlhahisa, a ipabolang ka mekhahlelo e mengata ea boits'oaro. Leha likamano tsena e ne e le matla a itekanetseng, ho lokela ho hlokomeloa hore liphetho tsena li pheletsong e holimo ea mefuta ea tse fumanehang lipakeng tsa boits'oaro le lipotso tsa boits'oaro tsa boitšoaro bo sa susumetseng (Helmers et al., 1995; Mitchell, 1999). Re fumane bopaki bo bong ba tšebeliso ea litheko tse matlafatsang bathong ba faneng ka boleng bo nepahetseng ho fihlela monyetla oa ho tseba MES, bo bonts'ang hore ts'ebetso ea mesebetsi e ka amana le boitlamo ba bophelo ba 'nete litloaelong tse batlang takatso.

Taba ea bobeli, ha ho fumana lithethefatsi ho thehiloe ho fokotseha ho hoholo ha boleng bo le bong (e leng boleng bo phahameng ba pele), tlhaloso e 'ngoe ea seo re se fumaneng ho tsoa ho Thutong ea 2 ke hore sena se emetse feela ts'ebetso e mpe. Leha ho le joalo, khahlano le tlhaloso ena, re fumane bopaki ba ts'epahalo e nepahetseng ea boleng ba boleng ba boleng ba boleng bo tsoang ho barupeluoa ba le bang ho feta likarolo tse ngata tsa pale ea rona ea lipale (Boitsebiso bo Eketsehileng).

Ntle le moo, ho hlophisa subgrouping bakeng sa Study 2 ho ipapisitse le phapang e fapaneng le khetho ea li-RT ho fapana le boleng ba θ ka setheo (le ha 2 e hokahane haholo). Re boetse re sebelisitse tekanyetso ea rona ea RT ho tloha molemong oa tlhahlobo ea bobeli kapa ea boraro (seboka sa placebo) ho ba nkang karolo ea sehlopha, leano leo ho bileng le phehisanoang ka lona ho thusa ho itšireletsa khahlanong le ho khutlisetsa litlamorao ho litlamorao.Barnett et al., 2005). Ha re kopane, re ka hanyetsa taba ea hore lintlha tsena li hanana le phello e fokolang ea haloperidol ho boleng ba MES tseleng kapa batho ba batlang maikutlo a phahameng.

Taba ea boraro, leha haloperidol e nkuoa e le mohanyetsi ea amohelang li-D2 (e tlama makhetlo a 15 ka matla ho D2 ho feta li-receptor tsa D1 ka likhoto le lisele tse entsoeng ka batho; Arnt le Skarsfeldt, 1998), e boetse e bontšitsoe hore e na le tumellano e ntle ea ho α-1 adrenoreceptor le serotonin 2A receptor ho kelello ea motho ea postmortem (Richelson le Souder, 2000). Ka hona, re ke ke ra ba le bonnete bo felletseng mabapi le mochini o hlahisang litlamorao tsa lithethefatsi tsa rona. Joalokaha haloperidol e kile ea tlalehoa ho kenya ts'ebetsong litekanyetso tse phahameng tsa bokaholimo ba D2 receptor maemong a fokolang a molomo (60-70% ho 3mg le 53-74% ho 2mg; Nordström et al., 1992; Kapur et al., 1997), re na le ts'epo ea hore tekanyetso e sebelisitsoeng thutong ea rona (2.5mg) e ne e lekane ho qhekella li-receptors tsa D2 tse kahare ho barupeluoa ba rona. Tlokotsi e 'ngoe e ka bang teng ke monyetla oa hore litla-morao tsa boitšoaro tseo re li boneng li bakoa ke phello e itseng ea kalafo ea haloperidol, mohlala, likotsi tse mpe tse bang teng ho barupeluoa. Leha ho le joalo, phello ea lithethefatsi ho boleng ba MES e ne e sa kopane le phapang ea maikutlo, tšusumetso, litekanyo tsa sedation kapa dysphoria, kapa tekanyo ea ts'ebetso ea rona ea psychomotor ka kakaretso lipakeng tsa lithethefatsi le placebo.

Ka kakaretso, paradigm ea nalane e hlahisitsoeng mona e bonahala e phahamisa sekhahla sa boikemisetso ba ho itaola maikutlo a matla le a sa tloaelehang, hammoho le ho khothatsa boits'oaro. Bakeng sa barupeluoa ba khethang ho atamela ho e-na le ho qoba mofuta ona oa tšusumetso, re fana ka maikutlo a hore o oa thabisa ka mokhoa o makatsang le hore, ka mokhoa o ts'oanang le liphumano tse tsoang ho lingoliloeng tsa liphoofolo, karabelo ena ea takatso e kenyelletsa D2 receptor dopamine system. Liphumano tsena li ka thusa ho etsa lipatlisiso tsa li-psychopathologies tse fapaneng tseo ho tsona lintlha tse batlang takatso e feteletseng e leng sesosa sa ho ba kotsing.

Polelo ea Thahasello

JPR ke moeletsi oa Cambridge Cognition mme o nkile karolo e le sebui se lefuoang boto ea likeletso tsa boralitaba bakeng sa Lundbeck. Bangoli ba bang kaofela ha ba na lithahasello tsa lichelete ho li senola.

Liteboho

Mosebetsi ona o tšehelitsoe ke Wellcome Trust (moputso 098282 ho MH) le Lekhotla la Patlisiso ea Bongaka UK.

Ena ke sengoloa sa Open Access se tsamaisitsoeng tlasa maemo a laesense ea Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/), e lumellang tšebeliso e sa thijoeng, phetiso le phetiso ea mofuta o fe kapa o fe, ha feela mosebetsi oa pele o boletsoe ka nepo.

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