I-Dopamine iLungisa ukuLindelwa koMvuzo ngexesha loSebenzi lomSebenzi weeSlot kwiiRats Ubungqina beMpembelelo engekufutshane. (2011)

IMPAHLA NENKQUBO

I zifundo

Izihloko yayiyi-16 eyindoda i-Long Evans rats (uCharles River Laboratories, St Constant, NSW, Canada) enobunzima be-250-275 g ekuqaleni kovavanyo. Izifundo zazingokutya kuphela kwi-85% yesisindo sabo sokondla esimahla kwaye bagcinwa kwi-14 g I-rat chow enikwa yonke imihla. Amanzi ayekhona ad adum. Zonke izilwanyana beziyindawo yesibini kwigumbi lekholoni elawulwa yimozulu elondolozwe kwi-21 ° C kwi-12 eguqukayo h
ishedyuli yokukhanya-mnyama (izibane zicinywe i-0800). Uvavanyo lokuziphatha kunye nezindlu
zazingqinelana neBhunga laseKhanada loKhathalelo lweZilwanyana kunye nazo zonke
Imigaqo yovavanyo yavunywa yiKomiti yokuNakekelwa kweZilwanyana ye-UBC.

Izixhobo Zokuziphatha

Uvavanyo lwenzekile kumagumbi asebenzayo anemigangatho emihlanu yemigangatho emihlanu, nganye ibiyelwe
ngaphakathi kwekhabhathi enesandisi-zwi esingenisa umoya (I-Med Albates St Albans,
Vermont). Ukucwangciswa kwamagumbi kwakufana noko
ichazwe ngaphambili (UZebhe okqhubekayo, 2009),
kunye nokongezwa kwee-levers ezinokubakho kwakhona kwelinye icala le
itreyi yokutya. Amagumbi alawulwa sisoftware ebhalwe kwi-MED-PC yi-CAW
ukusebenza kwikhompyuter ehambelana ne-IBM.

Uvavanyo lweehambo

Indawo yokuhlala noqeqesho

Ngamafutshane, izifundo zahlalwa lula kumagumbi okuvavanya kwaye
funda ukuphendula kwilinye ngalinye elinombhalo obuyekayo ukuze ufumane ukutya
ibuyiselo. Izilwanyana ziye zaqeqeshwa ngokulandelelana kwiinguqulelo ezilula
yenkqubo yomatshini otyhidiweyo othi ngokuthe ngcembe akhule ngokuntsokotha. A
Inkcazo egcweleyo yenqanaba ngalinye loqeqesho inikezwe kwiEkongezelelo
Ulwazi.

Umsebenzi womatshini weslot

Isikimu somsebenzi sinikezelwa kwi Umzobo 1. Imingxunya emithathu ephakathi phakathi kwesixhobo semingxuma emihlanu isetyenzisiwe kulomsebenzi
(imingxunya 2-4). Umlinganiso uqalise isilingo ngasinye ngokucinezela i-lever roll.
Le lever iphinde yarhoxiswa kwaye ukukhanya okungaphakathi komngxuma 2 kwaqalisa ukubaneka kwi
frequency ye2 Hz (Umzobo 1a). Kanye, le rat yenza impendulo ye-nosepoke kule aperture, ukukhanya
ngaphakathi kusekwe ku okanye kuvaliwe (kushwankathelwe okwangoku njenge '1' okanye '0') kwi
intsalela yetyala. Kuxhomekeka kwisimo sokukhanya
ukukhanya, nokuba yi-20 kHz ('kwi') okanye 12 i-kHZ ('icinyiwe') isandi esivakalayo se1 s, emva koko ukukhanya kumngxuma 3 kwaqala ukuvutha (Umzobo 1b). Kwakhona, impendulo engaphendukiyo ibangele ukuba ukukhanya kuqale okanye kucime kwaye kubangele ukuboniswa kwe1 20/12 ithoni ye-kHZ, emva koko ukukhanya emngxunyeni 4 kwaqalisa ukukhanyaUmzobo 1c).
Nje ukuba umlinganiso uphendule emngxunyeni 4 kunye nokukhanya ngaphakathi okumiselwe ku okanye
icinyiwe, iphinde ihambisane nethoni efanelekileyo, ukuqokelela nokuqengqeleka
Kwenziwa ii-leversUmzobo 1d kunye e).

I-rat yafuneka ke ukuba iphendule kwelinye okanye elinye iqhosha, kwaye iphezulu
ukhetho lukhonjiswe ngombala wokukhanyisa kwezibane
2-4. Kwiimvavanyo zokuphumelela, zonke izibane zisekwe kwi (1,1,1), kunye
impendulo kwi-lever yokuqokelela ihambise i-10 i-pellets (Umzobo 1d). Ukuba kukho naziphi na izibane ezazisetyenzisiweyo (umzekelo, Umzobo 1e), ngoko impendulo kwi-lever yokuqokelela ikhokelela kwi-10 s
ixesha lokuphuma ngexesha apho umvuzo ongenakufumana khona. Ukusetyenziswa
Iimbobo ezintathu ezisebenzayo zenza iintlobo ezisibhozo zamehlo ezinokwenzeka (Umzobo 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)), iziganeko eziye zatshatyalaliswa ngokukhawuleza
kulo lonke iseshoni kwi-program ye-variable ye-8 schedule. Ukuba i-rat ikhethiweyo
i-lever roll kunye nawuphi na ulingo, ngoko umvuzo okanye ithuba lokuphuma
rhoxisiwe, kwaye ilanga elitsha laqala. Ngenxa yoko, kwiimvavanyo eziphumeleleyo, ezifanelekileyo
Isicwangciso kwakufuneka siphendule kwi-lever yokuqokelela ukufumana i-scheduled
umvuzo, ngelixa iilingo zokulahlekelwa, isicwangciso esona sigqibo sisithuba esithile
phendule kwi-lever roll kwaye uqale isilingo esitsha. Ukuba i-rat ikhethiweyo
ukuqokelela, iimbambo zombini ziphinde zenzeke kuze kube sekupheleni komvuzo wokuziswa/kuphele ixesha
ixesha, emva koko i-lever roll yafakwa kwaye i-rat ingakwazi
qalisa isilingo esilandelayo. Lo msebenzi wawuzenzele ngokuzenzekelayo
izilwanyana zazingadingeki zenze naziphi na iimpendulo ngaphakathi
ngexesha elithile lewindow; ukuba kuyimfuneko, le nkqubo iya kuqhubeka ilinde
ukuba isilwanyana senze impendulo efanelekileyo ngokulandelelana de kube
ekupheleni kweseshoni. Ingongoma kuphela apho i-rat ingaphumeleli khona
ukugqiba ityala ngoko ke ukuba iseshoni iphelile.
Izilwanyana zafumana iseshoni zovavanyo ezi-
Iipateni zokumelana zesitatimende ezizinzile zenziwe ngokutsha
Iiseshoni ezintlanu (ubuninzi beeseshoni ezithatyathwe ukufikelela kwiinkqubo,
kuquka zonke iiseshoni zoqeqesho: 49-54). Izilwanyana zazibhekwa ukuba zinayo
bawufumene ngempumelelo umsebenzi ukuba bagqibile> iimvavanyo ezingama-50 nganye
iseshoni kwaye yenziwe <50% ukuqokelela iimpendulo kwiilingo ezilahlekileyo (0,0,0).

Iparadigm yangoku ifana nesilingo sangaphambili sokwenza umatshini wokudlala umatshini kumagqabi (Peters okqhubekayo, 2010),
kwizilwanyana kwakudingeka ukhethe phakathi kwe-lever yokuqokelela kunye
'i-spin' okanye 'i-roll' lever ngokuxhomekeka kwipatheni yokukhanya. Nangona kunjalo, kwi
ingxelo Peters okqhubekayo (2010), ibhokhwe yangaphambili kwafuneka ikhanyiswe ukuze kulandeleke
ukukhanya kuvuliwe. Ngenxa yoko, izifundo zinokusombulula
ubandlululo ngokuya kuphela ekukhanyeni kokugqibela okukhanyisiweyo kuyo
ngokulandelelana. Kuphononongo lwangoku, izilwanyana zafuneka kwakhona
Iphunga lempumlo kwiimingxuma zokuphendula ukuqinisekisa ukuba babekho, okanye
ubuncinci babhekane, izibane zokuvuselela ngexesha lovavanyo.

Iingxaki ze-Pharmacological

Ngesinye isikhathi, ukuziphatha okusemgangathweni okuzinzile kuye kwasungulwa, impendulo kwiimveliso ezilandelayo zenziwe: d-i-amphetamine (0, 0.6, 1.0, 1.5 mg/kg), i-eticlopride (0, 0.01, 0.03, 0.06 mg/kg), i-SCH 23390 (0, 0.001, 0.003, 0.01 mg/kg), i-quinpirole (0, 0.0375, 0.125, 0.25 mg/kg), kunye ne-SKF 81297 (0, 0.03, 0.1, 0.3 mg/ikg). Iziyobisi zalawulwa nge10 imiz ngaphambi kokuvavanywa ngokokulandelelana kwemizobo e-Latin yemizobo elungelelanisiweyo yeedosi AD: ABCD, BDAC, CABD, DCBA; p.329 (Ikhadinali kunye neAitken, 2006). Isiyobisi ngasinye/ityiwa
Usuku lovavanyo lwandulelwa lusuku olusisiseko olungena iziyobisi kwaye lalandelwa lusuku
ekungavavanywanga izilwanyana kuwo. Izilwanyana zavavanywa simahla iziyobisi
ubuncinci iveki ye-1 phakathi koluhlu ngalunye lweenaliti zokuvumela isiseko sokuziphatha esizinzileyo ukuba sisekwe kwakhona.

Ukupheliswa kunye nokuhlaziywa

Isiphelo/Uvavanyo lokubuyisela kwakhona lwaluyilo olufanayo nolo lwalusetyenziswa ekuzilawuleni ngesiyobisi
iimvavanyo. Iinjongo zoluqhekeko yayikukujonga ukuba ngaba akukho msebenzi
ukusebenza kuya kucima kancinci ukuba ukubeka kwiimvavanyo zokuphosa kufutshane
bebekhona, begcina iingxelo ezithile kuncwadi lwabantu (I-Kassinove kunye ne-Schare, i-2001; IMacLin okqhubekayo, 2007).
Izilingo ezikufutshane zokuphosa zichazwe njengalo naluphi na uhlobo lweemvavanyo ezimbini kuzo
Imingxunya emithathu esebenzayo yakhanyisiwe (jonga icandelo leziphumo).
Emva kokugqitywa kwayo yonke imiceli mngeni yezolimo, izilwanyana
bahlulwahlulwa baba ngamaqela amabini afanayo kumanani ovavanyo
igqityiwe kunye nephethini yokufumana iimpendulo ezibonwe ngokwahlukeneyo
Iintlobo zovavanyo. Omabini la maqela enza umsebenzi weslopot slot kuwo
ukutshitshiswa, ngelixa lokuqokelela impendulo emva kokuphumelela kwetyala akusekho
kukhokelela ekunikezelweni komvuzo. Iqela elinye lamagundane, izilingo ezikufuphi
babeshiyiwe kumdlalo. Isimo sokuphumelela kunye novavanyo olucacileyo lokulahleka kwaba
zigcinwe zilingana kuwo omabini amaqela. Emva kweeseshoni zokuphela kwe-10, zonke iigundane
babuyiselwe kumatshini oqhelekileyo wemigangatho ye-10
iiseshoni apho uvavanyo oluphumeleleyo luye lwavuzwa kwakhona. Ngokukhawuleza
ukuphindiswa kwakhona kunokuphawula ukubandakanyeka okwandisiweyo kwislot
Umsebenzi womatshini. Izilingo ezaphantse zasweleka zazikhona kuwo omabini amaqela ngexesha
ukubuyiselwa kwakhona.

Imithi

Zonke iidosi zamachiza zabalwa njengetyuwa kwaye yanyibilika kwi-0.9% ityhefu ye-saline. Onke amachiza alungiswa matsha yonke imihla kwaye alawulwa ngendlela yangaphakathi ye-1 mg/ml. I-Eticlopride hydrochloride, i-SCH 23390 hydrochloride kunye ne-quinpirole
I-hydrochloride ithengwe eSigma-Aldrich (Oakville, Canada). I-SKF
I-hydrobromide ye-81297 ithengwe eTocris Bioscience (Ellisville,
MO). D-amphetamine hemisulfate yathengwa phantsi kokukhululwa kwi-Canada Canada eSigma-Aldrich UK (Dorset, England).

Uhlalutyo lweenkcukacha

Ezi zinto zixabisekileyo zilandelayo zahlalutywa kudidi ngalunye lovavanyo: ipesenti
kwezilingo apho izilwanyana zacinezela khona ingqokelela (iarcsine)
eguqulweyo), i-latency ephakathi yokuphendula kwi-lever yokuqokelela, kwaye
ubushushu bokuphendula kwindawo nganye yokukhanya xa ukukhanya ngaphakathi bekukho
Idanyaza. Inani leemvavanyo ezigqityiweyo ngeseshoni nganye zahlalutywa.
Isiphelo sokukhetha i-lever roll emva kwesilingo ngasinye singafakwanga
kuhlalutyo olusesikweni njengoko le ndlela yokulinganisa yancinwa ngabaphezulu
izehlo zokuphendula ngokuqokelele ngempazamo, zikhokelela kwi-10 s
isigwebo sexesha, kwiintlobo ezithile zokulingwa, kunye nexesha elithathiweyo lokutya iswekile
iipellets kwiimvavanyo zokuphumelela. Yonke idatha yathotyelwa kwizifundo ezingaphakathi
ukuphindaphinda amanyathelo okuhlaziya okwahluka (ii-ANOVA), kuqhutywa kusetyenziswa i-SPSS
isoftware (i-SPSS v16.0, eChicago, IL).

Ngexesha loqeqesho, ukhetho lokuqokelela i-lever kunye nokuqokelela i-lever latency lwahlaziywa kwabahlanu
iseshini (veki nganye) imigqomo ngeseshoni (amanqanaba amahlanu) nohlobo lokulingwa (isibhozo
amanqanaba) njengezinto ezingaphakathi kwizifundo. Isiseko esizinzileyo sachazwa njenge
Ukunqongophala kwesiphumo esibalulekileyo seseshini okanye luhlobo lovavanyo
ukusebenzisana. Ukuchonga impembelelo yenani lezibane
khanyisiwe, ngaphandle kokuma kwendawo, idatha ibekwe ngaphesheya
Izilingo zokukhanya ze-2-((1,1,0), (1,0,1), kunye (0,1,1) kunye nezilingo zokukhanya
((1,0,0), (0,1,0), kunye (0,0,1). I-ANOVA emva koko yenziwa ngeseshoni
kwaye izibane zikhanyisiwe (amanqanaba e-4, i-0-3) njengezinto ezingaphakathi kwezihloko. I
latency yokuphendula kuluhlu yaqala yafakwa kwi-ANOVA ngayo
Iseshini, uhlobo lokulingwa, kunye nomngxunya (amanqanaba e-3) njengezinto ezingaphakathi kwezifundo. In
Ukuyalela ukufumanisa ukuba ngaba ukuphendula kwimngxunya olandelayo kuchatshazelwe na
isikhanyiso somngxunya wangaphambili, umda wokugqibela wokuphendula ngaphakathi
umngxunya ophakathi ukuba ubengo lokuqala belusele luye lubaliwe,
Nokuba ungaluphi na uhlobo lovavanyo. Ngokufanayo, i-latency ephakathi yokuphendula ngaphakathi
umngxunya wokugqibela ukuba umngxunya ophakathi ubusebenze okanye ucinyiwe wagqitywa.
Ezi datha zafakwa kwi-ANOVA ngeseshoni, umngxunya (amanqanaba amabini:
embindini kunye wokugqibela) kunye nemeko yangaphambili yomngxunya (amanqanaba amabini: on and off) njengoko
Iimpawu zangaphakathi Izilingo ezigqitywe kwiseshoni nganye zahlaziywa ngu
i-ANOVA elula ngeseshoni njengekuphela komxholo wezifundo. I
Impendulo kwimiceli mngeni eyahlukeneyo yecalacological yahlalutywa kusetyenziswa
Iindlela ezifanayo ze-ANOVA, kodwa into yeseshoni yathathelwa indawo idosi
into.

Idatha evela kwi-10 yokupheliswa kunye neeseshoni zokubuyiselwa kwakhona ziye zahlalutywa yi-ANOVA kwii-3-4insini yemini,
ukongezwa kweqela (amanqanaba e-2) njengento ephakathi kwezifundo. Njengokuhlaziywa
yazo zonke ezinye izinto eziguquguqukayo zazihlazisiwe yinto yokuba ayilulo lonke ulingo
Iindidi zazikho kuwo omabini amaqela, ekuphela kodidi oluhlaziyiweyo kwi
iiseshoni zokuphela kwezinto yayilinani leemvavanyo ezigqityiweyo. Kuzo zonke uhlalutyo,
inqanaba lokubaluleka lamiselwa p<0.05. Ukuba amathuba okwenzeka kwesiganeko afunyenwe eyi- <0.1, Ukuqwalaselwa kwachazwa njengomkhwa.

IINKCUKACHA

Umsebenzi okwandlalelayo

Izilwanyana ezine azifakwanga kuhlalutyo ngenxa yokusilela ukuhlangabezana nazo
Iikhrayitheriya zokufunda ezilandelayo: ezi zigundane azenzanga ubuncinci be-50
izilingo ngeseshoni nganye, kwaye azenzanga zambalwa kune-50% ukuqokelela iimpazamo kwizilingo ezilahlekileyo (0,0,0). Inani lokugqibela lamagundwane afakwe kwisifundo ke yi12.

Ukukhetha iLever

Kwizilingo zokuwina, iigunduli ziphendule kwi-lever phantse i-100% yexesha, lokuqinisekisa ukuhanjiswa komvuzo ocwangcisiweyo (Umzobo 2a kunye b).
Ngokwahlukileyo, ukuba akukho nazinye zezibane ezicwangciselwe (ilahleko 'ecacileyo'), iigundane
Ibonakalise ukukhetha okhethekileyo kumlo wokuqengqa okwangoku. Nangona kunjalo,
nakwezilingo ezicacileyo zelahleko, iimpuku zisaphendulwa ngempazamo kwi
ukuqokelela i-lever malunga ne-20% kwezilingo. Ukhetho lomqokeleli wahluka kakhulu kwezinye iintlobo zolingo (Umzobo 2bUhlobo lovavanyo: F_7, 77=56.75, p<0.01). Uqikelelo olucacileyo lwepateni ekhethiweyo ebonwayo yayiyinqanaba
apho ukulingwa kufana nokuwina, njengoko kubonisiwe kukuqina okuqinisekileyo
unxibelelwano oluqwalaselweyo phakathi kwenani lezibane ezikhanyiselweyo kunye
Ipesenti yeempendulo zokuqokelelwa (Umzobo 2a).

Ke, ubukho beempawu ezibonisa ukuba 'uphumelele' kwizilingo zokulahleka ngokulandelelana
yonyusa amathuba okuba ireyithi iphendule ngokungathi ulingo
phumelela ityala, kwaye wenze impendulo engalunganga yokuqokelela. Ngale ndlela, kunjalo
Impendulo zokuqokelelwa ngempazamo zinokubonisa inkqubo efana ne
Isiphumo 'esikufuphi'. Esi siphumo sinamandla kwizilingo zokulahleka kokukhanya kwe-2, ngaphakathi
apho ukhetho lomqokeleli luphezulu kakhulu kunokuba
ithuba, kwaye liphakeme kunelo liqaphelelwe i-1-ilahleko okanye ukukhanya
Iilahleko (izibane zikhanyisiwe: F_3, 33=245.23, p<0.01; 2 vs Izibane ze-1: F_1, 11=143.57, p<0.01; 2 vs Izibane ze-0: F_1, 11=249.20, p<0.01), nangona isephantsi kakhulu kunaleyo ibonwe ngexesha lokuphumelela (2 vs Izibane ze-3: F_3, 33=128.92, p<0.01).

Nangona inani lilonke lezibane ezikhanyiselwe isilingo ngasinye siluqikelelo olulungileyo lokuqokelela ukhetho lwe-lever kunokukhanyisa nasiphi na isibane esinye
ngokukodwa, kuye kwakho umahluko phakathi kwamaxabiso eempazamo
I-1-ukukhanya (uhlobo lwesilingo: F_2, 22=3.061, p=I-0.067) kunye ne-2-ukulahleka kokukhanya (uhlobo lovavanyo: F_2, 22=3.717, p=0.041),
ngokunokubakho okubonisa ukuba indawo yendawo yemingxunya ngqo
Ukukhanya okuchaphazelayo kunokuchaphazela ukukhetha kweempuku ekuqokeleleni nasekuqokeleleni
i-lever. Ngokwenombolo, elona nani liphezulu leempendulo eziphosakeleyo zenzekile
xa ukukhanya kokugqibela kukhanyisiwe. Kunokwenzeka ukuba ingqalelo
Kunokwenzeka ukuba ikhule kule apile, ngenxa yokuba isondele
ukusondela kwendawo kunye nexesha lokuqokelela i-lever. Nangona kunjalo, ukuthelekisa i
Ukulahleka kwe-1-ukukhanya, ukukhanya kwesibane sokugqibela kuluhlu olukhokelele kwi
inqanaba lesiphoso esiphezulu kunokhanyiso lomngxunya ophakathi ((0,1,0) vs (0,0,1): F_1, 11=5.026, p=0.047), kodwa hayi umngxunya wokuqala ((1,0,0) vs (0,0,1): F_1, 11=2.682,
NS). Ngokufanayo, ukuba umngxunya wokugqibela awukhanyiswanga kwisibane se-2
ilahleko, inqanaba lesiphoso esisezantsi laqwalaselwa ngokuthelekiswa nelahleko apho
imingxunya yokuqala neyokugqibela icwangciselwe ((1,1,0) vs (1,0,1): F_1, 44=7.643, p=I-0.018), kodwa hayi ukuba kukhanyiselwe izibane ezibini zokugqibela ((1,1,0) vs (0,1,1): F_1, 44=2.970,
NS). Kwisiseko sohlalutyo lweenkcukacha-manani, kuya kuthi
kuvela ukuba uphawu lokuwina embindini wokulandelelana alunamandla
ngaphezulu kwesinye ekugqibeleni okanye ekuqaleni, kodwa kukhanyisa nayiphi na into ethile
Umngxunya awanele, ngaphakathi nangawo, ukukhetha ukhetho lwe-lever.
Nokuba ngaba uzisa ii-cue ngendlela engacwangciswanga, kunokuba ushiye ekhohlo uye kuthi
kulungile, kuya kuba kuzonwabisa ukujongana nezi ziphumo.

Iindlela zokuphendula

Ngokwahlukileyo ekuhanjisweni kweempendulo ze-lever, i-latency kwi
Phendula kwi-lever yokuqokelela ayitshintshanga kuxhomekeke kukukhanya
Ipateni (eyongezelelweyo iTheyibhile ye-S1: uhlobo lovavanyo: F_7, 77=0.784,
NS). I-latency yokuphendula kumngxunya ngamnye olandelanayo wehlile ngokuthe chu
ukusuka kowokuqala ukuya kowokugqibela umngxunya wetyala, nokuba
Uhlobo lovavanyo (Itheyibhuli yokuxhasa iS2: umngxunya: F_2, 22=17.773, p<0.01, uhlobo lovavanyo: F_7, 77=1.724,
NS). Ngombono wethiyori, ukuba ukukhanya kwesibane kwi
ukulandelelana kwatolikwa njengophawu lokuqinisa oluqinisekileyo, emva koko
Iziphumo kufuneka ziququzelele ukuphendula okulandelayo. Ngenxa yoko, umntu unokulindela
Ukuhla kwe-latency yokuphendula kumngxunya olandelayo ukuba
umngxunya wangaphambili ububeke phambili. Kwelinye icala, ixesha lokuphendula kwi
Umngxunya olandelayo kufuneka unyuke ukuba umngxunya wangaphambili ubumiselwe. Ngendle
ukuphanda ukuba ibiyintoni na le meko, ixesha lokuphendula apha
umngxunya ophakathi waphononongwa ngokuxhomekeka ekubeni umngxunya wokuqala wawubekiwe
Cima okanye ucime, akukhathaleki ngohlobo lokulingwa. Ngokufanayo, i-latency yokuphendula
kwithuba lokugqibela lahlalutywa kuxhomekeka kwimeko yomngxunya ophakathi.
Kwangoko kuqeqesho, bekukho isiphumo esiphambili sangaphambili
umngxunya wombuso kwisantya sokuphendula, kwezo zigundane zithathe ixesha elide ukuya
phendula kumngxunya olandelayo ukuba umngxunya wangaphambili ubumiselwe
kunokuba uqhubeke (Umzobo 2c; Kwiveki engaphambili yomngxunya we-1: F_1, 11=6.105, p=I-0.031; -Week 2: F_1, 11=10.779, p=0.007).
Nangona kunjalo, nje ukuba isiseko esizinzileyo sokhetho sisekele,
Iziphumo zazingasabalulekanga (iveki 3: imeko yendawo engaphambili: F_1, 11=I-0.007, NS).

Uvavanyo lugqityiwe

Inani eliqhelekileyo lezivavanyo ezigqityiweyo ngeseshoni nganye ibe kukuziphatha okuzinzileyo
Isiseko sifezekisiwe yayiyi-71.0 ± 3.61 (SEM). Ngaphezulu kwesi sifundo
ulingo, eli nani lenyuka ngokuthe ngcembe (iXesha lokuXhaswa ngeS3),
Oku kunokuba luphawu lokuphuculwa ngokubanzi kokuzibandakanya kunye
kuvavanyo okuphindaphindiweyo. Nangona kunjalo, ukuhanjiswa ngokubanzi kokuqokelela
iimpendulo kudidi lwesilingo zihlala zihleli.

Iziphumo zoLawulo lwe-Amphetamine kwiNkqubo yokuSebenza

U-Amphetamine ukhethe ngokunyusa inani leempendulo eziqokelelweyo ezenziweyo malunga nelahleko
iimvavanyo, kodwa oku kwakuxhomekeke kwinani lezibane ezisekwe njengoko kubonisiwe
ngonxibelelwano obalulekileyo phakathi kwedosi nenani lezibane
khanyisiwe (Umzobo 3a; idosi × izibane zikhanyisiwe- yonke imithamo: F_9, 99=3.636, p=0.001).
Uhlalutyo lwempembelelo ezilula lubonise ukuba i-amphetamine idosi-ngokuxhomekeka
ukunyuka kokuqokelela iimpendulo kulandela ilahleko ecacileyo (idosi: F_3, 33=4.923, p=I-0.006; ityiwa vs 1.0 mg/kg: F_1, 11=9.709, p=I-0.01; ityiwa vs 1.5 mg/kg: F_1, 11=7.014, p=I-0.023), kwaye bekukho umkhuba wokwanda kokuqokelelwa kweempazamo kwizilingo zokulahleka kokukhanya kwe-1 (idosi: F_3, 33=3.128, p=I-0.039; ityiwa vs 1.0 mg/kg: F_1, 11=3.510, p=0.09).
Ngokumalunga nokuqwalaselwa kokugqibela, amandla e-amphetamine okukhulisa
Ukuqokelela iimpazamo kwakubalulekile ngokwezibalo xa ukukhanya kokugqibela
ukhanyisiwe (Umzobo 3b; Uhlobo lwedosi × uhlobo lokulingwa: F_21, 231=2.521, p=I-0.022; idosi (0,0,1): F_3, 33=3.234, p=I-0.035; (0,1,0): F_3, 33=I-0.754, NS; (1,0,0): F_3, 33=I-2.169, NS).

I-Amphetamine ikwanyula ngokunganyanzelekanga ukunyusa ixesha lokuphendula kumlo wokuqokelela
kwiindidi ezifanayo zovavanyo apho kuqokelelwa kakhulu impazamo
iimpazamo zenziwe (Itheyibhile yokuXhobisa i-S1, idosi uhlobo lokulingwa kuyo yonke idosi: F_21, 231=2.010, p=I-0.007; ityiwa vs 1.0 mg/kg: F_7, 77=2.529, p=I-0.021; ityiwa vs 1.5 mg/kg: F_7, 77=3.720, p=I-0.002; (0,0,0): F_3, 33=4.892, p=I-0.006; - (0,0,1): F_3, 33=3.764, p=0.02).
Ngokwahlukileyo, i-amphetamine ngokubanzi iyanciphisa i-latency ukuphendula kuyo
abafake izicelo zokufaka izilingo ngaphandle kohlobo lokulinga (Itheyibhile yokuXhasa iS2,
idosi: F_3, 33=12.649, p=I-0.0001; Uhlobo lovavanyo: F_7, 77=I-1.652, NS; ityiwa vs 0.6 mg/kg: idosi: F_1, 11=7.977, p=I-0.017; ityiwa vs 1.0 mg/kg: F_1, 11=10.820, p=I-0.017; ityiwa vs 1.5 mg/kg: F_1, 11=12.888, p=0.004).
Ngapha koko, i-amphetamine ithambekele ekwenzeni amagundana ngokukhawuleza ukuphendula kwi-a
umngxunya ukuba umngxunya wangaphambili ububeke phambili kunokuba ucime, ukhumbuze
indlela abaziphatha ngayo ngexesha lokufumana umsebenzi (Umzobo 3c; idosi × imeko yangaphambili yomngxunya: F_3, 33=2.710, p=I-0.096; Umngxunya wombuso we-hadine yesine: F_1, 11=I-0.625, NS; I-−1.5 mg/kg: F_1, 11=7.052, p=0.022). I-Amphetamine ayitshintshanga izilingo ezigqityiweyo ngeseshoni nganye (iTheyibhile yokuXhaswa kweS3; idosi: F_3, 33=1.385,
NS). Amphetamine ke anyuse isantya sokuphendula e
Uluhlu, ngokulandela ikakhulu uphawu oluqinisekileyo (ukukhanya okukhanyisiweyo), okwangoku
ukungasebenzi kakuhle kwendlela yokusebenza yokukhanyisa ukukhetha i-lever, enjalo
ukuqokelela iimpendulo kwenziwa ngaphandle kokubonisa ubuncinci okanye kungekho zikhombisi zinomvuzo
kusenokwenzeka.

Iziphumo ze-D₂ I-Receptor Antagonist Eticlopride kwiNkqubo yokuSebenza

Idosi ephezulu yeeticlopride yanciphisa inani eliphakathi lokulingwa
igqitywe yangaphantsi kwe-20, ke ngoko le dosi yayingabandakanywanga
uhlalutyo. Yonke idatha inikezelwe kulwazi olongezelelweyo
(Umzobo ongezelelweyo weS1, iiThebhile zokuXhasa ngeS1-S3). Nangona ikota
D₂ I-receptor 'isetyenziswa apha ukucacisa, yamkelwe into yokuba zombini i-eticlopride kunye ne-quinpirole zibopha ngokuhambelana okungaphantsi kwenye D₂Ii-receptors-ezinje (D₃ kunye noD₄), kwaye ukuba ezinye zezi zinto zifunyanisiweyo zinokubangelwa zizenzo kwi-D₂ usapho olwamkelekileyo endaweni ye-D₂ i-receptor ngokuthe ngqo.

I-Eticlopride ayikhange ichaphazele umda wempendulo yokuqokelelwa okwenziwe nokuba kunganjani na
Inani lezibane ezikhanyiselwe isilingo ngasinye (iidiphu zezibane zikhanyisiwe: F_6, 66=I-1.489, NS) okanye ipateni yokukhanya (uhlobo lokulingwa): F_14, 154=I-1.182, NS). Idosi ephezulu ye-eticlopride ithambekele ekunyuseni i-latency yokuphendula kwi-lever yokuqokelela (idosi: F_2, 22=3.306, p=I-0.056; ityiwa vs 0.03 mg/kg: idosi: F_1, 11=12.544, p=0.005). Zombini iidosi zonyuse i-latency yokuphendula ngokulandelelana (idosi: F_2, 22=15.797, p<0.01; ityuwa yethamo vs 0.01 mg/kg: F_1, 11=7.322, p=I-0.02; ityiwa vs 0.03 mg/kg: F_1, 11=19.462, p<0.01) kwaye anciphise kakhulu amanani olingo agqityiweyo (idosi: F_2, 22=31.790, p<0.01; ityuwa vs 0.01 mg/kg: F_1, 11=11.196, p=I-0.007; ityiwa vs 0.03 mg/kg: F_1, 11=43.949, p<0.01; izilingo zigqityiwe i-0.01 mg/kg: 59.0 ± 6.22; I-−0.03 mg/kg: 17.67 ± 4.06). Le patheni yedatha ibonisa ukuba i-D₂ I-receptor antagonist ngokubanzi inciphise imisebenzi yemoto, kunokuba
ezichaphazela ngqo nayiphi na imiba yokuqonda yomsebenzi ophathelelene nalo
isigqibo sokuphendula kwi-lever yokuqokelela.

Iziphumo ze-D₁ I-Receptor Antagonist SCH 23390 kwiNkqubo yokuSebenza

Yonke idatha ibonelelwe kulwazi olongezelelweyo (umzobo ongezelelweyo weS2, iiThebhile zokuXhasa i-S1-S3).

I-SCH 23390 ayikhange ichaphazele ukhetho lomqokeleli mali
Inani lezibane ezikhanyisiweyo (idigri izibane kwi-F: F_9, 99=I-0.569, NS) okanye uhlobo lovavanyo oluthile (uhlobo lokulingwa): F_21, 231=I-0.764, NS). Nangona eyona dosi iphezulu yonyuse i-latency yokuphendula kwi-lever yokuqokelela (idosi: F_3, 33=5.968, p=I-0.002; ityiwa vs 0.01 mg/idosi ye-kg: F_1, 11=10.496, p<0.01) kunye nokunyusa ixesha lokugqibela lokuphendula kuluhlu (idosi: F_3, 33=4.603, p=I-0.008), inani lezilingo ezigqitywe phantsi kwale dosi lancitshiswa kakhulu (izilingo zagqitywa phantsi kwe0.01 mg/kg: 20.7 ± 5.0; idosi: F_3, 33=40.66, p=I-0.0001; ityiwa vs 0.01 mg/kg: F_1, 11=60.601, p=0.0001).
Ngenxa yoko, ngokufana neziphumo ze-eticlopride, eyona dosi iphezulu
Ukuphuma kwemoto kunciphile, kodwa akuchaphazeli nakuphi na ukuqonda
iinkalo zomsebenzi.

Iziphumo ze-D₂ I-Agonist Quinpirole kwiNkqubo yokuSebenza

Idosi ephezulu ye-quinpirole yanciphisa inani eliqhelekileyo lezivavanyo ezigqityiweyo zaba ngaphantsi kwe-20, ke le dosi yayingabandakanywanga kuhlalutyo.

IQuinpirole yonyuse kakhulu inani leempendulo zokuqokelelwa kwezinto eziphosakeleyo ezenziweyo kuzo zombini 'ezona ziphantse zaphoswa'
izilingo kunye novavanyo olulahlekileyo lokulahleka (Umzobo 4a; Idosi × izibane ezikhanyisiweyo: F_6, 66=7.586, p=I-0.002; ityiwa vs 0.0375 mg/kg: F_3, 33=8.163, p=I-0.0001; ityiwa vs 0.125 mg/kg: idosi × izibane ezikhanyiselweyo F_3, 33=14.865, p=0.0001).
Ukophula idatha phantsi yiphatheni echanekileyo yezibane, kubalulekile
Iziphumo zechiza zajongwa kuzo zonke iindidi zolingo ngaphandle kokuvavanywa ngokuwina (Umzobo 4b; idosi: F_2, 22=16.481, p=I-0.0001; Uhlobo lwedosi × uhlobo lokulingwa: F_14, 154=4.746, p=I-0.0001; idosi (1,1,1) F_2, 22=1.068, NS zonke ezinye iintlobo zolingo F> 3.25, p<0.05).
Xa kuthelekiswa imithamo emibini yamachiza, idosi ephezulu yabonakala ikhuthaza u-a
ukunyuka okukhulu kweempazamo zokuqokelela, ngakumbi kwizilingo zokukhanya ze-0
(0.0375 vs 0.125 mg/kg: idosi Uhlobo lovavanyo: F_7, 77=2.880, p=0.01).

IQuinpirole yonyuse ubushushu bokuphendula kumqokeleli werhafu, nokuba kutheni
Uhlobo lovavanyo okanye idosi (eyongezelelweyo iTheyibhile S1; idosi: F_2, 22=14.035, p=I-0.0001, idosi uhlobo lokulingwa ngu-F_14, 154=I-0.475, NS; ityiwa vs 0.0375 mg/kg: F_1, 11=18.563, p=I-0.001; ityiwa vs 0.125 mg/kg: F_1, 11=30.540, p=0.0001).
Ngokufanayo, zombini iidosi zonyusa i-latency ukuba iphendule kuluhlu
Nokuba ungaluphi na uhlobo lovavanyo (Itheyibhile yokuxhasa iS2; idosi: F_2, 22=8.986, p=I-0.001; Uhlobo lwedosi × uhlobo lokulingwa: F_14, 154=I-1.500, NS; ityiwa vs 0.0375 mg/idosi ye-kg: F_1, 11=9.891, p=I-0.009; ityiwa vs 0.125 mg/idosi ye-kg: F_1, 11=20.08, p=I-0.001) okanye imeko yokukhanyisela umngxunya wangaphambili (Umzobo 4c; idosi × imeko yangaphambili yomngxunya: F_2, 22=0.291,
NS). Zombini iithamo ze-quinpirole nazo zinciphise inani lovavanyo
igqityelwe kwinqanaba elifanayo (iThebhile yokuXhasa i-S3; uvavanyo lugqityiwe
-0.0375 mg/kg: 47.08 ± 5.8; I-−0.125 mg/kg: 40.92 ± 3.8; idosi: F_2, 22=44.726, p=I-0.0001; ityiwa vs 0.0375 mg/kg: F_1, 11=45.633, p=I-0.0001; ityiwa vs 0.125 mg/kg: F_1, 11=57.513, p=0.0001; Xnumx vs 0.125 mg/kg: F_1, 11=1.268,
NS). Isishwankathelo, nangona i-quinpirole yenze ukunciphisa iziphumo zemoto, zombini
Iidosi zikhokelela ekwandeni kweempendulo eziqokelelweyo zempazamo kwizilingo zokulahleka
ezazibhengezwe ngokukodwa kwi-1-ukukhanya kunye ne-2-ukukhanya.

Iziphumo ze-D₁ I-Receptor Agonist SKF 81297 kwiNkqubo yokuSebenza

Yonke idatha inikezelwe kulwazi olongezelelweyo (umzobo ongezelelweyo
I-S3, iitheyibhile ezongezelelweyo iiS1-S3). I-SKF 81297 yayinefuthe elincinci kakhulu kuyo
ukwenziwa komsebenzi. Umda weempendulo zokuqokelelwa uhleli
engaguqukanga (idosi: F_3, 33=I-0.086, NS; Uhlobo lwedosi × uhlobo lokulingwa: F_21, 231=I-1.185, NS; Idosi × izibane ezikhanyisiweyo: F_9, 99=I-1.516, NS) njengoko kwenziwe ulandelelo lokucinezela ingqokelela (idosi: F_3, 33=I-0.742, NS; Uhlobo lwedosi × uhlobo lokulingwa: F_21, 231=I-0.765, NS). Eyona dosi iphezulu yancipha inani lezilingo ezigqityiweyo (idosi F_3, 33=4.764, p=I-0.007, i-saline vs 0.03 mg/kg: F_1, 11=10.227, p=I-0.008) kwaye yonyusa i-latency yokuphendula ngendlela efanayo nokuba sisikhanyiso siphi na semingxunya (idosi: F_3, 45=4.644, p=I-0.007; ityiwa vs 0.03 mg/kg: F_1, 11=15.416, p=I-0.002; idosi × imeko yangaphambili yomngxunya: F_3, 33=I-2.047, NS).

Ukupheliswa kunye nokuhlaziywa

Xa uqokelela iimpendulo emva kwezilingo zokuwina azange uphinde uvuzwe, zonke iigundane
Ibonise ukwehla okuzinzileyo kwenani lezilingo ezigqityiweyo (Umzobo 5a; usuku: F_9, 90=50.3, p<0.01). Ubukho okanye ukungabikho kovavanyo lwe-2-light 'near-miss' aluzange lutshintshe inqanaba lokuphela (usuku × iqela: F_9, 90=I-0.503, NS; iqela: F_1, 10=0.365,
NS). Nangona kunjalo, xa iimvavanyo zokuphumelela zaziphinde zibe zizibonakaliso ezifanelekileyo zokuba
umvuzo wawukhona, inani leemvavanyo ezigqityiweyo zaqala ukwanda
kwaye izilwanyana ziphinde zenza lo msebenzi. Nangona omabini amaqela ezilwanyana abekhona
ukwenza amanani athelekiswayo kwizilingo emva kweeseshini ze-10, ezokuqala
Ireyithi 'yokubuyiselwa' komdlalo wamatshini woku slot wayedla ngokukhawuleza kwiigundane
ebingakhange ihlangane nezilingo ezikufuphi xa kutshabalala (Umzobo 5a; Iintsuku 1-3: iseshini ye-x iqela: F_2, 20=4.310, p=I-0.028; Iintsuku 4-6: iseshini ye-x iqela: F_2, 20=4.677, p=I-0.022; Iintsuku 7-10 iseshini ye-x iqela: F_3, 30=1.323,
NS). Ngaphandle kwalo mahluko kwinani lezilingo ezigqityiweyo, i
umda wempendulo ye-lever eyenziwe kwiintlobo ezahlukeneyo zovavanyo,
kunye ne-latency yokucinezela ingqokelela, ayihlukanga phakathi kwe
amaqela nangaliphi na inqanaba ngexesha lokubuyiselwa (kwiintsuku ze-1-3, 4-6, kunye ne-7-10:
iseshoni × iqela, iseshoni × iqela × uhlobo lovavanyo, zonke ii-Fs <2.1, NS). Nkqu
Kwiintsuku zokuqala ze-3 zovavanyo, ukuhanjiswa kweempendulo
Kwiintlobo ngeentlobo zovavanyo olwahlukileyo lufana noko kubonwe ngaphambili
isipheloUmzobo 5b).

Njengoko inani leemvavanyo ezigqityiweyo ngeseshoni nganye lisanda, ukuya kuthi ga
ukuphendula kuluhlu lwehlile, kodwa oku kwaqwalaselwa kwinqanaba elinye
kuwo omabini amaqela (iThebhile yokuXhasa i-S2; iintsuku 1-3: iseshoni: F_2, 20=14.182, p=I-0.0001; iseshini ye-x group: F_2, 20=1.772,
NS; Iintsuku 4-6, 7-10: iseshoni, iseshoni × iqela: zonke iiFs <2.3, NS).
Nangona kunjalo, izilwanyana ezingakhange zivulelwe izilingo 'zokusilela' ngexesha
ukutshabalala kwakuchaphazeleka ngakumbi kwimeko yokukhanyisela
umngxunya wangaphambili ngeli thuba leseshoni zokubuyiselwa kwangoko, kuba
ithambekele ekuphenduleni ngokukhawuleza ukuba ukukhanya kwangaphambili kudlulile kunokuba
icimile (Umzobo 5c iintsuku 1-3: iseshini × imeko yangaphambili yomngxunya x iqela: F_2, 20=3.798, p=I-0.04; 'akukho ndawo iphosileyo' iqela- iseshini x imeko yangaphambili yomngxunya: F_2, 10=3.583, p=I-0.067; Iqela 'elikufutshane-elahlekileyo' iseshini ye-x yangoku yangoku: F_2, 10=0.234,
NS). Ke, nangona ubukho okanye ukungabikho kwezilingo zokuphosa kufutshane kwenziwe
ayichaphazeli kakubi imeko yokuphela, izilwanyana ezazingenayo
amava osondeleyo wokuphoswa phantsi kweemeko zokungafumani mvuzo ngokukhawuleza
ukuzibandakanya kwakhona emsebenzini.

UKUQALA

Iiakhawunti eziqondakalayo zokungcakaza zicebisa ukuba amava aphantse aphumelele anokuzinza iindlela zokungcakaza kwaye angakhuthaza i-PG kubantu abasesichengeni (I-Reid, 1986; I-Griffiths, i-1991; I-Clark, 2010). Apha, sibonisa ukuba iigundane ziyakwazi ukwenza umsebenzi onzima wocalucalulo (CD) ngendlela encomekayo yokwenza umatshini ocacileyo kumatshini olula. Iigundane zifunde ukuba ukukhanyiselwa kwazo zonke izibane ezithathu kuluhlu olutyikityiweyo lokuba loo mvuzo ukhona xa impendulo yenziwa kumqokeleli weqonga, ngelixa ukwenza le mpendulo emva kwayo nayiphi na enye indlela ekhanyayo kungakhokelela kwi-10 ixesha lokuphuma. Izilwanyana zikwazile ukukhetha ukuba impendulo kwi-lever yokuqokelela yayiluncedo kuninzi lweemvavanyo. Nangona kunjalo, iigundane ziye zenza inqanaba eliphezulu leempendulo eziqokelelweyo xa ezimbini zikhanyisiwe, kwaye ezi yayizezilingo kuphela apho izinga lempazamo lalisoloko likhona kwaye liphawuleka kakhulu kunelo thuba. Ukuphendula okungalunganga kuphakamisa ukuba iimvavanyo ezikhanyayo ze-2 zivelisa iziphumo ezikufuphi, kuba zitolikwa ngokufana nangophumeleleyo kunelahleko nangona bekukho ukungagungqi kokuziswa. Zombini amphetamine kunye ne-D₂ I-receptor agonist quinpirole yandise ukuqokelela iimpazamo kwizilingo ezingekho phantsi, ukucebisa ukuba ukonyusa umqondiso we-DA kunokuphucula ukulindelwa kokuhanjiswa komvuzo kwizilingo zelahleko.

Ngokuchasene nokufumana kwethu kwangaphambili ukuba i-eticlopride iphuculwe intsebenzo yomsebenzi wokungcakaza i rat (rGT; UZebhe okqhubekayo, 2009), i-D₂ I-receptor antagonist ayitshintshanga indlela yokuziphatha kumatshini weslot. TUkuthelekisa kwakhe rudimentary kuxhasa uluvo lokuba amakhompiyutha amayeza akazukuchaphazela iimpembelelo ezifanayo kuzo zonke iindlela zokuziphatha ngokungcakaza (Isibonelelo kunye noKim, 2006). Nangona kunjalo, kubalulekile ukuba uqaphele ukuba u-D₂ I-receptor antagonist haloperidol ineziphumo ezahlukeneyo kumdlalo wokudlala umatshini we-slot kulawulo olusempilweni vs abo banePG (I-Zack kunye nePoulos, 2007; Ukungcangcazela okqhubekayo, 2010), kwaye kufuneka ukhathalelo xa kuthathwa phakathi kweemodeli zezilwanyana kunye nokwanda kwabantu kwizigulana. Ukongeza, nangona le paradigm yeentonga yabelana ngeempawu ezithile ezithile ngomatshini olula, kukho umahluko ocacileyo ekufuneka uvunyiwe. Umzekelo, iigundwane azikwazanga ukuhlengahlengisa ubungakanani bewatch, okanye zikhethe ukubeka emngciphekweni inani elikhulu ngokufumana ithuba lokuhlawula ngaphezulu, nangona iimeko ezinje ngeenkcaso ziyinto yoomatshini abathile abarhwebayo (I-Kassinove kunye ne-Schare, i-2001; Ngemozulu okqhubekayo, 2004; Harrigan kunye Dixon, 2010).

Ngapha koko, iigundane kwakufuneka zimise ukukhanya nganye nganye, kunokuba zilinde zonke izibane ukuba zisete impendulo enye. Eli nqaku lisenokuba lazibandakanya ngokwahlukeneyo iindlela zokusebenza ezisisiseko ekufundeni ngokuhlawulela (i-Pavlovian) indlela yokuziphatha ecingelwa ukuba ibhekisa kwicala lokungcakaza ngomatshini (I-Reid, 1986; I-Griffiths, i-1991). Oko kwathethi, eminye imidlalo yanamhlanje yomatshini woku slot-inika amathuba abantu ukuba angenelele ekupheliseni i-re-spins ngqo kunye nefuthe ngexesha lemicimbi engenye (Harrigan, 2008). Ukungahambelani nale mida ingentla, ke, oUvavanyo lwe-ur lubonisa ukuba ulingo lokulahleka okufana nokuwina kungonyusa ukubonakaliswa kokulindelwa komvuzo kumabuvu ngendlela echazwe ziinkolelo zengqondo yokuziphatha ngokungcakaza, kwaye ukuba esi siphumo sinokuchaphazeleka kabini kwimirhumo ephindwe kabini yomsebenzi dopamine.

Kungaphikiswa ukuba uninzi lweempendulo zokuqokelelwa ezibonwe kwiimvavanyo zokulahleka kokukhanya kwe-2 zinokubakho nje ngenxa yokuba izilwanyana bezabalaza ukukhetha phakathi kwezi kunye ne-3-ukukhanya izilingo zokuphumelela kwinqanaba le-perceptual, kunokubonakalisa ukungafani kutoliko lokuqonda komgangatho Iziphumo zovavanyo. Nangona ukufana kwengqondo kufuneka, ide facto, ukufaka igalelo kwiziphumo ezibonwe apha, kukho izizathu ezahlukeneyo zokucinga ukuba iziphumo zethu azizizo izinto zocalulo zocalulo phakathi kweepateni ezikhanyayo. Kuqala, phantsi kweemeko ezisisiseko, bekucacile ukuba izilwanyana zikwazi ukukhetha phakathi kokuphumelela kunye nesiphumo esiphosakeleyo njengoko kubonakaliswa linani elikhulu kakhulu leempendulo zokuqokelela emva kokuthelekisa okwangaphambili. Okwesibini, inani leempendulo ezingalunganga zokuqokelelwa zaqwalaselwa kulandela iziphumo ezahlukeneyo ezibandakanya nje izibane ezibekiwe kwi (cf (1,1,0) vs (1,0,1)), iphinda ibonise ukuba iigundwane zinokucalucalula ngokuthembekileyo phakathi kweendlela ezahlukeneyo zokukhanya. Okwesithathu, iidosi ze-quinpirole ezivelise ukwanda okuphawulwayo kumanqanaba ezimpazamo kwizilingo ezikufutshane ezingaphazamisi ukuchaneka kokujongwa kojoliso kumsebenzi wexesha elinesihlanu lokuphendula, inyathelo eliqinisekiswe ngokufanelekileyo lokujonga ngamehlo.Winstanley okqhubekayo, 2010). Ezo datha zidla ngokungabandakanyi amathuba okuba ukuboniswa kwethu kweempembelelo ezikufuphi kakhulu kumvuzo wokulindeleka kumarhe kunokuthiwa bubunzima kucalucalulo lokubonakalayo.

Ngenye indlela, kunokwenzeka ukuba iimpendulo eziphosakeleyo kwi-lever eqokelelweyo emva kweempazamo eziphantse zabonisa kuphela iziphumo zoqeqesho lwangaphambili; njengoko ubunzima bomsebenzi bonyuswa ngokuthe ngcembe kumanqanaba oqeqesho ahlukeneyo, bekukho iimeko apho umvuzo wawuziswa ukuba kukhanye isibane esinye okanye ezibini. Nangona kunjalo, kwakhona, ukufumanisa ukuba iimpuku eziqokelela iimpendulo azange zisasazwe ngokulinganayo kwizilingo ezi-2 zokukhanya eziphikisanayo noko kunokwenzeka: ipateni
(I-1,0,1) ayikaze inxulumene nesiphumo esinomvuzo kuqeqesho, kodwa ukuqokelelwa kweempendulo yayihlala kulolu hlobo lovavanyo. Ngaphaya koko, ngenxa yovavanyo oluphindaphindiweyo olufuneka kwimiceli mngeni yezonyango, izilwanyana zinamava amakhulu e-2-ukukhanya kokulahleka kokukhanya ekuhambeni kwesivavanyo kuthelekiswa nenani elincinci
uvavanyo lwe-2-ulingo olukhanyayo olunamava kwiiseshini zoqeqesho ezimbalwa. Ayonto ingaqhelekanga ukuba izilwanyana zenziwe ziphendule ngexesha lokuqeqeshwa ukuze emva koko zithintele umsebenzi wokuqonda (umz. Ngexesha lokufunda ngobuchule.I-Floresco okqhubekayo, 2008)). Ke ngoko akunakulindeleka ukuba ixesha elincinci lokuqiniswa okufunyenwe ngexesha loqeqesho linokuphendula ngokukhetha okuqhubekayo komqokeleli kwizilingo ezikufuphi.

Idatha ye-latency yokuphendula ikwabonisa ukuba iirund zombini zazikwazi ukubona ubume bokukhanya kwemingxunya kwaye zazijongile ziziphumo, kuba xa umngxuma othile wawucimile, uphendula
kumngxunya olandelayo kwalandela kancinci. Nangona kunjalo, le mpembelelo yayi kuphela
kuqatshelwe ngaphambili kuqeqesho, phambi kokuba umsebenzi uzinziswe. Ngu
Le metric, kuya kubonakala ukuba izilwanyana ziya zincipha
ithathelwa ingqalelo kwingcaciso yomzuzu nexesha yokunikezelwa kwengxelo ngexesha lokulingwa
uqeqesho luqhubekile, nangona olo lwazi lungamisela ukuba
umvuzo wafumaneka ekugqibeleni. Kuyakulinga ukusebenzisa idatha enjalo kwi
phikisa ukuba ukusebenza komsebenzi uye waba 'kokuzenzekelayo' okanye wanyanzelwa
ixesha elidlulele (UJentsch noTylor, i-1999; URobbins no-Everitt, i-1999).
Nangona kunjalo, iigundane zihlala ziqwalasele ngokupheleleyo kurhoxiso
umvuzo olindelekileyo njengoko ubonakalisiweyo lokwehla ngokuqatha kwiimvavanyo ezigqityiweyo
ngexesha lokuphela. Ezi datha zinokubonisa ukuba ukusebenza bekusekho
ikakhulu zijolise ngqo kwinjongo kunokuziqhelanisa, nangona oku kusaqhubeka kunjalo
uqinisekisile ukusebenzisa uvavanyo oluqinisekileyo, njengokuvuma kunoku
shiya umvuzo olindelweyoI-Balleine kunye ne-Dickinson, i-1998).
Ngokuchasene neengxelo zangaphambili kwizifundo zabantu, ukupheliswa komsebenzi
ukusebenza bekungacothisi kubukho bezilingo ezikufuphi.
Nangona kunjalo, ukuphosa okukufutshane akusoloko kukubuyisa ukuphela, kunye nefuthe
Ibonakala ixhomekeka ngokunzulu kugxalathelwano lweziganeko zokuphoswa kufutshane (I-Kassinove kunye ne-Schare, i-2001kunye nenani lemidlalo yokungcakaza eyenziweyo (IMacLin okqhubekayo, 2007).
Iparadigm yokuphela kwezinto esetyenziswe apha, ngelixa kuqhelekileyo kuyilo lwe
ukulingwa kokufunda ngezilwanyana, nako akufani ngohlobo
ukutshabalala okukhoyo kwezinye iziqendu zokungcakaza apho uwinayo
basilele ukwenzeka. Umsebenzi ongaphezulu ke uyafuneka ukumiselwa
nokuba izilingo ezikufuphi ziyaphazamisa umlo wokuphela kwegundane kusetyenziswa a
iseti efanayo ye paramitha kwezi zisetyenziswa kuluntu oluchaphazelekayo
zifundo.

Nangona ukungabikho kwezilingo ezikufuphi kuyenzile
ayichaphazeli ikhosi yexesha lokubhujiswa, ukubuyiselwa emsebenzini
intsebenzo yakhawuleza ngakumbi kweli qela, kwaye ezi iigundane zazingaphezulu
ithathelwa ingqalelo imeko yokukhanyisa kwemingxunya yokuphendula ngexesha
iiseshoni ezimbalwa zokuqala. Yiyo loo nto, ukuba umnqweno osondeleyo ongazange ube ngokucacileyo
zibhangqwe ngokhuthazo lokuwina oluzotyiweyo, izilingo ezikufuphi ziye zagcinwa
ukukwazi ukubonisa abanye abantu ukuba banesiphumo esivumayo kunye nokubanika amandla
isimilo. Iya kubonakala ke into yokuba ukuthamba kukhuthazekile a
ukuvuselela okungafumanekiyo akuhlaziywa ngokuzenzekelayo xa inani le-hedonic
of win uyala. Uluvo lokuba iinkqubo ze-hedonic kunye nenkuthazo yexabiso
inokuqhawulwa yindawo ephakathi yokuvuselela ubuntu
Isinxibelelanisi sokuziphatha, apho ubume bendawo bume khona
iziyobisi ziza kuba nefuthe elinamandla ekuziphatheni nangona
uyolo olwehlayo olunxulumene nokuthatha iziyobisi (URobinson noBerridge, i-1993; Wyvell noBerridge, i2000, 2001).
Kuya kuba ngumdla ukumisela, ke ngoko, nokuba sikufuphi na na
abanesidima banendima efanayo ekuqhubekiseni indlela yokungcakaza njenge
Iimpawu ezinqunqelwayo iziyobisi zenza ngokubhekisele kugwenxa lweziyobisi, zikhuthaza ukubuyela umva
nokunqwenela nasemva kwexesha lokungazihiyi (UDackis no-O'Brien, 2001).
Singayijonga le ngcinga ngokucacileyo kwezinye iimvavanyo, umzekelo
Ngokujonga ukuba ngaba izilingo ze-2-ezikhanyayo ezikufuphi zinokuphucula ukubuyiselwa
nokuba uvavanyo lokuphumelela alukho. Iziphumo ezivezwe apha zikwacebisa
Ukophula unxibelelwano phakathi kwezilingo ezikufuphi kwaye kunomvuzo
Iziphumo zinokunciphisa umda kugcino lweendlela zokungcakaza. Kwi
ulingo lwangoku, oku kwenziwe ngokuzibhanqa ngokuvavanywa kwakhona kwezilingo ezikufuphi
nesikhuthazo sokuwina esingqiniswanga- umsitho ekunokuba nzima kuwo
yazisa ngokuzithemba kubagembuli babantu. Nangona kunjalo, umsebenzi wakutshanje ujolise kwi
Ukophula le mibutho ngoqeqesho lweCD kubonakalise ukhuthazo
iziphumo (UZlomke kunye noDixon, 2006; Dixon okqhubekayo, 2009), ukucebisa oku kunokuba bubudlelwane obubalulekileyo ekujolise kubo kwimbono yonyango.

Ukubonakaliswa okuphindaphindiweyo kweziyobisi ezinobukrelekrele kunokubangela imeko ye-hyper-dopaminergic state, kwaye oku kuhambisa umqondiso we-DA kucingelwa ukuba kugxila ubukhali bokuphucula imeko eziqwalaselweyo ezigcinwe kwizifundo ezixhomekeke kumachiza.EBerridge noRobinson, i-1998). Ngokunjalo, i-PG inokubandakanya ukubonakalisa ukungalunganga komvuzo ekuphazamiseni iindlela ze-DA (Ngaphandle okqhubekayo, 2005), kunye nokulawulwa okuphindaphindiweyo kwonyango lwe-agonist ye-DA kunokufaka i-PG kwezinye izigulana zeParkinsonia (Voon okqhubekayo, 2009). Iingxelo zengqondo zicebisa ukuba iimpawu zoomatshini abaxhasayo, kubandakanya nokubaleka, ukubonwa okucothayo kunye namazinga aphezulu okudlala, kungakhuthaza ukungcakaza okunyanzelekileyo okanye okunyanzelekileyo (I-Breen kunye neZimmerman, 2002; Harrigan, 2008; I-Choliz, i-2010). TInkqubo ye-DA ke inokudlala indima ebalulekileyo ekulamleni ukubandakanyeka koomatshini be-slot, kwaye idatha ebonisiweyo apha inika inkxaso ethile kule hypothesis.

Ulawulo lwe-psychostimulant amphetamine, enokuthi inyuse isenzo se-DA, yehle
isixhasi sokuphendula kuluhlu, ngakumbi emva kokubekwa kwembonakalo ye-winative win (ukukhanya okukhanyayo). Olu phononongo luhambelana nokukwazi okwaziwayo kwe-amphetamine ye-acute yokwandisa impendulo kwimiqolo ebekiweyo (Robbins, 1978; Beninger okqhubekayo, 1981; Iibhothi okqhubekayo, 1983; Mazurski kunye neBeninger, 1986). Ewe, ukwanda kweempendulo zokuqokelelwa okwenziwe emva kolawulo lwe-amphetamine kunokuba ngumnye nje umzekelo weli chiza
yongeza ukuphendula okunamandla ngaphambi komvuzo, njengoko kubonisiwe kumzekelo wonyuso
amaxabiso okuphendula kukwahluka okwahlukileyo kweeshedyuli ezinamaxabiso asezantsi (I-Segal, i-1962; Ingozi, 1978) kunye nokuphakama kwangaphambi kokuphendula kwisicelo sokukhetha isihlanu sexesha lokuphendulaI-Cole kunye neRobbins, i-1987; Harrison okqhubekayo, 1997).
Nangona kunjalo, nangona oku kungadlala indima kwiziphumo eziqwalaselweyo,
i-amphetamine ayonyusanga ukhetho kwi-lever yokuqokelela kuyo yonke into
uhlobo lolingo Ukuba iziphumo ze-amphetamine zivela ngokwanda
ukuqhuba ukuphendula kwi-lever ehambelana nomvuzo, ke oku kufanele ukuba kube
ijongiwe ngaphandle kwepateni yokukhanya. Ngapha koko, le mpembelelo kuphela
kufikelelwe ngokubaluleka kokulahleka okuncinci kwe-1-kunye nokuvavanywa kokulahleka okucacileyo, okt
kwizilingo apho uninzi lwazo lunesimo esihle sokuvuselela imeko (isikhuthazi
ezinxulumene nokuhanjiswa kwembuyekezo: CS+) bebekhona. Ngapha koko, iimpendulo ezingalunganga zokuqokelelwa kweempendulo zenziwe ngu-amphetamine zenziwa ngokuthe ngcembe, zibonakalisa ukuphucuka kokungahambelani kwezigqibo, kwaye siphinda sibale naluphi na uluvo lokuba izilwanyana beziyinyamezele ekukhetheni impendulo enxulumene nomvuzo (Robbins, 1976). Yiyo loo nto, nangona izilwanyana zibonakala zi-ethe-ethe kwimeko yokukhanya kwezibane ezizodwa, amandla e-amphetamine ekuphuculeni ukuphendula umvuzo okanye inkuthazo enomvuzo ayonelanga ukuchaza iziphumo zeziyobisi kukhetho lwe-lever.

Nangona kunjalo, i-amphetamine inikwe ingxelo yokuba ibangela ukusilela kumsebenzi we-CD, kunjalo
izilwanyana azikwazanga ukusebenzisa imikhondo ukumisela ukuba leliphi na inyathelo elifanelekileyo (Dunn okqhubekayo, 2005).
Ifana ngokufana neempendulo zokuhamba kwexesha esikubonileyo apha, i
Ulwazi oluchanekileyo olufakwe kwiikhowudi ezisetyenziswa kwi-CD lwalusekhona
Iqhubekekile, njengoko kubonisiwe kudluliso lwethala le-PavlovianDunn okqhubekayo, 2005).
Iziphumo ze-Amphetamine kumatshini wokulungiselela umsebenzi zinokubakho
inikwe umsebenzi we-CD ophazamisekileyo. Nangona kunjalo, i-CD yokonakala
okubangelwa yi-amphetamine kuguqulwa umva kulawulo lwentsebenzo ka-D₁, kodwa hayi D₂UmchasiUDunn noKillcross, 2006), ucebisa ukuba ukusebenza ngokuchanekileyo kwe-CD kuphenjelelwa ngu-D₁Umsebenzi wokuxhomekeka Ukufumanisa ukuba D₁-nyanzelekile
iikhompawundi azichaphazelekanga ukhetho olunokufunyanwa ngumqokeleli
ukuba ngaphezulu kobunzima bokujongana nemigaqo yoxhomekeko ayinakukwazi ngokupheleleyo
Chaza iziphumo zeamphetamine. Ngapha koko, ukusebenza komsebenzi kwakungekho
jikelele: Izilwanyana zazingama-100% zichanekile kwiimvavanyo zokuwina, kwaye amaxabiso ezimpazamo zazo ayengatshintshiwe kwi
Uninzi lweentlobo zovavanyo. Ngenxa yokuba ezona mpazamo zinkulu zaye zakhona
kuqatshelwe kwiimvavanyo zokulahleka okucacileyo ezazincinci, kunokuba uninzi, ezifanayo
ukuphumelela, kubonakala ngathi akunakwenzeka ukuba i-amphetamine isebenze ngokwandisa
I-gradient yovuselelo ngokubanzi, nangona eli chiza lifunyenwe
Ukonyusa iimpazamo ezibonisa ubuxoki kwimisebenzi yocalulo ebonakalayo (Hampson okqhubekayo, 2010).

Inkcazo enye yeziphumo ze-amphetamine kukuba ukubanakho kwesikhuthazi esinokubangela ukuba umqondiso we-DA uguqulwe ubonakalisiwe, nto leyo ekhokelela kukhetho ekuphenduleni kwisikhuthazo ngokungathi
babhinqiswe umvuzo. Ukuxhasa le ngcebiso, u-D₂ I-receptor agonist quinpirole yayineziphumo ezifanayo kwi-amphetamine, idosi-ngokuxhomekeka yandisa inani lokuqokelela iimpazamo kwizilingo zokulahleka, nangona le mpembelelo ibhengezwe ngakumbi kwi-1- kunye ne-2-izilingo zokukhanya kunokulahleka okucacileyo kwidosi ephantsi. Malunga nokuba isiphumo sinokubonakalisa ukwanda kwempendulo yangaphambi kokunikwa komvuzo, iidosi ezisezantsi zequinpirole esetyenziswe apha azikukhuthazi ukuphendula ngokungafaniyo kwi-CS+ (UBeninger kunye noRanaldi, 1992), kunye nokuhla esikhundleni sokonyusa impendulo kwi-5CSRT (Winstanley okqhubekayo, 2010). Ummiselo we-CS+ ikhokelela kwisikhephe sokukhutshwa kwe-DA, lo gama ukucinyelwa komvuzo olindelekileyo kukhokelela kwilize kwimisebenzi yedopaminergic (Schultz okqhubekayo, 1997; Kum okqhubekayo, 2010). Ngenxa yesi sizathu esiqhelekileyo, kunokwenzeka ukuba ukukhanya okukhanyayo komngxunya wokuphendula okukhanyayo kuvelise ukunyuka kwexeshana kwi-DA, ngelixa kungekho lutshintsho okanye mhlawumbi idiphu kwi-DA ingakhokelela ekubeni umngxunya ubekwe kwindawo yokuma. Ezi zimpawu zinokwenza isiseko sempazamo yokuxelwa komvuzo oya kukhetha ukuba uqokelele okanye uqengqeleze ii-levers, njengoko kucetyiswa yimpendulo yee-dopaminergic neurons ukuya kwisimangalo esivuselela inkcaso yomvuzo kwiinkawu (Nomoto okqhubekayo, 2010).

Kwimodeli zamva nje, kucetyisiwe ukuba ukwenziwa kwe-D ngaphezulu₂ Ii-receptors ziyakuthintela ucalucalulo lokungabikho kolwazi olungafanelekanga ngokunciphisa umqondiso wokuya kwingxolo, kunye nokuthintela ukumiswa kwempendulo ye-DA (I-Floresco okqhubekayo, 2003; I-Seamans kunye neYang, 2004). Kananjalo, impendulo dopaminergic kunyuselo lwelahleko iya kufana neyaqwalaselwe emva kokuvuselela iwine, izilwanyana zikhetha ukukhethwa komqokeleli. Kuphando olwenziweyo lokudlala ngomatshini, umdlalo we-midbrain dopaminergic yengingqi ukuphendula ukungafumaneki kakuhle kwahambelana nenqanaba lokungcakaza okungqongqo kwezongcakazo lokuzonwabisa (Chase kunye noClark, 2010), kunye nokusasazwa kweempawu kwakufana nokuphumelela kwiziphumo zokungcakaza kodwa zaphulukana neziphumo zolawulo olungelulo olwe-pathological (I-Habib kunye ne-Dixon, i-2010). Ngokudibeneyo, ezi ziphumo zibonisa ukuba imisebenzi ngaphakathi kwenkqubo ye-DA inegalelo elikhulu kubungakanani bokungcakaza ngokungalunganga. Ngokubhekisele kwisifo sika-Parkinson, kucetyisiwe ukuba kukhuthazwe okungapheliyo ku-D₂ Ii-receptors-ubukhulu becala ngaphakathi ezindleleni ezingathanga-zithintela ukubonwa kwethambeka kwimisebenzi ye-dopamine elandela iziphumo zesigqibo esibi, kwaye ke oko kukhuthaza indlela yokungcakaza kubantu ababuthathaka. (Frank okqhubekayo, 2004; UFrank noClaus, 2006). Ngenxa yoku kuqaphela, enye injongo yophando kwixa elizayo
misela ukuba ingaba amandla e-quinpirole okukhuthaza ukukhulisa iimpendulo kwiziphumo zetyala lokulahleka ngenxa yokungakwazi ukufumana impazamo yokuxela kwangaphambili (ukungakhathali kwesohlwayo) okanye isizukulwana sokulindelwa komvuzo, okanye zombini.

Kudala kuxelwa ukuba izilingo ezikufuphi, nangona zinokuphambuka, zandisa umnqweno wokuqhubeka nokungcakaza koomatshini be-slot (I-Kassinove kunye ne-Schare, i-2001; Cote okqhubekayo, 2003; IMacLin okqhubekayo, 2007), kwaye oku kunokuchaphazela isantya eziqala ngaso izifundo zokungcakaza olandelayo. Ngelishwa, ixesha lokuphendula kwi-lever roll linakho
Ungasetyenziselwa ukuvavanya intshukumisa yokuqalisa isilingo esilandelayo, njengoko eli nyathelo lalichaphazeleka lixesha elathatyathwa kukudla iipellets zeswekile emva kokuwina kunye ne-10 Ixesha lokuphuma kubangelwa yimpendulo yengqokelela engalunganga. Kubandakanya ixeshana lokulingana, ukuze impendulo ye-lever eyahlukileyo ifuneke ukuqala ulingo olulandelayo, inokuphucula ukunyaniseka koku
ukulinganisa, kunye nokusenza sikwazi ukubona ukuba ngaba uhlobo oluthile lovavanyo lukuchaphazele kusini na ukuvuma kwetyala elitsha. Ukurekhodwa ngokuchanekileyo kolu tshintsho kunokubonisa kwakhona ukuba ngaba amaqhinga aphindwe atshintsha inani lezilingo ezigqityiweyo, kwaye/okanye ukhetho oluchaphazelekileyo lomqokeleli werhafu, uguqulwe ngokwahlukileyo kulo msebenzi wokuzibandakanya.

Ukulinganisa iinkqubo zokungcakaza kwizilwanyana nasebantwini, kubandakanya nokukhathalela okuqondayo okubonisa ukuba sesichengeni kokuphazamiseka kwengqondo (ILadouceur okqhubekayo, 1988; Toneatto okqhubekayo, 1997), inokubonelela ngamathuba inoveli ukumisela i-neural ejikelezayo kunye neesistim ze-neurotransmitter ezilamla idrive ukuya kungcakaza (UCampbell-Meiklejohn okqhubekayo, 2011). Umboniso obonisa ukuba iigundwane zinokwenza umsebenzi ofana nomatshini otyibilikayo, kwaye zibonise ubungqina besiphumo esiphosileyo, inokubonisa ukuba iigundwane zichaphazeleka kwezinye zeempazamo ezibonakalayo ekucingelwa ukuba zinegalelo ekugcineni indlela yokungcakaza (I-Clark, 2010; I-Griffiths, i-1991; I-Reid, 1986). Idatha echazwe apha ikwabonisa ukuba i-DA, nge-D₂ ii-receptors, zinokuba nendima ebalulekileyo ekumodareyiteni okulindelweyo komvuzo ngexesha lokudlala kumatshini weslot. Ngokudibaniselana nophando lweklinikhi, le ndlela inokuphucula indlela esiziqonda ngayo iindlela zokuzonwabisa kunye neengxaki zokungcakaza, kunye nokwenza lula uphuhliso lwamayeza amatsha ePG.

Ukugqubana kwemidla

I-CAW ngaphambili ibonisene ne-Theravance kumcimbi ongahambelaniyo. Hayi
Ababhali banalo naluphi na olunye ungqubano lomdla okanye ukubhengezwa kwezezimali. 

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