Dopamine Amapanga Mphoto Yopindulitsa Pa Ntchito ya Slot Machine Ntchito mu makoswe Zizindikiro Zowonongeka Kwambiri. (2011)

ZIDA NDI NJIRA

Ophunzira

Nkhani zake anali makoswe a 16 a Long Evans makoswe (Charles River Laboratories, St Constant, NSW, Canada) masekeli 250-275 g poyambira kuyesa. Nkhani zake zinali chakudya zoletsedwa ku 85% kulemera kwawo kwaulere kwaulere ndikusungidwa pa 14 g rat chow kuperekedwa tsiku lililonse. Madzi anali kupezeka ad libitum. Nyama zonse zinkakhala ndi chipinda chodyeramo nyengo yolumikizidwa ndi 21 ° C pa 12 h
dongosolo loyatsa-lakuda (kuyatsa kuchokera ku 0800). Kuyeserera koyeserera nyumba ndi nyumba
zinali mogwirizana ndi Canadian Council of Animal Care ndi onse
zoyesera zoyeserera zidavomerezedwa ndi UBC Animal Care Committee.

Zida Zogwiritsa Ntchito

Kuyesedwa kunachitika muzipinda zisanu ndi zisanu ndi zitatu zogwiritsika ntchito zolumikizana, chipinda chilichonse chokhoma
mkati mwa kakhitchini yolumikizana ndi makina (Med Associates St Albans,
Vermont). Kapangidwe ka zipinda zinali zofanana ndi izo
zofotokozedwa kale (Zeeb Et al, 2009),
ndi kuwonjezera kwa levers yotheka kumbali zonse ziwiri za
thireyi yazakudya. Zipinda zinkayendetsedwa ndi pulogalamu yolembedwa mu MED-PC ndi CAW
ikuyenda pa kompyuta yogwirizana ndi IBM.

Kuyeserera kwa Khalidwe

Zochita ndi kuphunzitsa

Mwachidule, mitu yoyamba idakhazikitsidwa m'zipinda zoyesera ndipo
adaphunzira kuyankhapo pa aliyense wakubwerekera kuti apeze chakudya
mphotho. Nyama zimaphunzitsidwa motsatana mwa mitundu yosavuta
ya makina a slot makina omwe pang'onopang'ono amawonjezeka muzovuta. A
Kufotokozera mwatsatanetsatane gawo lililonse lophunzitsira limaperekedwa mu Zowonjezera
Zambiri.

Ntchito ya makina osenda

Ntchito yoyeserera imaperekedwa Chithunzi 1. Mabowo atatu apakati mkati mwa zida zisanu anagwiritsidwa ntchito
(mabowo 2-4). Khosweyo amayambitsa kuyesa kulikonse pokanikiza chikwangwani.
Chikwangwani ichi chidachokanso ndipo kuwalako mkati mwa dzenje 2 kudayamba kuwala
ma pafupipafupi a 2 Hz (Chithunzi 1a). Nthawi ina, makoswewo adayankha pamalopo, kuwala
mkati kukhazikika kapena kutsitsa (mwachidule kuyambira pano '1' kapena '0') kwa
otsala a mlanduwo. Kutengera kuunikira kwa
kuwala, kaya 20 kHz ('pa') kapena 12 kHZ ('off') kamvekedwe ka 1 s, pambuyo pake kuwunika kwa dzenje 3 kunayamba kuwalira (Chithunzi 1b). Apanso, kuyankha kopanda chidwi kunapangitsa kuunikako kuyimitsa kapena kuyimitsa ndikuyambitsa kuwonetsa kwa 1 ndi 20/12 kamvekedwe ka kHZ, pambuyo pake kuwalako mu dzenje 4 kunayamba kuwalira (Chithunzi 1c).
Nthawi yomweyo ratayo idayankha mu dzenje 4 ndi kuyatsa mkati mwake kukhala kapena
kusiya, kuphatikizanso ndi kamvekedwe koyenera, zonse zosonkhanitsa ndi yokulungira
anthu opatsirana anaperekedwaChithunzi 1d ndi e).

Khomalo limafunikira kuyankha pa chikondwerero chimodzi kapena china, komanso chokwanira
kusankha kunawonetsedwa ndi mawonekedwe a kuwunikira kwa nyali mu mabowo
2-4. Pazoyesa zopambana, magetsi onse atatu adakhazikitsidwa pa (1,1,1), ndi a
Kuyankha kwa osunga lever omwe adapereka ma 10 pellets a shuga (Chithunzi 1d). Ngati nyali iliyonse ikazimitsidwa (mwachitsanzo, Chithunzi 1e), kenako kuyankha kwa lever yosonkhanitsa kumabweretsa 10 s
nthawi yopumira yomwe mphotho yake sikanalandiridwe. Kugwiritsa ntchito
Mabowo atatu ogwira ntchito adabweretsa mitundu isanu ndi itatu yoyesa (Chithunzi 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)), zomwe zimachitika mwakabisira zimagawidwa mwachisawawa
mgawo lonse pamakonzedwe osintha a 8. Ngati ratayo adasankha
woponya mayeso pachiyeso chilichonse, ndiye kuti mphotho yake kapena mwayi wathera
kuthetsedwa, ndipo mlandu watsopano unayamba. Chifukwa chake, pamayesero opambana, mulingo woyenera
Njira inali yoti ayankhe pa wolola kuti atenge ndalama zomwe anakonza
mphotho, pomwe mayesero otaika, njira yoyenera inali m'malo mwake
Yankhani pa roll lever ndikuyambanso kuyesa kwatsopano. Ngati ratayo adasankha kutero
sonkhanitsani, onse opuma obwererana kufikira kumapeto kwa kubwezera/lekeza panjira
Nthawi, pambuyo pake wopukutira njirayo amaperekedwa ndipo khomalo limatha
yambitsani mlandu wotsatira. Ntchitoyi idangodzipangira yokha pamenepa
nyama sizinkayenera kuyankha mwanjira iliyonse a
nthawi yenera; ngati kuli kofunikira, pulogalamuyo ipitilizabe kudikirira
kuti nyama ipange yankho lovomerezeka motsatira mpaka
kumapeto kwa gawo. Pokhapokha pokhapokha chingwe chingalepherepo
malizitsani kuyeserera kunali ngati gawo litatha.
Nyama zinalandira magawo asanu oyesa tsiku lililonse pa sabata mpaka
Njira zoyankhira zowerengera zidakhazikitsidwa kale
magawo asanu (kuchuluka kwa magawo omwe atengedwa kuti akwaniritse njira,
kuphatikiza magawo onse ophunzitsira: 49-54). Nyama zimanenedwa kuti zimakhala nazo
anapeza bwino ntchitoyi ngati akamaliza> mayesero 50 pa
gawo ndikupanga <50% sonkhanitsani mayankho pazoyesedwa zomveka (0,0,0).

Paradigm yapano ndi yofanana ndi kuyesera kofanizira koyeserera makina osewera pamakoswe (Peters Et al, 2010),
M'malo mwake nyama zimayenera kusankha pakati pa khola
'spin' kapena 'roll' lever kutengera mtundu wopepuka. Komabe, mu
lipoti la Peters Et al (2010), dzenje loyambirira lidayenera kuwunikira kuti lotsatira
kuyatsa. Zotsatira zake, maphunziro amatha kuthetsa
tsankho pakupezeka kokha ku kuunika komaliza kuwunikira mu
kutsatira. Mu kafukufuku wapano, nyamazo zimafunikiranso kutero
nosepoke pamabowo oyankha kuti awonetsetse kuti akumvera, kapena
osayang'anizana, zowunikira zimayatsa nthawi ya mayesero.

Zovuta Za Pharmacological

Kamodzi, machitidwe oyambira oyamba adakhazikitsidwa, kuyankha kuzinthu zotsatirazi zidatsimikizika: 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), ndi SKF 81297 (0, 0.03, 0.1, 0.3 mg/kg). Mankhwala anali kutumizidwa 10 mphindi ndisanayesedwe molingana ndi zojambula zingapo zoyeserera mu Latin Latin za ma AD: ABCD, BDAC, CABD, DCBA; p.329 (Kadinala ndi Aitken, 2006). Aliyense mankhwala/mchere
tsiku loyesa lidanenedweratu ndi patsiku lopanda mankhwala ndipo kenako tsiku
Pomwe nyama sizinayesedwe. Nyama zoyesedwa zopanda mankhwala
sabata laling'ono la 1 pakati pa jakisoni iliyonse kuti mulole maziko oyambira kuti akhazikitsidwe.

Kutha Kwambiri ndi Kukonzanso

Kutha/mayeso obwezeretsanso anali machitidwe ofanana ndi omwe amagwiritsidwa ntchito pakudzipangira nokha mankhwala
kuyesa. Cholinga cha kusintha kumeneku chinali kuwona ngati ntchito
magwiridwe antchito amatha kuzimitsa pang'onopang'ono ngati mayesero oyeserera pafupi nawo
analipo, mogwirizana ndi malipoti ena m'mabuku a anthu (Kassinove ndi Schare, 2001; MacLin Et al, 2007).
Mayeso omwe anali pafupi-fupi anali kufotokozedwa ngati mtundu uliwonse wa mayeso pomwe awiri mwa awa
mabowo atatu ogwira ntchito amawunikira (onani gawo la zotsatira).
Pambuyo pa kumaliza zovuta zonse zamankhwala, nyama
adagawika m'magulu awiri ofanana pa onse mayeso
yatsirizidwa komanso njira yotolera mayankho osiyanasiyana
mitundu yoyesa. Magulu onsewa adagwira ntchito yomakina mu
Kutha, pomwe kuyankha kwatha pambuyo poti wapambana ayesanso
zinabweretsa kupereka mphotho. Kwa gulu limodzi la makoswe, mayeso aposachedwa
sanasiyidwe kumasewera. Chiwopsezo cha kupambana komanso mayesero omveka bwino otayika anali
akhale ofanana pamagulu onse awiri. Pambuyo pamagulu owonongeka a 10, makoswe onse
adabwezeretsedwa pamakina oyika ntchito a 10
magawo omwe mayesero opambana adalipiranso. Mwachangu kwambiri
kubwezeretsedwenso kungawonetse kuchuluka kochita nawo gawo
ntchito yamakina. Mayeso oyandikira kwambiri analipo pamagulu onsewa nthawi
kubwezeretsedwanso.

mankhwala

Mlingo wonse wa mankhwala amawerengedwa ngati mchere ndikusungunuka mu 0.9% mchere wosabala. Mankhwala onse amakonzedwa mwatsopano tsiku lililonse ndikuyendetsedwera kudzera mu njira yophatikizira mwa 1 mg/ml. Eticlopride hydrochloride, SCH 23390 hydrochloride ndi quinpirole
hydrochloride idagulidwa ku Sigma-Aldrich (Oakville, Canada). SKF
81297 hydrobromide idagulidwa ku Tocris Bioscience (Ellisville,
MO). D-amphetamine hemisulfate adagula mchikakamizo kuchokera ku Health Canada ku Sigma-Aldrich UK (Dorset, England).

Kusanthula Deta

Zosinthidwa zotsatirazi zidasinthidwa pamitundu yoyesera iliyonse: kuchuluka kwake
za mayesero omwe nyama zimakankhira wosonkhetsa lecsine (arcsine
chosinthika), pafupifupi latency yoyankha pa lever yosonkhetsa, ndipo
masinthidwe oyankhira kubzala aliyense pamene kuwala mkati kunali
kung'anima. Chiwerengero cha mayesero omwe adamalizidwa gawo lililonse adawunikiranso.
Zoyeserera kuti musankhe cholumikizira pambuyo pa vuto lililonse sikunaphatikizidwe
powunikira mwatsatanetsatane m'mene muyesowo unakhazikitsidwa ndi okwera
mayankho olakwika amatenga mayankho, zomwe zimayambitsa 10 s
chilango chapanthawi, pamitundu ina yoyeserera, ndi nthawi yomwe imapezedwa kudya shuga
pellets pa kupambana mayesero. Zambiri zimayang'aniridwa mkati mwa maphunziro
kusanthula mobwerezabwereza kusanthula kwamitundu (ANOVA), kochitidwa pogwiritsa ntchito SPSS
mapulogalamu (SPSS v16.0, Chicago, IL).

Pa maphunziro, zosankha za lever ndikusonkha lever latency zidawunikidwa zisanu
magawo (sabata) mabampu okhala ndi gawo (magawo asanu) ndi mtundu woyeserera (eyiti
magawo) monga mkati mwa maphunziro. Maziko oyambira amatanthauzidwa kuti
kusowa kwakukulu kwa gawo kapena mtundu wamayesero × gawo
kulumikizana. Kuti mudziwe kuchuluka kwa magetsi
zowunikira, mosasamala momwe malo angakhalire, deta idayatsidwa
Mayeso a 2-light ((1,1,0), (1,0,1), ndi (0,1,1) ndi mayeso amodzi
((1,0,0), (0,1,0), ndi (0,0,1). Kenako ANOVA idachitidwa ndi gawo
ndi magetsi owunikira (magulu a 4, 0-3) ngati zinthu mkati. The
latency kuyankha pamtundu woyamba adagonekedwa ndi ANOVA ndi
gawo, mtundu woyeserera, ndi dzenje (milingo ya 3) monga zinthu zamumutu. Mu
kuti muwone ngati kuyankha pa bowo lotsatira kudakhudzidwa ndi
kuwunikira kwa dzenje lam'mbuyomu, pafupifupi latency yoyankha
dzenje lapakati ngati dzenje loyambirira lidayamba kuwerengetsera
mosasamala mtundu wa mayeso. Momwemonso, ufulu womvera kuti uchitepo kanthu
dzenje lomaliza ngati dzenje pakati limatsimikiza kapena kutsika linatsimikizika.
Izi zimayikidwa pa ANOVA ndi gawo, dzenje (magawo awiri:
pakati ndi komaliza) ndi dzenje dzenje (magawo awiri: on and off) as
mkati mwa zinthu. Ziyeso zomalizidwa pa gawo lililonse zinasinthidwa ndi a
ANOVA yosavuta ndi gawo ngati chinthu chokhacho mkati mwa zinthu. The
Yankho la zovuta zosiyanasiyana zamatekinoloje zidasinthidwa ndikugwiritsa ntchito
njira zofananira za ANOVA, koma gawo limasinthidwa ndi mlingo
chinthu.

Zambiri zochokera pakutha kwa 10 komanso kubwezeretsanso magawo zinafufuzidwa ndi ANOVA mu ma 3-4 mabins a day, ndi
kuphatikiza kwa gulu (ma 2 level) ngati chinthu chapakati pa zinthu. Monga kusanthula
zamitundu ina yonse zidasokonekera chifukwa chakuti si mayesero onse
Mitunduyi idalipo pamagulu onse awiri, yosinthika yokha yomwe idasinthidwa kuchokera
magawo owonjezera anali chiwerengero cha mayeso omwe adamalizidwa. Pa kusanthula konse,
kuchuluka kwake kwakadalipo p<0.05. Ngati kuthekera kwa chochitika chomwe chapezeka chikupezeka kuti ndi <0.1, zomwe awonazo zidafotokozedwa ngati zomwe zikuchitika.

ZINTHU

Ntchito Yotsogolera

Nyama zinayi sizinayesedwe kusanthula chifukwa cholephera kuzakumana ndi
Kutsatira njira zophunzirira: makoswe awa sanachite pafupifupi 50
mayesero pa gawo lililonse, komanso sanapangire zochepa kuposa 50% sonkhanitsani zolakwa pamayeso omveka bwino (0,0,0). Chiwerengero chomaliza cha makoswe ophatikizidwa phunziroli chinali 12.

Kusankha kwa lever

Pazoyeserera zopambana, makoswe adayankha pa yosonkhetsa pafupifupi 100% Pomwepo, kuonetsetsa kuti mphoto yake idakonzedwa (Chithunzi 2a ndi b).
Mosiyana ndi izi, ngati kulibe magetsi omwe amakhala (kutaya 'bwino), makoswe
adawonetsa kukonda kwambiri kwa wobwezeretsa wopindulitsa pano. Komabe,
ngakhale pamayeso omveka bwino otayika, makoswe amayankhirabe zolakwika pa
sonkhanitsani lever pafupifupi 20% za mayesero. Zokonda pa leto zosonkhetsa zimasiyanasiyana kwambiri pamitundu yina yoyesa (Chithunzi 2b, mtundu woyeserera: F_7, 77=56.75, p<0.01). Woneneratu momveka bwino wamachitidwe osankhidwa omwe adawonedwa anali muyezo wa
pomwe mayesowo amafanana ndi opambana, monga akuwonetsera ndi cholimba
malumikizidwe owoneka pakati pa kuchuluka kwa nyali zowunikira ndi
kuchuluka kwa mayankhoChithunzi 2a).

Chifukwa chake, kukhalapo kwa chizindikiritso cha 'win' cholemetsa pakuyesa mayeso motsatira
zinawonjezera mwayi woti makoswewo angayankhe ngati mayeso anali
kupambana mlandu, ndikupanga yankho loipa. Mwanjira imeneyi
mayankho olakwika aumboni atha kuwonetsa njira yofanana ndi a
'pafupi-padera' zotsatira. Zotsatirazi ndizolimba pamayesero amtundu wa 2-light light, mu
chomwe makonda a lever ndi okwera kwambiri kuposa
mwayi, komanso wapamwamba kuposa womwe umawonedwa XXUMX-kuwala kutayika kapena kumveka
Zowonongeka (nyali zowunikira: F_3, 33=245.23, p<0.01; 2 vs Zoyimira za 1: F_1, 11=143.57, p<0.01; 2 vs Zounikira za 0: F_1, 11=249.20, p<0.01), ngakhale ikadali yotsika kwambiri kuposa yomwe idawonedwa pamayesero opambana (2 vs Zounikira za 3: F_3, 33=128.92, p<0.01).

Ngakhale kuchuluka kwa magetsi komwe kumawunikira pamayeso kuli kolosera zabwinoko kuposa kuwunikira
makamaka, zikuwoneka kuti panali kusiyana pakati pa mitengo yolakwika
1-kuwala (mtundu woyeserera: F_2, 22=3.061, p=0.067) ndi 2-kuwala kuwonongeka (mtundu woyeserera: F_2, 22=3.717, p=0.041),
kutha kuwonetsa kuti malo omwe mabowowo ali
Kuunikiridwa kumatha kukhudza kukondera kwa makoswe kulumikizana kapena kutolera
lever. Nthawi zambiri, chiwerengero chachikulu cha mayankho olakwika chinachitika
pamene kuunika komaliza kuwunikiridwa. N`zotheka kuti chidwi
kukondera mwina kudayamba kupezeka, mwina chifukwa chakuyandikira
kuyandikira kwa malo ndi nthawi kwa osonkhanitsa chopondera. Komabe, kuyerekezera kwa
Kuwonongeka kwa-1-kuwala, kuwunikira kwa kuwala komaliza pamndandanda kunatsogolera a
mulingo wolakwika kwambiri kuposa kuunikira kwa dzenje lapakati ((0,1,0) vs (0,0,1): F_1, 11=5.026, p=0.047), koma osati dzenje loyamba ((1,0,0) vs (0,0,1): F_1, 11=2.682,
NS). Momwemonso, ngati bowo lomaliza silikuwunikira mu 2-light
kutayika, zolakwika zochepa zimawonedwa poyerekeza ndi kutayika komwe
mabowo oyamba ndi omaliza akhazikitsidwa ((1,1,0) vs (1,0,1): F_1, 44=7.643, p=0.018), koma osati ngati magetsi awiri omaliza awunikiridwa ((1,1,0) vs (0,1,1): F_1, 44=2.970,
NS). Pamaziko a zowerengera, zitha
onetsetsani kuti chizindikiro chakumina pakatikati kotsatirana sichikhala champhamvu kwambiri
kuposa chimodzi kumapeto kapena koyambira, koma kuwunikira kulikonse
dzenje silikwanira, lokha, lokha, kuti lizisankha zosankha.
Kaya ndikupereka ndalamazi mwachisawawa, m'malo kuchokera kumanzere kupita
chabwino, angakonze zotsatirazi zikuyenera kutsimikizika.

Kuyankha koyankha

Mosiyana ndi kufalitsa kwa mayankho a lever, latency kuti
kuyankha pa chopereka lever sikunasinthe kutengera ndikuwala
pateni (Zowonjezera Tebulo S1: mtundu woyeserera: F_7, 77=0.784,
NS). Zoyeserera kuyankha mu bowo lililonse motsatizana zidachepa pang'onopang'ono
kuchokera woyamba mpaka dzenje lomaliza kudutsa mlandu, osatengera
mtundu wa kuyesa (Gawo lowonjezera S2: dzenje: F_2, 22=17.773, p<0.01, mtundu woyesera: F_7, 77=1.724,
NS). Kuchokera pakuwunika, ngati kuwunikira kwa
kutsatira njira kumasulira ndikumasulira bwino, ndiye izi
Zotsatira zake ziyenera kuyambitsa kuyankha kwamtsogolo. Chifukwa chake, wina angayembekezere
kutsika kwa latency kuyankha mu bowo lotsatira ngati
dzenje lakale linali litakhazikika. Komanso, ufulu womuyankha pa
bowo lotsatira liyenera kukulira ngati bowo lomaliza limazimitsidwa. Ndicholinga choti
kuti afufuze ngati ndi momwe zinaliri, zomwe zimachitika kuti ayankhe pa
dzenje lapakati lidasinthidwa kutengera kuti dzenje loyamba lidayamba
yatsani kapena yatsani, mosayang'ana mtundu wa mayesero. Mofananamo, masinthidwe oyankha
dzenje lomaliza lidasinthidwa kutengera mtundu wa dzenje lapakati.
M'mbuyomu mu maphunziro, panali zotsatira zazikulu zam'mbuyomu
dzenje pa liwiro la kuyankha, kuti makoswe adatenga nthawi yayitali
yankhani dzenje lotsatira ngati bowo lomaliza litachoka
m'malo mopitilira (Chithunzi 2c; dzenje lapita sabata sabata 1: F_1, 11=6.105, p=0.031; -Week 2: F_1, 11=10.779, p=0.007).
Komabe, njira yokhazikika yoyambira ikakhazikitsidwa,
izi sizinatanthauzenso (sabata 3: state hole hole: F_1, 11=0.007, NS).

Mayesero anamaliza

Chiyeso chambiri chomwe chimamalizidwa pamutu uliwonse chimakhala chokhazikika
Zomwe zidakwaniritsidwa zinali 71.0 ± 3.61 (SEM). Pa nthawi yonse ya
kuyesa, chiwerengerochi chidakwera pang'onopang'ono (Supplementary Table S3),
zomwe zitha kukhala chidziwitso cha kusintha kwakukulu pantchito
kuyesedwa mobwerezabwereza. Komabe, kugawa kwathunthu kwasonkhanitsa
Mayankho pamayesero amtundu wonse adakhalabe.

Zotsatira za Amphetamine Administration pa Ntchito Magwiridwe

Amphetamine mosamala adaonjezera kuchuluka kwa mayankho omwe atengedwa atayika
mayeso, koma izi zimatengera kuchuluka kwa magetsi omwe amakhazikitsidwa monga akuwonetsera
mwa mgwirizano wapakati pa mlingo ndi kuchuluka kwa magetsi
Kuwala (Chithunzi 3a; dozi × magetsi owunikira - onse Mlingo: F_9, 99=3.636, p=0.001).
Kusanthula kwa zotsatira zosavuta kunawonetsa kuti mlingo wa amphetamine modalira
kuchuluka kotenga mayankho kutsatira zomveka kutayika (mlingo: F_3, 33=4.923, p=0.006; mchere vs 1.0 mg/kg: F_1, 11=9.709, p=0.01; mchere vs 1.5 mg/kg: F_1, 11=7.014, p=0.023), ndipo panali njira yakuwonjezeka kwa zolakwika za mayeso a 1-kuwala kwatsitsi (mlingo: F_3, 33=3.128, p=0.039; mchere vs 1.0 mg/kg: F_1, 11=3.510, p=0.09).
Ponena za kuwonera kotsirizira, kuthekera kwa amphetamine kukweza
sonkhanitsani zolakwa zinali zofunikira kwambiri pakuwala komaliza
kuwunikiridwa (Chithunzi 3b; mtundu × mayeso mtundu: F_21, 231=2.521, p=0.022; mlingo (0,0,1): F_3, 33=3.234, p=0.035; (0,1,0): F_3, 33=0.754, NS; (1,0,0): F_3, 33=2.169, NS).

Amphetamine adasinthiratu kusankha komweko kuti ayankhe pa lever
pamilandu yomweyi yomwe amalolera molakwika kwambiri
zolakwika zidapangidwa (Powonjezera Pezani S1, mtundu wa kuyesayesa × mitundu yonse: F_21, 231=2.010, p=0.007; mchere vs 1.0 mg/kg: F_7, 77=2.529, p=0.021; mchere vs 1.5 mg/kg: F_7, 77=3.720, p=0.002; (0,0,0): F_3, 33=4.892, p=0.006; - (0,0,1): F_3, 33=3.764, p=0.02).
Mosiyana ndi izi, amphetamine nthawi zambiri yachepetsa mphamvu yochita kuyankha
ovomerezeka mosasamala mtundu wa mayeso (Powonjezera Table S2,
mlingo: F_3, 33=12.649, p=0.0001; mtundu woyeserera: F_7, 77=1.652, NS; mchere vs 0.6 mg/kg: mlingo: F_1, 11=7.977, p=0.017; mchere vs 1.0 mg/kg: F_1, 11=10.820, p=0.017; mchere vs 1.5 mg/kg: F_1, 11=12.888, p=0.004).
Kuphatikiza apo, amphetamine ankapanga makoswe mwachangu kuti ayankhe mu
dzenje ngati dzenje loyambalo lidakhazikika m'malo motalikiramo, zokumbutsa za
machitidwe awo panthawi yopeza ntchito (Chithunzi 3c; mlingo × dzenje lomwelo: F_3, 33=2.710, p=0.096; dzenje lomwelo boma saline: F_1, 11=0.625, NS; −1.5 mg/kg: F_1, 11=7.052, p=0.022). Amphetamine sanasinthe mayeso athunthu omwe anamaliza gawo lirilonse (Powonjezera Powonjezera S3; mlingo: F_3, 33=1.385,
NS). Amphetamine kotero adakulitsa liwiro la kuyankha ku
osiyanasiyana, makamaka kutsatira chizindikiro cholondola (kuunikira), komabe
idasokoneza kugwiritsa ntchito mawonekedwe owunikira kuti azitsogolera osankhidwa, kuti
sonkhanitsani mayankho anapangidwa ngakhale panali zochepa kapena ayi
mwina.

Zotsatira za D₂ Receptor Antagonist Eticlopride pa Ntchito Yogwira

Mlingo wapamwamba kwambiri wa eticlopride unachepetsa mayeso angapo
atakwanitsa mpaka 20, chifukwa chake mankhwalawa sanaphatikizidwe
kusanthula. Zambiri zimaperekedwa muzowonjezera
(Chithunzi Chowonjezera S1, Mathebulo Owonjezera S1-S3). Ngakhale mawuwo
'D₂ receptor 'amagwiritsidwa ntchito pano pomveketsa, amavomerezedwa kuti onse eticlopride ndi quinpirole amamangirira osagwirizana pang'ono ndi D ina₂-malandirira ngati (D₃ ndi D₄,, ndikuti zina mwazotsatira zatheka chifukwa cha zochita za D₂ banja lolandila osati kwa D₂ cholandirira makamaka.

Eticlopride sizinakhudze kuchuluka kwa mayankho omwe amapangidwa mosasamala kanthu
kuchuluka kwa nyali zowunikira pamiyeso iliyonse (mlingo wa mankhwalawa × kuwunikira: F_6, 66=1.489, NS) kapena mtundu weniweni wa kuwala (mtundu wa kuyesa wa ×): F_14, 154=1.182, NS). Mlingo wapamwamba wa eticlopride umakonda kuwonjezera kuchuluka kwa zotumphukira pamiyeso ya omwe akutenga kachilomboka_2, 22=3.306, p=0.056; mchere vs 0.03 mg/kg: mlingo: F_1, 11=12.544, p=0.005). Mlingo onse awiri unachulukitsa latency kuyankha pamndandanda wambiri: mlingo: F_2, 22=15.797, p<0.01; mchere wamchere vs 0.01 mg/kg: F_1, 11=7.322, p=0.02; mchere vs 0.03 mg/kg: F_1, 11=19.462, p<0.01) ndikuchepetsa kwambiri kuchuluka kwamayeso omwe adamalizidwa (mlingo: F_2, 22=31.790, p<0.01; mchere vs 0.01 mg/kg: F_1, 11=11.196, p=0.007; mchere vs 0.03 mg/kg: F_1, 11=43.949, p<0.01; mayesero omaliza 0.01 mg/kg: 59.0 ± 6.22; −0.03 mg/kg: 17.67 ± 4.06). Mtundu wa data uwu umawonetsa kuti D₂ antagonist ambiri amachepetsa magalimoto, m'malo
zikukhudza magawo aliwonse azidziwitso a ntchito yomwe ikuchitika
chisankho choyankha pa lever.

Zotsatira za D₁ Receptor Antagonist SCH 23390 pa Magwiridwe a Ntchito

Zambiri zimaperekedwa mu Zowonjezera Zowonjezera (Chithunzi Chowonjezera S2, Mathebulo owonjezera S1-S3).

SCH 23390 sizinakhudze zokonda za wophatikiza lever mosasamala kanthu
kuchuluka kwa nyali zowunikira (magetsi × magetsi pa: F_9, 99=0.569, NS) kapena mtundu wa mayeso enieni (mtundu wa kuyeserera × mtundu: F_21, 231=0.764, NS). Ngakhale mlingo waukulu kwambiri unakulitsa chochita kuti ayankhe pa wolandira lever (mlingo: F_3, 33=5.968, p=0.002; mchere vs 0.01 mg/Kilo mlingo: F_1, 11=10.496, p<0.01) ndikuwonjezera kachedwedwe kakuyankha pagulu (mlingo: F_3, 33=4.603, p=0.008), kuchuluka kwa mayesero omwe adamalizidwa pansi pa mankhwalawa adachepetsedwa kwambiri (mayesero omwe adatsirizidwa pansi pa 0.01 mg/kg: 20.7 ± 5.0; mlingo: F_3, 33=40.66, p=0.0001; mchere vs 0.01 mg/kg: F_1, 11=60.601, p=0.0001).
Chifukwa chake, ofanana ndi zotsatira za eticlopride, mlingo waukulu kwambiri
makina ochepetsera magalimoto pang'ono, komabe sizinakhudze kuzindikira kulikonse
mbali za ntchitoyo.

Zotsatira za D₂ Agonist Quinpirole pa Ntchito Magwiridwe

Mlingo wapamwamba kwambiri wa quinpirole unachepetsa mayeso angapo omwe anamalizidwa mpaka osakwana 20, chifukwa chake mankhwalawa sanaphatikizidwe pakuwunikira.

Quinpirole adakulitsa kwambiri kuchuluka kwa mayankho olakwika omwe amapangidwa pa onse 'pafupi-padera'
mayesero komanso mayeso omveka a kutayika (Chithunzi 4a; dozi × magetsi owunikira: F_6, 66=7.586, p=0.002; mchere vs 0.0375 mg/kg: F_3, 33=8.163, p=0.0001; mchere vs 0.125 mg/makilogalamu: muyeso × magetsi amayatsa F_3, 33=14.865, p=0.0001).
Kuphwanya mfundozo mwatsatanetsatane wa magetsi, kwakukulu
Zotsatira za mankhwalawa zimawonedwa pamitundu yonse yoyesa kupatula mayeso oyesa (Chithunzi 4b; mlingo: F_2, 22=16.481, p=0.0001; mtundu × mayeso mtundu: F_14, 154=4.746, p=0.0001; mlingo (1,1,1) F_2, 22=1.068, NS mitundu yonse yamayesero F> 3.25, p<0.05).
Poyerekeza milingo iwiri ya mankhwalawa, mlingo wapamwamba unawonekera kukopa a
kuchuluka kwakukulu kwa zolakwitsa, makamaka pa mayeso a 0-light
(0.0375 vs 0.125 mg/makilogalamu: mlingo × mayeso a mtundu: F_7, 77=2.880, p=0.01).

Quinpirole adakulitsanso chowongolera kuti ayankhe paopeza ndalama, ngakhale atatero
mtundu wa mayeso kapena mlingo (Powonjezera Piritsi S1; mlingo: F_2, 22=14.035, p=0.0001, mtundu wa kuyeserera kwa mphindi x: F_14, 154=0.475, NS; mchere vs 0.0375 mg/kg: F_1, 11=18.563, p=0.001; mchere vs 0.125 mg/kg: F_1, 11=30.540, p=0.0001).
Mofananamo, onse awiri Mlingo unakulitsa latency kuyankha pamndandanda
mosasamala mtundu wa mayeso (Gawo lowonjezera la S2; mlingo: F_2, 22=8.986, p=0.001; mtundu × mayeso mtundu: F_14, 154=1.500, NS; mchere vs 0.0375 mg/Kilo mlingo: F_1, 11=9.891, p=0.009; mchere vs 0.125 mg/Kilo mlingo: F_1, 11=20.08, p=0.001) kapena chowunikira cha dzenje lapitalo (Chithunzi 4c; mlingo × dzenje lomwelo: F_2, 22=0.291,
NS). Mlingo onse a quinpirole nawonso unachepetsa mayesero
chatsirizidwa pamlingo wofanana (Powonjezera Table S3; mayeso atatsirizika
-0.0375 mg/kg: 47.08 ± 5.8; −0.125 mg/kg: 40.92 ± 3.8; mlingo: F_2, 22=44.726, p=0.0001; mchere vs 0.0375 mg/kg: F_1, 11=45.633, p=0.0001; mchere vs 0.125 mg/kg: F_1, 11=57.513, p=0.0001; 0.0375 vs 0.125 mg/kg: F_1, 11=1.268,
NS). Mwachidule, ngakhale kuti quinpirole idachepetsa kutulutsa kwamagalimoto, onse awiri
Mlingo umayambitsa kuwonjezeka kwa mayankho olakwika pamayeso otaika
omwe adatchulidwa makamaka pa 1-light ndi 2-light kuwala.

Zotsatira za D₁ Receptor Agonist SKF 81297 pa Magwiridwe a Ntchito

Zambiri zimaperekedwa mu Zowonjezera Zowonjezera (Chithunzi Chowonjezera
S3, Mathebulo owonjezera S1-S3). SKF 81297 inali ndi zotsatirapo zochepa
magwiridwe antchito. Gawo la mayankho osonkhanitsa lidatsalira
osasinthika (mlingo: F_3, 33=0.086, NS; mtundu × mayeso mtundu: F_21, 231=1.185, NS; dozi × magetsi owunikira: F_9, 99=1.516, NS) monga momwe zimakhalira kukanikiza njira yosungira lever (mlingo: F_3, 33=0.742, NS; mtundu × mayeso mtundu: F_21, 231=0.765, NS). Mlingo wapamwamba kwambiri umachepetsa kuchuluka kwa mayeso omwe anamalizidwa (mlingo F_3, 33=4.764, p=0.007, saline vs 0.03 mg/kg: F_1, 11=10.227, p=0.008) ndikuwonjezera latency kuyankha pamtundu uliwonse mosasamala kanthu kuti pali mabowo aliwonse (mlingo: F_3, 45=4.644, p=0.007; mchere vs 0.03 mg/kg: F_1, 11=15.416, p=0.002; mlingo × dzenje lomwelo: F_3, 33=2.047, NS).

Kutha Kwambiri ndi Kukonzanso

Pamene sonkhanitsani mayankho mukapambana mayeso sanapatsidwenso mphotho, makoswe onse
yawonetsa kuchepa kwamphamvu kwa chiwerengero cha mayesero omwe adamalizidwa (Chithunzi 5a; tsiku: F_9, 90=50.3, p<0.01). Kupezeka kapena kupezeka kwa mayesero a 2-light 'near-miss' sikunasinthe kuchuluka kwakutha (tsiku × gulu: F_9, 90=0.503, NS; gulu: F_1, 10=0.365,
NS). Komabe, pamene mayesero opambana adakhalanso zizindikiritso zovomerezeka zomwe
mphoto inali kupezeka, kuchuluka kwa mayeso omwe adamalizidwa kunayamba kuchuluka
ndipo nyama zizigwiranso ntchitoyo. Ngakhale magulu onse a nyama anali
kuchita mayeso ofanana pambuyo pa magawo a 10, oyamba
Mlingo wa 'kubwezeretsedwanso' pamasewera olimbitsa makina anali wowonjezereka mwachangu makoswe
omwe sanakumanepo ndi mayeso oyandikira posowaChithunzi 5a; masiku 1-3: gawo × gulu: F_2, 20=4.310, p=0.028; masiku 4-6: gawo × gulu: F_2, 20=4.677, p=0.022; masiku 7-10 gawo x gulu: F_3, 30=1.323,
NS). Ngakhale izi zidasiyana pamiyeso yomwe idamalizidwa, a
kuchuluka kwa mayankho omwe amaperekedwa pamitundu yoyesera,
ndi zomangirira kukanikiza zotsalira, sizinasiyane pakati pa
magulu pa nthawi iliyonse yobwezeretsanso (masiku 1-3, 4-6, ndi 7-10:
gawo × gulu, gawo × gulu × mtundu woyesera, onse Fs <2.1, NS). Ngakhale
m'masiku oyambirira a 3 poyesa, kugawa kwa mayankho
mitundu yosiyanasiyana ya mayesedwe amafanana kwambiri ndi zomwe zidawoneka kale
kuthaChithunzi 5b).

Pomwe kuchuluka kwa mayeso omwe adamalizidwa kumawonjezera gawo, latency ikuyenera
kuyankha pamtunduwu kunachepa, koma izi zidawonedwa pamlingo womwewo
m'magulu onse awiri (Gawo lowonjezera S2; masiku 1-3: gawo: F_2, 20=14.182, p=0.0001; gululo × gulu: F_2, 20=1.772,
NS; masiku 4-6, 7-10: gawo, gawo × gulu: onse Fs <2.3, NS).
Komabe, nyama zomwe sizinakumanepo ndi mayesero a 'pafupi-padera' nthawi
Kutha kunali koganizira kwambiri kuwunika kwa
dzenje lam'mbuyomu pamasiku oyambirirawa, kuti
ankakonda kuyankha mwachangu ngati kuwunika koyamba kumakhalapo m'malo
off (Chithunzi 5c masiku 1-3: gawo × m'mbuyomu dzenje boma gulu: F_2, 20=3.798, p=0.04; 'palibe pafupi-padera' gulu- gawo × gawo lomwelo: F_2, 10=3.583, p=0.067; 'pafupi-padera' gulu- gawo × gawo lomwelo: F_2, 10=0.234,
NS). Chifukwa chake, ngakhale kukhalapo kapena kusakhalapo kwa mayeso oyandikira kunatero
Osakhudza kwambiri kuchuluka kwa kuzimiririka, nyama zomwe sizinatero
zokumana nazo zoyesedwa pafupi ndi nyengo ya mphotho sizinali zachangu
kuyambiranso kugwira ntchitoyo.

KUKANGANANI

Nkhani zachidziwitso zokhudzana ndi kutchova juga zimalimbikitsa kuti zomwe anthu opambana atha kuchita zitha kupititsa patsogolo njuga ndipo zitha kulimbikitsa PG mwa anthu osatetezeka (Reid, 1986; Griffiths, 1991; Clark, 2010). Apa, tikuwonetsa kuti makoswe amatha kuchita ntchito yovuta yotsutsa (CD) yomwe imakhala yofananira makina osavuta. Makoswe adaphunzira kuti kuwunikira kwa magetsi onse atatu omwe adasindikizidwa kunasindikizidwa kuti mphothoyo ikanapezeka ngati yankho lingaperekedwe kwa wolipiritsa, pomwe kupanga izi pambuyo pa mawonekedwe ena aliwonse kungayambitse 10 nthawi yoti ithe. Nyama zidatha kusankha bwino kaya kuyankha kwa wolumayo kunali kopindulitsa pazambiri zoyesa. Komabe, makoswe nthawi zonse amapanga mayankho olakwika pamene magetsi awiri mwa atatuwo anali kuwunikiridwa, ndipo awa anali mayeso okhawo pomwe cholakwika chinali chosasinthika komanso chopanda mwayi. Kuyankha kolakwika kotereku kumayesa kuti mayeso a 2-kuwala amayambitsa zotsatira zaposachedwa, chifukwa amatanthauziridwa ofanana kwambiri ndi wopambana kuposa kutayika ngakhale kuti palibe cholimbitsa chomwe chimaperekedwa. Onse amphetamine ndi D₂ receptor agonist quinpirole achulukitsa zolakwitsa pamayeso omwe sanapambane, kuwonetsa kuti kuwonjezeka kwa DA kungapangitse chiyembekezo chakuwonetsa mphotho pakayesedwe kotayika.

Mosiyana ndi zomwe tidapeza m'mbuyomu kuti eticlopride idasintha magwiridwe antchito ya njuga (rGT; Zeeb Et al, 2009), a D₂ wolimbana ndi receptor sanasinthe machitidwe pamakina oyendetsa. Tkuyerekezera kwake kwamwano kumachirikiza lingaliro loti mankhwala opangira mankhwala sangakhale ndi zotsatirapo zamitundu yonse yamtundu wa juga (Grant ndi Kim, 2006). Komabe, ndikofunikira kudziwa kuti D₂ receptor antagonist haloperidol imabweretsa zosiyana pamasewera olimbitsa makina muzoyendetsa bwino vs omwe ali ndi PG (Zack ndi Poulos, 2007; Thupi Et al, 2010,, ndipo chisamaliro chikuyenera kuchitika mukamakhala pakati pa mitundu yazinyama ndi anthu odwala. Kuphatikiza apo, ngakhale paradigm yotsogola iyi imagawana zina zazikulu ndi makina osavuta, pali zosiyana zina zomwe zikuyenera kuvomerezedwa. Mwachitsanzo, makoswe sakanatha kusintha kukula kwa zovala, kapena kusankha kuwayika chiwopsezo chambiri kuti alandire ndalama zambiri, ngakhale zovuta ngati izi ndi gawo la makina ena oyatsira (Kassinove ndi Schare, 2001; Nyengo Et al, 2004; Harrigan ndi Dixon, 2010).

Kuphatikiza apo, makoswe amayenera kuyimitsa nyali iliyonse payekhapayekha, m'malo mongodikira kuti magetsi onse atatu akhale ndikuyankha limodzi. Izi zitha kukhala kuti zidapanga njira zophunzitsira zothandizidwa ndi (Pavlovian) mchitidwe womwe amaganiza kuti umayambitsa njuga zamakina (Reid, 1986; Griffiths, 1991). Izi zati, masewera ena amakono ogwiritsa ntchito amakono amapereka mwayi kwa anthu kuti alowererepo kuti athetse mwachindunji spel-spins ndikuwongolera nthawi ya zochitika zosakonzekera (Harrigan, 2008). Osalimbana ndi malire omwe ali pamwambawa,, okuyesa kwa ur kumawonetsa kuti mayesero otayika omwe amafanana ndi kupambana amatha kukulitsa chiwonetsero chazakuyembekeza mu mphoto m'njira zofotokozedwera malingaliro a malingaliro amtundu wa njuga, ndikuti izi zitha kupezeka kawiri kawiri kawiri kawiri kawiri ka ntchito za dopamine.

Titha kunena kuti kuchuluka kwa mayankho omwe adawonetsedwa pazoyeserera zakuwala za 2 zitha kuchitika chifukwa nyama zimalimbana ndi kusankhana pakati pa izi ndi mayeso a 3-light win on the perceptual level, m'malo mwakuwonetsa kusiyana pakumvetsetsa kwazindikiritso zotsatira zoyesa. Ngakhale kufanana kwenikweni kuyenera, de A facto, zimathandizira pazomwe zikuwoneka pano, pali zifukwa zingapo kuganiza kuti zomwe tapeza sizinthu zakale zosalakwika pakati pa mawonekedwe. Poyamba, pansi pazoyambira, zinali zowonekeratu kuti nyama zimatha kusankha bwino pakati pa zopambana ndi zotsatira zophonya monga zikuwonekera ndi kuchuluka kwakukulu kwa mayankho potsatira zomwe zidachitika poyerekeza ndi zakale. Chachiwiri, kuyankha kosiyanasiyana kolakwika kunawonedwa zotsatila zosiyanasiyana zopanga magetsi awiri okhazikitsidwa (cf (1,1,0) vs (1,0,1)), ndikuwonetsanso kuti makoswe amatha kusiyanitsa modalirika pakati pa mawonekedwe osiyanasiyana. Chachitatu, Mlingo wa quinpirole womwe umapanga kuchuluka kotereku pamamayesero osayandikira samayipa kulondola kwa kuzindikira kwa ntchito isanu yoyeserera yochitira nthawi yayitali, muyeso wovomerezeka wa kuzindikira kwapang'onopang'ono (Winstanley Et al, 2010). Zambiri zimasiyanitsa mwayi woti chiwonetsero chathu cha zotsatira zoperewera pazokhalitsa mphoto m'makoma titha kungonena kuti ndizovuta pakusankhika.

Kapenanso, ndizotheka kuti mayankho olakwika omwe amabwera kwa omwe akutsata omwe akutsata pafupi akuwonetsa zoyipa zakuphunzitsidwa koyambirira; popeza kuvuta kwa ntchitoyi kudakulirakulira pang'onopang'ono pamadongosolo osiyanasiyana ophunzitsira, panali zochitika zomwe mphothoyo imaperekedwa ngati nyali imodzi kapena ziwiri zounikiridwa. Komabe, kupezanso kuti makoswe amatenga mayankho awo sanagawidwe mofananamo pamayeso owunikira awiri akutsutsa izi:
(1,0,1) silinaphatikizidwe konse ndi zotsatira zopindulitsa pamaphunziro, komabe mayankho omwe amapezeka nthawi zambiri pamtunduwu woyeserera. Kuphatikiza apo, chifukwa chakuwunika mobwerezabwereza komwe kunafunikira zovuta zamapangidwe azachipatala, nyama zinakumana ndi zowonongeka mazana angapo a 2 pazowunikira izi poyerekeza ndi chiwerengero chochepa kwambiri cha
kudalitsa mayeso a 2-light omwe adakumana nawo m'magawo angapo ophunzitsira. Sizachilendo kuti nyama zizipangika poyankha pomwe zimafunikira kuti zizilepheretsa kugwira ntchito yodziwitsa ena (mwachitsanzo nthawi yophunzira mwaukadaulo (Floresco Et al, 2008)). Chifukwa chake sizokayikitsa kuti nthawi yochepa yolimbikitsidwa yomwe ingaphunzitsidwe imatha kuyambitsa kukopeka kwa woperekayo pamayeso omwe sanachitike.

Zomwe zimachitika ndikuyankhananso ndikuwonetsa kuti makoswe onsewo amatha kudziwa kuwunika kwa mabowo ndipo anali tcheru ndi zotsatirapo zake, chifukwa pomwe bowo linalimira, kuyankha
dzenje lotsatira linali kuchepera. Komabe, izi zinangokhala chabe
anawona kale mu maphunziro, ntchito isanakhazikike. Mwa
metric iyi, zikuwoneka kuti nyama zachepa
tcheru ndi mayankho amakono apanthawi yomwe mwayesedwa
maphunziro adapitilirabe, ngakhale chidziwitsochi chitha kudziwa ngati
mphotho inapezeka. Akuyesa kugwiritsa ntchito izi kuti
amanenanso kuti kugwira ntchitoyo kunakhala 'kokhazikika' kapena kukakamizidwa
popita nthawi (Jentsch ndi Taylor, 1999; Robbins ndi Everitt, 1999).
Komabe, makoswe anakhalabe tcheru ndi kufalikira kwa
mphoto yomwe ikuyembekezeredwa monga zikuwonetsera ndi kugwa koyimba m'mayesero omwe adamalizidwa
pakutha. Izi zitha kuwonetsa kuti ntchito idalipo
Cholinga chokhazikitsidwa kwambiri m'malo mochita mwamwayi, ngakhale izi zikuyenera kukhalabe
adatsimikizira kugwiritsa ntchito kuyesa kotsimikizika, monga devaluing m'malo
sanataye mphotho yomwe akuyembekeza (Balleine ndi Dickinson, 1998).
Mosiyana ndi malipoti ena am'mbuyomu a anthu, kuwonjezereka kwa ntchito
magwiridwe antchito sanapite pang'onopang'ono pamaso pa mayesero aposachedwa.
Komabe, zophophonya sizimangotayika, ndipo izi zimachitika
akuwoneka kuti amadalira mozama pafupipafupi zochitika zaposowa (Kassinove ndi Schare, 2001) ndi kuchuluka kwa njuga zomwe zachitika (MacLin Et al, 2007).
Paradigm yotayika yomwe imagwiritsidwa ntchito pano, pomwe imakonda kupangidwira
zoyeserera zophunzirira nyama, sizofanananso ndi mtundu wa
Kutha komwe kumachitika mu njuga zomwe zimapambana
ingolephera kuchitika. Ntchito inanso ndiyofunikira kudziwa
kaya mayeso oyandikira-akukhudza kuchuluka kwa kutha kwa makoswe pogwiritsa ntchito a
magawo ofanana ndi omwe amagwiritsidwa ntchito mwa munthu woyenera
maphunziro.

Ngakhale kusapezeka kwa mayeso oyandikira kunatero
sizingakhudze nthawi yamalizira, kubwezeretsedwanso pantchito
magwiridwe antchito anali ofulumira kwambiri pagululi, ndipo makoswe anali ochulukirapo
chidwi ndi kuwunikira kwa mayankho mabowo nthawi
magawo ochepa oyamba. Chifukwa chake, ngati zoyipa zapafupi-nazo sizikadatchulidwa
opakidwa ndi chidwi chopindulira, zoyeserera zomwe zakonzedwa posachedwa zidakhalabe
Kutha kupangitsa kuti anthu awoneke bwino komanso opatsa mphamvu
machitidwe. Zikuwoneka kuti kukhudzidwa kwa a
kukondoweza kwaposachedwa sikukonzedwa zokha mukakhala mtengo wa hedonic
wopambana akutsikira. Lingaliro kuti machitidwe a hedonic komanso othandizira
ikhoza kuchekedwa ndi gawo lachigawo chapakati lolimbikitsira chidwi
malingaliro osokoneza bongo, momwe chilengedwe chimayenderana
Mankhwala amabwera kuthandizira kwambiri kuchita ngakhale
zosangalatsa zosachepera zomwe zimachitika pakumwa mankhwala osokoneza bongo (Robinson ndi Berridge, 1993; Wyvell ndi Berridge, 2000, 2001).
Ndizosangalatsa kudziwa, kaya ndiposachedwa
stimuli ali ndi udindo wofananawo pakuthandizira njuga
miyambo yokhala ndi mankhwala osokoneza bongo imachita pankhani yokhudza kugwiritsa ntchito mankhwala osokoneza bongo, zomwe zimalimbikitsa kubwereranso
komanso kukhumba ngakhale utakhala nthawi yodziletsa (Dackis ndi O'Brien, 2001).
Titha kuwunikanso lingaliroli pamayeso ena, mwachitsanzo
pakuwona ngati mayesero a 2-kuwala pafupi-kuphonya angalimbikitse kubwezeretsedwa
ngakhale mayeso opambana sapezekapo. Zotsatira zomwe zaperekedwa pano zikuperekanso lingaliro
kuti kuswa chiyanjano pakati pa mayeso oyandikira komanso kopindulitsa
Zotsatira zake zimatha kuchepetsa mayendedwe a njuga. Mu
kuyesa kwaposachedwa, izi zidachitika mwa kubwereza mayeso pafupipafupi
ndi cholimbikitsira chopambana chosakakamizidwa - chochitika chomwe chitha kukhala chovuta
zidziwitsani motsimikiza kwa otchova njuga. Komabe, ntchito yaposachedwa yoyang'ana ku
kuswa mabungwe amenewa kudzera mu maphunziro a CD kwalimbikitsa
zotsatira (Zlomke ndi Dixon, 2006; Dixon Et al, 2009,, kunena kuti uwu ukhoza kukhala ubale wofunika kulinga kuchokera ku malingaliro achire.

Kudziwitsidwa mobwerezabwereza kwa mankhwala osokoneza bongo kukhoza kuyambitsa vuto la hyper-dopaminergic state, ndipo kuyimitsa kwa DA komweku kumaganiziridwa kuti kumatsimikizira chidwi chazomwe zimachitika pazokambirana zomwe zimadalira mankhwala.Berridge ndi Robinson, 1998). Momwemonso, PG ikhoza kuphatikizaponso mphotho yovutikira kuwonetsa kudzera pakusokoneza njira za DA (Zosintha Et al, 2005), ndikuwongolera mobwerezabwereza chithandizo cha agonist cha DA chitha kupangitsa odwala mu Parkinsonia (Onani Et al, 2009). Nkhani za Psychological zikusonyeza kuti mawonekedwe amakina amakina, kuphatikizapo zopota zapafupi, zidziwitso zochepa komanso kusewera kwambiri, zitha kulimbikitsa kutchova juga kwambiri kapena mokakamiza (Breen ndi Zimmerman, 2002; Harrigan, 2008; Choliz, 2010). Tiye dongosolo la DA atha kukhala ndi gawo lofunikira pakuyanjanitsa zochitika ndi makina olowetsa, ndipo zomwe zaperekedwa apa zimapereka chothandizira pa izi.

Kuwongolera kwa psychostimulant amphetamine, komwe kumapangitsa zochita za DA, kudatsika
omasulira kuyankha pamtundu wambiri, makamaka atapereka chizindikiro chopambana (kuwala kwounikira). Kuwona uku kumagwirizana ndi luso lodziwika bwino la acute amphetamine kuti awonjezere kuyankha pazowoneka bwino (Mabotolo, 1978; Beninger Et al, 1981; Mabalabvu Et al, 1983; Mazurski ndi Beninger, 1986). Zowonjezera, kuwonjezeka kwa mayankho omwe apangidwa pambuyo pa kayendetsedwe ka amphetamine kungakhale chitsanzo china chokhoza kwa mankhwalawa
onjezani kuyankha koyambira kuti mudzalandire mphotho, monga momwe zimasonyezedwera ndi kuchuluka
mayankho pamathandizo osiyanitsa magawo ochepera (Segal, 1962; Sanger, 1978) ndikukweza oyankha asanakonzekere pa chisankhoCole ndi Robbins, 1987; Harrison Et al, 1997).
Komabe, ngakhale izi zitha kupanga gawo pazotsatira zomwe zapezeka,
amphetamine sanawonjezere zokonda za wosonkhanitsa aliyense
mtundu wa mayeso. Ngati zotsatira za amphetamine zimatuluka kudzera pakuwonjezeka
pagalimoto kuti muyankhe pa lever yomwe ili ndi mphotho, ndiye izi ziyenera kutero
zimawonedwa ngakhale mawonekedwe. M'malo mwake, izi zokha
adapeza tanthauzo pa kutayika kwina kwa 1-mayeso komanso mayesero omveka otayika, mwachitsanzo
pa mayesero omwe owoneka bwino kwambiri (olimbikitsa
zogwirizana ndi kutumiza mphotho: CS+) analipo. Kuphatikiza apo, mayankho olakwika omwe amachitika ndi amphetamine adapangidwa pang'onopang'ono, kuwonetsa kuwongolera kwa zisankho, ndikuwunikanso lingaliro lililonse loti nyama zimangopirira posankha yankho lomwe limayenderana ndi mphotho (Mabotolo, 1976). Chifukwa chake, ngakhale nyama zimawoneka ngati zosakhudzidwa ndi kuwunikira kwa magetsi aliwonse, kuthekera kwa amphetamine kukulitsa kuyankha pamalipiro kapena zoyeserera sikokwanira kufotokoza zomwe zimachitika chifukwa cha kusankha kwa lever.

Komabe, amphetamine adanenedwa kuti amabweretsa zolakwika pa ntchito ya CD, mwakuti
nyama sizinathe kugwiritsa ntchito ndere kuti zitha kudziwa zoyenera (Dunn Et al, 2005).
Zofanana ndi zotsatira zoyipa zomwe takambirana pano,
chidziwitso chogwirizana ndi makina omwe amagwiritsidwa ntchito mu CD ndidakali
kukonzedwa, monga momwe kusinthidwa kwachidziwikire kwa Poslovian-to-instrumentalDunn Et al, 2005).
Zotsatira za Amphetamine pamakina oyeserera atha kukhala
akuti chifukwa cha kusokonekera kwa ma CD. Komabe, kusokonekera kwa CD
oyambitsidwa ndi amphetamine amasinthidwanso ndikuyanjana kwa D₁, koma osati D₂, wotsutsana naye (Dunn ndi Killcross, 2006,, kutanthauza kuti kugwira ntchito molondola kwa CD kumayendetsedwa ndi D₁- ntchito yodalirika. Kupeza kuti D₁-selective
mankhwala sanakhudze zomwe amakonda omwe angatengere lever angasonyeze
kuti kuvuta kwambiri pakukhazikitsa malamulo okonzedwa sikungakhale kokwanira
Fotokozani zomwe amphetamine amachita. Kuphatikiza apo, magwiridwe antchito sanali
padziko lonse lapansi: Nyama zidakali 100% zolondola pamayeso opambana, ndipo zolakwika zawo sizinasinthidwepo pa
Mitundu yambiri yamayesero. Popeza kuti kuchuluka kwakukulakwitsa kwambiri kunali
anawona pazoyeserera zomveka bwino zomwe zinali zochepa, kuposa zambiri, zofanana
kwa wopambana, zikuwonekeranso kuti sizingatheke kuti amphetamine adachita zambiri
kukondoweza kwapangitsidwe kazinthu, ngakhale mankhwalawa apezeka
kukulitsa zolakwika zakanama pa ntchito yotsutsana (Hampson Et al, 2010).

Kulongosola kumodzi kwamphamvu za amphetamine ndikuti kuthekera kwa chosonkhezera kuchititsa kuti DA asinthe maimidwe osintha zotsatira, zomwe zimapangitsa kuti akhale ndi tsankho poyankha zokhumudwitsa ngati kuti
ophatikizidwa ndi mphotho. Kuchirikiza lingaliro ili, a D₂ receptor agonist quinpirole anali ndi zotsatira zina zofanana ndi amphetamine, modalira modzaza kuchuluka kwa zolakwika pamayeso otaika. ngakhale zoterezi zidatchulidwa pa 1- ndi mayesero a 2-kuwala m'malo motayika zomveka pamtengo wotsika kwambiri. Pakuwona ngati izi zitha kuwonetsa kuwonjezeka kwa kuyankha koyamba kwa mphotho, milingo yotsika ya quinpirole yomwe imagwiritsidwa ntchito pano sikuti imapangitsa kuyankha mosiyanasiyana ku CS+ (Beninger ndi Ranaldi, 1992), ndikuchepera m'malo kuwonjezera kuwonjezera poyankha pa 5CSRT (Winstanley Et al, 2010). Kufotokozera kwa CS+ kumabweretsa chiphuphu potulutsidwa ndi DA, pomwe kuchotsedwa kwa mphotho yomwe akuyembekeza kumabweretsa kuyeserera mu ntchito ya dopaminergic (Schultz Et al, 1997; Gan Et al, 2010). Poganizira nkhaniyi, ndizotheka kuti kuwunikira kosavuta kwa dzenje kumabweretsa kukula kwakanthawi mu DA, pomwe sikungasinthe kapena kusuntha mu DA kungachitike ngati dzenje litayimitsidwa. Zizindikiro izi zitha kukhala maziko a cholosera cholosera cholakwika chomwe chingapangitse kuti anthu asonkhanitse kapena kuwatsogola, monga momwe dopaminergic neurons imanenera zovuta zolosera za mphotho.Nomoto Et al, 2010).

M'mitundu yaposachedwa, akuwonetsedwa kuti kuonjezera kwa D₂ receptors ikhoza kusokoneza kusankhidwa kwa chidziwitso chosafunikira pakuchepetsa chiwonetsero cha phokoso, ndikulepheretsa kuyankhidwa koyenera kwa yankho la DA (Floresco Et al, 2003; Seamans ndi Yang, 2004). Mwakutero, kuyankha kwa dopaminergic ku mphamvu yotsitsa kumafanana ndi kukondwerera kopambana, kukondera nyama posankha wolanda. Kafukufuku waposachedwa waposachedwa wamasewera olimbitsa makina, kuwonetsa gawo la dbaminergic dera poyankha kufooka komwe kunaphatikizidwa kwambiri ndi kuchuluka kwa kutchova juga pamasewera osangalatsa (Chase ndi Clark, 2010), ndikugawa kwa siginecha kunali ngati kupambana pamasewera azamisala koma kutaya zotsatira muulamuliro wosatsata wazotsatira (Habib ndi Dixon, 2010). Zonsezi pamodzi, izi zikuwonetsa kuti ntchito mu dongosolo la DA zimathandizira kwambiri kuthekera kwa kutchova njuga molakwika. Ponena za matenda a Parkinson, akuti kukakamiza kopitilira muyeso kwa D₂ ma receptor, makamaka munjira zosadziwika, amalepheretsa kuwoneka kwa ma dopamine omwe amatsatira zotsatira zoyipa, chifukwa chake amalimbikitsa mchitidwe wa njuga mwa anthu osatetezeka (Frank Et al, 2004; Frank ndi Claus, 2006). Poona izi, cholinga chimodzi chofufuzira ndi
Dziwani ngati kuthekera kwa quinpirole kolimbikitsa kusonkhanitsa mayankho pamayeso amomwe angatayikire chifukwa cholephera kuzindikira cholakwika cholosera (kusazindikira chilango) kapena m'badwo wokhala ndi chiyembekezo chindapusa, kapena zonse ziwiri.

Zanenedwapo kale kuti ziyeso zaposachedwa, ngakhale ndizosasangalatsa, zimakulitsa kufunitsitsa kupitiliza kutchova juga pamakina opanga (Kassinove ndi Schare, 2001; Cote Et al, 2003; MacLin Et al, 2007), ndipo izi zimatha kukhudza liwiro lomwe maphunziro akuyamba kuyambitsa njuga yotsatira. Tsoka ilo, kusinthaku kuyankha pa lever ya roll kungathe
musagwiritsidwe ntchito kuwunika chikhumbo choyambitsa kuyesa kwotsatira, popeza izi zidakhudzidwa ndi nthawi yonse yomwe amatenga mafuta oti atenge shuga atapambana ndi 10 Nthawi yochepetsedwa ndi nthawi yolakwika chifukwa chakuyankha molakwika. Kuphatikiza ndi nthawi yoyeserera, kuti mayankho osiyana ndi omwe amayambitsidwa kuti ayambenso kuyambanso mlandu, atha kusintha kutsimikizika kwa izi
yerekezerani, ndikutithandizanso kudziwa ngati mtundu wina woyeserera wakhudza kufunitsitsa kuyesa kwatsopano. Kujambula molondola za kusinthaku kungavumbulutsenso ngati zosintha zomwe zasintha kuchuluka kwa mayesedwe, ndipo/kapena chisankho chautolere, chomwe chimasinthidwa mwanjira iyi.

Kuyerekeza njuga mu nyama ndi anthu, kuphatikiza zinthu zomwe zimapereka chiopsezo pamavuto am'magazi (Ladouceur Et al, 1988; Toneatto Et al, 1997), itha kupereka mwayi kwa zidziwitso zamagetsi a neural circry ndi neurotransmitter omwe amayendetsa kuyendetsa njuga (Campbell-Meiklejohn Et al, 2011). Chiwonetsero chakuti makoswe amatha kugwira ntchito yofanana ndi makina osewerera, ndikuwonetsa umboni waposachedwa kwambiri, zitha kuwonetsa kuti makoswe amatengeka ndi zolakwika zina zazing'ono zomwe zimaganiziridwa kuti zimathandizira kukhalabe ndi njuga (Clark, 2010; Griffiths, 1991; Reid, 1986). Zomwe zanenedwa pano zikuwonetsanso kuti DA, kudzera pa D₂ ma receptors, atha kukhala ndi gawo lalikulu pakusintha kuyembekezera mphoto panthawi yamakina osewerera. Molumikizana ndi kafukufuku wachipatala, njirayi ikhoza kupititsa patsogolo kamvedwe kathu ka zosangalatsa komanso kavuto, ndikuthandizira kukhazikitsa chithandizo chatsopano cha PG.

Kusamvana kwa chidwi

CAW idafunsapo kale za Theravance pankhani yosagwirizana. Ayi
olemba ali ndi mikangano ina iliyonse yokhudza chidwi kapena kutulutsa ndalama komwe apange. 

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