Bothata ba ho Qala Khatello ea Kelello ho Etsa Hore Motho a E-na le Mathata a Matla, empa a se ke a ba le Tšusumetso, Boits'oaro ho Basali (2015)

Behav Neurosci. Jun ea 2015; 129 (3): 300–308.

doi:  10.1037 / bne0000059

PMCID: PMC4450884

 
Rebecca D. Burwell, Mohlophisi
Nichola M. Bridges,mongoli ea tšoanang1,2,* Megan C. Holmes,1 Anjanette P. Harris,1 Rudolf N. Cardinal,3,4,5 'me Jeremy Hall6,7

1Setsi sa Saense ea Cardiovascular, Univesithi ea Edinburgh
2Neuroscience le Setsi sa Patlisiso ea Bophelo bo Botle ba kelello, Cardiff University School of Medicine
3Setsi sa Behavial and Clinical Neuroscience Institute, Lefapha la Psychiatry, Univesithi ea Cambridge
4Tšebeletso ea Liaison Psychiatry, Cambridgeshire
5Peterborough NHS Foundation Trust, Khampasi ea Cambridge Biomedical, United Kingdom
6Setsi sa Saense ea Cardiovascular, Univesithi ea Edinburgh
7Neuroscience le Setsi sa Patlisiso ea Bophelo bo Botle ba kelello, Cardiff University School of Medicine

inahaneloang

Liphihlelo tse bohloko nakong ea bongoana li amana le nts'etsopele ea maloetse a kelello hamorao bophelong. Haholo-holo, tlhekefetso ea bana le ho se tsotelle ke lintho tse ka bang kotsi bakeng sa mathata a lemallo, a joalo ka tšebeliso e mpe ea lithethefatsi le papali ea papali ea chelete. Ho potlaka le ho qobelloa ke likarolo tsa bohlokoa tsa mafu ana. Ka hona, re fuputse hore na mathata a bongoana a ka eketsa tlokotsi ea mafu a bokhoba ka ho khothaletsa boits'oaro bo khothalletsang le bo sa susumetsang. Likhoto li ile tsa pepesetsoa protocol e khutšoane ea bongoana kapa ea ho iketelletsa pele (matsatsi a ho qetela a matsatsi a 25-27), mme boits'oaro ba bona mosebetsing oa ho fokotsa litšitiso bo bapisoa le oa liphoofolo tse laoloang ha e se e le motho e moholo. Khatello ea kelello esale pele e hlahisitse basali ba mofuta o tlamang. Haholo-holo, basali ba tepelletseng ba bonts'a likarabo tse sa nepahalang nakong ea khetho ea mosebetsi, ba phehella ka ho arabela ka nosepoke ho e-na le ho khetha pakeng tsa levers tse peli. Basali ba sithabetseng le bona ba bontšitse mathata a ho ithuta nakong ea thupelo ea mosebetsi. Leha ho le joalo, khatello ea maikutlo pele ho nako e ne e sa amane le nts'etsopele ea boits'oaro bo potlakileng, kaha litheko tsa ho lieha ho lieha ha li amehe ho tsa bong kapa tsa bong. Mathata a bongoana a ka kenya letsoho ho thehoeng le ho boloka mafu a lemallo ka ho eketsa mamello ho basali. Boitšoaro bo phehellang ka hona bo ka fana ka sepheo se matla sa kalafo bakeng sa ho thibela nts'etsopele ea mathata a lemallo ho batho ba pepesitsoeng litsietsing tsa bongoana. Litlamorao tsena li ne li sa bonoe ho banna, tse totobatsang liphapang tsa thobalano ho arabela khatello ea bophelo ba pele.

Keywords: ho qobelloa, ho susumetsoa, ​​ho tiisetsa, khatello ea bongoana, phapang ea thobalano

Ho pepesetsoa litsietsing bongoaneng ho amana le nts'etsopele ea mafu a kelello a fapaneng hamorao bophelong (; ; ; ). Likhokahano tse matla li ba teng lipakeng tsa tikoloho e kenang e kenngoeng kahare le maemo a sa foleng a ho ba motho e moholo, le "tšimoloho ea" lefu la setho sa botona "hypothesis e ts'ehelitsoe hantle (; ; ). Leha ho le joalo, ha ho tsejoehale ka litlamorao tsa nako e telele tsa khatello ea maikutlo nakong ea bongoana kapa karolo ea bophelo ba pele ho bophelo. Boko ba pelehi bo bontša phapang e kholo ea sebopeho le tšebetso ho boko ba kelello le ba batho ba baholo. Haholo-holo, likarolo tsa corticolimbic tse kang hippocampus, amygdala, le preortal cortex (PFC) lia hola nakong ea bongoaneng le bohlankeng (; ; ). Mathata a bongoana a amana le nts'etsopele ea mafu a mangata a kelello a ho ba motho e moholo.; ; ; ; ; ), ka lebaka leo, karolo ea bongoana e hloahloa le ho feta e le nako e tebileng eo ka eona boko bo ka bonts'ang likotsi tse itseng tsa litlamorao tsa khatello ea maikutlo (; ).

Tsietsi ea ho ba le ngoana ke ntho e ka bang kotsi haholo bakeng sa tšebeliso e mpe ea lithethefatsi le mathata a mang a ho lemalla hamorao bophelong.; ). Litšobotsi tse susumetsang le tse qobelloang tsa boitšoaro li amana le mathata ana (; ; ; ), empa hore na kamano ena e le lebaka kapa e sa bohlokoa ha e hlake (). Haeba ho baka, ho pepesehela mabaka a mabe a tikoloho, joalo ka tsietsi ea bongoana, ho ka eketsa kotsi ea likhathatso ka ho eketseha ka boits'oaro bo qobelloang. Ho nahanisisa ho nahanoa ho bapala karolo ea ho qala boits'oaro bo lematsang; mohlala, likhoto tse khethollotsoeng haholo li ne li ka ba le monyetla oa ho iphumanela koae ka litekanyetso tse potlakileng haholo ho feta tse khetholloang (; ). Mohato o le mong oa ho susumetsoa ke ho theola nako ea ho lieha (mofuta oa ho qobella ho khetha), e bolelang ho theoha ha boleng ba moputso e le ts'ebetso ea ho lieha ho amohela.). Ho rata moputso o nyane, oa hang hang holim'a moputso o moholo empa o liehang ho hlalosoa o hlalosoa e le khetho e sa susumetsoang, athe khetho ea moputso o liehang ho lieha ke khetho e itaolang (). Ka hlakoreng le leng, ho qobella, e hlalosoang e le ketso e pheta-phetoang boemong boo, ho nahanoa hore e khothaletsa tlhokomelo ea boits'oaro bo lematsang (; ). Tiisetso ke mofuta oa boits'oaro bo qobelloang, 'me hangata bo nkuoa e le "tloaelo ea ho arabela khafetsa khothatsong e itseng, leha e se karabelo kapa karabelo" (, leq. 754). Ho theola litheko ka bobeli le tiisetso ho eketsoa hoa tšebeliso e mpe ea lithethefatsi le mathata a papali ea chelete.; ; ).

Phuputsong e teng hona joale, re ikemiselitse ho etsa lipatlisiso hore na khatello ea bongoana kapa khatello ea bongoana e ka eketsa menyetla ea mafu a lemallang ka ho eketsa mofuta oa khatello le boitšoaro bo potlakileng ho ba motho e moholo. Re sebelisitse mosebetsi oa ho theola sekhahla ka ho lieha mme re ba le maikutlo a hore liphoofolo tse pepesitsoeng khatello ea bophelo ba pele li tla bonts'a boitšoaro bo potlakileng ba ho liehisa (boitšoaro bo potlakileng) le maemo a phahameng a ho arabela ka ho mamella (boits'oaro bo khothalletsang) ha bo bapisoa le liphoofolo tse laoloang ke batho ba baholo. Re lekile liphoofolo tse tona le tse tšehali, kaha ho na le bopaki ba liphapang tsa thobalano ho nts'etsopele ea mafu a mangata a kelello (; ).

Method

Animals

Basali ba leshome le metso e robong le ba batona ba 33 ba Lister ba roetse likhoto ba kentsoe ka tlung ho tsoa ho batho ba baholo ba 11 (Charles River, Tranent, UK). Kamora ho khoesoa (Postnatal Day [PND] 21), liphoofolo li ne li lekanngoa beke le beke 'me li lula ka lihlopha tsa ba babeli le ba bararo nako eohle ea tlhahlobo ka maemo a lekanang, a bong bo le bong, litheko tse ts'oanang. ) e kentsoe ka lipalo tsa lehong (Lillico UK), ka potoloho ea lijo tse bobebe tse leshome le metso e 'meli ka lijo (standard rat chow, RM61, Special Services Diet; Lillico, Surrey, UK) le libitum tsa metsi. Mocheso le mongobo li ne li bolokiloe lipakeng tsa 43.5 ° C le 21.5 ° C le 12% le 12%, ka ho latellana. Literata tse tšeletseng li ile tsa abeloa ka tšohanyetso ho sehlopha se hatisitsoeng pele (PPS), litter tse hlano tse setseng li ile tsa sebelisoa e le taolo (sehlopha sa taolo). Ka kakaretso, basali ba 1 le banna ba 19 ba qopile sehlopha sa PPS; Basali ba 21 le banna ba 45, sehlopha se laolang. Likhoto li ile tsa bonoa ka mehele ea sesupa se sa feleng ho potoloha mohatla, mme ba bolaoa ka ho phahama ha CO2 qetellong ea liteko. Ts'ebetso tsohle li entsoe ho latela Molao oa Liphoofolo tsa lapeng tsa UK Home Office (Saense Proc inqubo) (1986) le tataiso ea melao ea lehae.

Matšoenyeho a Prepubertal

Liphoofolo li ile tsa fuoa protocol e khutšoane e fapaneng ea PPS, e seng e hlalositsoe pele (; ). Ka bokhutšoanyane, ho PND 25, liphoofolo li ile tsa ba le khatello ea ho sesa ea metsotso e 10 ka tankeng ea ho sesa e bonojoang (25 cm, bolelele ba 34 cm, 12-L) e nang le metsi a 6 L a 25 ± 1 ° C. Ka PND 26, liphoofolo li ile tsa kenngoa ka har'a methapo ea polasetiki (15 cm cm, bophara ba 5 cm) bakeng sa likarolo tse tharo tsa metsotso e 30, li arotsoe ke likhefu tsa metsotso e 30 ka lekarecheng la lapeng. Ka PND27, liphoofolo li fuoe 6 × 0.5mA, maoto a tsubang a fetang halofo tse 0.5 (e 'ngoe le e' ngoe ka 3 s) ka lebokoseng le sebetsang (30 cm × 30 cm, 25 cm e phahameng, mekoallo ea 32 e nyarosang; Lisebelisoa tsa Coulbourn, Lehigh, PA ).

Ho fokotsa Mosebetsi

Hang ha liphoofolo li se li le batho ba baholo (PND 60), li ne li tšoaroa letsatsi le leng le le leng metsotso e mehlano mme li ile tsa qala ho thibeloa lijo butle-butle ka beke e le 'ngoe. Liphoofolo li ile tsa bolokoa lipakeng tsa 5% le 85% ea boima ba tsona ba ho fepa mahala bakeng sa nako ea tlhahlobo. Liteko li etsahetse pakeng tsa lihora tsa 90 le 0800, 'me lithuto tsa motho ka mong li ile tsa lekoa ka nako e ts'oanang ea letsatsi ka phapusing e le' ngoe ea basebetsi. Liphoofolo li ne li fuoa phihlello ea mahala ea lijo bakeng sa 1500 hr letsatsi le letsatsi ka mor'a tlhahlobo.

didirisiwa

Ho sebelisitsoe likamore tse 'ne tse tšoanang tsa boemo bo sebetsang (kamore e tloaelehileng ea rat, Lisebelisoa tsa Campden, Loughborough, Leicestershire, UK). Kamoreng e 'ngoe le e' ngoe ho ne ho e-na le khanya ea ntlo e kaholimo, mabili a mabeli a neng a khona ho khutla (ka ho le letšehali le ka ho le letona) le setei sa lijo pakeng tsa likhoto tse ka fetohang lipompo tse 45 mg (li-Campden, Loughborough, Leicestershire, UK). Letlapa la lijo le ne le e-na le khanya ea lona, ​​'me lehong le benyang le ne le lumella ho kenella kahare ka har'a moqomo oa lijo. Likamore tsena li ne li kentsoe ka mabokoseng a fanang ka molumo. Sisteme ea taolo ea Whisker () e sebelisitsoe ho tsamaisa kemiso e hlophisitsoeng e tloaelehileng ea boikoetliso le mosebetsi o moholo oa theolelo oa ho lieha (karolo ea mosebetsi). Mokhahlelo oa thupelo le mosebetsi o ne o thehiloe litlalehong tse fetileng (), mme li hlalositsoe ka tsela e latelang.

Phokotso ea ho liehisa — Mohato oa Koetliso

Qalong litoeba li ne li koetliselitsoe ho hatisa levers (koetliso ea lever). Ka nako ea metsotso e 30, liphoofolo li ne li ka tobetsa mooko o leqele ntle le moeli, mochini o mong le o mong o hlahisang phello e potlakileng. Lever ha e-so ka e khutlisoa sethaleng sena, 'me liphoofolo li ile tsa tsoela pele ka kemiso ea letsatsi le letsatsi ho fihlela li fumane kakaretso e akaretsang ea li-pellets tse 50. Sena se ile sa phetoa bakeng sa lever e nepahetseng. Likhoto li ile tsa fetisetsoa thupelong ea nosepoke-mona li ile tsa koetlisetsoa hore li qale ho hlahisa tlhahiso ea motho ea lemaletseng. Nyeoe e 'ngoe le e' ngoe e ne e qala ka hore ba lepehang ba lelekoe hape kamoreng e lefifing. E mong le e mong oa 40s, ntlo le mabone a marang-rang a ne a bonesoa, ho bontša ho qaleha ha nyeoe. Taba e ne e na le boholo ba 10 s ho etsa karabo ea nosepoke, kapa nyeoe e ile ea tlosoa 'me kamore e khutlela lefifing. Haeba taba e sa hlakoloa kahare ho 10 s, khanya ea motlakase e ile ea tima 'me ea hlahisoa ke lere e le ngoe. Rato e ne e na le 10 s ho arabela ho lever, ho seng joalo lever e ne e huloa hape kamore e lefifi. Haeba rat e ne e araba, pellet e le 'ngoe e ne e tlisoa hang-hang' me leseli la motlakase le khanye ho fihlela pellet e bokelloa (kapa 10 s e ne e se e felile, mme kamore e ne e fifala). Karolong e 'ngoe le e' ngoe ea liteko, mong le e mong o ne a hlahisoa hanngoe (ka ho le letšehali le ka ho le letona), ka tatellano ea nehelano ka tšohanyetso ka har'a para ka 'ngoe. Likhoto li ile tsa koetlisetsoa ho ba tekanyetso ea liteko tse 60 tse atlehileng ho 1 hr (boholo bo ka khonehang, liteko tse 90 tse atlehileng), thupelong e le 'ngoe ka letsatsi. Ba ile ba fallisetsoa karolo ea mosebetsi.

Ho fokotsa litšenyehelo — Karolo ea Mosebetsi

Liphoofolo li ne li fuoa linako tsa letsatsi le letsatsi tse nang le lithibelo tse hlano tsa ho lieha, 'me lebato ka leng le na le liteko tse 12. Likarolo li ile tsa tsoela pele matsatsi a 19, ho netefatsa hore boitšoaro bo tsitsitseng ba motheo boa fihlelleha. Seboka se seng le se seng sa matsatsi se ne se nka metsotso e 100, 'me teko ka' ngoe e ne e nka 100 s, ho sa tsotelloe khetho ka sehlooho. Liteko li ile tsa qala ka hore levers e hlakoloe hape le mabone kantle (maemo a lipakeng). Ha ts'oarelo ea ntlo e bonts'oa ha qalo ea nyeoe e qala, 'me ka mor'a moo, lekhalo lena le ne le na le 10 s ho tlohella ka thoko ea lijo hore li hlahise tlhahiso ea motho ea nang le lever kapa ea levers. Liteko tse peli tsa pele tsa block e 'ngoe le e' ngoe ea ho lieha e bile liteko tse qobelloang - ho ile ha hlahisoa motho a le mong feela (nyeoe e le 'ngoe bakeng sa motho e mong le e mong). Haeba rat e ne e sitoa ho araba kahare ho 10 s e nang le nosepoke ho thoto ea lijo kapa ka mokoloto o kahare ho 10 s ea tlhahiso (karolo ea khetho), ho ne ho sa tsoaleha 'me lebokose le khutlisetsoa naheng ea bohanyetsi ho fihlela nyeoe e latelang e reriloe qala. Liteko tse 10 tse setseng nakong ea lieha ha e ngoe le e 'ngoe e ne e le liteko tsa khetho e se nang boikhethelo,' me li ile tsa hlahisoa. Ho arabela ho lever e le 'ngoe (e khethiloeng e le Lever A) kamehla ho ne ho fella ka ho tsamaisoa ha pellet e le 1 hanghang; lever e 'ngoe (e khethiloeng ke Lever B), phumants'o ea li-pellets tse 4 kamora ho lieha ho fapaneng (mohato oa ho lieha). Sebopeho sa batho ba tlohang ka letsohong le letšehali joalo ka ha A le B se ne se loantšana pakeng tsa lihlopha le bong. Ha lithibelo tsa lietsahala li ntse li tsoela pele, ho lieha ho ea ho moputso o moholo (4 pellets — Lever B) ho ile ha eketseha ho tloha ho 0 s ka lebokoseng la ho lieha ho fihla ho isa ho 10 s ho lebelo la bobeli la ho lieha, 20 s ho leqhubu la ho lieha la boraro, 40 s ho lebelo la ho lieha la bone, le 60 s ho block ea lietsahala. Ho lieha ho fumana moputso o monyane (1 pellet-Lever A) khafetsa e ne e le 0 s. Kamora ho lieha ho loketseng, ho qala ha lets'oao la traylight le saenneng lijo, kamora lebokose le ile la khutlisetsoa naheng ea mahareng (ea nakoana).

Boitsebiso ba Lintlha

Lintlha tsohle li ile tsa hlahlojoa ho sebelisoa mefuta e akaretsang ea li-linear (software ea JMP ea lipalo; SAS Institute, Cary, NC), 'me ea hlahlojoa hore na ke phapang efe kapa efe ea phepelo le homogeneity ea phapang. Moo likhakanyo tsena li sa kopaneng, phetoho e ile ea sebelisoa ho hlahisa tekanyo e haufi, 'me e hlokomeleha ka liphetho. Ho ile ha lekoa liphetoho tse 'maloa bakeng sa tlhaiso e' ngoe le e 'ngoe e sa hlophisoang pele ho tlhahlobo e eketsehileng,' me ho ile ha khethoa phetoho e ntle bakeng sa data e ngoe le e ngoe e hlophisitsoeng (phetoho e hlahisitseng maemo a loketseng hantle haholo le maemo a phapang e fapaneng). Boitsebiso ba liphoofolo bo ne bo kengoe ka har'a litšila le sehlopha, 'me litšila li kenelletse ka har'a sehlopha' me mantsoe ana a kenyellelitsoe e le lintlha tse sa reroang mehlaleng eohle ho ikarabella bakeng sa litekanyo tse ngata ho phoofolo e le ngoe le tšebeliso ea liphoofolo tse ngata bakeng sa litšila). Tšebelisano lipakeng tsa mantsoe 'ohle ka har'a mofuta o mong le o mong e ne e kengoe. Liteko tsa bohlokoa tsa Post hoc Tukey ka botšepehi li ile tsa sebelisoa ho etsa lipatlisiso tse ling tsa bohlokoa, 'me ho hlahisoa sephetho sa mantlha le sa bohlokoa sengoloeng. Mokhoa oa thibelo ea lijo o ne o reretsoe ho theola liphokotso tse tšoanang ho boima ba botona le botšehali, empa ho bolela boima ba 'mele e ne e le 15% ho ba batona le 10% ho basali. Ka hona, ho theola boima ba liperesente ho kenyelelitsoe le litlhahlobisong tsohle, empa ha hoa ka ha bolela esale pele boits'oaro (ho feta ka thobalano). Ho lekola phihlello ea mesebetsi karolong ea thupelo, ho ile ha hlahlojoa litlamorao tsa sehlopha le tsa thobalano ho fumana likhatiso tse 50 tse tlohetsoeng le tse 50, le ho tlatsa liteko tse 60 tse nepahetseng sebokeng se le seng nakong ea thupelo ea nalepoke. Ho lekola ho ithuta nakong ea karolo ea mosebetsi, phello ea seboka, sehlopha, thobalano le thibelo ea palo ea likarabo bakeng sa moputso o moholo (Lever B) le kakaretso ea likhetho li ile tsa hlahlojoa. Karabo e ne e tsitsitse (ke hore, "letsatsi" e ne e se e se ntho ea bohlokoa mme boits'oaro bo tsitsitseng bo fihlellehile) bakeng sa lihlopha le bong ka Sesebelisoa 11, ka hona tlhahlobisong e latelang, tlhaiso-leseling e tsoang ho Karolo ea 12 ho isa ho ea 19 e sebelisitsoe feela. Ho hlahloba tšusumetso le ho nka karolo mohatong oa mesebetsi, re theha mehlala ea ho sekaseka phello ea sehlopha, thobalano, le ho lieha ha palo ea liteko tse qalileng (nosepoke ho kena ka terakeng ea lijo ho qala teko le tlhahiso ea ba-levers) le palo e felletseng ea liteko e arabetse (a khetha lever hang ha a hlahisoa). Ho lekola karabelo ea karabelo, litlamorao tsa sehlopha, thobalano le thibelo ea ho lieha ho qala liteko, ho arabela levers hang ha li hlahisoa, 'me ho bokella moputso ho ile hoa hlahlojoa. Tiisetso e ile ea hlahlojoa ka mehlala e fuputsang phello ea sehlopha, thobalano le thibelo ea nako ka nako e sebelisitsoeng ka leqekae kaharepeng ea lijo nakong ea khetho, mohato oa ho lieha (o arotsoe ke boiphihlelo ba ho lieha), nako ea maiketsetso (e arotsoe ke karohano ea nako e telele), le moputso karolo ea pokello. Ha lipalo tsa liteko tse arabeloang li ne li le tlase haholo bakeng sa lihlopha tse ling lithutong tsa ho lieha tsa morao-rao, ho ile ha sebelisoa maeto a bobeli ho etsa lipatlisiso mabapi le kamano lipakeng tsa palo e felletseng ea likarabo le liperesente tsa likarabo bakeng sa moputso o moholo (Lever B). Maemong a karabelo a 0 %-40%, ho bile le khokahano e nepahetseng pakeng tsa likarabo le karolo ea likarabo tse neng li le bakeng sa moputso o moholo. Ka hona, ho ile ha hlahlojoa feela lithibelo tsa ho lieha tse 40% 'me ka holimo li ile tsa sebelisoa tlhahlobisong e latelang: Ho lekola ho susumetsoa hoa khetho (ho theola sekhahla) litlamorao tsa thobalano, sekhahla sa ho lieha, le sehlopha ka tekanyo ea likarabo bakeng sa moputso o moholo li lekiloe. Leha ho le joalo, ho bohlokoa ho hlokomela hore kenyelletso ea liteko tse sa arabeloang ka tlase ho 40% ha e fetole bohlokoa ba liphetho. Mohlala oa ho qetela o ile oa etsa lipatlisiso ka litlamorao tsa sehlopha, thobalano le lilemo ho boima ba 'mele pele liteko tsa batho ba baholo li qala.

Results

Karolo ea Koetliso

Ho ikoetlisa ka matsoho

Litšoantšo 1a 'me And1b1b bonts'a palo ea lithuto tse nkuoeng bakeng sa liphoofolo ho fumana koetliso ea lesere le letšehali. Ha ho PPS kapa thobalano e ammeng ho ithuta ho tobetsa lever ea pele (ka ho le letšehali) bakeng sa moputso (Box-Cox e fetotsoe; ); sehlopha, F(1, 5.65) = 0.0001, p = .99; thobalano, F(1, 35.26) = 0.005, p = .95; Sehlopha sa thobalano, F(1, 35.26) = 2.28, p = .14. Leha ho le joalo, basali ba laoloang ba ile ba nka linako tse fokolang ho feta banna ba laolang ho ithuta ho tobetsa ea bobeli (ka ho le letona) makhetlo a 50; Log e fetotsoe, Sehlopha sa thobalano, F(1, 47.15) = 6.51, p = .01, leha ho ne ho se na litlamorao tsa sehlopha, F(1, 6.43) = 0.28, p = .61, kapa thobalano, F(1, 47.15) = 0.45, p = .51.

Setšoantšo sa 1  

Palo ea likarolo tsa taolo (Con) le tse hatisitsoeng esale pele (PPS) likhoto tsa banna le basali ho (a) ho ithuta ho tobetsa lever ea pele (ka ho le letšehali) bakeng sa moputso, (b) ho ithuta ho tobetsa ea bobeli (ho le letona) bakeng sa moputso , le (c) ho fihlella litekanyetso lithupelong tsa nalepoke. ...

Koetliso ea Nosepoke — ho ithuta

Setšoantšo sa 1c e bontša hore basali ba PPS ba nkile nako e telele ho feta ho laola basali le ba batona kaofela ho fihlela boemo ba mosebetsi oa nalepoke; sehlopha, F(1, 25.1) = 4.7, p = .035; thobalano, F(1, 54.9) = 10.28, p = .002; Sehlopha sa thobalano, F(1, 23.94) = 4.48, p = .04.

Mokhahlelo oa

Ithuta

Palo ea mechine ea khatiso ea lever bakeng sa moputso o moholo (Lever B) e ile ea tsitsa (ke hore, seboka e ne e se e se ntho ea bohlokoa) ke Karolo ea 6 ho basali ba taolo, Karolo ea 8 ho basali ba PPS, Sesebelisoa 4 ho ba batona ba taolo, le Setsi sa 3 ho banna ba PPS ; arcsine e fetotsoeng: Karolo ea thuto ea sehlopha x F(18, 4507) = 2.16, p = .003. Ho arabela ka kakaretso ho ile ha fetoha ho tsitsitseng (ke hore, seboka ha e sa le ntho ea bohlokoa) ke Karolo ea 11 lihlopheng le ho tsa bong bo fapaneng; arcsine e fetotsoe, letsatsi, F(18, 4507) = 2.12, p = .004.

Palo ea liteko e qalile

Setšoantšo sa 2a e bontša hore liphoofolo li qalile liteko tse fokolang (ka ho kenella kahareng ea lijo) ha lithibelo li ntse li tsoela pele; arcsine e fetotsoeng, block ea lietsiso, F(4, 2012) = 119.23, p <.0001. Le ha mokhoa o hlakileng oa ho fokotseha ha lits'ebetso o ne o fapana lipakeng tsa lihlopha, ha oa ka oa fetoloa ke PPS; sehlopha, F (1, 7.33) = 1.28, p = .29; thobalano, F(1, 46.91) = 0.003, p = .96; kapa Sehlopha sa thobalano F (1, 38.04) = 0.04, p = .85.

Setšoantšo sa 2  

Palo e lekanang ea liteko (a) tse qaliloeng le (b) tse arabelloang ke taolo (Con) le likhakanyo tsa pelehi (PPS) tsa banna le basali. Ho hlahisoa lintlha tse ncha. Liphoso tsa liphoso li emela phoso e le 'ngoe.

Palo ea liteko e arabetsoe

Setšoantšo sa 2b e bonts'a hore basali ba PPS ba arabetse hanyane ho li-levers tse hlahisitsoeng ho feta lihlopha tsohle tse ling nakong ea Delay Blocks 40 le 60, athe banna ba taolo ba ile ba arabela ho feta lihlopha tse ling tsohle nakong ea Delay Blocks 20 le 40; arcsine e fetotsoeng, Sehlopha sa x ho kopanela liphate × ho lieha ho thibela, F(4, 2012) = 3.66, p = .006. Basali ba sithabetseng ba arabile hanyane ha ho lieha ho eketseha, basali ba laolehang le banna ba sithabetseng ba arabela hanyane ho fihlela ho lieha metsotsoana e 40, mme ho sena phapang pakeng tsa lietsahala tse 40 le 60, mme banna ba laolehang ba arabile ho lieha ha metsotso e 0 le 10 ho feta ho lieha ho hong, liehisoa ke ho lieha ha 40 le 60 ho feta litšitiso tse ling tsohle; Sehlopha x Ho Kopana ho Kopana le Ho Reroha F(4, 2,012) = 3.66, p = .006.

Methati

Liphoofolo tsohle li ile tsa qala liteko (ho qala teko ka ho kenella kaharepeng ea lijo) butle butle molemong oa ho qetela (60) ha li bapisoa le lebelo la ho lieha la 0 (XNUMX); log e fetotsoe, block block, F(4, 3,674) = 29.44, p <.0001, empa sena ha sea angoa ke PPS; sehlopha, F(1, 0.28) = 0.18, p = .83; thobalano, F(1, 7.17) = 0.67, p = .44; kapa Sehlopha sa thobalano F(1, 9.9) = 1.01, p = .34).

Setšoantšo sa 3a e bonts'a karabelo ea moraorao ha ho hlahisitsoe nyeoe (kamora ho qaloa ha nyeoe). Karabelo ea karabelo e ile ea eketseha bakeng sa liphoofolo tsohle ha lithibelo tsa lietsahala li ntse li tsoela pele, leha mokhoa o tšoanang o ne o fapana lipakeng tsa lihlopha le bong; log e fetotsoe, block block, F(4, 1,892) = 88.33, p <.0001. Basali ba PPS ba ne ba e-na le nako e telele ea ho arabela ho feta banna ba PPS ho Delay Blocks 20 le 40, hape le ho feta ho laola basali le banna bohle setopong sa ho qetela se liehang (60); log e fetotsoe, Group × Delay Block × Thobalano, F(4, 1,892) = 2.44, p = .045. Ka kakaretso, tse tšehali li ne li e-na le karabelo e telele ho feta ea banna; thobalano, F (1, 41.69) = 4.59, p = .04.

Setšoantšo sa 3  

(a) Karabelo ea karabelo le (b) nako e sebelisitsoeng ho se sebetse nakong ea khetho bakeng sa taolo (Con) le likhakanyo tsa khatello (PPS) tsa banna le basali. Ho hlahisoa lintlha tse ncha. Liphoso tsa liphoso li emela phoso e le 'ngoe.

Basali ba ne ba e-na le mokhoa o mongata oa ho bokella meputso ho feta banna ba Delay Block 60, mme basali ba ne ba e-na le pokello ea nako e telele ho Delay Block 60 ho feta Delay Block 0; Matla a fetotsoeng, Delay Block × Thobalano, F(4, 3,194) = 242, p = .046.

Ho se ts'oarelle — boitšoaro bo qobelloang

Litšoantšo 3b e bonts'a nako eo liphoofolo li qetetseng ho qeta nakong ea khetho (tlhahiso ea lever). Basali ba PPS ba sebelisitsoe nako e telele haholo ho feta ho laola basali le banna bohle ba kenang kahareng ea lijo nakong ea Delay Blocks 40 le 60; motlakase o fetotsoeng, Sehlopha x O lieha ho thibela × Thobalano, F(4, 1,876) = 2.57, p = .04. Liphoofolo tsohle li ile tsa eketsa nako ha li qeta ho senya, ha lithibelo li ntse li tsoela pele; thibelo ea nako, F(4, 1,892) = 16.37, p <.0001. Ho ne ho se na tšusumetso e kholo ea PPS; sehlopha, F(1, 8.26) = 0.19, p = .67; thobalano, F(1, 41.33) = 3.84, p = .06; kapa Sehlopha sa thobalano F (1, 44.81) = 2.11, p = .15.

Nakong ea nako ea ho lieha, liphoofolo li qetile nako e fokolang ho sobetsa ha lithibelo tsa lietsahala li eketseha ho tloha ho 0 ho isa ho 40, empa ho ne ho sena phapang lipakeng tsa Delay Blocks 40 le 60; thibelo ea nako, F(3, 2,859) = 58.29, p <.0001. Ho ne ho se phello ea sehlopha, F(1,8.03) = 0.003, p = .96; thobalano, F(1, 45.73) = 3.04, p = .09; kapa Sehlopha sa thobalano F(1, 46.69) = 0.03, p = .87, ka nako e sebelisitsoeng ho se sebetse nakong ea karolelano ea ho lieha.

Basali ba sebelisitse nako e nyane nakong e sa sebetseng (ITI) ho Delay Blocks 40 le 60 ha ba bapisoa le lithibelo tse ling kaofela, athe ba batona ba qeta nako e nyane ba sa hlapolle lithibelo tsa Delay 20, 40, le 60 ho isa ho 0 le 10; Log e fetotsoe, Delay Block × Ho kopanela liphate, F(4, 3,676) = 3.4, p = .009. Ho ne ho se na liphapang lipakeng tsa lihlopha, F(1, 1.16) = 1.12, p = .46, kapa bong, F(1, 19.88) = 0.34, p = .57, ka nako e sebelisitsoeng ho sa natefeloe nakong ea ITI. Nakong ea pokello ea meputso, liphoofolo li sebelisitse nako e nyane ho etsa joalo ha lithibelo tsa lietsahala li tsoetse pele ho tloha ho 0 ho isa ho 20, empa ho ne ho sena phapang lipakeng tsa Delay Blocks 20, 40, le 60; thibelo ea nako, F(4, 3,686) = 86.75, p <.0001. Ho ne ho se na phello ea PPS; sehlopha, F(1, 47) = 0.02, p = .89; thobalano, F(1, 47.01) = 0.95, p = .34; kapa Sehlopha sa thobalano F(1, 47) = 0.15, p = .7.

Ho lieha ho theola sekhahla — boitšoaro bo sa potlakeheng

Setšoantšo sa 4 e bonts'a likhetho tsa liperesente tse tsa moputso o moholo ha ho lieha ho fumana moputso o moholo ho eketseha. Ba batona ba khethile moputso o moholo ha o lieha ho lieha, athe basali ba khethile moputso o tlase ha litšeho li eketseha ho ba metsotsoana e 40, empa ba sa bontše phapang lipakeng tsa ho lieha ha metsotsoana e 40 le 60; Thobalano F(4, 1,615) = 3.18, p = .004; bona Setšoantšo sa 4. Ho ne ho se na litlamorao tse kholo tsa PPS; sehlopha, F(1, 8.42) = 0.02, p = .88; thobalano, F(1, 42.18) = 3.68, p = .06; kapa Sehlopha sa thobalano F(1, 44.83) = 0.12, p = .73, khetho ea moputso o moholo oa liperesente.

Setšoantšo sa 4  

Khetho ea peresente ea moputso o moholo joalo ka ho lieha ho eketseha ha moputso o moholo bakeng sa taolo (Con) le likhatello tse fetisitsoeng (PPS) tsa banna le basali. Ho hlahisoa lintlha tse ncha. Liphoso tsa liphoso li emela phoso e le 'ngoe.

Boima ba 'mele PND 21-56

Boima ba 'mele (Lebokose le Cox le fetotsoeng) le ne le sa fapana lipakeng tsa beke beke pele PPS e fanoa (PND 21); leha ho le joalo, PPS e ile ea fella ka ho fokotsa boima ba 'mele ho liphoofolo tse tona le tse tšehali ka PND 28, mme sena sa tšoarella ho fihlela PND 56 ho basali le PND 42 ho ba batona; Ho etsa thobalano le beke beke le beke F(5, 228.1) = 2.59, p = .03; bona Setšoantšo sa 5. Tse tona li ne li le boima ho feta basali ho PND 49; Ho etsa thobalano le beke beke le beke F(5, 228.1) = 259, p = .03; bona Setšoantšo sa 5.

Setšoantšo sa 5  

Litekanyo tsa taolo (Con) le khatiso ea li-preubertally (PPS) (a) basali le (b) likhoto tsa banna. Ho hlahisoa lintlha tse ncha. Liphoso tsa liphoso li emela phoso e le 'ngoe.

Puisano

Ho pepesehela PPS ho hlahisitse boitšoaro bo tlamang ba batšehali (perseverative nosepoking), athe ba batona ba nang le PPS ba ne ba sa fapana le taolo. PPS ha ea ka ea hlahisa boitšoaro bo sa potlakiseng ho tsa bong bo bong, kaha lihlopha tsohle li bontšitse litheko tse ts'oanang tsa ho liehisa ha ho lieha ho fumana moputso o moholo ho eketseha. Ho ithuta ho ne ho senyehile ho basali ba PPS nakong ea koetliso ea mosebetsi le karolo e kholo, phello e sa bonoeng ho banna ba PPS. Liphoofolo tsa PPS tsa ba batona le ba batšehali li ile tsa imeloa haholo ho feta taolo nakong ea PND 28-56 (basali) le PND 28-42 (banna), phello e tlalehiloeng mohlaleng ona (; ; ).

Ithuta

Basali ba nang le PPS ba bonts'itse mathata a ho ithuta nakong ea thupelo ea mosebetsi, ho nka nako e telele haholo ho feta sehlopha leha e le sefe ho fihlela tlhahlobo nakong ea thupelo ea nalepoke. Khaello ena e ne e sa bonoe ho banna ba nang le PPS kapa molemong oa boikoetliso ba lever o fetileng. Sena se bonts'a basali ba PPS ba ne ba sa senyeha feela ha mekhatlo e neng e fetoha lipakeng tsa ts'usumetso: Boikoetliso ba Lever bo ne bo hloka hore phoofolo e tobane feela le lever hore e fumane moputso, athe koetliso ea nosepoke e hloka karabelo ea nosepoke (ho araba ntlo le teraka leseli) ka mochine oa khatiso. Basali ba PPS le bona ba nkile nako e telele ho feta sehlopha leha e le sefe ho khetha khetho ea meputso (e kholo ho fapana le e nyane) mosebetsing o moholo, ba fana ka maikutlo a ho sitisoa ha ho ithuta mekhatlo e rarahaneng ho feta. Mekhoa ea Neural e sebelisang mekhoa e bonolo e sebetsanang le maemo a mang a rarahaneng a sebetsang, e fapana ka tlhaho.). Leha ho le joalo, ho na le bopaki ba hore striatum e ka tlase e sebetsang e sebetsang ka kakaretso (; ). Boithuto bo fetileng bo bontšitse PPS e sitisa ho ithuta tlasa khatello ea maikutlo maemong a mabeli a ts'ireletso, mosebetsi le ona o thehiloeng ho striatum (; ). Ho kopantsoe le thuto ea hona joale, sena se fana ka maikutlo a hore ho pepesetsoa PPS ho ka sitisa ts'ebetso ea striatal, ho fella ka thuto e sa sebetseng. Leha ho le joalo, liteko tse ling li hlokahala ho fuputsa mohopolo ona ho ea pele. Mabapi le mathata a ho lemalla, ts'ebetso ea dorsal e kentse letsoho ho nts'etsopele ea boitšoaro bo khothalletsang ba ho sebelisa lithethefatsi, ka lebaka la karolo ea bona ho ts'usumetso ea karabelo ea ho ithuta (). Pejana re fumane hore likhoto tsa banna le tsa basali tse nang le PPS li bonts'a boitšoaro bo ntlafalitsoeng ba mofuta oa ho tšoenyeha (); leha ho le joalo, ha re lumele hore matšoenyeho a ntlafalitsoeng a ne a ikarabella bakeng sa mathata a ho ithuta a bonoang ho basali ba hatelletsoeng: basali ba PPS ba ile ba ithuta mosebetsi oa pele oa boikoetliso hammoho le lihlopha tse ling (khatiso e bonolo ea lever ho fumana moputso oa lijo ho tsoa mokotleng oa moputso), ts'enyeho ena e ne e sa bonoe ho banna. Liphoofolo li ne li fallisoa mesebetsing e meholo ha feela li se li fihlile mothating oa ho ithuta, kahoo ho lieha ho ithuta ho lokela ho se ke ha ama ts'ebetso mohato oa morao oa mosebetsi.

Boitšoaro bo Matla

Ho pepesehela PPS ho felletse ka mofuta o qobelloang oa boitšoaro ho basali: Ba entse likarabo tse fokolang ho ba levers mme ho fapana le moo ba ile ba qeta nako e ngata ba sa tsebe letho ka leqebeng la lijo nakong ea Delay Blocks 40 le 60. Mona, basali ba PPS ba bonahala ba tiisetsa ka boitšoaro bo seng bo sa lokelang. bakeng sa boemo (ho kheloha ka leqhepheng la lijo ho e-na le ho khetha lever) joalo ka ho lieha ho nyolleloa moputsong o moholo. Tiisetso e atoloha ho eketseha ha litlhoko tsa ho eketseha ha mohopolo tse sebetsang, tse ka hlalosang lebaka leo phello ena e bonoang feela ho Delay Blocks 40 le 60 (). Boitšoaro bo qobelloang (ho kenyeletsa mamello) le boits'oaro bo sa tsotelleng bo bonoa maemong a mangata a kelello, ho kenyelletsa tšebeliso e mpe ea lithethefatsi le mathata a ho becha (; ; ; ). Hore na boitšoaro bo qobelloang le bo sa susumetseng ke sesosa kapa phello ea mafu ana ke taba ea ngangisano e itseng. Phuputso ea morao-rao e fumane khokahano e nepahetseng lipakeng tsa likhathatso tsa bana le liphoso tsa mamello ho Tlhahlobo ea Card Card ea Sorton ho sechaba se phetseng hantle (se kopantsoeng le catechol-O-methyltransferase genotype; ). Ha e kopantsoe le thuto e teng hona joale, sena se fana ka maikutlo a hore litsietsi tsa bongoana li ka kenya letsoho ho holisa mafu a lemalloang ka ho eketsa boitšoaro bo hatellang hamorao bophelong. Hoa thahasellisa hore khatello ea karohano ea bo-mme kapa basali (ho PND 9) e fella ka boitšoaro bo mamellehang litšoantšong tsa banna le basali, athe khatello ea batsoala ha e (; ), ho fana ka maikutlo a hore nako le mofuta oa tlokotsi li bohlokoa ho khetholla sephetho sa ho ba motho e moholo.

Liphoofolo tsohle li ile tsa qala hanyane ka hanyane mme tsa arabela hanyane ka hanyane litekong tse fokolang ha lithibelo tsa lietsahala li ntse li tsoela pele, tse ka bonts'ang ho eketseha ha satiety ha meputso e fumanoa. Leha ho le joalo, ho ne ho se na phapang lipakeng tsa lihlopha le bong ka bongata ba liteko tse qalileng, ho fana ka maikutlo a hore lihlopha tsohle li ne li susumetsoa ka mokhoa o ts'oanang ho nka karolo mosebetsing ona ha li-block tsa nakoana li ntse li tsoela pele. E ka ba ho khahlisang ho khutlisa ho lieha ha teko ena le ho fumana hore na mekhoa e tšoanang ea ho araba le ho tiisetsa e bonoa, haholo hobane lithuto tsa morao-rao li fumane hore mokhoa oo likhahla li fetohileng ka oona o ka fetola ho lieha ho theola boits'oaro (haholo khetho ea ba baholo matlafatsa; ; ).

Boitšoaro bo Boholo

Ha re fumane bopaki ba hore PPS e eketsa ho iketelletsa pele, joalo ka ha ho lekantsoe mosebetsing oa ho theola sekhahla. Ka lehlakoreng le leng, khatello ea karohano ea bo-mme nakong ea PND ea 2 - 21 ka litoeba e bakile ho fokotseha ha khetho (), hape fana ka maikutlo a karolo ea bohlokoa bakeng sa nako le mofuta oa koluoa. Boithuto ho batho bo hlahisitse liphetho tse fapaneng, ha ba bang ba fumana litheolelo tse fokotsang tsa ho lieha, ba bang ba sa fumane phetoho kamora ho pepesetsoa litsietsing tsa bana (; ). Tlhaloso e ka bang teng mabapi le phapang ena ke hore nako e tobileng ea tlokotsi ea bana ha e nkuoe hloko (mohlala, pele ho nako le morao ho bongoana). Ho boetse ho na le bopaki ba hore genotype (mohlala, D4 dopamine receptor variants) e ka sebelisana le mathata a bongoana ho khetholla ho ikhetholla ho khethollo (). Ho ts'oaroa ke ts'ebetso e kopantsoeng, 'me ho pepesetsoa khatello ea bokhachane le PPS ka litoeba, le tsietsing ea bongoana bathong, li tsamaellana le ho eketseha ha likoloi, tse ka eketsang kotsi ea ho qala le ho boloka mafu a ho lemalla (; ; ). Joalo ka ha ts'usumetso e le moaho o kopanetsoeng, tlhaloso e 'ngoe e ka bang teng bakeng sa karohano e fumanehang ka har'a lingoliloeng ke tsela eo ho ts'oaroa ho lekantsoeng ho lekantsoeng ka eona, ka mohlala, khetho le khahlano le ho khanneloa ke koloi. Ka karolelano, liphoofolo li khetha moputso o moholo 80% ea nako ho Delay Block 0 (ha ho ts'oarello moputso o moholo kapa o monyane). Boemo bona ba khetho hangata bo bonoa setulong sa pele sa ho liehisa lithuto ka litoeba (). Re fana ka maikutlo a hore liphoofolo li ke ke tsa khetha lekhalo lena la 100% ea nako hobane li ka etsahalla sampuli e ngoe.

Pharologanyo ya thobalano

Ho pepesehela PPS ho felletse ka karabelo e tiileng ho liphoofolo tsa basali empa eseng tsa banna, ho ts'ehetsa maikutlo a hore ho na le liphapang tsa botona le botšehali ho nts'etsopele ea mathata a amanang le neuropsychiatric kamora ho pepesetsoa khatello ea bophelo ba pele. Sena se totobatsa tlhokahalo ea ho nahana ka ba batona le ba batšehali ka thoko ho mehlala ea mathata a neuropsychiatric (; ).

Ho laola basali ho ithutile ka potlako ho feta ho laola banna nakong ea thupelo ea lever, athe ba batona ba fumana lipapatso tse tsitsitseng tsa moputso o moholo kapele ho feta tse tšehali. Lithuto tsa pejana li kile tsa fumana tšehali, ka linako tse ling e le monna, monyetla mesebetsing e fapa-fapaneng ea ho ithuta le ho hopola, le mekhoa e ka tlas'a mohopolo ho nahanoang hore e kenyelletsa phapang ho li-hormone tsa thobalano le khatello ea maikutlo, lits'ebetso tse amanang le neurogeneis, mabaka a neurotrophic (mohlala, neurotrophic factor). ) le phapang ea boholo ba li-receptor tse fapaneng bokong, ho kenyelletsa dopamine le nerve ukukhula factor factor receptors (; ). Leha ho le joalo, ha ho hlake hore na hobaneng phapang ena e le teng thutong ea joale.

fihlela qeto e

Ho pepesetsoa protocol e khutšoane e fapaneng ea PPS ho felletse ka mamello e eketsehileng le thuto e sa sebetseng lithutong tsa basali ba baholo. Sena se fana ka maikutlo a hore litsietsi tsa bongoana li ka kenya letsoho ho holiseng le ho boloka mafu a lemalloang ka ho eketsa boitšoaro bo khothalletsang basali. Boithuto bo eketsehileng bo hlokahala hore bo hlakise ka botlalo mekhoa e tataisang liphetoho tsena, le ho fana ka lipheo tsa ho kenella ha kalafo.

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