LITLHAHISO: Seo se bonts'ang ke hore likhoto li rata ho becha, ka hona ke monyetla oa ho becha. E bonts'a hape hore liphoso tse haufi li ka eketsa karabelo ea dopamine. Joalokaha ho boletsoe, haeba papali ea chelete e ka fetola boko ba maoto le matsoho, ka sebele litšoantšo tsa bootsoa li ka khona. Hape ke khopotso ea hore re arolelana mesebetsi ea mantlha ea maoto le bo-motsoala ba rona ba anyesang.
Neuropsychopharmacology. 2011 April; 36(5): 913-925.
Lefapha la Psychology, Univesithi ea British Columbia, Vancouver, BC, Canada.
Litlaleho tse nang le kelello tsa papali ea chelete li fana ka maikutlo a hore boiphihlelo ba hoo e ka bang ba hapileng seo ho thoeng ke 'haufi-ufi'-ba khothaletsa papali e tsoelang pele le ho akofisa nts'etsopele ea papali ea chelete ea papali ea chelete (PG) ho batho ba tlokotsing. Tlhaloso e le 'ngoe ea phello ena ke hore lipehelo tse haufi li saena liphetho tse tlang tsa ho hapa le ho eketsa tebello ea moputso, ho matlafatsa papali e ngoe. Ho tseba lits'ebetso tsa methapo ea pelo tse tsamaisang papali ea papali ea chelete ho ka thusa ho nts'etsapele kalafo e sebetsang ho PG. Re na le sepheo sena kelellong, re ile ra lekola tšebetso ea likhoto ho mofuta oa papali ea papali ea papali, mofuta oa papali ea chelete eo ho eona liketsahalo tse haufi haholo li hlahelletseng. Lihlooho li arabetse letotong la mabone a mararo a phatsimang, a sa ts'oaneng le mabili a mochini oa slot, a etsa hore mabone a `` bule '' kapa 'a tima'. Sephetho se hapileng se ile sa tšoauoa haeba mabone a mararo a ne a bonesitsoe. Qetellong ea teko e 'ngoe le e' ngoe, likhoto li ile tsa khetha pakeng tsa ho arabela ho 'bokella' lever, ho fella ka moputso ho liteko tsa win, empa kotlo ea nako litekong tsa tahlehelo, kapa ho qala teko e ncha.
Lits'ila li bonts'itse khetho ea letšoao la mokoloto ha mabone a mabeli le a mararo a bonesitsoe, e bonts'ang tebello e kholo ea tebello ea meputso kamora ho hloloheloa ho tšoanang le oa. Likarabo tse fosahetseng tsa ho bokella li ile tsa eketsoa ke amphetamine le D (2) li-receptor agonist quinpirole, empa eseng ka D (1) receptor agonist SKF 81297 kapa receptor subtype khetha antds.
Lintlha tsena li fana ka tlhahiso ea hore dopamine e fetole litebello tsa moputso ka mor'a boiphihlelo ba hoo e ka bang ho hapa nakong ea papali ea slot mochini, ka ts'ebetso ho li-receptors tsa D (2), 'me sena se ka etsa hore ho be le ts'ebetso e ntlafatsang le ho potlakisa papali ea chelete.
SELELEKELA
Batho ba becha leha ba tseba hore mathata a teng molemong oa ntlo. Boitšoaro bona bo felletse ka indasteri ea papali ea chelete e etsang phaello e tsoelang pele ho hola le nakong ea moruo. Ha papali ea chelete e ntse e ata le ho amoheleha sechabeng, ngangisano ea sechaba e ntse e hola mabapi le litlamorao tsa eona tse ka bang kotsi (Shaffer le Korn, 2002). Batho ba bangata ba thabela papali ea chelete ea boithabiso ha e na litlamorao. Leha ho le joalo, bakeng sa bonyenyane bo boholo, papali ea chelete e fetoha boitšoaro bo qobelloang le ba kelello bo ts'oanang le ts'ebeliso e mpe ea lithethefatsi (Potenza, 2008), le likhakanyo tsa hajoale mabapi le phallo ea bophelo ba papali ea papali ea tšenyo ea nako (PG) li fapana pakeng tsa 0.2-2% (Shaffer et al a, 1999; Petry et al a, 2005) .Ka ho hlahloba hore na hobaneng batho ba becha ka hona ho ka fana ka leseli la bohlokoa boitshwarong bo tlatselletsang, hammoho le ho nts'etsapele tsebo ea rona ea ho etsa liqeto tse sa tloaelehang kapa tse sa utloahaleng.
Litlaleho tse nang le temohisiso ea PG li fana ka maikutlo a hore papali ea chelete e ts'oaroa ka lebaka la
litumelo tse fosahetseng kapa tse fosahetseng mabapi le boikemelo ba liphetho tsa papali ea chelete, ho kenella ka lehlohonolo, le bokhoni ba tsebo ea motho ea ho fana ka katleho ha papali ea chelete (Ladouceur et al a, 1988; Toneatto et al a, 1997).
Khopolo-taba e 'ngoe e tummeng ke hore boiphihlelo ba hoo e batlang e le ba win-bao ho thoeng ke' haufi haholo '— bo ka matlafatsa ts'ebetso ea papali ea chelete,' me bo ka potlakisa nts'etsopele ea PG ea motho ea hlaselehang habonolo.s (Reid, 1986; Griffiths, 1991; Clark, 2010). Liketsahalo tse haufinyane li ka hlahisa liphetoho tse tšoanang kelellong le 'meleng joalo ka litholoana tse hapileng (Griffiths, 1991). Metsoako e haufinyane e ka eketsa tebello ea moputso ka lebaka la ho ts'oana ha bona le ho hapa, ba etsa hore papali e tsoelepele monyetla oa ho feta (Reid, 1986). Tumellanong le mohopolo ona, liphoso tse haufi li bontšitsoe ho eketsa takatso ea ho tsoela pele ho becha (Kassinove le Schare, 2001; Cote et al a, 2003; MacLin et al a, 2007) le ho ntlafatsa ts'ebetso ea neural kahare bokong le bohareng ba moea (le ventral striatum (Clark et al a, 2009; Habib le Dixon, 2010). Litlhokomeliso tsena li fana ka maikutlo a hore mehala e haufinyane e fana ka letšoao le letle la moputso le kentsoeng ke liserekisi tsa dopaminergic tse tšehetsang tebello ea moputso le ho matlafatsa thuto (Schultz et al a, 1997; Schultz, 1998; Fiorillo et al a, 2003).
Ho kenyelletsa ts'ebetso ena e akaretsang, lithethefatsi tse fetolang ts'ebetso ea dopaminergic li bontšitsoe ho fetola papali ea slot-Machine, mofuta oa papali ea chelete eo ho haelloang haholo haholo ho ona.. Sethethefatsi sa psychostimulant
amphetamine, e ka etsang liketso tsa dopamine (DA), e ka eketseha
Khothatso ea ho bapala metjeko e tsamaeang (Zack le Poulos, 2004), athe khethoa D2 receptor antagonist, haloperidol, e ka ntlafatsa thepa e ruisang ea boitšoaro bo joalo (Zack le Poulos, 2007). Ho saena le ho hlonama ha DA ke karolo ea bohlokoa ea bokhoba ba lithethefatsi, 'me e khannela litšitiso tse eketsehang tsa litheko tse kengoang ke lithethefatsi tse sebelisang matla a ho batla lithethefatsi (Robinson le Berridge, 1993). Ho elelloa hore mochini oa slot o bapala hangata ke ntho e atileng ho becha ho becha ho lebisitse tlhahiso ea hore papali ea chelete ea slot e ka ba boima haholo (Breen le Zimmerman, 2002; Choliz, 2010). Ka ha lipatlisiso tsa liphoofolo li hatetse pele kutlwisiso ea rona mabapi le boits'oaro bo lebisitsoeng ho sepheo le bokhoba, papali ea liphoofolo ea papali ea slot e ka kenya letsoho haholo lipatlisisong tsa ho becha (Potenza, 2009), mme tlaleho ea pele e bonts'a hore likhoto li khona ho ithuta mosebetsi o joalo (Peters et al a, 2010).
Ho akaretsa, bopaki ba hona joale bo bonts'a hore ts'ebetso ea DA e kanna ea ameha ka matla ho ntlafatsong ea papali ea methapo ea methapo ea methapo, le ponts'ong ea phello e haufi. ka lebaka la karolo e bohlokoa ho supeng tebello ea moputso. Ho lekola lits'ebetso tsa methapo e thehileng tebello ea moputso ha papali ea chelete e ka thusa ho ntlafatseng kalafo e sebetsang ea PG. Re sebelisa mofuta o mocha oa "rodent slot Machine paradigm", ka hona re ne re ikemiselitse ho tseba hore na boiphihlelo ba 'hoo e batlang bo hapile' bo ka eketsa polelo ea boits'epo ba meputso ka likhoto ka tsela e ananang le phello e haufi-ufi, le hore na boitšoaro bo joalo bo ka fetoloa ke dopaminergic lithethefatsi.
LISEBELISOA LE MEKHOA
Lihlooho
Lihlooho e ne e le likhoto tsa 16 tsa banna ba Long Evans (Charles River Laboratories, St Constant, NSW, Canada) e boima ba 250-275 g qalong oa ho etsa tlhahlobo. Lihlooho e ne e le lijo tse lumelloang ho 85% tsa boima ba tsona ba ho fepa mahala le ho bo hlokomela 14 g rat chow fuoa letsatsi le letsatsi. Metsi a ne a le teng ad libitum. Liphoofolo tsohle li ne li lutse ka bobeli ka kamoreng ea kolone e laoloang ke maemo a leholimo e hlokometsoeng 21 ° C ho 12 e khutlang. h
kemiso e bobebe-e lefifi (mabone a tima 0800). Teko ea boits'oaro le matlo
li ne li tsamaisana le Lekhotla la Canada la Tlhokomelo ea Liphoofolo le tsona kaofela
protocol ea liteko e amohetsoe ke Komiti ea Tlhokomelo ea Liphoofolo ea UBC.
Lisebelisoa tsa Boitšoaro
Liteko li etsahetse likamoreng tse robeli tse sebetsang tse tseletseng ka mekoting e mehlano, e 'ngoe le e' ngoe e kentsoe
ka har'a khabinete ea moea e kenyelletsang molumo (Med Associates St Albans,
Vermont). Ho hlophisoa ha likamore ho ne ho tšoana hantle le seo
e hlalositsoe pele (Zeeb et al a, 2009),
le tlatsetso ea levers e ka khutlisetsoang e ka lehlakoreng la bobeli ba
terei ea lijo. Likamore li ne li laoloa ke software e ngotsoeng ho MED-PC ke CAW
e sebetsa ka har'a komporo e lumellanang ea IBM.
Teko ea Boitšoaro
Tloaelo le koetliso
Ka bokhutšoanyane, lithuto li ne li lula ka likamoreng tsa liteko mme
o ithutile ho araba motho e mong le e mong ea kenyang chelete hore a fumane lijo
moputso. Liphoofolo li ile tsa koetlisoa ka ho latellana tsa mefuta e nolofalitsoeng
ea lenaneo la mochini oa slot o ileng oa eketseha butle ka thata. A
Tlhaloso e qaqileng ea mohato o mong le o mong oa koetliso e fanoa ho tlatsetso
Tlhahisoleseling.
Mosebetsi oa mochini oa slot
Morero oa tšebetso o fanoa ka Setšoantšo sa 1. Ho ile ha sebelisoa masoba a mararo a bohareng kahara masoba a mahlano mosebetsing ona
(likoti 2-4). Rate e ile ea qala nyeoe ka 'ngoe ka ho tobetsa roll lever.
Lever ena e ile ea khutla mme leseli le ka hare ho 2 le ile la qala ho bonesa ho
maqhubu a 2 Hz (Setšoantšo sa 1a). Nako nngwe, rat e ile ea araba ka mokhoa ona oa sethala, o bobebe
ka hare e behiloeng kapa e koetsoe (ho akaretsoa ho fihlela joale '1' kapa '0') bakeng sa
masala a nyeoe. Ho latela maemo a khanya a
lebone, ekaba 20 kHz ('ka') kapa 12 kHZ ('off') molumo oa molumo oa 1 s, kamora moo leseli le lesobeng la 3 le ile la qala ho khanya (Setšoantšo sa 1b). Hape, karabelo e sa hlonepheng e ile ea etsa hore leseli le qale ho kapa ho tima le ho tsosa tlhahiso ea 1 le 20/12 molumo oa kHZ, ka mor'a moo leseli le neng le le kahara 4 le ile la qala ho khanya (Setšoantšo sa 1c).
Hang ha rat e se e arabetse ka mokoting 4 le leseli le kahare le behiloeng ho
hlakola, hape e tsamaea le molumo o loketseng, ea bokella le ho phutha
Ho ile ha hlahisoa litseboSetšoantšo sa 1d le e).
Setšoantšo sa 1.
Setšoantšo sa Schematic se bonts'ang sebopeho sa teko ea mosebetsi oa mochini oa slot. A
Karabelo holima lever e qala mabone a pele a khanya (a). Hang ha
phoofolo e arabela sebakeng se seng le se seng se bobebe se khanyang, leseli le ka hare
kapa ho khumama ebe lesoba le haufi le qala ho benya (b, c). Hang ha li le tharo
mabone a behiloe, rat e na le khetho ea ho qala nyeoe e ncha, ka
ho araba moqololong, kapa ho araba mokoloto. Ka katleho
liteko, moo mabone ohle a lutseng ho tsona, karabo ea ho bokella
e hlahisa li-pellets tsa tsoekere tsa 10 (d). Haeba mabone a fetile, a
Karabelo ho lever ea pokello ho fapana le hoo e fella ka 10 s
nako ea khefu (e). Ho na le lipaterone tse robeli tse ka bang bonolo (f). Win
e bonahala ka ho hlaka ke mabone ohle a mararo a lebileng pele, mme tahlehelo e hlakileng
e bonahala ha mabone ohle a tima.
Palo e feletseng le pale (99K)Khoasolla Matla Letlapa la ntlha (1,304 KB)
Ka mor'a moo, rat e ne e hlokahala hore e arabele lever kapa e 'ngoe
khetho e bontšitsoe ke boemo ba khanya ea mabone a maboteng
2-4. Litekong tsa win, mabone ohle a mararo a hlophiselitsoe ho (1,1,1), le a
karabelo ho lever e tlisoang ke li-pellets tsa tsoekere tsa 10 (Setšoantšo sa 1d). Haeba lebone le leng le ne le ka tima (mohlala, Setšoantšo sa 1), ebe karabelo ho "lever lead" e lebisang ho 10 s
Nako ea ho tlohela nako eo moputso o sa kang oa fumanoa. Ts'ebeliso ea
likoti tse tharo tse sebetsang li felletse ka mefuta e robeli e ka khonehang ea liteko (Setšoantšo sa 1f,
(1,1,1); (1,1,0); (1,0,1); (0,1,1); (1,0,0); (0,1,0); (0,0,1);
(0,0,0)), ketsahalo eo e ileng ea hasoa ka boomo ka tšohanyetso le ka mokhoa o sa lekanyetsoang
nakong eohle ea kemiso e fapaneng 8 ratio. Haeba rat e ile ea khetha
the roll lever holim'a liteko life kapa life, ka nako eo moputso o neng o ka ba teng kapa nako e felile
e hlakotsoe, 'me teko e ncha ea qala. Kahoo, litekong tsa win, e nepahetseng
Leano e ne e le ho araba moholli oa pokello ho fumana se reriloeng
moputso, athe litekong tsa tahlehelo, leano le nepahetseng e ne e le sebaka
araba karong ea moqolo ebe o qala nyeoe e ncha. Haeba rat e ile ea khetha
bokella, bobeli ba litefiso ba khutliselitsoe ho fihlela qetellong ea nehelano ea moputso/khefutso
Nako, ka mor'a moo moqomo oa kalimo o ile oa hlahisoa 'me lekhalo le khona
qala nyeoe e latelang. Mosebetsi o ne o ikakhetse ka setotsoana ho seo
liphoofolo ha lia ka tsa botsoa ho etsa leha e le efe ea likarabo ka har'a a
fensetere ea nako e itseng; ha ho hlokahala, lenaneo le ne le tla tsoela pele ho ema
bakeng sa phoofolo ho etsa karabo e latelang e nepahetseng ka tatellano ho fihlela
qetellong ea thuto. Ntlha feela eo rat e ka atlehang ho eona
Ho phethela nyeoe ka hona haeba karolo e ile ea fela qetellong.
Liphoofolo li fumane linako tse hlano tsa tlhahlobo ea letsatsi le letsatsi ka beke ho fihlela
Mekhahlelo e tsitsitseng ea lipalo e ne e thehiloe holim'a
Likopano tse hlano (palo e kholo ea lithuto tse nkuoeng ho fihlela lintlha,
ho kenyelletsa linako tsohle tsa koetliso: 49-54). Liphoofolo li ne li nkuoa e le tsona
ba fumane mosebetsi ka katleho haeba ba phethile> liteko tse 50 ka ho
setulo mme se entsoe <50% bokella likarabo mabapi le liteko tse hlakileng tsa tahlehelo (0,0,0).
Paradigm ea hajoale e tšoana le teko ea pejana ea ho bapala papali ea slot mo likhotong (Peters et al a, 2010),
ka hore liphoofolo li ne li kopuoa ho khetha pakeng tsa mokoloto oa mali le
'spin' kapa 'roll' lever ho latela mohlala o bobebe. Leha ho le joalo, ka har'a
tlaleha ke Peters et al a (2010), lesoba le fetileng le ne le tlameha ho bonesoa e le hore le ka latela
leseli le bonesitsoeng. Ka lebaka leo, lithuto li ka rarolla
khethollo ka ho ea feela leseli la ho qetela le bonesitsoeng ka har'a
tatellano. Thutong ea hona joale, liphoofolo le tsona li ile tsa hlokoa ho
li-nosepoke tse ka mekotleng ea karabo ho netefatsa hore li hlokomela, kapa
bonyane ho tobana le, mabone a susumetsang nakong ea nyeoe.
Liphephetso tsa Pharmacological
Hang, ha boitšoaro bo tsitsitseng ba motheo bo se bo thehiloe, karabelo ho likhomphutha tse latelang e reriloe: d-amphetamine (0, 0.6, 1.0, 1.5 mg/kg), eticlopride (0, 0.01, 0.03, 0.06 mg/kg), SCH 23390 (0, 0.001, 0.003, 0.01 mg/kg), quinpirole (0, 0.0375, 0.125, 0.25 mg/kg), le SKF 81297 (0, 0.03, 0.1, 0.3 mg/kg). Lithethefatsi li fanoe ka 10 metsotso pele ho ho hlahlojoa ho latela tatellano ea meralo e lekantsoeng ea setšoantšo sa sekwere sa Latin bakeng sa litekanyetso tsa AD: ABCD, BDAC, CABD, DCBA; p.329 (Mok'hadinale le Aitken, 2006). Setlahare ka seng/letsoai
letsatsi la teko le ile la tla pele ke letsatsi la motheo le senang lithethefatsi mme la lateloa ke letsatsi
eo ho eona liphoofolo li neng li sa lekoa. Liphoofolo li ile tsa lekoa lithethefatsi mahala
bonyane beke ea 1 pakeng tsa liente tse ling le tse ling ho lumella motheo o tsitsitseng oa boitšoaro hore o thehe hape.
Ho felisoa le ho ntlafatsoa
Ho felisoa/Teko ea ho khutlisetsoa e ne e le ea moralo o ts'oanang le o sebelisoang ho itaola lithethefatsi
liteko. Morero oa ho qhekella hona e ne e le ho bona hore na ke mosebetsi
ts'ebetso e ka tima butle butle ha liteko tse haufi tsa ho hloloheloa
ba ne ba le teng, tumellanong le litlaleho tse ling lingoloeng tsa batho (Kassinove le Schare, 2001; MacLin et al a, 2007).
Liteko tse haufi le ho fetoa li ile tsa hlalosoa e le mofuta o mong le o mong oa liteko tseo ho tsona tse peli ho tsona
ho ile ha bonesoa masoba a mararo a sebetsang (bona karolo ea sepheo sa mabaka).
Kamora ho phethela mathata ohle a meriana, liphoofolo
ba arotsoe ka lihlopha tse peli tse lekanang palo ea liteko
e phethetsoe le mokhoa oa ho bokella likarabo o bonoang ka ho fapana
mefuta ea liteko. Lihlopheng ka bobeli li ile tsa etsa mosebetsi oa mochini oa slot ho
ho timela, eo ho eona karabelo e tla bokelloa kamora teko ea win
e lebisitse ho tliso ea moputso. Bakeng sa sehlopha se le seng sa likhoto, liteko tse haufi
li qheletsoe ka ntle ho papali. Boemo ba ho hapa le liteko tse hlakileng tsa tahlehelo e ne e le
e bolokiloe e lekana ho lihlopha ka bobeli. Kamora linako tsa 10 tsa ho timela, litoeba tsohle
li ile tsa khutlisoa mesebetsing e tloaelehileng ea mochini oa slot bakeng sa 10 e eketsehileng
Linako tseo liteko li ileng tsa atleha ho tsona li ile tsa putsoa hape. Ka potlako haholo
ho khutlisetsoa ka matšoao e ka ba sesupo sa karolo e kenelletseng ea tšebetsong
mosebetsi oa mochini. Liteko tse haufi-ufi li ne li le teng bakeng sa lihlopha tsena ka bobeli ka
khutlisoa.
lithethefatsi
Lithako tsohle tsa lithethefatsi li ne li baloa e le letsoai le ho qhibiliha ho 0.9% letsoai le letsoai. Lithethefatsi tsohle li ne li lokisoa li le ncha letsatsi le leng le le leng 'me li tsamaisoa ka tsela e kenellang ka bongata ho 1 mg/ml. Eticlopride hydrochloride, SCH 23390 hydrochloride le quinpirole
hydrochloride e ile ea rekoa ho Sigma-Aldrich (Oakville, Canada). SKF
Hydrobromide ea 81297 e rekile ho Tocris Bioscience (Ellisville,
MO). D-amphetamine hemisulfate e rekiloe tlasa tokollo ho Health Canada ho Sigma-Aldrich UK (Dorset, England).
Boitsebiso ba Lintlha
Ho ile ha hlahlojoa mefuta e latelang e latelang bakeng sa mofuta o mong le o mong oa teko: liperesente
tsa liteko tseo ho tsona liphoofolo li neng li tobetsa ea lata (arcsine)
fetotsoeng), latency e tloaelehileng ea ho arabela ho lever ea pokello, le
latency ea ho araba ka mokhoa o mong le o mong oa ho fifala ha leseli le ka hare le ne le
e bonesang. Palo ea liteko tse phethiloeng thutong e ngoe le e ngoe e ile ea hlahlojoa.
Monono oa ho khetha lever roll kamora teko e 'ngoe le e' ngoe o sa kenyelelitsoe
tlhahlobisong e hlophisitsoeng kaha mohato ona o ne o reretsoe ke ba phahameng
koluoa ea likarabo tse fosahetseng tsa bokella, e fella ka 10 s
kotlo ea nako, mefuta e meng ea liteko, le nako e nkiloeng ho ja tsoekere
li-pellets litekong tsa win. Lintlha tsohle li ne li behiloe ka tlas'a lithuto
tekolo e pheta-pheto ea tekanyo ea phapang (ANOVA), e etsoang ho sebelisoa SPSS
software (SPSS v16.0, Chicago, IL).
Nakong ea koetliso, khetho ea lere le ho bokella lever latency e ile ea hlahlojoa ka tse hlano
likopano (beke le beke) likheoana ka karolo (maemo a mahlano) le mofuta oa liteko (tse robeli
maemo) e le lintlha ka hare ho lithuto. Motheo o tsitsitseng o ile oa hlalosoa e le
ho haella ha phello e kholo ea nako ea thuto kapa mofuta oa teko
tšebelisano. Ho tseba phello ea palo ea mabone
e bonesitsoe, ho sa natsoe boemo ba sebaka, datha li ne li kentsoe ka nqane
Liteko tsa khanya tsa 2-((1,1,0), (1,0,1), le (0,1,1) le liteko tsa leseli le le leng
((1,0,0), (0,1,0), le (0,0,1). Joale ANOVA e ile ea etsoa ka kemiso
le mabone a bonesitsoeng (mekhahlelo ea 4, 0-3) e le lintlha tse kahare. The
latency ea ho araba ka har'a sehlopha sa pele e ile ea beoa ANOVA le
seboka, mofuta oa teko, le lesoba (mekhahlelo ea 3) e le lintlha ka hare ho lithuto. Ho
odara ho bona hore na ho araba lesoba le latelang ho amme ke
khanya ea lesoba le fetileng, moeli oa nako e telele oa ho arabela
lesoba le bohareng haeba sekoti sa pele se ne se lekantsoe kapa se emisitsoe,
ho sa tsotelloe mofuta oa teko. Ka mokhoa o ts'oanang, latency e tloaelehileng ea ho arabela ka hare
lesoba la ho qetela haeba sekoti se bohareng se ne se thehile kapa se tlohile.
Lintlha tsena li ile tsa kenngoa ANOVA ka kemiso, lesoba (mekhahlelo e 'meli:
bohareng le ba ho qetela) le mmuso oa lesoba le fetileng (mekhahlelo e 'meli: ho ea pele le ho tloha) joalo ka
ka har'a lintlha. Liteko tse phethoang ka thuto e ngoe li ile tsa hlahlobisisoa ke
ANOVA e bonolo e nang le kemiso e le eona feela ntlha ea lithuto. The
Karabelo mathateng a fapaneng a pharmacological e ile ea hlahlojoa ho sebelisoa
mekhoa e ts'oanang ea ANOVA, empa ntlha ea thuto e ile ea nkeloa sebaka ke lethal dose
sesosa.
Lintlha tse tsoang matsatsing a 10 a ho felisoa le ho khutlisetsoa morao li ile tsa hlahlojoa ka mokhoa o tšoanang ke ANOVA ho liqhomane tsa letsatsi tsa 3-4, ka
kenyelletso ea sehlopha (maemo a 2) joalo ka ntlha ea lithuto. Joalo ka ho sekaseka
tsa mefuta eohle e meng e ne e ferekantsoe ke taba ea hore ha se liteko tsohle
mefuta e ne e le teng bakeng sa lihlopha ka bobeli, e leng tsona feela tse fapaneng tse hlahlobisisitsoeng ho tsoa ho
linako tsa ho felisoa e ne e le palo ea liteko tse phethetsoeng. Litlhahlobong tsohle,
boemo ba bohlokoa bo behiloe ho p<0.05. Haeba monyetla oa ketsahalo e etsahalang o fumanoe e le <0.1, maikutlo a hlalosoa e le mokhoa.
LIPOTSO
Ts'ebetso ea Motheo
Liphoofolo tse 'ne li ne li sa khetholloe ka lebaka la ho sitoa ho kopana le
Mekhoa e latelang ea ho ithuta: likhoto tsena ha lia ka tsa etsa bonyane 50
liteko ka nako e 'ngoe le e' ngoe, ebile ha lia ka tsa etsa tlase ho 50% bokella liphoso litekong tse hlakileng tsa tahlehelo (0,0,0). Palo ea ho qetela ea likhoto tse kenyelitsoeng thutong ka hona e ne e le 12.
Khetho ea lever
Litekong tse atlehileng, likhoto li ile tsa araba moqokelli a batla a le 100% ea ka nako eo, ka tsela eo e tla etsa bonnete ba ho tlisa moputso o hlophisitsoeng (Setšoantšo sa 2a le b).
Ka lehlakoreng le leng, haeba ho se na mabone a lebisitsoeng ho 'ona (tahlehelo ea' hlakileng '), likhoto
e bontšitse khetho e matla bakeng sa lever ea hajoale e nang le monyetla. Empa,
leha liteko tse totobetseng tsa tahlehelo li bonahala, litoeba li ntse li arabeloa ka phoso ho
bokella lever hoo e ka bang 20% tsa liteko. Lintho tse ratoang bakeng sa mokoloto oa mali oa pokello li fapane haholo ho mefuta ea liteko tse ling.Setšoantšo sa 2b, mofuta oa teko: F7, 77=56.75, p<0.01). Ponelopele e hlakileng ea mokhoa o khethiloeng o khethiloeng e ne e le tekanyo ea
eo nyeoe e neng e tšoana le win, joalo ka ha e bonts'oa ke 'nete e tiileng
khokahano e hlokometse lipakeng tsa palo ea mabone a bonesitsoeng le
liperesente tsa likaraboSetšoantšo sa 2a).
Kahoo, boteng ba lipontšo tsa "win" tse behang ho liteko tsa tahlehelo ka tatellano
e ile ea eketsa monyetla oa hore rat e arabe joalo ka ha eka ke teko
hlola nyeoe, 'me u etse karabo e fosahetseng. Ka tsela ena, ho joalo
Likarabo tse fosahetseng tsa ho bokella li ka bonts'a mokhoa o ts'oanang le a
'haufi-miss' phello. Phello ena e matla ho liteko tsa tahlehelo ea khanya ea 2, ho
eo khetho ea lere e bokelletsoeng e phahame haholo ho feta
monyetla, hape e phahame ho feta se bonoang bakeng sa tahlehelo ea khanya ea 1 kapa e hlakile
tahlehelo (mabone a bonesitsoe: F3, 33=245.23, p<0.01; 2 vs Mabone a 1: F1, 11=143.57, p<0.01; 2 vs Mabone a 0: F1, 11=249.20, p<0.01), leha e ntse e le tlase haholo ho feta e bonoang nakong ea liteko tsa win (2 vs Mabone a 3: F3, 33=128.92, p
Setšoantšo sa 2.
Ts'ebetso ea mantlha ea mosebetsi oa mochini oa slot. Litekong tsa win, ha tsohle li le tharo
mabone a ne a se a etelletse pele ((1,1,1)), liphoofolo li ikhethetse lever 100% ea nako (a, b). Ha palo ea mabone e ntse e fokotseha, ho joalo
entse se ratoang ke mokoloto (a). Liphoofolo kamehla
e bonts'itse khetho e matla bakeng sa lere ea bokello ho tahlehelo ea khanya ea 2, kapa
liteko tse haufi-ufi. Karolo ea likarabo tsa ho bokella tse entsoeng ka bobeli
Lipheko tsa 2-light le 1-light li boetse li fapane ho latela mohlala o nepahetseng
ea mabone a bonesitsoeng (b). Bekeng ea pele ea boikoetliso, litoeba li ne li le teng
o lieha ho araba ka sekoting se latelang haeba lesoba le fetileng le ne le se le fihlile
tima (c). Leha ho le joalo, phello ena e khethollang ha e sa hlola e bonoa hang
boitšoaro bo tsitsitseng ba khetho e se e thehiloe. Mokhoa ona o ile oa bonoa
bakeng sa likoti tse bohareng le tsa ho qetela, ka hona, graph e bonts'a
data e kopaneng e tsoang masoba ka bobeli. Lintlha tsohle tse bontšitsoeng ke moelelo ho isa ho tse hlano
mananeo ± SEM.
Palo e feletseng le pale (60K)Khoasolla Matla Letlapa la ntlha (709 KB)
Leha palo e akaretsang ea mabone e boneselitsoe ka teko e 'ngoe e le ponelopele e ntle ea ho bokella likhetho ho fapana le ho bonesa leseli le le leng ho
haholoholo, ho bile le phapang pakeng tsa litefiso tsa phoso ho
1-leseli (mofuta oa teko: F2, 22=3.061, p=0.067) le tahlehelo ea khanya ea 2 (mofuta oa teko: F2, 22=3.717, p=0.041),
ka mohlomong ho bonts'a sebaka sa libaka tse nang le likoti tse nepahetseng
leseli le ka ama leeme la likhoto mabapi le pokello kapa moqolo
lere. Ka lipalo, palo e phahameng ka ho fetisisa ea likarabo tse fosahetseng e etsahetse
ha leseli la ho qetela le bonesoa. Ho ka etsahala hore e tlhokomelo
khethollo e kanna ea ba e tsoetse letamong lena, mohlomong ka lebaka la hore le haufi
ho ba haufi le sebaka le nako ho mokoloto oa koleke. Leha ho le joalo, ho bapisoa le
Tahlehelo ea khanya ea 1, khanya ea leseli la ho qetela letotong e lebisitse ho
sekhahla sa phoso e phahameng ho feta leseli la lesoba le bohareng ((0,1,0) vs (0,0,1): F1, 11=5.026, p=0.047), empa eseng lesoba la pele ((1,0,0) vs (0,0,1): F1, 11=2.682,
NS). Ka mokhoa o ts'oanang, haeba lesoba la ho qetela le ne le sa bonesoa ka lebone la 2
tahlehelo, sekhahla sa phoso e tlase se ile sa bonoa ha se bapisoa le tahlehelo eo ho eona
lesoba la pele le la ho qetela le behiloe ho ((1,1,0) vs (1,0,1): F1, 44=7.643, p=0.018), empa eseng ha ho ne ho bonesitsoe mabone a mabeli feela a ho qetela ((1,1,0) vs (0,1,1): F1, 44=2.970,
NS). Motheong oa tlhahlobo ea lipalo, ho ka ba joalo
bonahala eka lets'oao la win bohareng ba tatellano ha le na matla
ho feta e le 'ngoe qetellong kapa ho qala, empa ho bonesa ka mokhoa o ikhethileng
lesoba ha le lekane, ka bo lona, ho khetha khetho ea lever.
Hore na o hlahisa li-cue ka tatellano e hlophisitsoeng, ho fapana le ho tloha letsohong le letšehali ho ea ho le leng
ka nepo, na ho tla thabisa hore litlamorao tsee li lokela ho tsejoa?
Boitlhotlhollo ba karabelo
Ha a bapisoa le kabo ea likarabo tsa likhoto
araba ka mokoloto oa mokoloto ha oa ka oa fapana ho latela lebone
mohlala (Lethathamo la Li-S1 tsa tlatsetso: Mofuta oa teko: F7, 77=0.784,
NS). Tsela ea ho araba ka sekoting se seng le se seng se latelang e ile ea fokotseha butle-butle
ho tloha lesoba la pele ho isa ho la ho qetela tekong, ho sa tsotelehe
mofuta oa teko (Tafole e Ntle ea S2: lesoba: F2, 22=17.773, p<0.01, mofuta oa teko: F7, 77=1.724,
NS). Ho ea ka pono ea theoretical, haeba leseli la leseli ho
tatelano e ile ea hlalosoa e le lets'oao le matla la ho matlafatsa, joale sena
sephetho se lokela ho tsamaisa karabelo e latelang. Kahoo, motho a ka lebella
fokotseha hoa latency ho araba ka sekoting se latelang haeba
lesoba le fetileng le ne le tsoetse pele. Ka lehlakoreng le leng, latency ho arabela ho
lesoba le latelang le lokela ho hola ha lesoba le fetileng le ka senyeha. Ka tatellano
ho etsa lipatlisiso hore na ho bile joalo, latency ea ho araba ho
lesoba le bohareng le ile la hlahlobisisoa ho latela hore na lesoba la pele le behiloe ho eng
ho bulela kapa ho tima, ho sa tsotelehe mofuta oa teko. Ka mokhoa o ts'oanang, latency ea ho araba
holima ho qetela ho ile ha hlahlojoa ho latela boemo ba lesoba le bohareng.
Pejana thupelong, ho bile le phello e kholo ea se fetileng
hole state ka lebelo la ho arabela, ho hore likhoto li nkile nako e telele ho
araba ka sekoting se latelang haeba lesoba le fetileng le ka senyeha
ho fapana le ho (Setšoantšo sa 2c; beke e fetileng ea masimong 1: F1, 11=6.105, p=0.031; -week 2: F1, 11=10.779, p=0.007).
Leha ho le joalo, hang ha mokhoa o ikhethileng oa motheo o thehiloe,
phello ena e ne e se e sa bohlokoa (beke 3: boemo bo fetileng ba lesoba: F1, 11=0.007, NS).
Liteko li felile
Palo e lekantsoeng ea liteko e phethoe ka thupelo e le ngoe ka nako e tšoanang
motheo o ne o fihlelitsoe e ne e le 71.0 ± 3.61 (SEM). Ha nako e ntse e ea
teko, palo ena e ile ea eketseha hanyane ka hanyane (Supplementary Table S3),
e ka bang sesupo sa ntlafatso e akaretsang ea boikamahanyo ba mesebetsi le
tlhahlobo e phetoang. Leha ho le joalo, kabo ea kakaretso ea pokello
Likarabo ho latela mofuta oa teko li ne li lula li le teng.
Kameho ea Tsamaiso ea Amphetamine ka Ts'ebetso ea Mosebetsi
Amphetamine ka boomo o ile a eketsa palo ea likarabo tsa ho bokella tse entsoeng mabapi le tahlehelo
liteko, empa sena se ne se ipapisitse le palo ea mabone a neng a behiloe ho latela
ka tšebelisano ea bohlokoa lipakeng tsa lethal dose le palo ea mabone
e bonesitsoe (Setšoantšo sa 3a; lethopi mabone a bonesitsoeng - litekanyetso tsohle: F9, 99=3.636, p=0.001).
Tlhahlobo ea litla-morao tse bonolo e bonts'itse lethathamo la amphetamine-ka kotloloho
eketseha likarabo tse latelang ho latela tahlehelo e hlakileng (lethal dose: F3, 33=4.923, p=0.006; letsoai vs 1.0 mg/kg: F1, 11=9.709, p=0.01; letsoai vs 1.5 mg/kg: F1, 11=7.014, p=0.023), 'me ho ne ho na le mokhoa oa keketseho ea ho bokella liphoso litekong tsa tahlehelo ea khanya ea 1 (lethal dose: F3, 33=3.128, p=0.039; letsoai vs 1.0 mg/kg: F1, 11=3.510, p=0.09).
Mabapi le tlhokomeliso ea morao-rao, bokhoni ba amphetamine ba ho matlafala
bokella liphoso e ne e le tsa bohlokoa feela ka lipalo ha leseli la ho qetela
e bonesitsoe (Setšoantšo sa 3b; mofuta oa mofuta oa mofuta oa liteko oa tekanyetso: F21, 231=2.521, p=0.022; lethalinyana (0,0,1): F3, 33=3.234, p=0.035; (0,1,0): F3, 33=0.754, NS; (1,0,0): F3, 33=2.169, NS).
Setšoantšo sa 3.
Liphetho tsa amphetamine ts'ebetsong ea mochini oa slot. Amphetamine
tekanyetso-ka tsela e itšetlehileng ka eketsa palo ea liphoso tsa bokella ka ho hlaka
tahlehelo le liteko tsa tahlehelo ea khanya ea 1-a (a). Haholo-holo, amphetamine
Likarabo li eketsehile haholo ka (0,0,0) le (0,0,1)
mefuta ea liteko (b). Tekanyetso e tlaase le e phahameng ka ho fetisisa ea amphetamine e boetse e entsoe
liphoofolo tse tsotellang haholoanyane boemo ba leseli tsa masoba, ka hore
ba ne ba bile ba potlakile ho arabela haeba sekoti se fetileng se ne se tsoetse pele
ho ena le ho tima (c). Lintlha li bontšoa e le moelelo oa ± SEM.
Palo e feletseng le pale (78K)Khoasolla Matla Letlapa la ntlha (819 KB)
Amphetamine e boetse e khetha ka mokhoa o ikhethileng hore e arabele ho motho ea bokellang
ka mefuta e tšoanang ea teko eo ho eona ho bokelloang liphoso tse ngata haholo
liphoso li entsoe (Tafole e tlatselletsang ea S1, mofuta oa tekanyetso × litekanyetso tsohle: F21, 231=2.010, p=0.007; letsoai vs 1.0 mg/kg: F7, 77=2.529, p=0.021; letsoai vs 1.5 mg/kg: F7, 77=3.720, p=0.002; (0,0,0): F3, 33=4.892, p=0.006; - (0,0,1): F3, 33=3.764, p=0.02).
Ka lehlakoreng le leng, amphetamine ka kakaretso e fokolitse latency ho arabela ho
ba butsoitseng ho sa tsotelehe mofuta oa teko (Tafole ea tlatsetso S2,
tekanyetso: F3, 33=12.649, p=0.0001; mofuta oa teko: F7, 77=1.652, NS; letsoai vs 0.6 mg/kg: Tekanyetso: F1, 11=7.977, p=0.017; letsoai vs 1.0 mg/kg: F1, 11=10.820, p=0.017; letsoai vs 1.5 mg/kg: F1, 11=12.888, p=0.004).
Ntle le moo, amphetamine e ne e tloaetse ho etsa likhoto kapele ho araba
hole haeba lesobo le fetileng le ne le qalile ho fapana le ho tloha, ba hopole
boits'oaro ba bona nakong ea ho fumana mosebetsi (Setšoantšo sa 3c; tekanyo × seemo sa hole sa hole: F3, 33=2.710, p=0.096; lesoba la boemo bo fetileng saline: F1, 11=0.625, NS; −1.5 mg/kg: F1, 11=7.052, p=0.022). Amphetamine ha a ka a fetola liteko tsohle tse phethetsoeng ka nako e ngoe le e ngoe (Tafole ea Tlatsetso ea S3; lethal dose: F3, 33=1.385,
NS). Amphetamine ka hona a eketsa lebelo la ho arabela ho
safu, haholoholo ho latela letšoao le nepahetseng (leseli le bonesitsoeng), leha ho le joalo
e sitisitse tšebeliso ea sebopeho sa lebone ho tataisa khetho ea lever
bokella likarabo li entsoe leha ho se na matšoao a fokolang kapa a sena letho
mohlomong.
Kameho ea D2 Receptor Antagonist Eticlopride mabapi le Ts'ebetso ea Mosebetsi
Tekanyo e phahameng ka ho fetisisa ea eticlopride e fokolitse palo e tloaelehileng ea liteko
e tlatsitsoe ho fihlela tlase ho 20, ka hona lethal dose lena ha lea ka la kenyelletsoa ho
tshekatsheko. Lintlha tsohle li fanoe ka tlhaiso-leseling e tlatselletsang
(Tlhahisoleseling ea S1 e tlatsetsang, Tafole e tlatsetsang S1-S3). Leha e le polelo
'D2 receptor 'e sebelisoa mona bakeng sa ho hlakisa, ho amoheloa hore bobeli le eticlopride le quinpirole li tlama ka kamano e fokolang ho D tse ling.2- Li-receptors tse kang (D3 le D4), le hore tse ling tsa liphumano tsena li ka hlahisoa ke liketso ho D2 lelapa la receptor ho fapana le ho D2 receptor ka kotloloho.
Eticlopride ha ea ka ea ama karolo ea likarabo tse bokelloang tse entsoeng ho sa tsotelehe
palo ea mabone a boneselitsoeng ka teko e ngoe le e ngoe (lethal dose mabone a bonesitsoeng: F6, 66=1.489, NS) kapa mofuta o nepahetseng oa leseli (mofuta oa mofuta oa teko: F14, 154=1.182, NS). Tekanyo e phahameng ea eticlopride e atisitse ho eketsa latency ho arabela ho lever (lethal dose: F2, 22=3.306, p=0.056; letsoai vs 0.03 mg/kg: Tekanyetso: F1, 11=12.544, p=0.005). Ka bobeli litekanyetso li ne li eketsa latency ho arabela ka bongata: lethal dose: F2, 22=15.797, p<0.01; letsoai la tekanyo vs 0.01 mg/kg: F1, 11=7.322, p=0.02; letsoai vs 0.03 mg/kg: F1, 11=19.462, p<0.01) le ho fokotsa haholo lipalo tsa liteko tse phethetsoeng (lethal dose: F2, 22=31.790, p<0.01; letsoai vs 0.01 mg/kg: F1, 11=11.196, p=0.007; letsoai vs 0.03 mg/kg: F1, 11=43.949, p<0.01; liteko li phethetsoe ka 0.01 mg/kg: 59.0 ± 6.22; −0.03 mg/kg: 17.67 ± 4.06). Mokhoa ona oa data o bonts'a hore D2 receptor antagonist ka kakaretso e fokotsehile ts'ebetso ea makoloi, ho fapana le
e ama ka kotloloho likarolo life kapa life tsa kelello tse mabapi le mosebetsi o amanang le
qeto ea ho arabela holima mokoloto.
Kameho ea D1 Receptor Antagonist SCH 23390 mabapi le Ts'ebetso ea Mosebetsi
Lintlha tsohle li fanoe ka tlhaiso-leseling e tlatselletsang (Setšoantšo sa tlatsetso S2, Tafole ea Tlatsetso S1-S3).
SCH 23390 ha ea ka ea ama khetho ea moqapi oa koleke ho sa tsotelehe
palo ea mabone a boneselitsoeng (mabone a khanyang ea konkreiti ka: F9, 99=0.569, NS) kapa mofuta o ikhethileng oa teko (mofuta oa mofuta oa teko: F21, 231=0.764, NS). Leha lethalano le phahameng ka ho fetisisa le ile la phahamisa morolo oa ho arabela ho lever (lethal dose: F3, 33=5.968, p=0.002; letsoai vs 0.01 mg/Kilo ea kilo: F1, 11=10.496, p<0.01) le ho eketsa latency ea ho arabela ka bongata (tekanyetso: F3, 33=4.603, p=0.008), palo ea liteko tse phethiloeng tlasa lethal dose ena le eona e fokotsehile haholo (liteko tse phethoang tlasa 0.01 mg/kg: 20.7 ± 5.0; tekanyetso: F3, 33=40.66, p=0.0001; letsoai vs 0.01 mg/kg: F1, 11=60.601, p=0.0001).
Kahoo, joalo ka litlamorao tsa eticlopride, lethal dose le phahameng ka ho fetisisa
Lits'ebetso tse fokotsehileng ka tsela e itekanetseng, leha ho le joalo ha lia ka tsa ama ho utloahala
dikarolo tsa mosebetsi.
Kameho ea D2 Agonist Quinpirole mabapi le Ts'ebetso ea Mosebetsi
Tekanyetso e phahameng ka ho fetisisa ea quinpirole e fokotsitse palo e lekantsoeng ea liteko tse phethetsoeng ho ba ka tlase ho 20, ka hona, lethal dose lena ha lea ka la kenyelletsoa tlhahlobisong.
Quinpirole e ile ea eketsa haholo karabelo ea likarabo tse fosahetseng tsa bokello bo entsoeng ka bobeli ba 'haufi-poso'
liteko le liteko tse hlakileng tsa tahlehelo (Setšoantšo sa 4a; lethal. mabone a khantšitsoeng: F6, 66=7.586, p=0.002; letsoai vs 0.0375 mg/kg: F3, 33=8.163, p=0.0001; letsoai vs 0.125 mg/kg: lethaliti mabone a khantšitsoeng F3, 33=14.865, p=0.0001).
Ho hlakola data ka mokhoa o nepahetseng oa mabone, ho bohlokoa
litlamorao tsa lithethefatsi li ile tsa bonoa mefuteng eohle ea liteko ntle le liteko tsa win (Setšoantšo sa 4b; tekanyetso: F2, 22=16.481, p=0.0001; mofuta oa mofuta oa mofuta oa liteko oa tekanyetso: F14, 154=4.746, p=0.0001; lethalinyana (1,1,1) F2, 22=1.068, NS mefuta eohle ea liteko F> 3.25, p
Ha ho bapisoa le litekanyetso tse peli tsa lithethefatsi, lethal dose le phahameng le ile la bonahala le hohela a
keketseho e kholo ea liphoso tsa ho bokella, haholo-holo ho liteko tsa khanya tsa 0
(0.0375 vs 0.125 mg/kg: lethal dose mofuta oa teko: F7, 77=2.880, p=0.01).
Setšoantšo sa 4.
Liphetho tsa quinpirole mabapi le ts'ebetso ea mochini oa slot. Quinpirole
tekanyetso-kholo ea ho bokella liphoso tse tsoang ho liteko tsohle tsa tahlehelo (a, b).
Phello ena e boletsoe ka ho khetheha ho tahlehelo ea khanya ea 1-X le 2-
lethalano le tlase ka ho fetisisa le lekiloeng. Quinpirole le eona e ile ea eketsa latency ho
araba ka mokhoa o fapaneng ho sa tsotelehe maemo a maseli a masoba
(c). Lintlha li bontšoa joalo ka moelelo oa ± SEM.
Palo e feletseng le pale (78K)Khoasolla Matla Letlapa la ntlha (830 KB)
Quinpirole e boetse e matlafalitse bokhoni ba ho araba motho ea kolokang, ho sa tsotelehe
mofuta oa teko kapa lethal dose (Lethathamo la tlatsetso S1; lethal dose: F2, 22=14.035, p=0.0001, mofuta oa mofuta oa tekanyetso x: F14, 154=0.475, NS; letsoai vs 0.0375 mg/kg: F1, 11=18.563, p=0.001; letsoai vs 0.125 mg/kg: F1, 11=30.540, p=0.0001).
Ka mokhoa o ts'oanang, litekanyetso ka bobeli li matlafalitse bokhoni ba ho arabela hangata
ho sa tsotelehe mofuta oa teko (Tafole ea tlatsetso S2; lethal dose: F2, 22=8.986, p=0.001; mofuta oa mofuta oa mofuta oa liteko oa tekanyetso: F14, 154=1.500, NS; letsoai vs 0.0375 mg/Kilo ea kilo: F1, 11=9.891, p=0.009; letsoai vs 0.125 mg/Kilo ea kilo: F1, 11=20.08, p=0.001) kapa boemo ba khanya ea lesoba le fetileng (Setšoantšo sa 4c; tekanyo × seemo sa hole sa hole: F2, 22=0.291,
NS). Methapo ka bobeli ea quinpirole le eona e fokotse palo ea liteko
e phethetsoe ka tekanyo e ts'oanang (Tafole ea tlatsetso S3; liteko li phethetsoe
-0.0375 mg/kg: 47.08 ± 5.8; −0.125 mg/kg: 40.92 ± 3.8; tekanyetso: F2, 22=44.726, p=0.0001; letsoai vs 0.0375 mg/kg: F1, 11=45.633, p=0.0001; letsoai vs 0.125 mg/kg: F1, 11=57.513, p=0.0001; 0.0375 vs 0.125 mg/kg: F1, 11=1.268,
NS). Ka kakaretso, le ha quinpirole e ile ea fokotsa tlhahiso ea makoloi, ka bobeli
dose li lebisa keketseho ea likarabo tse fosahetseng tsa ho bokella litekong tsa tahlehelo
tse ileng tsa phatlalatsoa haholo ka tahlehelo ea khanya ea 1-X le 2-light.
Kameho ea D1 Receptor Agonist SKF 81297 mabapi le Ts'ebetso ea Mosebetsi
Lintlha tsohle li fanoe ka tlhaiso-leseling e tlatselletsang (Setšoantšo sa tlatsetso
S3, litafole tse tlatsetsang S1-S3). SKF 81297 e bile le phello e fokolang haholo ho
tshebetso ya mosebetsi. Karolo ea likarabo tsa bokello e ile ea sala
e sa fetoheng (lethalinyana: F3, 33=0.086, NS; mofuta oa mofuta oa mofuta oa liteko oa tekanyetso: F21, 231=1.185, NS; lethal. mabone a khantšitsoeng: F9, 99=1.516, NS) joalo ka ha ho etsoa morao-rao ho tobetsa ea mokoloto (lethal dose: F3, 33=0.742, NS; mofuta oa mofuta oa mofuta oa liteko oa tekanyetso: F21, 231=0.765, NS). Tekanyetso e phahameng ka ho fetisisa e fokolitse palo ea liteko tse phethiloeng (lethal dose F3, 33=4.764, p=0.007, saline vs 0.03 mg/kg: F1, 11=10.227, p=0.008) le ho eketsa latency ho araba ka mokhoa o fapaneng ho sa tsotelehe boemo ba leseli ba mabone a mang le a mang (lethal dose: F3, 45=4.644, p=0.007; letsoai vs 0.03 mg/kg: F1, 11=15.416, p=0.002; tekanyo × seemo sa hole sa hole: F3, 33=2.047, NS).
Ho felisoa le ho ntlafatsoa
Ha bokella likarabo kamora liteko tsa win li ne li se li sa putse, likhoto tsohle
e bontšitse ho fokotseha ho sa feleng ha palo ea liteko tse phethiloeng (Setšoantšo sa 5a; letsatsi: F9, 90=50.3, p<0.01). Ho ba teng kapa ho ba sieo ha liteko tsa 2-light 'near-miss' ha hoa ka ha fetola sekhahla sa ho fela (letsatsi × sehlopha: F9, 90=0.503, NS; sehlopha: F1, 10=0.365,
NS). Leha ho le joalo, ha liteko tsa win e ne e boetse e le lipontšo tse sebetsang tsa hore
moputso o ne o fumaneha, palo ea liteko tse phethiloeng e ile ea qala ho eketseha
mme liphoofolo li boetse li etsa mosebetsi oo. Le hoja lihlopha tseo ka bobeli li ne li le teng
ho etsa lipalo tse ka bapisoang tsa liteko kamora linako tsa 10, ea pele
Sekhahla sa "ho khutlisetsoa" papaling ea slot mochini o potlakile ho feta ho litoeba
e sa kang ea ba le liteko tse haufi le nakong ea ho timela (Setšoantšo sa 5a; matsatsi 1-3: sehlohlolo sehlopha sa: F2, 20=4.310, p=0.028; matsatsi 4-6: sehlohlolo sehlopha sa: F2, 20=4.677, p=0.022; matsatsi 7-10 fa setlhopha se kopane × sehlopha: F3, 30=1.323,
NS). Leha ho na le phapang ena palong ea liteko tse phethiloeng,
Karolo ea likarabo tsa loto tse tsoang mefuteng e fapaneng ea liteko,
le latency ea ho tobetsa ea mokokotlo, e ne e sa fapana lipakeng tsa
lihlopha maemong afe kapa afe nakong ea ho khutlisetsoa (matsatsi a 1-3, 4-6, le 7-10:
seboka × sehlopha, seboka × sehlopha × mofuta oa teko, tsohle Fs <2.1, NS). Le
matsatsing a pele a 3 a tlhahlobo, kabo ea likarabo tsa bokello
mefuta eohle e fapaneng ea liteko e tšoana hantle le e boneng pele
ho timela (Setšoantšo sa 5b).
Setšoantšo sa 5.
Phello ea ho tlosa liteko tse haufi le tsa nakong ea ho felisoa ka tekanyo ea bobeli
ho felisoa le ho khutlisetsoa morao hoa ts'ebetso ea mosebetsi. The
ho ba teng kapa ho se be teng ha liteko tse haufi-ufi ha hoa ka ha ama boemo ba
ho timela joalo ka ha ho bonts'itsoe ke palo ea liteko tse phethoang ka thuto ka 'ngoe
(a). Leha ho le joalo, likhoto tse neng li sa thulana le liteko tsa haufi-ufi nakong ea
timetso e ile ea potlaka ho nka mosebetsi hape ha liteko tsa win li ne li
moputso. Mothating ona oa ho khutlisetsa, liteko tse haufi haholo li ne li boetse li le teng
hlahisa bakeng sa lihlopha tsena ka bobeli. Leha ho na le phapang lipalo tsa liteko
ea phethoa, karolo ea likarabo tse bokelloang tse entsoeng ka nqane ho tse fapaneng
Mefuta ea liteko e ne e tšoana lihlopheng tsena ka bobeli, esita le har'a a mararo a pele
linako tsa ho khutlisetsoa (b). Le hoja likhoto li sa ka tsa ba teng
liteko tse haufi haholo nakong ea ho timela li ne li potlakile ho arabela kahare
lesoba le latelang haeba lesoba le fetileng le ne le se le fihlile ho (c), lihlopha ka bobeli
ea likhoto li ne li ela hloko boemo ba leseli ba masoba ke
pheletso ea khutlisetso (c, d).
Palo e feletseng le pale (135K)Khoasolla Matla Letlapa la ntlha (1,352 KB)
Ha palo ea liteko e phethoa ka thupelo e ntse e eketseha, latency ho
Karabelo hangata-holo e fokotsehile, empa sena se ile sa bonoa ka tekanyo e tšoanang
ka lihlopha tsena ka bobeli (Tafole ea tlatsetso S2; matsatsi 1-3: thuto: F2, 20=14.182, p=0.0001; sehlopha sa sehlopha sa ×: F2, 20=1.772,
NS; matsatsi a 4-6, 7-10: setlhopha se kopane, sehlopha × sehlopha: kaofela Fs <2.3, NS).
Leha ho le joalo, liphoofolo tse neng li sa pepesetsoa liteko tsa 'haufi-ufi' nakong ea
ho timela ho ne ho ameha haholo ka boemo ba leseli la
hole hole nakong ea linako tsena tsa khutlisetsoo ea pele, ka hore
tloaelo ea ho arabela ka potlako haeba leseli le fetileng le ne le sentse ho e-na le hoo
tima (Setšoantšo sa 5c matsatsi 1-3: session × sehlopha sa hole sa hole × sehlopha: F2, 20=3.798, p=0.04; 'ha ho haufi-taolo' sehlopha- seboka × seemo sa hole sa hole: F2, 10=3.583, p=0.067; sehlopha sa "haufi-fositse" sehlopha sa sebopeho sa boemo bo fetileng: F2, 10=0.234,
NS). Kahoo, leha ho ba teng kapa ho ba sieo ha liteko tse haufi haholo ho entse
ha e ame maemo a phahametseng feela, liphoofolo tse neng li sa
liteko tse hlokahalletsoeng haufi le maemo a ho se moputso li ile tsa potlaka haholo
ho etsa mosebetsi hape.
TŠOHLOA
Litlaleho tse bonojoang tsa papali ea papali ea chelete li fana ka maikutlo a hore boiphihlelo ba hoo e batlang e le bo hapileng bo ka boloka boitšoaro ba papali ea chelete mme bo ka khothaletsa PG ho batho ba tlokotsing (Reid, 1986; Griffiths, 1991; Clark, 2010). Mona, re bonts'a hore likhoto li khona ho etsa mosebetsi o rarahaneng oa khethollo (CD) e rarahaneng ka mochini o bonolo oa slot. Rats o ithutile hore leseli la mabone 'ohle a mararo ka har'a letšoao le pakiloeng hore moputso o ne o le teng haeba karabelo e entsoe ho lever, athe ho etsa karabo ena kamora mokhoa o mong o bobebe ho ka lebisa ho 10 nako ea ho tsoa. Liphoofolo li atlehile ho khetholla hore na karabelo ho mokoloto oa tsona o ne o le molemo ho liteko tse ngata. Leha ho le joalo, likhoto li ne li lula li fana ka likarabo tse ngata tse fosahetseng ha mabone a mabeli ho a mararo a bonesitsoe, 'me e ne e le liteko feela tseo ho tsona sekhahla sa phoso se neng se sa lekana ebile se ne se phahame haholo ho feta monyetla. Karabelo e fosahetseng joalo e fana ka maikutlo a hore liteko tsa bobebe tsa 2-light li hlahisa sephetho se haufi-ufi, ka hore li hlalosoa li tšoana hantle le win ho feta tahlehelo leha ho sa na matla a ho tlisoa. Ka bobeli amphetamine le D2 receptor agonist quinpirole eketseha bokella liphoso litekong tse sa win, ho fana ka maikutlo a hore ho eketseha ha letšoao la DA ho ka ntlafatsa tebello ea ho tlisoa ha moputso litekong tsa tahlehelo.
Ho fapana le seo re se fumaneng hore eticlopride e ntlafalitse ts'ebetso ea papali ea papali ea chelete (rGT; Zeeb et al a, 2009), D2 molateli oa receptor ha a ka a fetola boitšoaro mosebetsing oa mochini oa slot. Tpapiso ea hae ea rogimentary e ts'ehetsa tlhahiso ea hore metsoako ea litlhare e ke ke ea ba le litlamorao tse tšoanang mefuteng eohle ea boitšoaro ba papali ea chelete. (Grant le Kim, 2006). Leha ho le joalo, ho bohlokoa hape ho hlokomela hore D2 li-receptor antagonist haloperidol li na le litlamorao tse fapaneng papaling ea slot-Machine maemong a phetseng hantle vs tse nang le PG (Zack le Poulos, 2007; Tremblay et al a, 2010), 'me tlhokomelo e lokela ho nkuoa ha ho eketsoa pakeng tsa mehlala ea liphoofolo le palo ea bakuli ba batho. Ntle le moo, le ha paradigm ena ea rodent e arolelana likarolo tsa bohlokoa ka mochini o bonolo oa slot, ho na le liphapang tse totobetseng tse lokelang ho ananeloa. Mohlala, likhoto li ne li sa khone ho fetola boholo ba wager, kapa hona ho khetha ho beha chelete e ngata bakeng sa monyetla oa ho patala ho feta, leha maemo a joalo e le karolo ea mechini e meng ea slot (Kassinove le Schare, 2001; Boemo ba leholimo et al a, 2004; Harrigan le Dixon, 2010).
Ho feta moo, likhoto li ne li hlokoa ho emisa leseli ka leng ka bonngoe, ho fapana le ho emela mabone ohle a mararo ho latela karabo e le 'ngoe. Karolo ena e kanna ea ba e arolelana ka mokhoa o felletseng mekhoa ea ho ithuta e sa hlokeng tšitiso ea (Pavlovian) boits'oaro boo ho nahanoang hore bo ipapisitse le karolo ea papali ea chelete ea slot (Reid, 1986; Griffiths, 1991). Seo se boletse, lipapali tse ling tsa sejoale-joale tse sebelisang mochini oa slot li fa batho menyetla e mengata ea hore ba kenelle ho felisa li-spel ka ho toba le ho susumetsa nako ea liketsahalo tse sa sebetseng hantle (Harrigan, 2008). Eseng ho mamella meeli e kaholimo, ka hona, oLiteko tsa ur li bonts'a hore liteko tsa tahlehelo tse tšoanang le ho hloloa li ka holisa polelo ea menyetla ea tebello ea moputso ho likhoto ka mokhoa o hlalositsoeng ke likhopolo tsa kelello tsa boitšoaro ba papali ea chelete, le hore phello ena e ka fetoha bonyane makhetlo a mabeli a ts'ebetso ea dopamine.
Ho ka phetoa khang ea hore karolo e phahameng ea likarabo tse bokelletsoeng ho liteko tsa tahlehelo ea leseli tsa 2 e kanna ea hlaha hobane liphoofolo li ile tsa thatafalloa ho khetholla pakeng tsa liteko tsena tsa 3-light win on the perceptual level, ho fapana le ho bonts'a phapang e teng puong e hlakileng ea sephetho sa liteko. Le ha ho tšoana hantle de Khao facto, kenya letsoho ho litlamorao tse bonoang mona, ho na le mabaka a 'maloa a ho nahana hore seo re se fumaneng ha se lintho tse khetholloang tse khethiloeng pakeng tsa lipampiri tse bobebe. Taba ea mantlha, tlas'a maemo a mantlha, ho ne ho hlakile hore liphoofolo li khona ho khetholla ka mokhoa o hlakileng lipakeng tsa sephetho se hapileng le se haufi haholo joalo ka ha ho bonahatsoa ke palo e kholo ea likarabo kamora tse latelang ha li bapisoa le tsa pele. Taba ea bobeli, lipalo tse fapaneng tsa karabo e fosahetseng li ile tsa bonoa kamora liphetho tse fapaneng tse nang le mabone a mabeli a behiloeng ho (cf (1,1,0) vs (1,0,1), hape e bonts'a hore likhoto li ka khetholla ka mokhoa o ts'epahalang lipakeng tsa mefuta e fapaneng ea mabone. Taba ea boraro, litekanyetso tsa quinpirole tse hlahisitseng keketseho e joalo ea litekanyetso tsa liphoso litekong tse haufi-ufi ha li fokotse ho nepahala ha ho fumanoa ha morero nakong ea likhetho tse hlano tsa khetho ea nako ea bohlano, mohato o netefalitsoeng oa tlhokomeliso ea visuospatial (Winstanley et al a, 2010). Lintlha tse joalo li kenyelletsa ntle le monyetla oa hore pontšo ea rona ea liphetho tse sa lebelloang mabapi le tebello ea moputso litotong e ka hlahisoa feela ke mathata a khethollo.
Ntle le moo, ho ka etsahala hore likarabo tse fosahetseng ho lever e latelang li hlolohetsoe feela li bonts'a litlamorao tsa koetliso ea pejana; kaha ho rarahana ha mosebetsi hanyane ka hanyane ho ne ho hola ka mekhahlelo e fapaneng ea koetliso, ho ne ho na le maemo ao ho 'ona moputso o neng o ka fanoa ha ho bonesoa lebone le le leng kapa a mabeli feela. Leha ho le joalo, hape, ho fumana hore likhoto li bokella likarabo ha lia abuoa ka mokhoa o ts'oanang litekong tse peli tse bobebe ho hanyetsa monyetla ona: paterone
(1,0,1) ha e e-so ka e amahanngoa le sephetho se atlehang sa thupelo, leha ho le joalo likarabo tsa ho bokella li ne li atisoa khafetsa mofuteng ona oa teko. Ntle le moo, ka lebaka la tlhahlobo e sa khaotseng e hlokahalang bakeng sa liphephetso tsa meriana, liphoofolo li bile le tahlehelo ea khanya ea 2 e makholo-kholo nakong ea liteko ha e bapisoa le palo e nyane ea
moputso oa liteko tsa 2-light tse bileng teng libokeng tse 'maloa tsa boikoetliso. Ho tloaelehile hore liphoofolo li bopehe ho fana ka karabelo nakong ea thupelo eo ka nako eo li tlamehang ho thibela mosebetsi oa ho lemoha (mohlala nakong ea ho ithuta ka leano)Floresco et al a, 2008)). Ka hona ha ho na monyetla oa hore nako e lekanyelitsoeng ea khothaletso e fumanoeng nakong ea thupelo e ka baka boikhethelo bo ntseng bo tsoela pele bakeng sa mokoloto oa litekanyetso litekong tse haufi le ho feta.
Lintlha tsa morao-rao tsa karabelo li boetse li bonts'a hore likhoto ka bobeli li ne li khona ho bona boemo ba mabone mme li ne li ela hloko litlamorao, ka hore ha sekoti se itseng se ne se tlo ema, se araba
ka mokoting o latelang o ne o tsamaea butle. Leha ho le joalo, phello ena e bile feela
e hlokometsoe pejana lithupelong, pele ts'ebetso ea mosebetsi e tsitsa. Ka
metric ena, ka hona ho tla bonahala eka liphoofolo li fokotseha
amehang ka karabo ea motsotsoana oa motsotso o fanoeng nakong ea teko joalo ka
Koetliso e ile ea tsoela pele, leha leseli le ne le ka tseba hore na
moputso o ile oa fumaneha qetellong. E ntse e hohela ho sebelisa data e joalo ho
ba pheha khang ea hore ts'ebetso ea mosebetsi e ile ea e-ba 'ea boiketsetso' kapa ea ho qobella
ka mor'a nako e itseng (Jentsch le Taylor, 1999; Robbins le Everitt, 1999).
Leha ho le joalo, likhoto li ile tsa lula li tsotella ho hlakoloa ha
moputso o lebelletsoeng joalo ka ha ho pakoa ke ho theoha ho matla ha liteko tse phethiloeng
nakong ea ho timela. Lintlha tsena li ka supa hore ts'ebetso e ne e ntse e le teng
haholo-holo e etselitsoe sepheo ho fapana le tloaelo, leha e le hona e ntseng e lokela ho ba
netefalitsoe ho sebelisa teko e batlang e batla, joalo ka ho thuisa ho e-na le
siea moputso o lebelletsoeng (Balleine le Dickinson, 1998).
Ho fapana le litlaleho tse ling tsa pejana lithutong tsa batho, ho felisoa hoa mosebetsi
Ts'ebetso ha ea ka ea lieha ho ba teng ha liteko tse haufi le.
Leha ho le joalo, liphoso tse haufi ha se kamehla li khutlang ho felisoa, le phello ena
e bonahala e itšetleha haholo ka makhetlo a liketsahalo tsa haufi-ufi (Kassinove le Schare, 2001) le palo ea lipapatso tse entsoeng (MacLin et al a, 2007).
Paradigm ea ho timela e sebelisitsoeng mona, ha e ntse e le sebopeho se tloaelehileng bakeng sa
tlhahlobo ea thuto ea liphoofolo, le eona ha e tšoane le mofuta oa
ho timela ho bileng teng nakong ea liketsahalo tsa papali ea chelete moo ho hlolang
feela hloleha ho etsahala. Kahoo ho hlokahala mosebetsi o eketsehileng
hore na liteko tsa haufi-ufi li ama sekhahla sa ho felisoa hoa likhoto li sebelisa a
litekanyetso tse tšoanang le tsa tse sebelisoang ho motho ea amanang
lithuto.
Leha ho ba sieo ha liteko tse haufi-ufi ho ile ha etsa joalo
ho se ame nako ea ho felisoa, ho khutlisetsoa mosebetsing
ts'ebetso e ne e potlakile sehlopheng sena, 'me likhoto tsena li ne li le ngata le ho feta
hlokomela boemo ba leseli la masoba a karabelo nakong ea
likarolo tse seng kae tsa pele. Kahoo, haeba tšusumetso ea motho ea haufi-ufi e ka be e se ka mokhoa o hlakileng
liteko tse haelloang haholo li ile tsa lula li tiisitsoe ka matla
bokhoni ba ho tsosa setšoantšo sa sephetho se nepahetseng le se matlafatsang
boits'oaro. Ka hona ho ka bonahala eka tšusumetso ea ho hlohlona ea a
tlhahiso-leseling e haufi-ufi ha e ntlafatsoe ka bohona ha boleng ba hedonic
ea win e fokotseha. Mohopolo oa hore litsamaiso tsa boleng ba hedonic le tšusumetso
e ka khaoloa ke karolo e bohareng ea khothaletso-maikutlo
khopolo ea ho lemalla, eo ho eona tikoloho e amanang le eona
lithethefatsi li ka ba le tšusumetso e matla litekanyetsong tsa boitšoaro ntle le
thabo e nyenyefatsang e amanang le tšebeliso ea lithethefatsi (Robinson le Berridge, 1993; Wyvell le Berridge, 2000, 2001).
E tla ba ho khahlisang ho tseba, ka hona, hore na o haufi-ufi
stimuli le karolo e ts'oanang ea ho tsamaisa boitšoaro ba papali ea chelete joaloka
litumelo tse tsamaeang le lithethefatsi li etsa mabapi le tlhekefetso ea lithethefatsi, e khothalletsang ho oela hape
le ho lakatsa le kamora nako ea ho itima lintho tse ling (Dackis le O'Brien, 2001).
Re ka hlahloba mohopolo ona ka ho hlaka litekong tse ling, mohlala
ka ho bona hore na liteko tsa 2-light-near-miss li ka ntlafatsa puseletso
leha liteko tsa win li le sieo. Se fumanoeng mona se fana ka maikutlo
hore ho senya setsoalle lipakeng tsa liteko tse haufi-ufi le tse khotsofatsang
sephetho se ka fokotsa ts'ebetso ea ts'ebetso ea papali ea chelete. Ka har'a
liteko tsa hajoale, sena se entsoe ka ho pheta-pheta liteko tsa haufi-ufi
ka tšusumetso ea win e sa matlafatsoang - ketsahalo eo ho ka bang thata ho
tsebisa ka mokhoa o kholisang ho libapali tsa batho. Leha ho le joalo, mosebetsi oa morao-rao o ikemiselitseng ho
Ho senya mekhatlo ena ka thupelo ea CD ho hlahisitse khothatso
liphetho (Zlomke le Dixon, 2006; Dixon et al a, 2009), ho fana ka tlhahiso ea sena e ka ba kamano ea bohlokoa eo motho a ka e batlang ho latela pono ea kalafo.
Ho pepesetsoa khafetsa ho lithethefatsi tse lemalloang ho ka baka boemo bo phahameng ba dopaminergic, 'me ho tšoaetsoa ha motho ea sa tsebeng letho ka DA ho nahanisisa hore ho tiisa maikutlo a ntlafalitsoeng a maemo a susumetsoang a shejoang lithutong tse itšetlehileng ka lithethefatsi.Berridge le Robinson, 1998). Ka mokhoa o ts'oanang, PG e kanna ea kenyelletsa moputso o sa bonahaleng oa moputso ka ho sitisoa ha litsela tsa DA (Reuter et al a, 2005), le taolo e pheta-pheto ea kalafo ea agonist ea DA e ka baka PG ho bakuli ba bang ba Parkinsonia (Bona et al a, 2009). Litlaleho tsa Psychological li fana ka maikutlo a hore litšobotsi tsa sebopeho sa mochini oa slot, ho kenyelletsa le likotsi tse haufi, tlhokahalo e tlase ea kelello le litekanyetso tse phahameng tsa papali, li ka khothaletsa papali ea chelete e ngata kapa e tlamang.Breen le Zimmerman, 2002; Harrigan, 2008; Choliz, 2010). Teena Sistimi ea DA ka hona a ka ba le karolo ea bohlokoa ho hokahanyetsano le mochini oa slot, mme data e hlahisitsoeng mona e fana ka tšehetso e itseng bakeng sa boikaketsi bona.
Tsamaiso ea psychostimulant amphetamine, e ka etsang hore liketso tsa DA li fokotsehe
latency ea ho araba ka tatellano, haholo-holo kamora tlhahiso ea letšoao la win win (leseli le bonesitsoeng). Ho shebella hona ho lumellana le bokhoni bo tsebahalang ba amphetamine e matla ea ho eketsa karabelo ho li-cuishene tse nang le maemo (Robbins, 1978; Beninger et al a, 1981; Robbins et al a, 1983; Mazurski le Beninger, 1986). Ho joalo, keketseho ea likarabo tse bokelletsoeng kamora tsamaiso ea amphetamine e kanna ea ba mohlala o mong oa bokhoni ba sethethefatsi sena
eketsa karabelo ea pele bakeng sa moputso, joalo ka ha e hlahisoa ke ho eketseha
litefiso tsa karabelo holima matlafatso ea linako tse tlase (Segal, 1962; Sanger, 1978) le ho araba pele ho nako pele ho khethoa ka nako ea khetho ea bohlano ea karabelo ea (Cole le Robbins, 1987; Harrison et al a, 1997).
Leha ho le joalo, leha sena se ka bapala karolo litlamorao tse bonoeng,
amphetamine ha ea ka ea eketsa khetho ea mokoloto ho mong le o mong
mofuta oa teko. Haeba litlamorao tsa amphetamine li hlaha ka keketseho
ho khanna ho arabela ka mokokotlo o bonoang ke moputso, ke hona ho lokelang ho ba joalo
e shebiloeng ho sa tsotelehe semelo sa lebone. Ebile, phello ena feela
e fihletse bohlokoa ho tahlehelo e itseng ea 1-light le liteko tse hlakileng tsa tahlehelo, i.e.
Litekong tseo ho tsona ba bang ba khothalelitsoeng ka mokhoa o khothatsang haholo
e amanang le phano ea moputso: CS+) ba ne ba le teng. Ntle le moo, likarabo tse fosahetseng tsa bokhelohi bo hlahisitsoeng ke amphetamine li entsoe butle butle, li bonts'a khohlano e ntlafalitsoeng ea liqeto, mme ba boela ba bala tlhahiso efe kapa efe ea hore liphoofolo li ne li tiisetsa ha li khetha karabelo e amanang le moputso (Robbins, 1976). Kahoo, leha liphoofolo li bonahala li sa tsotelle boemo ba khanya ea mabone ka bomong, matla a amphetamine a ho ntlafatsa karabelo bakeng sa moputso kapa tšusumetso e khotsofatsang ha a lekana ho hlalosa litlamorao tsa sethethefatsi ho khetho ea lever.
Leha ho le joalo, ho tlalehiloe hore amphetamine e baka liphoso mosebetsing oa CD, joalo joalo
liphoofolo ha li na ho sebelisa mekhoa ea ho khetha hore na ke mohato o fe o loketseng (Dunn et al a, 2005).
A batla a tšoana le litlamorao tsa karabelo ea moraorao eo re e boneng mona,
tlhahisoleseling e kopantsoeng ke likhoele tse sebelisitsoeng ho CD e ne e ntse e le teng
sebetswa, joalo ka ha ho bonts'oa phetisetso e matla ea Pavlovian-to-instrumental (Dunn et al a, 2005).
Liphello tsa Amphetamine mosebetsing oa mochini oa slot li ka ba joalo
e hlahisitsoe ka lebaka la ts'ebetso ea CD e senyehileng. Le ha ho le joalo CD e senyeha
e bakoang ke amphetamine e khutlisoa ke tsamaiso ea tšebelisano ea D1, empa eseng D2, mohanyetsi (Dunn le Killcross, 2006), ho fana ka maikutlo a hore ts'ebetso e nepahetseng ea CD e susumetsoa ke D1- Ketsahalo e tšepahalang. Ho fumana hore D1-selebello
metsoako ha ea ka ea ama se ratoang ke ha motho ea bokellang a ka bontšang
hore boima bo boholo ba ho sebetsa melao ea dipehelo ha e khonehe ka botlalo
hlalosa litlamorao tsa amphetamine. Ntle le moo, ts'ebetso ea ts'ebetso e ne e se joalo
lefats'e ka bophara: liphoofolo li ne li ntse li le 100% e ne e nepile litekong tsa win, 'me litefiso tsa bona tsa liphoso li ne li sa fetoloe ho
Bongata ba mefuta ea liteko. Ho latela hore keketseho e kholo ka ho fetisisa ea liphoso e bile
ho hlokometsoe ka liteko tse hlakileng tse lahlehileng tse neng li le bobebe ho fapana le tse ngata
ho win, ho boetse ho bonahala ho sa ratehe hore amphetamine o sebelitse ka ho atoloha
gradient ea susumetsang maikutlo, le ha e le setlhare sena se fumanoe
ho eketsa liphoso tse mpe tse fosahetseng mosebetsing oa khethollo ea pono (Hampson et al a, 2010).
Tlhaloso e le 'ngoe ea litlamorao tsa amphetamine ke hore bokhoni ba se susumetsang ho hlahisa matšoao a DA a fetotsoeng, a lebisang ho leeme ho arabeleng tšusumetso joalo ka ha eka
li ne li entsoe ka moputso. Ho ts'ehetsa tlhahiso ena, D2 receptor agonist quinpirole e bile le litlamorao tse batlang li tšoana le amphetamine, lethal dose-le tšepahalang le ntseng le eketsa palo ea liphoso tsa ho bokella litekong tsa tahlehelo, leha phello ena e ile ea boleloa haholoanyane ho liteko tsa 1- le 2-light ho fapana le tahlehelo e hlakileng ka tekanyo e tlase. Mabapi le hore na phello ee e ka bonts'a keketseho ea karabelo ea pele ho moputso, litekanyetso tse tlase tsa quinpirole tse sebelisitsoeng mona ha li ntlafatse karabelo e fapaneng ho CS+ (Beninger le Ranaldi, 1992), le ho fokotseha ho fapana le ho eketsa karabelo pele ho 5CSRT (Winstanley et al a, 2010). Tlhahiso ea CS+ e lebisa ho hobosoa hoa ho lokolloa ha DA, athe ho hlakoloa hoa moputso o lebelletsoeng ho lebisa ho sefuba mosebetsing oa dopaminergic (Schultz et al a, 1997; hlola et al a, 2010). Ha re nahana ka moelelo ona o akaretsang, ho ka etsahala hore leseli le sa fetoheng la karabo e benyang le hlahise keketseho ea nakoana ho DA, athe ha ho phetoho kapa mohlomong ho kenella kahare ho DA ho ka baka haeba lesoba le theotsoeng moahong. Lipontšo tsena li ka theha motheo oa phoso ea ho bolela moputso e ka khethang ho bokella kapa ho tsamaisa litšepe, joalo ka ha ho fanoe ka karabelo ea li-neuron tsa dopaminergic ho susumetso e kholo ea meputso e boletsoeng esale pele ho litšoene (Nomoto et al a, 2010).
Mefuteng ea morao-rao, ho fanoa ka tlhahiso ea hore ts'ebetso e fetang ea D2 li-receptors li ka fokotsa khethollo ea letsoalo leseling le sa hlokeng letho ka ho fokotsa palo ea molumo-le-lerata, le ho thibela ho ts'oaroa ha karabo e nepahetseng ea DA (Floresco et al a, 2003; Li-Seamans le Yang, 2004). Ha ho le joalo, karabelo ea dopaminergic molemong oa tahlehelo ea tahlehelo e ka tšoana le e bonoang kamora ho hlohlelletsa ho win, liphoofolo tse ratang ho khetha khetho ea mokoloto. Boithutong ba morao-rao ba morao-rao ba papali ea slot-Machine, ts'ebetso ea lebatooa la midbrain dopaminergic sebakeng sa karabelo e haufi-hlokoang e ne e tsamaellana hantle le boemo ba boloi ba papali ea chelete papaling ea boithabiso (Chase le Clark, 2010), le kabo ea matšoao e ne e batla e tšoana le sephetho sa papali ea papali ea papali ea chelete empa e le tahlehelo liphellong tse laoloang tse seng tsa nnete (Habib le Dixon, 2010). Ka kopanelo, liphumano tsena li fana ka maikutlo a hore tšebetso kahare ho sistimi ea DA e kenya letsoho haholo tekanyetsong ea papali ea chelete. Mabapi le lefu la Parkinson, ho 'nile ha fanoa ka maikutlo a hore ts'usumetso e sa foleng ea D2 li-receptors — hangata litseleng tse sa tsamaellaneng — li thibela ho bonoa ha lits'oants'o tsa tšebetso ea dopamine tse latelang sephetho se fosahetseng, ka hona e khothaletsa boitšoaro ba papali ea chelete ho batho ba tlokotsing. (Frank et al a, 2004; Frank le Claus, 2006). Ka lebaka la litlhahiso tsena, sepheo se seng sa lipatlisiso tsa bokamoso ke
etsa qeto ea hore na bokhoni ba quinpirole ba ho khothaletsa ho bokella likarabo liphellong tsa liteko tsa tahlehelo ke ho se khone ho fumana phoso e sa lebelloang ea ho noha (ho hloka kutloelo-bohloko kotlong) kapa moloko oa tebello e ntle ea moputso, kapa ka bobeli.
Ho kile ha tlalehoa hore liteko tsa haufi-ufi, leha li le ngata haholo, li eketsa takatso ea ho tsoela pele ho becha ka metjhini ea slot (Kassinove le Schare, 2001; Cote et al a, 2003; MacLin et al a, 2007), mme sena se ka ama lebelo leo lithuto li qalang motjeko o latelang. Ka bomalimabe, morusu oa ho araba moqolo oa roll o ka khona
e se sebelisoe ho hlahloba tšusumetso ea ho qala nyeoe e latelang, kaha mohato ona o ile oa angoa ke nako ka bobeli ea ho sebelisa li-pellets tsa tsoekere kamora ho hapa le 10 Linako tsa ho tlohela nako tse bakoang ke karabelo e fosahetseng ea bokello. Ho kenyelletsa nako ea tlhahlobo ea liteko, e le hore karabelo e arohaneng ea lever e ka hlokoa ho qala nyeoe e latelang, e ka ntlafatsa bonnete ba sena
lekanya, 'me re khone ho tseba hore na mofuta o itseng oa teko o amme boikemisetso ba ho qala nyeoe e ncha. Ho rekota ka nepo phapang ena ho ka senola hore na maano a fetotseng palo ea liteko a phethiloe, mme/kapa khetho e amehang ea mokoloto oa pokello, e hlophisitsoeng ka mokhoa o ikhethileng molemong oa boikarabello ba mosebetsi.
Ho etsa mehlala ea ho becha liphoofolong le ho batho, ho kenyeletsa le khethollo ea kelello e pepesang kotsi ea tšoaetso ea methapo ea mafu (Ladouceur et al a, 1988; Toneatto et al a, 1997), e ka fana ka menyetla ea ho khetha lits'ebetso tsa "neural circry and neurotransmitter" tse tsamaisang mokokotlo oa ho becha (Campbell-Meiklejohn et al a, 2011). Pontšo ea hore likhoto li ka etsa mosebetsi o ts'oanang le mochini oa slot, mme li bonts'a bopaki ba phello e haufi-ufi, li ka bonts'a hore likhoto li angoa ke liphoso tse ling tsa kelello tse nahanoang hore li kenya letsoho ho bolokeng boitšoaro ba papali ea chelete (Clark, 2010; Griffiths, 1991; Reid, 1986). Lintlha tse tlalehiloeng mona li bonts'a hore DA, ka D2 li-receptors, li ka ba le karolo ea bohlokoa ho fetoleng tebello ea moputso nakong ea papali ea slot mochini. Ka kopanelo le lipatlisiso tsa bongaka, mokhoa ona o ka ntlafatsa kutloisiso ea rona ea papali ea boithabiso le mathata, mme oa tsamaisa nts'etsopele ea liphekolo tse ncha tsa PG.
Khohlano ea thahasello
CAW e kile ea buisana le Theravance ka taba e sa amaneng. Che
Bangoli ba na le likhohlano leha e le life tsa menyaka kapa tse hlahisitsoeng ke lichelete.
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