Kukhalitsa kwanthawi yaitali kwa njuga-monga ndondomeko ya mphotho zowonongeka zowonjezera zingathandize kulimbitsa amphetamine mu makoswe (2014)

Martin Zack^1*, Robert E. Featherstone², Sarah Mathewson³ ndi Paul J. Fletcher³

• ¹Chidziwitso Cognitive Psychopharmacology Laboratory, Dipatimenti Yopanda Maphunziro a Zachilengedwe, Center for Addiction and Mental Health, Toronto, ON, Canada
• ²Ndondomeko yotanthauzira sayansi, Dipatimenti ya Psychiatry, Sukulu ya Mankhwala, Yunivesite ya Pennsylvania, Philadelphia, PA, USA
• ³Gawo la Biopsychology, Dipatimenti Yophunzitsa Anthu, Mapulogalamu Othetsera Matenda ndi Matenda a Maganizo, Toronto, ON, Canada

Kuledzera amawoneka kuti ndi matenda a ubongo omwe amapezeka chifukwa cha mankhwala osokoneza bongo osatha. Kuonetsetsa kuti machitidwe a ubongo wa dopamine (DA) amathandizira kwambiri. Kutchova njuga kumatenda (PG) amaonedwa kuti ndi khalidwe lachiwerewere. Choncho, PG ikhoza kuwonetsedwa ndi kutchova njuga kosatha. Kudziwa kutchova njuga-kutengeredwa kwachitetezo kwa madongosolo a DA kungathandizire izi. Kutchova njuga kumapereka mwayi wotulutsa DA. Chigawo chimodzi cha makina osindikizira amasintha momwe DA akuyankhira kuchokera ku mphotho yopereka mphotho kuti ayambe kuyambira (kuyendayenda) kuti adzalandire mphotho, mogwirizana ndi mfundo zosiyana siyana za kuphunzira. Choncho, kukakamizidwa (CS) kumagwira ntchito yofunika kwambiri ku mayankho a DA pakutchova njuga. M'maboma, mayankho a DA kwa CS ali amphamvu kwambiri pamene mwayi wapadera ndi 50%. Pansi pa ndondomekoyi CS imapereka mwayi wa mphotho koma sichidziwitsa ngati izi zidzachitika pa yesero. Pa kutchova njuga, pulogalamu ya 50% iyenera kuchititsa kuti DA atuluke. Izi zimagwirizana ndifupipafupi mphoto (46%) pa makina opanga malonda. DA kumasulidwa kungathandizire kulimbikitsa, makamaka amphetamine. Kuwonekera kwanthawi yayitali kwa CS yomwe imaneneratu kuti mphoto ya 50% ya nthawi ikhoza kutsanzira zotsatirazi. Tinayeseratu mfundoyi mu maphunziro atatu ndi makoswe. Nyama zalandira 15 × 45-min exposure kwa CS yomwe inaneneratu mphoto ndi mwayi wa 0, 25, 50, 75, kapena 100%. CS anali kuwala; mphoto inali yankho la 10% sucrose. Pambuyo pophunzitsidwa, makoswe amalandira mphamvu yolimbitsa thupi yosiyana siyana (1 mg / kg) ya d-amphetamine. Pomalizira adalandira 0.5 kapena 1 mg / kg mpikisano wa amphetamine musanayese zochitika za 90 mphindi zosangalatsa. Mu maphunziro atatu onse a 50% gulu linawonetsa ntchito yaikulu kuposa magulu ena potengera mayendedwe onse awiriwa. Zochita zogwira mtima zinali zodzichepetsa koma zosasinthasintha, monga zikuwonetsedwa ndi gulu lalikulu (rank = ranking) (φ = 0.986, p = 0.025). Kukhalitsa kwanthawi yaitali ku njuga-monga ndondomeko ya mphotho zowonongeka zowonongeka zingalimbikitse amphetamine kukhala ngati kufanana ndi amphetamine wokha.

Introduction

Kusokoneza bongo kwadziwika ngati matenda a ubongo chifukwa chotsutsidwa ndi mankhwala osokoneza bongo (Leshner, 1997). Kugwiritsidwa ntchito kwa matenda opatsirana pogonana kumaganiziridwa kuti kuthandizire zotsatira za kuwonetseredwa kotereku (Nestler, 2001). Kuonetsetsa kuti machitidwe a ubongo wa dopamine (DA) ndiwotchulidwa ndi ubongo wamtunduwu umaphatikizapo kuwonetseratu mphamvu zokhudzana ndi mankhwala osokoneza bongo (CS) za mankhwala osokoneza bongo, ndi kufunafuna mankhwala osokoneza bongo (Robinson ndi Berridge, 2001). Kuwonetsa mphamvu kwadzidzidzi kwakhala kotanthauzidwa ndi kuwonjezeka kwa DA kumasulidwa kuyankha kwa CS chifukwa cha mphotho ndi kuwonjezeka kwa mayendedwe okhudzana ndi mankhwala a DA (Robinson ndi Berridge, 1993; Pierce ndi Kalivas, 1997; Vanderschuren ndi Kalivas, 2000). Ngakhale kulimbikitsidwa ndi chimodzi mwa kusintha kwa ubongo komwe kumayambitsidwa ndi chizoloŵezi (cf. Robbins ndi Everitt, 1999; Koob ndi Le Moal, 2008), kusintha kwa presynaptic dopamine kumasulidwa kumatanthauzidwa kuti ziyimirire njira zomwe zimagwiritsidwa ntchito mowa mankhwala osokoneza bongo (mwachitsanzo, kubwerezabwereza), mwa mankhwalawa omwe amachititsa kuti azidziwitsira kuti aziteteza (monga morphine) kapena vuto lamphamvu (mwachitsanzo, amphetamine) , zimayambitsanso kubwezeretsa mayankho ogwiritsidwa ntchito kwa heroin kapena cocaine self-administration-Vanderschuren et al., 1999). Umboni umene umalimbikitsa kulimbikitsana (kuwonjezeka kwa mtengo wa mankhwala) umatchulidwa kwambiri ngati mankhwala oledzeretsa amayamba kuwonetsa kuti kuwalimbikitsa kungakhale kovuta kumayambiriro kwa ukapolo komanso (Vanderschuren ndi Pierce, 2010).

Matenda otchova njuga (PG) amatchulidwa ngati khalidwe lachiwerewere ndipo posachedwa amadziwika kuti ali ndi vuto lodzidalira kwadongosolo m'dongosolo la 5th la Diagnostic and Statistical Manual of Mental Disorders (Frascella et al., 2010; APA, 2013). Izi zikutanthauza kuti PG ikhoza kuyambitsidwa ndi kutchova njuga monga ntchito, njira zomwe zimagwirizanitsa zotsatira zowchova njuga ndi kusokoneza mankhwala (Zack ndi Poulos, 2009; Leeman ndi Potenza, 2012); ndipo kutsegulidwa kwa ubongo DA njira zingakhale chinthu chofunikira kwambiri pa njirayi.

Zolemba zachipatala zimagwirizana ndi izi: Kugwiritsa ntchito positron emission tomography (PET) Boileau ndi anzake adapeza kuti nkhani zachimuna za PG zikuwonetseratu kumasulidwa kwakukulu kwa DA chifukwa cha amphetamine (0.4 mg / kg)Boileau et al., 2013). Kusiyanitsa kwa gulu lonse kunali kofunika kwambiri mu mgwirizanitsi ndi somatosensory striatum. Mu limbic striatum, yomwe imaphatikizapo nucleus accumbens, maguluwo sanali osiyana. Komabe, mu nkhani za PG, DA yotulutsidwa mu limbic striatum imagwirizana kwambiri ndi kulemera kwa zizindikiro za PG. Zotsatirazi zikugwirizana ndi kuwonetseratu njira za ubongo za DA m'magulu a PG, komanso zimapereka kusiyana kwakukulu ndi anthu omwe amadalira thupi lawo komanso ndi zitsanzo za nyama za amphetamine. Mosiyana ndi nkhani za PG ndi zinyama zosonyeza kuti amphetamine ndi otsika kwambiri (cf. Robinson et al., 1982), anthu omwe ali ndi chidaliro chodziwika ndi zinthu zochepa zomwe adaziwonetsa, adachepetsanso DA kumasulidwa (Volkow et al., 1997; Martinez et al., 2007), komanso umboni wa zinyama ukusonyeza kuti izi zikhoza kusokoneza ntchito ya DA panthawi yoyamba ya kudziletsa pakutsata machitidwe ozunguza bongo (Mateo et al., 2005). Kufufuza komwe kulimbikitsana kochititsa chidwi kwa nyama, kupititsidwa patsogolo kwa DA kumawonekera mu limbic striatum mmalo mwa kugonana (associative, somatosensory) striatum (Vezina, 2004). Komabe, kugwiritsira ntchito mankhwala osokoneza bongo (ie, chikhalidwe) kufunafuna mankhwala m'zilombo mobwerezabwereza kuti akuwonekere ku cocaine wathandizidwa ndi kumasulidwa kwa DA mu dorsal striatum, zotsatira zomwe zimagwiritsidwa ntchito kuti ziwonetsere njira yowonjezera yogwira ntchito (Ito et al., 2002). Choncho, kukula kwa DA kumasulidwa m'zigawo za PG kungagwirizane ndi chizoloŵezi chofunafuna mphotho (inflexible, routinized) kufunafuna "potsatira kuchoka ku ventral kupita ku madera ena a statum" (Everitt ndi Robbins, 2005, p. 1481), pomwe kudumidwa kwa DA mwamphamvu mu limbic striatum mu nkhanizi kungagwirizane kwambiri ndi kulimbikitsana kotsitsimula monga momwe zimawonetsera zinyama. Maphunziro a PET sangathe kuwonekeratu ngati DA hyper-reactivity inalipo kale pazinthu izi, chifukwa cha kutchova njuga, kapena zotsatira za njira ina yonse. Kuti muyankhe funso ili, m'pofunika kusonyeza kudulidwa kolimbikitsa ndi kutchova njuga kosatha m'mitu yomwe ili yachizolowezi chisanafike. Izi zimabweretsa mafunso pa zomwe zimakhala za njuga zimakhala zolimbikitsa kwambiri.

Skinner adazindikira kuti dongosolo losinthira linali lofunikira pakukopa njuga (kapena kupitiriza kwake) (Khungu, 1953). Kuchita maseŵero a maseŵera pamasewera a masewera ogwiritsira ntchito masewera kumagwirizana ndi mfundo zofunika kwambiri zogwiritsira ntchito makina, monga momwe zikuwonetseratu mgwirizano womwe ulipo pakati pa phindu la ndalama ndi kupaka kwapakati pazitsulo zofanana (Tremblay et al., 2011). Motero, kufotokozera kwapakati pazomwe zimawonekera kumawoneka kuti kumapereka chitsanzo choyenera cha makina otchova njuga.

Kafukufuku waposachedwapa ndi zinyama amapereka chithandizo choyamba chothetsera vuto la kutchova njuga polimbikitsa. Singer ndi anzake akufufuza zotsatira za 55 1-h magawo a tsiku ndi tsiku (FR20) kapena osinthika (VR20) saccharin reinforcement m'malo opatsirana pogwiritsira ntchito mankhwalawa (0.5 mg / kg) amphetamine wathanzi ( Kumwaza Dawley) makoswe (Singer et al., 2012). Iwo amaganiza kuti, ngati njuga imayambitsa mphamvu, makoswe omwe amawoneka ngati osasintha, omwe amatsanzira njuga, ayenera kuwonetsa kuti amphetamine ayankhidwe kwambiri kuposa makoswe omwe ali ndi ndondomeko yoyenera. Monga ananenedweratu, gulu la VR20 liwonetsera 50% yankho lalikulu la amttamine kusiyana ndi gulu la FR20. Mosiyana ndi zimenezi, maguluwa amawonetsa chiwonongeko chofanana chotsatira jekeseni wa saline. Zofukufukuzi zimatsimikizira kuti kukhala ndi moyo wosasinthika kumakhala kokwanira kuti zithetse vuto la DA ku zinyama zogwiritsidwa ntchito panthawiyi.

Mafunso angapo amachokera ku zotsatira izi: Choyamba, kodi chidziwitso chosowa-kapena kusowa kwake-pakati pa zomwe akuchitapo kanthu ndi zotsatira zake zimayanjanitsa zotsatirazi? Powerenga, kodi izi zimaphatikizapo "kuyembekezera zotsatira," kapena zotsatira zoterezo ziwonetseke pokhapokha ngati palibenso yankho lothandizira, mwachitsanzo, "chiyembekezo chotsatira-chotsatira" muzithunzi za Pavlovian (cf. Bolles, 1972)? Chachiwiri, kodi kuchuluka kwa zochitika pakati pa zochitikazo (kuyankha kapena zolimbikitsa) ndi zotsatira zake zimakhudza chiwerengero cha chidziwitso?

Funso lachiwiri likukhudza udindo wosatsimikizika pakulimbikitsa. Mwachitsanzo, kodi masewera omwe zotsatira zake ndi zowonongeka-zosadziŵika bwino-zingathe kuchititsa chidwi kwambiri kuposa masewera omwe amavomereza kuti apambane akufotokozedwa momveka bwino koma osasintha, ngakhale ngati mphotho ya malire ndi yochepa? Kafukufuku wamakono akuyankha mafunsowa.

Kupanga kuyesera kunadziwitsidwa ndi phunziro la seminal pa nthawi ya malipiro ndi yankho la DA neuron mu nyani (Fiorillo et al., 2003). Zinyama mu phunzirolo zidalandira mphoto ya madzi (US) pansi pa 0, 25, 50, 75, kapena 100% ndondomeko yofanana yofanana. Ndondomekoyi inasankhidwa ndi 1 ya 4 yosiyana CS (zithunzi). Mndandanda wa 0% unapereka mphotho nthawi zambiri monga 100% ndondomeko, koma anasiya CS. Kuwombera kwa DA neurons pa nthawi pakati pa CS onset ndi US yobereka kapena kuperewera kunali njira yodalira kwambiri. Phunzirolo linapeza kuti mayankho a DA akuwonjezeka monga ntchito yosatsimikizirika ya kupereka malipiro. Choncho, pansi pa 100% nthawi yomwe CS inachotsa ntchito yaying'ono, pansi pa 25 ndi 75% ndandanda, CS inachititsa kuti ntchito zowonongeka ndi zofanana, ndi pansi pa 50% pulogalamu ya CS iwononge ntchito yaikulu. Pazifukwa zonse, chiwerengero cha kuwombera chikuwonjezeka pa nthawi ya CS-US, mwachitsanzo, pamene kuyembekezera kunayandikira.

Zofukufukuzi zikusonyeza kuti ntchito ya DA siinangosinthika ngati palipadera (Fixed Ratio) kapena yosadziwika (Variable Ratio), komanso imasiyanasiyana muzomwe zikugwirizana ndi kuchuluka kwa chidziwitso chokhudzana ndi kupereka mphoto kwa CS. Mu chikhalidwe cha 100%, CS amavomereza nthawi ya malipiro komanso amawonetseratu za kubweretsa kwake. Mu mkhalidwe wa 25 ndi 75%, CS imabweretsa chiyembekezo ndikuwonetsa mphotho yobweretsera katatu kapena kanayi. Mu 50% chikhalidwe cha CS chimasintha chiyembekezo koma sichidziwitsa zambiri za mphotho yoperekedwa mosavuta. Malingana ndi zomwe apeza, Fiorillo et al. anamaliza kuti: "Kuwonjezeka kwadzidzidzi kwa dopamine kungachititse kuti phindu la njuga likhale lopindulitsa" (p. 1901).

Zotsatira za mphotho yosinthika ya 50% mu gawo limodzi sayenera kusintha pakapita magawo angapo chifukwa kuthekera kwa mphotho kumakhalabe kosayembekezereka pamayesero aliwonse. Chifukwa chake, polingalira zomwe zingawonjezere kuyambitsa kwakanthawi kwa ma neuron a DA pamabuku obwereza omwe amatchova juga dongosolo la 50% liyenera kupangitsa kuti azikhala opirira komanso olimba kwambiri. Izi ndizodziwika bwino chifukwa mphotho yayitali (mphotho> 0) yowonera zikwizikwi zama spins pamakina ogulitsa anali 45.8% (Tremblay et al., 2011). Motero, mphoto yosinthika ya 50% ikuwoneka kuti ikuwonetsa molondola ndondomeko yowonjezera yomwe imaperekedwa ndi zipangizo zenizeni za juga.

Kafukufukuyu adagwiritsa ntchito magawo ofanana ndi a Fiorillo et al. mosavomerezeka, mawonekedwe apakati pamagulu ndi makoswe. Nyama zimakhala ~ masabata atatu azigawo zatsiku ndi tsiku, pomwe CS (kuwala) idalumikizidwa ndi US (pang'ono sucrose). Pambuyo pa gawo lophunzitsiralo, nyama zidapumula asanawunikiridwe za kulimbikitsidwa komwe kumayankhidwa ndi oyendetsa ndege ku amphetamine. Kutengera ndi zolembedwazo, zidanenedweratu kuti makoswe omwe ali ndi magawo osiyanasiyana amphotho sangasiyane ndi machitidwe awo osagwiritsa ntchito mankhwala osokoneza bongo koma angawonetse mayendedwe osiyanasiyana motsatizana ndi amphetamine, pomwe gulu la 3% likuwonetsa kuyankha kwakukulu kwa omwe akukhudzidwa ndi mankhwalawo magulu enawo pamlingo woyeserera, mtundu womwe ungayembekezeredwe ngati nyama za 50% zikadapatsidwa mankhwala owonjezera a amphetamine omwe (mwachitsanzo, kuwalimbikitsa).

Yesani 1

Zida ndi njira

Ophunzira

Magulu anayi (n = 8 / gulu) la akuluakulu (300-350 g) Amphongo a Sprague-Dawley (Charles River, St. Constant, Quebec, Canada) adakhala m'mabuku a polycarbonate bwino (20 × 43 × 22 cm) pansi pa 12: 12 kuwala-mdima. Iwo adalandira ad libitum kupeza kwa chakudya ndi madzi, ndikugwiritsidwa ntchito tsiku ndi tsiku ndi kuyesa kwa masabata a 2 isanafike phunziro. Gulu lirilonse linakhazikitsidwa pansi pa imodzi ya ndondomeko zowonjezera mphotho: 0, 25, 50, kapena 100%. Gulu la 75% linasiyidwa mu phunziro loyambali, monga Fiorillo et al. (2003) DZIWANI ZA Mayankho a M'Baibulo Mboni za Yehova KOPERANI Magazini Mabuku Nyimbo Mavidiyo Zina ... NKHANI ZOTHANDIZA Anthu Apabanja Ndiponso Makolo Achinyamata Ana TIPEZENI Pemphani Munthu Woti Aziphunzira Nanu Baibulo Bwerani Kumisonkhano Yathu Dzaoneni Malo Kumaofesi Athu Tilembereni Kalata Ikani mizere

zida

Kufikira kwa sucrose zowonetseratu ndi CS zinaperekedwa payekha mabokosi ogwiritsira ntchito (33 × 31 × 29 cm). Bokosi lirilonse linali ndi magazini ya reinforcer, yomwe ili pa khoma lakunja. Kuwala pamwamba pa magazini kunatengedwa ngati CS. Chombo chogwiritsidwa ntchito mothandizidwa, chomwe chimagwiritsidwa ntchito pamtunda, chikhoza kukwera pansi pa magaziniyo. Zochitika mu bokosi zinali kuyang'aniridwa ndi zipangizo za Ma Med Associates, pogwiritsa ntchito pulogalamu ya m'nyumba yomwe inalembedwa ku MED-PC. Kuyezetsa kwapadera kunkachitika payekha muzitsulo za Plexiglas (27 × 48 × 20 masentimita). Ngwewe iliyonse inali ndi dongosolo loyang'anira lomwe lili ndi maselo asanu ndi limodzi ojambula chithunzi kuti azindikire kuyenda kozungulira.

Kayendesedwe

Training. Phunziroli linkachitika motsatira ndondomeko zoyendetsera ntchito za Canada Council on Animal Care. Makoswe anali chakudya-kokha ku 90% ya kulemera kwa thupi kwa nthawi yonse yophunzira ndikukhala payekha. Pulogalamu iliyonse inalandira masiku 15 ofunsira maphunziro a mphoto (10% madzi yothetsera 0.06 ml pa mphotho): Masiku 5 otsatizana ndi masabata 3, ndi mapeto a sabata. Nyama zinagwiritsidwa ntchito pa chow yoyenera asanayambe komanso pambuyo pake; Kupititsa patsogolo kwazomweku kunali kokha kwa magawo khumi ndi asanu ~ 40-min maphunziro. Gawo lirilonse la tsiku ndi tsiku linali ndi mafotokozedwe a 15 (kuwala; CS), aliyense wolekanitsidwa ndi nthawi yowerengera ya 120 s. Kuwala kunali pamtundu wapamwamba wa magazini, ndipo anakhalabe pa 25 s, ndi sucrose yomwe inapezeka mu 5 s last. Pankhani ya gulu la 0, chomera cha sucrose chinaleredwa ndi 140 s (kwa 5 s) koma kuwalako sikuwunikira. Izi zikugwirizana ndi nthawi pakati pa zowonjezera za gulu la gulu la 0 ndi magulu ena (120 + 25). Gawo lililonse la mankhwala linatenga ~ 40 min. Pafupipafupi, gulu la 25 linalandira sucrose kamodzi pa mauthenga anayi onse a CS; gulu 50 linalandira sucrose kamodzi pa mafotokozedwe awiri a CS, ndipo gulu la 100 linalandira sucrose pambuyo pa chiwonetsero chilichonse cha CS.

kuyezetsa. Patangotha ​​masabata awiri mutha kukhala ndi mwayi wopeza sucrose (kapena "conditioning") gawoli, yankho loyendetsa d-amphetamine (AMPH; ip) linayesedwa. Makoswe anapatsidwa magawo atatu a 2-h kuti apite ku bokosi loyendetsa, motsogozedwa ndi magawo asanu ndi limodzi a kuyesa AMPH. Masiku akuyesa AMPH amachitika pa nthawi ya 1-wk. Patsiku la mayeso, makoswe anapatsidwa 30 min kuti azikhala mabokosi kenaka analandira 0.5 mg / kg mlingo wa AMPH pambuyo pake, pamisonkhano yosiyanasiyana ya mlungu ndi mlungu, ndi asanu osachepera 1.0 mg / kg (dose imodzi patsiku) pa masiku oyesa 1 kupyolera mu 5 . Kupuma kwa AMPH kwasindikizidwa kwa 90 min pa gawo lililonse.

Kusanthula kwadongosolo

Kufufuza kwa chiwerengero kunachitika ndi SPSS (v. 16 ndi v. 21; SPSS Inc., Chicago IL). Kuyankha mwakhama kwa a CS kunayesedwa pang'onopang'ono m'mapapo pomwe sucrose inaperekedwa. Nkhungu zowonjezera nthawiyi (5 s per trial) ndiye zikufaniziridwa ndi mphuno yeniyeni yokhala ndi nthawi yofanana (5 s) yomwe inalembedwa panthawi yomwe CS analibe. Gulu × Makhalidwe a ANOVA a mphuno ndi khungu la CS panopa komanso alibe anapeza kuti anthu amatsutsa ndondomeko ya chisankho komanso zosankha zosiyana siyana panthawiyi panthawi ya maphunziro a 15 asprose.

Zotsatira za mayendedwe a oyendetsa magetsi zinayesedwa ndi gulu la ANOVA la Gawo lachizolowezi choyambitsa mankhwala osagwiritsira ntchito mankhwala osokoneza bongo (magawo atatu), chisanayambe kudziwitsa 0.5 mg / kg Mpopopopera wa AMPH (gawo limodzi), komanso panthawi ya chisanu cha 1 mg / kg AMPH zolimbikitsa, pamene magulu amayenera kusiyana poyankha mafupipafupi a AMPH. Gulu × Misonkhano ya ANOVA imayesetsanso mayankho ogulitsa mankhwala osokoneza bongo m'kati mwa gawo la 30-pre-injection habituation kuyambira gawo lililonse la kuyesa AMPH. Kufananitsa kwapangidwe kunayesedwa kusiyana kwa zochitika zogwirizana ndi gulu la 50 vs. gulu 0 (palibe kuyembekezera kwa kuyembekezera) ndi gulu 100 (palibe kukayikira kokayikitsa), kudzera t-zinthu (Howell, 1992), pogwiritsa ntchito zolakwika za MS komanso df zolakwika za zotsatira zake (mwachitsanzo, gulu kapena gulu × mgwirizano wa gawo) kuchokera ku ANOVA (Wopambana, 1971). Kafukufuku wa kafukufuku wamaphunziro akuyesera kuyesa kuyesedwa maonekedwe a kusintha pa masewera.

Kuti mudziwe ngati njira yothetsera kuyang'ana ndi kupezeka kwa CS mu nthawi ya maphunziro a 15 sucrose inathandiza kuti pakhale kusiyana kwa mayendedwe a AMPH, kapena kusiyana pakati pa gulu la AMPH, kuyanjana kwa covariance (ANCOVAs) pa AMPH Deta yamtundu, kuphatikizapo mphuno zowonjezera (zowerengera za 15 sessions) pamene CS sanalipo monga covariate. Zopweteka kwambiri za covariate zikhoza kusonyeza kuti njira zopanda mankhwala zimayesedwa (zimakhudza mphamvu ya) zotsatira za gulu kapena gawo. Kuchepetsa kufunika kwa zotsatira za gulu kapena gawoli pamaso pa zochitika zazikuluzikulu zingasonyeze kuti mayankho omwe amayankhidwa (omwe amawerengera) zotsatira za gulu kapena gawo. Kuperewera kwa kufunikira kwa zotsatira za gulu kapena magawo pokhala opanda chochitika chofunika kwambiri kungasonyeze kutayika kwa chiwerengero cha mphamvu chifukwa chokhazikitsanso df kuchoka pa mphulupulu mpaka kufika pamtima, ndipo sichidzatha kutanthauzira zotsatira za gulu kapena gawo.

Results

Mphuno imapangika pa nthawi ya sucrose

CS ilipo. Chithunzi 1A Zimasonyeza kuti phokoso limakhala lopangidwa ndi gulu la 25, 50, ndi 100 pamene CS analipo pa nthawi ya 15 yomwe imapangidwira minofu (zolemba zenizeni sizinalembedwe kwa gulu 0, lomwe silinalandire CS). Gulu la 3 × 15 Gawo la ANOVA linapanga zotsatira zazikulu za Gulu, F_{(2, 21)} = 5.63, p = 0.011, ndi Gawo, F_{(14, 294)} = 14.00, p <0.001, limodzi ndi kulumikizana kwakukulu kwa Gulu × Gawo, F_{(28, 294)} = 2.93, p <0.001. Chithunzi 1A akuwonetsa kuti zotsatira zazikulu za phunziroli zikusonyeza kuwonjezeka kwa mphuno kumapangika magawo m'magulu onse atatu, ndipo zotsatira zazikulu za Gulu zikuwonetsera zambiri zapamwamba mu gulu la 100 vs. gulu la 25 ndi ziwerengero zapakati pa gulu 50. Gulu lalikulu × Kuyanjana kwa gawo kwa chikhalidwe cha cubic, F_{(2, 21)} = 4.42, p = 0.030, imasonyeza kuwonjezereka, kuvikira, ndi kuyeza mofulumira pamphuno pogwiritsa ntchito magawo mu gulu la 100, poyerekeza ndi kuwonjezeka kwa magawo pa magawo a gulu la 50, ndi kuwonjezeka kwakukulu kwazomwe zikuchitika pa gulu 25.

 

Chithunzi 1. Njira zowonjezera (SE) zimayankha (mphuno) pamaphunziro a 15 sucrose m'magulu a makoswe a Sprague Dawley (n = 8 / gulu) lomwe likuwonetsedwa kuti lidzapatse mphoto (10% yankho) yoperekedwa pansi pa 0, 25, 50, kapena 100% ndandanda zosinthika. Chotsatiracho chinali chowala (120 s). Gulu 0 linalandira mphoto zomwezo monga gulu la 100 pokhapokha palibenso zokakamizidwa. (A) Zambiri pamene CS analipo (mayesero a 5 s × 15). (B) Zambiri pamene CS sanalipo (pafupifupi 5 × 15 pamene kuwala kunali kutayika).

CS palibe. Chithunzi 1B Zimasonyeza kuti mphuno zimapangitsa kuti magulu onse anayi akhale ndi nthawi yofanana (5 s × 15 mayesero) oposa nthawi yomwe CS analibe. Gulu la 4 × 15 Gawo la ANOVA linapanga zotsatira zazikulu za Gulu, F_{(3, 28)} = 7.06, p = 0.001, ndi Gawo F_{(14, 392)} = 2.84, p <0.001, limodzi ndi kulumikizana kwakukulu kwa Gulu × Gawo, F_{(42, 392)} = 3.93, p <0.001. Kuyanjana kwakukulu kwa Gulu × Gawo lazomwe zikuyenda, F_{(3, 28)} = 3.91, p = 0.019, kuphatikizapo kusagwirizana kwa chikhalidwe cha cubic, F_{(3, 28)} <0.93, p > 0.44, idawonetsa mbiri ya "inverted-U" ya mphuno pazokambirana pagulu 0, motsutsana ndi mbiri yokhazikika pamagulu ena.

Kuzoloŵera kwa zipinda zamagetsi

Gulu la 4 × 3 Gawo la ANOVA linapereka zotsatira zazikulu za Gawoli, F_{(2, 56)} = 5.67, p = 0.006, ndipo palibe zotsatira zina zofunikira, F_{(3, 28)} <1.60, p > 0.21. Kutanthauza (SE) mitengo yopumira pa 2 h m'mabokosi oyendetsa ndege anali 1681 (123) pagawo 1, 1525 (140) pagawo 2, ndi 1269 (96) pagawo 3. Kufanizira komwe kudakonzedwa sikunapeze kusiyana pakati pa gulu 50 ndi gulu 0 kapena gulu 100 pagawo loyamba kapena lomaliza, t₍₈₄₎ <1.69, p > 0.05. Chifukwa chake, pakalibe AMPH, kuwonetsedwa mobwerezabwereza m'mabokosi oyeserera kumalumikizidwa ndi kuchepa kwazomwe zimachitika modzidzimutsa m'magulu anayi (mwachitsanzo, Gawo lamaphunziro), ndipo palibe yankho losiyana ngati gawo la maphunziro a sucrose (osagwirizana) .

Gawo la mayesero

Zotsatira za kuyambitsanso zowonjezereka 0.5 mg / kg mpikisano wa AMPH.

Kutuluka kwa jekeseni koyamba. Gulu la 4 njira imodzi ya ANOVA ya kuyankhidwa kwa ogwira ntchito panthawi ya 30 min-pre-injection habitual phase sizinawonongeke, F_{(3, 28)} <1.05, p > 0.38. Kufanizira komwe kwakonzedwa sikunapeze kusiyana kwakukulu pakati pa gulu 50 ndi gulu 0 kapena gulu 100, t₍₃₂₎ <0.87, p > 0.40. Chifukwa chake, kusiyana koyambira koyambira koyambitsa jekeseni sikunayambitse kusiyana kwamagulu poyankha kwa AMPH. Kutanthauza (SE) mitengo yopumira pazitsanzozo anali 559 (77).

Kupuma kwa jekeseni kamodzi pamapeto ndi gawo lomaliza la mankhwala osagwiritsa ntchito mankhwala. Gulu la 4 × 2 Gawo la ANOVA lidafanizira mayankho am'magulu pamaphunziro omaliza, ndipo atangomaliza kuthana ndi vuto la 0.5 mg / kg AMPH. Zambiri zapa zokambirana (120 min) zidakwezedwa kuti zigwirizane ndi nthawi yoyeserera ya AMPH (90 min) (yaiwisi ya habituation × 90/120). Kuwunikaku kudapangitsa gawo lalikulu, F_{(1, 28)} = 34.16, p <0.001, ndipo palibe zovuta zina, F_{(3, 28)} <2.26, p > 0.10. Zotsatira za Gawoli zikuwonetsa kuwonjezeka kwa zophulika zazitsulo (SE) poyankha mlingowo, kuchokera ku 952 (72) mpaka 1859 (151). Kufanizira komwe kwakonzedwa sikunapeze kusiyana kulikonse pakati pa gulu 50 ndi gulu 0 kapena gulu 100 poyankha mlingowo, t₍₅₆₎ <1.72, p > 0.10. Komabe, kuchuluka kwa mitengo yopuma (M; SE) yogwirizana ndi malingaliro: gulu 50 (2205; 264)> gulu 0 (2025; 203)> gulu 100 (1909; 407)> gulu 25 (1296; 299) .

Zotsatira za 1 mg / kg AMPH.

Kutuluka kwa jekeseni koyamba. Gulu la 4 × 5 Gawo la ANOVA la kuyankhidwa kwa ogwira ntchito panthawi ya 30 min-pre-injection chizolowezi pa 1 mg / kg makapu oyezetsa magazi a AMPH adapereka zotsatira zazikulu za Gawo, F_{(4, 112)} = 43.64, p <0.0001, ndipo palibe zovuta zina, F_{(3, 28)} <0.97, p > 0.42. Kufanizira komwe kudakonzedwa sikunapeze kusiyana kwakukulu pakati pa gulu 50 ndi gulu 0 kapena gulu 100 poyesa koyamba kapena komaliza, t₍₁₄₀₎ <0.84, p > 0.30. Chifukwa chake, kusiyana koyambira pakusunthika sikunayambitse kusiyana kwamagulu poyankha kwa AMPH. Kutanthauza (SE) mitengo yopumira pamiyeso isanakwane gawo pazigawo 1-5 zinali: 454 (30), 809 (53), 760 (36), 505 (35), 756 (39).

Kupuma kwa jekeseni. Chithunzi 2 amasonyeza zotsatira za jekeseni zisanu za 1 mg / kg AMPH (imodzi pa sabata) pachithunzi chochita zambiri m'magulu anayi. Gulu la 4 × 5 Gawo la ANOVA linapereka zotsatira zazikulu za Gawoli, F_{(4, 112)} = 8.21, p <0.001, zotsatira zoyambira m'mbali za Gulu, F_{(2, 45)} = 3.28, p = 0.085, ndipo palibe kugwirizana kwakukulu, F_{(12, 122)} <0.77, p > 0.68.

 

Chithunzi 2. Yankho lokhazikika (SE) lovotor (chiwerengero cha mapulogalamu a magetsi pa 90 min) kwa 1 mg / kg d-amphetamine (ip) pa magawo a 5 mlungu ndi mlungu m'magulu a makoswe a Sprague Dawley (n = 8 / gulu) kale lomwe likuwonetsedwa ndi 15 masewera tsiku lililonse ndi sucrose mphoto (10% yankho) yoperekedwa pansi 0, 25, 50, kapena 100% ndandanda zosinthika. Chotsatiracho chinali chowala (120 s). Gulu 0 linalandira mphoto zomwezo monga gulu la 100 pokhapokha palibenso zokakamizidwa. *p <0.05 yamatanthauzidwe apakati pa gulu 50 ndi gulu 0 komanso gulu 100, kutengera kufananiza komwe kumakonzedwa.

Zowonongeka zomwe zinagwiritsidwa ntchito zikuwonetsa kuti gulu la 50 linasiyana mosiyana ndi gulu la 0, t₍₁₄₎ = 2.19, p = 0.037, ndi gulu 100, t₍₁₄₎ = 2.36, p = 0.025 [ndipo amasiyana mosiyana kuchokera ku gulu 25, t₍₁₄₎ = 2.03, p = 0.051]. Choncho, mu gulu la 50, kuyankha kwa ogwira ntchito ku 1 mg / kg AMPH modalirika kudapambana ndi magulu ena atatuwa pa magawo asanu a mayesero. Kufufuza kwa kayendetsedwe ka zinthu zamagetsi kunadziwika kuti ndi quadratic yofunika kwambiri pa magawo, F_{(1, 28)} = 32.47, p <0.0001, ndipo palibe zochitika zina zofunika, F_{(1, 28)} <1.78, p > 0.19. Chithunzi 2 ikuwonetsa kuti zotsatira izi zikuwonetsera ndondomeko ya "I yosinthidwa" pamasewu onse.

Kusintha kwa kusintha kwa mphuno poke kuyankha pa maphunziro a sucrose

Zotsatira za ANCOVA za mayankho ogwira ntchito ku 1 mg / kg AMPH, okhala ndi mphuno (CS panopa) monga covariate, m'magulu atatu omwe adalandira CS, adatulutsa mbali yaikulu ya Gulu, F_{(2, 20)} = 3.07, p = 0.069, ndipo palibe zotsatira zofunikira zokhudzana ndi mpweya, F_{(4, 80)} <0.05, p > 0.85. Chifukwa chake, mayankho omwe adayankhidwa panthawi yamaphunziro sanatanthauze kusiyanasiyana kwakukulu pakuyankha kwa oyendetsa ku 1 mg / kg AMPH m'magulu 25, 50, kapena 100.

Zotsatira za ANCOVA za mayankho ogwira ntchito ku 1 mg / kg AMPH, okhala ndi mphuno (CS palibe) monga covariate, F_{(1, 27)} = 6.17, p = 0.020, zotsatira zazikulu za Gulu, F_{(3, 27)} = 4.13, p = 0.016, gawo lachigawo × Kugwirizanitsa, p = 0.080, ndipo palibe zotsatira zina zofunikira, F_{(4, 108)} <1.48, p > 0.21. Chifukwa chake, kuyankha kosasankhidwa (kosasankha) poyankha panthawi yamaphunziro kudalongosola kusiyanasiyana kwakukulu pakuyankha kwa oyendetsa 1 mg / kg AMPH. Komabe, kusiyanaku sikunali kokulumikizana ndi kusiyanasiyana kokhudzana ndi gulu, chifukwa kuphatikiza kwa covariate pakuwunikaku kunakulirakulira m'malo mochepetsa kufunika kwa gululi.

Kukambirana

Deta ya mphuno pamene CS inkawonetsedwa kuti magulu adapeza mgwirizano pakati pa CS ndi sucrose yobereka monga momwe akuwonetsera ndi kuwonjezeka kwa mayankho ophika pa maphunziro. Mbiri ya kuyankhidwa pa magawo pomwe CS inapezeka kuti ndondomeko za 100 ndi 50% CS-US zinali zofanana poyesa kuyandikira, pamene 25% ndondomekoyi inachititsa kuti kuwonjezereka kochepetsetsa kwa njira yochepetsera. Deta ya mphuno pamene CS sanalipo imasonyeza kuti magulu omwe analandira ndondomeko iliyonse ya maphunziro a CS-sucrose (gulu 25, 50, 100) mwamsanga anaphunzira kuchepetsa mphuno zawo popanda CS, pamene nyama zogulu la 0 , omwe sanalandire CS, adaphunzira kuti achepetse njira zawo zoyenera kuchita pokhapokha ataphunzitsidwa kwambiri.

Deta ya chizoloŵezi imasonyeza kuti maguluwo sanali osiyana pamaso pa AMPH ndipo kuti kuwonetsedwa mobwerezabwereza ku mabokosi oyesedwa kunagwirizanitsidwa ndi yankho la kuchepetsa mankhwala osachepera. Choncho, kusiyana pakati pa magulu ndi kuwonjezereka kwa mayankho pafupipafupi za AMPH sikungakhalepo chifukwa cha kusiyana komwe kunakhalapo kale mu khalidwe lachikondi.

Zotsatira za vuto loyambitsanso chithandizo ndi 0.5 mg / kg AMPH linatsimikizira kuti mankhwalawa adakula kwambiri ntchito zokhudzana ndi mankhwala osagwiritsa ntchito mankhwala osokoneza bongo. Mogwirizana ndi lingaliro, gulu la 50 linkapambana kuposa magulu a 0 kapena 100 (komanso gulu la 25) poyankha moyenerera mlingo, ngakhale kuti kusiyana pakati pa magulu sikunali kofunikira.

Pazigawo zolimbikitsa, kuyerekezera komwe kudachitika pakati pa magulu awiriwa kunawonetsa kuti kuwonetsedwa koyambirira kwa 50% yokhala ndi mphotho ya sucrose kudapangitsa kuwonjezeka kwakukulu pakuyankha kwa oyendetsa ndege pamlingo wa 1.0 mg / kg wa amphetamine poyerekeza ndi magawo ena atatuwo. Izi zidawonekera pamlingo woyamba ndipo sizinasinthe moyenera pamlingo wobwereza. Kuwunika kwamachitidwe kunawonetsa kuyankha kwa biphasic (pachitsanzo chonse) kubwereza kuchuluka kwa AMPH, kukulira mpaka gawo lachitatu ndikuchepa pambuyo pake. Zotsatira zakutsata kwa ANCOVA zokhala ndi mphuno (CS kulibe) pomwe covariate idatsimikizira kuti kusiyanasiyana kwama mayankho a oyendetsa magulu ku 1 mg / kg AMPH sikunayanjanitsidwe ndi njira yosayankhidwa yomwe ikuyankha panthawi yamaphunziro a sucrose.

Zomwe gulu limakhudza panthawi yolimbikitsa zimagwirizana ndi maganizo athu. Gawoli lachiwirili silimagwirizana ndi kuwonjezeka kwakukulu kwa mayankho ogwira ntchito ndi mayendedwe afupipafupi a AMPH. Izi zikhoza kukhala zokhudzana ndi nthawi ya dosing. Pofuna kuthetsa vutoli, ndondomeko (njira zina zosawerengera tsiku lililonse) zowonetsera kuti zikhale zovuta kwambiri pakuyankhidwa kwa 1.0 mg / kg Mlingo wa AMPH (mwachitsanzo, kudziwitsira khalidwe) ayenera kugwiritsidwa ntchito. Zotsatira za mphamvu yolimbikitsa ya AMPH potengera yankho lachiwiri la mliri wa 0.5 mg / kg likhoza kuthandizira kuti izi zitheke. Kuphatikizidwa kwa vuto la saline pamaso pa AMPH lingasankhe udindo wa chiyembekezo kapena zokhudzana ndi jekeseni (mwachitsanzo, kupanikizika) zotsatira pa kuyankhidwa kwa AMPH. Kuphatikizidwa kwa 75% yokhala ndi kagulu ka sucrose kungathandize kufotokoza mbali ya malipiro osatsimikizika ndi mphotho yoperewera pa chitsanzo cha mayankho kwa magulu 50 ndi gulu 25. Kuonjezera apo, kulola kuunika (ndi ANCOVA) mwa zopereka zopanda mankhwala osagwiritsidwa ntchito ndi mankhwala osokoneza bongo pansi pa AMPH (kugwiritsa ntchito mphuno ndi CS pano monga covariate), mphuno zinalembedwanso kwa gulu 0 panthawi yomwe CS analipo m'magulu anayi (mwachitsanzo, kotero kuti mphuno kuchokera m'magulu onse-kuphatikizapo gulu 0 lomwe silinalandire CS-lingaphatikizidwe pofufuza covariance ndi CS panopa monga covariate). Zosintha izi zinaphatikizidwa mu kuyesa 2.

Yesani 2

Zida ndi njira

Njira yodziyesera 2 inali yofanana ndi yowunika 1 koma inakonzedweratu kuti ikhale yowonjezereka bwino kayendedwe kamene kamapezeka kuti kachulukitseni AMPH kudziwitsidwa (Fletcher et al., 2005). Kusintha kunali motere: (a) 75% CS-sucrose gulu (n = 8) anaphatikizidwa; (b) Pa maphunziro a sucrose, makoswe (kupatula gulu 0) analandira maonekedwe a 20 CS (kuwala) (mosiyana ndi 15 mu kuyesa 1); (c) mafotokozedwe a CS aliwonse amasiyanitsidwa ndi nthawi yapakati yoyesera ya 90; Zosiyanasiyana: 30-180 s (vs vs. 120 s kuyesa 1), zomwe zimapangitsa kuwonjezeka kwa mayesero kuti azindikire nthawi yomwe maphunziro amaphunzitsira ndi kuyesera 1; (d) Nthawi yonse ya nthawi zitatu izi zinachepetsedwa kuchoka ku 120 kufika ku 90 min kuti zigwirizane ndi nthawi ya magawo oyesera; (e) Mavuto a saline (ip, 1 ml / kg) (90 min) anawonjezeredwa (8 tsiku lophunzitsidwa ndi post-sucrose), kuti aone zotsatira zoyendetsera jekeseni pa se (mwachitsanzo, kuyembekezera, nkhawa); (f) Zolinga za 1 mg / kg zimakhala zochitika tsiku limodzi (masiku apatsiku maphunziro 12-21) mmalo mokhala pakati pa mlungu uliwonse monga momwe ayesa 1; (g) Pogwiritsa ntchito chithandizo choyambitsa chithandizo cha 0.5 mg / kg AMPH (tsiku lophunzirako 9) chidziwitso chachiwiri chithandizo cha 0.5 mg / kg AMPH chinawonjezeredwa (tsiku lophunzitsira la 28 tsiku lotsatira), kuti ayese kuthandizira kuwonetsa mitundu yonse; (h) mphuno pamene CS analipo anali kulembedwa kwa magulu onse (kuphatikizapo gulu 0); (i) mphuno pamene CS sanalipo inalembedwa kuchokera pa nthawi ya 5 nthawi yomweyo isanayambe kulowera kwa CS kuti ayambe kufotokozera nthawi yayitali.

Results

Mphuno imapangika pa nthawi ya sucrose

Gulu la 5 × 15 Gawo × 2 Phase (CS ikupezeka, CS palibe) ANOVA ya mphuno ikukula kwambiri zotsatira za Gulu, F_{(4, 19)} = 2.89, p = 0.050, Gawo F_{(14, 266)} = 2.28, p = 0.006, ndi Phase, F_{(1, 19)} = 14.72, p = 0.001, komanso njira yayikulu yothandizira, F_{(56, 266)} = 1.38, p = 0.050. Magulu (A, B) Chithunzi 3 Konzani magulu am'magulu amphuno am'magulu a CS omwe alipo komanso CS sapezeka, motsatana. Kuyerekeza kwa magawo awiriwa kukuwonetsa kuti gawo lalikulu lachigawochi likuwonetsa mayankho ambiri a mphuno pomwe CS analipo pomwe kulibe. Chifukwa chake, mayankho omwe adasinthidwa amapezeka pafupipafupi kuposa mayankho osadulidwa asanabadwe. Zotsatira zazikulu za Gulu ndi Gawo sizinatanthauziridwe mosavuta chifukwa chothandizana kwambiri. Zotsatira zomalizazi zikuwonetsa kusunthika kwa zambiri m'magulu asanuwa pamlingo wotsika pang'ono pamasamba pomwe CS kulibe (Chithunzi 3B), kuphatikizapo kusiyana kwa zigawo zambiri (gulu 75, gulu la 100), pakatikati (gulu 50), ndi gulu lachepa (gulu 0, gulu la 25) la mphuno la mphuno likuyankha panthawi yomwe CS analipo (Chithunzi 3A). Mwa njira zochepa za polynomial (zowonjezereka, quadratic, cubic) njira yokhayo yokambirana itatu ya mchitidwe wamakono inayandikira kufunika, F_{(4, 19)} = 2.32, p = 0.094, kuwonetsa kuwonjezeka kwachilengedwe kwa mphuno pokhala pa magawo mu gulu la 75 ndi kukhazikika mofulumira kwambiri pamtunda wapamwamba, wapakatikati, ndi wotsika poyankha magulu ena pamene CS analipo.

 

Chithunzi 3. Njira zowonjezera (SE) zimayankha (mphuno) pamaphunziro a 15 sucrose m'magulu a makoswe a Sprague Dawley (n = 8 / gulu) lomwe likuwonetsedwa kuti liwononge mphoto (10% yankho) yoperekedwa pansi pa 0, 25, 50, 75, kapena 100% ndandanda zosinthika. Chotsatiracho chinali chowala (120 s). Gulu 0 linalandira mphoto zomwezo monga gulu la 100 pokhapokha palibenso zokakamizidwa. (A) Zambiri pamene CS analipo (mayesero a 5 s × 20). (B) Zambiri pamene CS sanalipo (pafupifupi 5 × 20 pamene kuwala kunali kutayika).

Kuzoloŵera kwa mabokosi ogulitsa

Gulu la 5 × 3 Gawo la ANOVA la mayankho ogulitsa mankhwala osokoneza bongo linapindulitsa kwambiri pa Gawoli, F_{(2, 70)} = 60.01, p <0.0001, ndipo palibe zovuta zina, F_{(4, 35)} <0.70, p > 0.60. Kufananiza komwe gulu la 50 lidakhala ndi gulu 0 komanso gulu 100 pamaphunziro oyambira ndi omaliza sanapindule chilichonse, t's <0.84, p > 0.40. Chifukwa chake, kutanthauza kuyankha kosagwiritsa ntchito mankhwala osokoneza bongo m'magulu ofunikira sikunasiyane asanayesedwe. Kutanthauza (SE) kuchuluka kwa zopumira pamphindi 90 panali 2162 (118) pagawo 1, 1470 (116) pagawo 2, ndi 1250 (98) pagawo 3.

Gawo la mayesero

Saline. Gulu la 5 × 2 Gawo la ANOVA linagwirizanitsa mayankho ogwira ntchito pamapeto omaliza maphunzirowa ndi gawo lovuta la saline. ANOVA inapereka zotsatira zazikulu za Session, F_{(1, 35)} = 62.46, p <0.0001, ndipo palibe zovuta zina, F_{(4, 35)} <0.65, p > 0.64. Chithunzi 4 Kugwirizanitsa gululi kumatanthauza ndikuwonetsa kuti Gawoli likuwonetsa kuchepa kwakukulu kwa kuyankhidwa kwa ogwira ntchito kuchokera ku gawo lomaliza la mankhwala osagwiritsa ntchito mankhwala kupita ku gawo la saline, lomwe silinasinthe ndi gulu. Choncho, kuchepa kwa mayankhidwe a ogwira ntchito kuwonetseredwa kuwonetseredwa kwa machitidwe atatuwa kunapitiliza pazitsulo zachinayi zopanda mankhwala ku mabokosi oyesera.

 

Chithunzi 4. Yankho lokhazikika (SE) lovotor (chiwerengero cha mapulogalamu osokoneza bongo pa 90 min) pamapeto omaliza maphunziro osokoneza bongo a 3 ndi gawo lotsatira pambuyo pa jekeseni wa saline (ip, 1 ml / kg) magulu a Sprague Dawley makoswe (n = 8 / gulu) kale lomwe likuwonetsedwa ndi 15 masewera tsiku ndi tsiku ndi sucrose mphoto (10% yankho) yoperekedwa pansi pa 0, 25, 50, 75, kapena 100% ndandanda zosinthika. Chotsatiracho chinali chowala (120 s). Gulu 0 linalandira mphoto zomwezo monga gulu la 100 pokhapokha palibenso zokakamizidwa.

Zotsatira za 0.5 mg / kg AMPH.

Kutuluka kwa jekeseni koyamba. Gulu la 5 × 2 Gawo la ANOVA la kupweteka koyambako (30-min) musanayambe kulandira chithandizo 0.5 mg / kg Mwezi woyezetsa magazi wa AMPH wapereka zotsatira zazikulu za Gawo, F_{(1, 35)} = 13.39, p = 0.001, ndipo palibe zotsatira zina zofunikira, F_{(4, 35)} <1.79, p > 0.15. Zofanizira zomwe zidakonzedwa sizinapeze kusiyana kulikonse pakati pa gulu 50 ndi gulu 0 kapena gulu 100 pagawo loyamba, t₍₇₀₎ <1.00, p > 0.30. Komabe, pagawo lachiwiri (post-sensitization) gulu la 50 (1203; 121) lawonetsa kwambiri zopumira za jekeseni zisanachitike (M; SE) kuposa momwe gulu 100 (756; 103), t₍₇₀₎ = 5.11, p <0.001, koma sinali yosiyana ndi gulu 0 (1126; 211), t₍₇₎ <0.88, p > 0.40. Chifukwa chake, kusiyana koyambira pakusunthika sikunaganizire kusiyana kwamagulu poyankha oyambira ku 0.5 mg / kg mlingo woyamba wa AMPH koma mwina zidawonjezera kusiyana pakati pa gulu 50 ndi gulu 100 poyankha oyendetsa ku 0.5 mg / kg yachiwiri ya AMPH . Kutanthauza (SE) kuphulika kwa gawo loyambilira jekeseni woyamba ndi wachiwiri 0.5 mg / kg magawo oyesa a AMPH anali 757 (41) ndi 974 (59).

Kupuma kwa jekeseni. Gulu la 5 × 2 Gawo la ANOVA lakumvera kwa 0.5 mg / makilogalamu AMPH isanayambe ndipo pambuyo poti 5-dose yolimbikitsa chidziwitso chimabala zotsatira zazikulu za Gawo, F_{(1, 35)} = 76.05, p <0.0001, ndipo palibe zovuta zina, F_{(4, 35)} <1.10, p > 0.37. Chithunzi 5 imasonyeza tanthauzo la gulu lililonse ndi gawo.

 

Chithunzi 5. Yankho lokhazikika (SE) locomotor response (chiwerengero cha mapulogalamu ophatikizira pa 90 min) kwa 0.5 mg / kg d-amphetamine pa magawo osiyana asanayambe ndi pambuyo pa gawo la 5 kulimbikitsa mphamvu ya d-amphetamine (1.0 mg / kg; ip gawo lililonse) m'magulu a makoswe a Sprague Dawley (n = 8 / gulu) kale lomwe likuwonetsedwa ndi 15 masewera tsiku ndi tsiku ndi sucrose mphoto (10% yankho) yoperekedwa pansi pa 0, 25, 50, 75, kapena 100% ndandanda zosinthika. Chotsatiracho chinali chowala (120 s). Gulu 0 linalandira mphoto zomwezo monga gulu la 100 pokhapokha palibenso zokakamizidwa. *p <0.05 yamatanthauzidwe apakati pa gulu 50 ndi gulu 0 komanso gulu 100, kutengera kufananiza komwe kumakonzedwa.

Chiwerengerochi chikuwonetsa kuti gawoli limaphatikizapo kuwonjezeka kwakukulu kwa (SE) kuphulika kwazitsulo pa 90 min kuchokera ku 0.5 mg / kg mlingo 1, 3674 (216) mpaka 0.5 mg / kg mlingo 2, 6123 (275). Kulephera kwa mgwirizano kapena kagulu kameneka kunapangitsa kuti kulimbikitsidwa kwa AMPH kusasinthe mosiyanasiyana m'magulu. Ngakhale kuti alibe ANOVA, zotsatira zake zimasonyeza kuti gulu la 50 likuwonetsa kwambiri yankho lachiwiri ndi lachiwiri la 0.5 mg / kg. Kuyerekezera kwapadera kuyankha kwa chiwerengero choyamba cha 0.5 mg / kg sikunapangitse kusiyana kwakukulu pakati pa gulu 50 ndi gulu 0 kapena gulu 100, ts₍₃₅₎ <0.48, p > 0.50. Komabe, poyankha yachiwiri (post-sensitization) 0.5 mg / kg mlingo, gulu 50 limawonetsa kutulutsa kwakukulu kuposa gulu 0, t₍₃₅₎ = 2.00, p <0.05, komanso gulu 100, t₍₃₅₎ = 3.29, p <0.01.

Malingana ndi kusiyana kwakukulu kwa gulu pa kukwera koyambitsa matendawa pa yachiwiri 0.5 mg / kg AMPH gawo lofotokozedwa pamwambapa, gulu lotsogolera 5 × 2 Gawo la ANCOVA la kuyankha kwa ogwira ntchito ku 0.5 mg / kg AMPH idapangidwa, kulandira jekeseni pachigawo chachiwiri. Kufufuza kumeneku kunapangitsa chidwi kwambiri cha covariate, F_{(1, 34)} = 8.65, p = 0.006, zotsatira zazikulu za Gawo F_{(1, 34)} = 10.83, p = 0.002, ndipo palibe zotsatira zina zofunikira, F_{(4, 34)} <0.85, p > 0.50. Chofunika kwambiri, kuyerekezera komwe kudakonzedwa kutengera kulakwitsa kwa MS ndi df cholakwika kuchokera ku ANCOVA kunatsimikizira kuti kuyankha kwa oyendetsa galimoto ku gawo lachiwiri la 0.5 mg / kg la AMPH lidakhalabe lalikulu pagulu 50 kuposa gulu 100, t₍₃₄₎ = 3.09, p <0.01, ndi gulu 0, t₍₃₄₎ = 1.88, p <0.05 (mchira umodzi), pomwe jekeseni asanaperekedwe kuchokera pagawo 2 idawongoleredwa. Chifukwa chake, gulu la 50 lidawonetsa kuyankha kwakanthawi kochulukitsa kwambiri kwa 0.5 mg / kg AMPH kuposa momwe gulu 100 kapena gulu 0, ndipo kusiyana kwamagulu uku sikunayanjanitsidwe ndi kutulutsa kwa jekeseni usanachitike masiku oyesa.

Zotsatira za 1.0 mg / kg AMPH.

Kutuluka kwa jekeseni koyamba. Gulu la 5 × 5 Pulogalamu ya ANOVA ya 30-min yomwe yisanayambe kulandira kwa 1 mg / kg makapu okudziwitsira AMPH yatulutsa zotsatira zazikulu za Gawo, F_{(4, 140)} = 16.70, p <0.0001, ndipo palibe zovuta zina, F_{(4, 35)} <0.94, p > 0.45. Zofanizira zomwe zidakonzedwa sizinapeze kusiyana kulikonse pakakokedwe koyambitsa jekeseni pakati pa gulu 50 ndi gulu 0 kapena gulu 100 pagawo loyamba, t₍₁₇₅₎ <1.66, p > 0.10. Komabe, pagawo lomaliza, gulu la 50 (1167; 140) lawonetsa zopumira kwambiri (M; SE) kuposa momwe gulu 100 (1000; 99), t₍₁₇₅₎ = 2.35, p <0.05, koma sinali yosiyana ndi gulu 0 (1085, 120), t₍₁₇₅₎ <1.16, p > 0.20. Chifukwa chake, kusiyanasiyana kwa kutulutsa kwa jakisoni asanachitike kunapangitsa kuti pakhale kusiyana pakati pamagulu 50 ndi 100 poyankha oyendetsa pamlingo womaliza wa 1 mg / kg AMPH. Kutanthauza (SE) kuphulika kwathunthu pamiyeso panthawi yopangira jekeseni la Gawo 1 mpaka 5 anali: 810 (46), 784 (52), 760 (53), 726 (46), 1009 (51).

Kupuma kwa jekeseni. Gulu la 5 × 5 Gawo la ANOVA la mayankho a 1 mg / kg AMPH linapanga zotsatira zazikulu za Gawo, F_{(4, 140)} = 6.72, p <0.001, gulu laling'ono × Kuyanjana kwa gawo, F_{(16, 140)} = 1.57, p = 0.085, ndipo palibe zotsatira za Gulu, F_{(4, 35)} <0.44, p > 0.77. Kusanthula kwamachitidwe a Polynomial kuwulula njira yodziwika bwino, F_{(1, 35)} = 9.19, p = 0.005, ndi chikhalidwe cha cubic, F_{(1, 35)} = 21.63, p <0.001, pamisonkhano 1 mpaka 5. Chithunzi 6 imasonyezera zofunikira zotsatsa zokwanira gulu lirilonse ndi gawo.

 

Chithunzi 6. Yankho lokhazikika (SE) lovotor (chiwerengero cha mapulogalamu a magetsi pa 90 min) kwa 1 mg / kg d-amphetamine (ip) pa magawo a 5 mlungu ndi mlungu m'magulu a makoswe a Sprague Dawley (n = 8 / gulu) kale lomwe likuwonetsedwa ndi 15 masewera tsiku ndi tsiku ndi sucrose mphoto (10% yankho) yoperekedwa pansi pa 0, 25, 50, 75, kapena 100% ndandanda zosinthika. Chotsatiracho chinali chowala (120 s). Gulu 0 linalandira mphoto zomwezo monga gulu la 100 pokhapokha palibenso zokakamizidwa.

Chiwerengerochi chikuwonetsa kuti Gawoli likuwonetsa kuwonjezeka kwakukulu kwa zochitika zonse (SE) zopuma zazitsulo kuti zitha kuwonetsedwa kuchokera ku gawo 1, 4624 (213) mpaka gawo 5, 5736 (272), kutsimikizira kuti kutulukira kwa mphamvu kwa AMPH. Chikhalidwe cha cubic chimaimira maxima pa magawo 1, 3, ndi 5, ndi ma dips pa magawo 2 ndi 4, makamaka kwa magulu 0 ndi 50. Chiwerengerocho chikuwonetsanso kuti, ngakhale kuti panalibe kugwirizana kwakukulu, gulu la 25 linawonetsa yankho lopambana pang'onopang'ono pazokambirana ndipo linasiyana mosiyana ndi magulu ena pa magawo 4 ndi 5 (9 ndi 22% oposa, kuposa gulu lotsatira kwambiri). Zowonongeka zomwe zapezeka kuti gulu la 50 silinali losiyana kwambiri ndi magulu a 0 kapena 100, t₍₁₇₅₎ <0.89, p > 0.40 pamayeso oyesa 1 mg / kg AMPH oyambira kapena omaliza.

Kusintha kwa kusintha kwa mphuno poke kuyankha pa maphunziro a sucrose

Gulu la 5 Gulu × 2 Gawo la ANCOVA la kuyanjanitsa kwa 0.5 mg / kg AMPH isanayambe ndi pambuyo poyambitsa chidziwitso, kuphatikizapo mphuno pa maphunziro a sucrose ndi CS panopa ndipo CS sakhala ngati covariate yosiyana, F_{(1, 18)} <1.03, p > 0.31. Chifukwa chake, kuyankha poyankha panthawi yamaphunziro sikunathetsere kusiyana kwamagulu poyankha 0.5 mg / kg AMPH.

Gulu la 5 Group × 5 Gawo la ANCOVA la anthu ogwira ntchito ku 1 mg / kg panthawi yolimbikitsana ndi mphuno zonse (CS panopa, CS palibe) ngati mapepala osiyana omwe sanagwiritsidwe ntchito kwambiri pamene CS analipo, F_{(4, 104)} <1.04, p > 0.38, ndi zotsatira zoyambilira za covariate pomwe CS kulibe, F_{(1, 18)} = 3.32, p = 0.085.

Kukambirana

Zotsatira za phunziroli sizimagwirizana nthawi zonse kuti gulu la 50 lingasonyeze yankho lapamwamba la ogwira ntchito pa magawo poyerekeza ndi magulu ena. Dongosolo la 1 mg / kg AMPH linatsimikizira kuti kutuluka kwa mphamvu kukuthandizidwa ndi mayendedwe a masiku ena. Chitsanzo pamagulu chinawonetsa chizoloŵezi cholimbikitsana kwambiri pamapeto a gulu la 25, popanda umboni wotero wa gulu la 50. Mosiyana ndi zimenezi, zotsatira za 0.5 mg / kg zimasonyeza kuti zimakhala zolimbikitsa kwambiri mu gulu la 50, pomwe panthawi imodzimodziyo zimatsimikizira kuwonjezeka kwakukulu kwa mayankhidwe oyendetsa magulu awiri mpaka awiri poyerekeza ndi chiwerengero choyamba cha 0.5 mg / kg AMPH mlingo. Kulephera kwa jekeseni wa saline kunatsimikizira kuti kuyembekezera kapena vuto lopangidwira jekeseni silinapangitse AMPH zotsatira.

Deta yolumikiza mphuno inavumbulutsira kuwonjezeka kwakukulu kwa njira yomwe ikuyankhidwa panthawi ya maphunziro pamene CS analipo, popanda kuwonjezeka komweku pamene CS analibe. Choncho, nyamazo zimawoneka kukhala ndi mgwirizano pakati pa CS ndi chiyembekezo cha sucrose mphotho. Kusiyana kwa magulu pafupipafupi pamphuno kumapangika pamene CS analipo ikugwirizana mofanana ndi mafupipafupi a kubwezera mphotho pansi pa ndondomekoyi, ndi magulu a 75 ndi 100 akuwonetsa mphuno zambiri, gulu la 50 likuwonetsera mphuno, ndi magulu a 0 25 ikuwonetsa mphuno yochepa kwambiri. Zotsatira izi zikusonyeza kuti CS anabwera kudziteteza njira yochitapo mwanjira yogwirizana ndi mwayi wonse wa mphotho. Ngakhale kuti zowonongeka, chimodzi mwazifukwa zowonjezera ma phokoso omwe ali ndi CS akupezeka mu gulu 50 mu kuyesa 2 ndi kuyesa 1 kungakhale kuchepetsana kwa nthawi yoyesera, pamene nthawi yayitali yambiri (kuyesera 1) ikuwoneka kuti ikulimbikitsani zizoloŵezi ndipo izi zikukhudzana ndi kuwonjezeka kwa DA m'zaka zam'mbuyo zodziwika, prelimbic ndi infralimbic cortices (Dalley et al., 2002). Choncho, 30% kuchepetsa nthawi yoyesera mkati mwa kuyesa 2 (ndi 3) kungasinthe mavoti a DA ndikumalimbikitsa kwambiri (mwachitsanzo, motsogoleredwa ndifupipafupi). Kuyankha gulu la 50 pa mayesero ophunzirira mu kuyesa 2 poyerekeza ndi kuyesera 1.

Kuperewera kwa zochitika zazikulu zokhudzana ndi mphuno za mphuno zomwe zimachitika mu CS zilipo tsopano mu ANCOVAs zikusonyeza kuti njira yothandizira pa maphunziro a sucrose sizinagwirizanitse zotsatira za machitidwe osiyanasiyana a CS-sucrose pa mayankho a AMPH. Zomwe zimachititsa kuti HIV isakhalepo kwa ANCOVA ya mayankho a 1 mg / kg AMPH ikusonyeza kuti chizoloŵezi chokhala ndi mankhwala osagwiritsidwa ntchito mopanda msanga, chinafotokozera zina mwa kusintha kwa zotsatira za AMPH panthawi yolimbikitsa.

Pamodzi, umboniwu umasonyeza kuti zotsatira za mbiri yabwino zimakhala zoonekeratu ndi 0.5 AMPH kusiyana ndi 1 mg / kg AMPH, komanso kuti puloteni yomwe imapangitsa chidziwitso ngati palibe vuto lina lililonse likhoza kusokoneza kapena kubweretsa zotsatira zoopsa za putative Kulimbikitsana-kulimbikitsa kugwiritsira ntchito khalidwe (mwachitsanzo, nthawi yosasinthika).

Kulimbikitsidwa kwa khalidwe kwa AMPH kumakhudza kwambiri laboratori. Komabe, kunja kwa labotale, ndi anthu ochepa okha omwe amatha kuthamanga nthawi zambiri mpaka kufika povuta. Ngakhale kuti chiopsezo chodziwitsidwa chikugwirizana ndi chiopsezo cha kuledzera (kapena kufunafuna mankhwala), makamaka kwa psychostimulants (Vezina, 2004; Lembani ndi al., 2008), zinthu zambiri kuphatikizapo chiopsezo chodziwitsa ena zingayambitse munthu kukhala wodetsedwa (mwachitsanzo, Verdejo-Garcia et al., 2008; Conversano et al., 2012; Volkow et al., 2012). Komabe, zifukwa zomwe zimapangitsa kuti chiopsezo chisawonongeke zingagwirizane ndi mbiri yakale kuti iwononge zotsatira za mphotho yosadziŵika (ie, 50% CS-US ndandanda) pa DA system reactivity. Pofufuza zotsatirazi, kuyesa 3 kunagwiritsidwa ntchito mofanana ndi kuyesera 2 koma ntchito ya Lewis m'malo mwa makoswe a Sprague Dawley.

Kukwapula makoswe a Dawley akuwonetsa maulendo apakati a DA otumiza katundu, okhala ndi mazenera ochepa kuposa makoswe a Wistar (Zamudio et al., 2005), koma maulendo apamwamba kuposa makoswe a Wistar-Kyoto (vuto "lopweteka") mu nucleus accumbens, amygdala, ventral tegmental area ndi substantia nigra (Jiao et al., 2003). Mbiriyi ikhoza kupereka madyerero a Sprague Dawley pokhapokha atagwirizana ndi zochitika zachilengedwe kapena mankhwala a DA ntchito. Mosiyana ndi zimenezi, makoswe a Lewis amavumbulutsa otsika a DA otumiza katundu pamodzi ndi D2 ndi D3 DA receptors mu nucleus accumbens ndi dorsal striatum poyerekeza ndi mavuto ena (mwachitsanzo, F344) (Flores et al., 1998). Kusiyana kwamakhalidwe kotereku kumatha kuchititsa makoswe a Lewis kuyankha mosiyanasiyana pakuwongolera kwa DA. Makoswe a Lewis amawonetsanso mayankho angapo okweza pamankhwala oyeserera poyerekeza ndi mitundu ina (mwachitsanzo, F344). Chofunika koposa, makoswe a Lewis amawonetsa chidwi chachikulu ku methamphetamine, yodziwika ndi kuchepa kwamankhwala oyambilira koma kuyankha kwakukulu kumayeso amtsogolo (Camp et al., 1994). Mphuno ya Lewis imasonyezeranso kuti kulimbikitsidwa kwakukulu kwa mitundu yosiyanasiyana ya cocaine (Kosten et al., 1994; Haile et al., 2001). Pogwiritsa ntchito zotsatirazi, tinaganizira kuti makoswe a Lewis angatipangitse kufufuza ngati kukhudzidwa kuchitsimikiziridwa kumapangitsa kuti pakhale zotsatira za kukhazikika kwa AMPH.

Yesani 3

Zida ndi njira

Njirayi inali yofanana ndi kuyesera 2, kupatulapo kugwiritsa ntchito makoswe a Lewis (200-225 g pofika, Charles River, Quebec, Canada).

Results

Mphuno imapangika pa nthawi ya sucrose

Gulu la 5 × 15 Gawo × 2 Phase (CS ikupezeka, CS palibe) ANOVA ya mphuno ikukula kwambiri zotsatira za Gulu, F_{(4, 34)} = 6.12, p = 0.001, Gawo, F_{(14, 476)} = 3.42, p <0.001, ndi Gawo, F_{(1, 34)} = 20.83, p <0.001, komanso kulumikizana kwakukulu m'njira zitatu, F_{(56, 476)} = 1.56, p = 0.008. Magulu (A, B) Chithunzi 7 Konzani magulu am'magulu amphuno am'magulu a CS omwe alibe komanso CS omwe alibe, motsatana. Kuyerekeza kwa magawo awiriwa kukuwonetsa kuti gawo lalikulu lachigawochi likuwonetsa mayankho ambiri a mphuno pomwe CS analipo pomwe kulibe. Chifukwa chake, mayankho okonzedwa amapezeka pafupipafupi kuposa mayankho omwe sanakhwime msanga. Zotsatira zazikulu za Gulu ndi Gawo sizinatanthauziridwe mosavuta chifukwa chothandizana kwambiri. Kulumikizana kwa njira zitatu kumawonetsa kuphatikiza kwa magulu asanuwo pamlingo wotsika pang'ono pamasamba pomwe CS kulibe [Gulu (B)], kuphatikizapo kusiyana kwa zinthu zambiri pamene CS anali kupezeka mu mbiri zosalongosoka za gulu lirilonse lomwe linkafanana ndi kachitidwe kawo ka mphotho: kuchokera pamwamba (gulu 100) kupita pansi (gulu 25) [Panema (A)]. Njira yokhayo yokhudzana ndi kugwirizana inali yofunika, F_{(4, 34)} = 4.03, p = 0.009, kusonyeza kuwonjezereka kosalekeza kwa mphuno pokhala pa magawo mu gulu la 100 pamene CS analipo motsutsana ndi mbiri yosagwirizana ya kuwonjezeka kwa mphuno popanga magawo m'magulu ena panthawiyi.

 

Chithunzi 7. Njira zowonjezera (SE) zimayankha (mphuno) pamaphunziro a 15 asprose m'magulu a makoswe a Lewis (n = 8 / gulu) lomwe likuwonetsedwa kuti liwononge mphoto (10% yankho) yoperekedwa pansi pa 0, 25, 50, 75, kapena 100% ndandanda zosinthika. Chotsatiracho chinali chowala (120 s). Gulu 0 linalandira mphoto zomwezo monga gulu la 100 pokhapokha palibenso zokakamizidwa. (A) Zambiri pamene CS analipo (mayesero a 5 s × 20). (B) Zambiri pamene CS sanalipo (pafupifupi 5 × 20 pamene kuwala kunali kutayika).

Kuzoloŵera kwa mabokosi ogulitsa

Gulu la 5 × 3 Gawo la ANOVA linapereka zotsatira zazikulu za Gawoli, F_{(2, 70)} = 23.07, p <0.0001, ndipo palibe zovuta zina, F_{(8, 70)} <1.47, p > 0.18. Njira ya curvilinear of mean (SE) locomotor scores idatuluka pagawo 1, 1076 (74), kudzera gawo 2, 644 (48), kufikira gawo 3, 762 (59). Kuyerekeza kofananira kwa gulu 50 ndi gulu 0 komanso gulu 100 pamisonkhano yoyamba ndi yomaliza yophunzitsira kuwulula kocheperako kamitengo kagulu ka 50 (M = 911; SE = 109) vs. gulu la 0 (M = 1103; SE = 176) pazokambirana za 1, t₍₁₀₅₎ = 2.02, p <0.05, koma palibe kusiyana pakati pa gulu 50 ndi gulu 100 (M = 1066; SE = 150), t₍₁₀₅₎ <1.20, p > 0.20, pagawoli. Gulu 50 silinasiyane kwambiri ndi gulu 0 kapena gulu 100 pamapeto omaliza maphunziro, t₍₁₀₅₎ <0.93, p > 0.30. Chifukwa chake, kutanthauza kuyankha kwa omwe alibe mankhwala osokoneza bongo m'magulu ofunikira sanasiyane mosiyanasiyana asanayesedwe.

Gawo la mayesero

Saline. Gulu la 5 × 2 Gawo la ANOVA la mayankho omaliza pa zokambiranazo ndi gawo la kuyesera kwa saline linapindulitsa kwambiri pa Gawoli, F_{(1, 35)} = 50.12, p <0.0001, ndipo palibe zovuta zina, F_{(4, 35)} <0.57, p > 0.68. Chithunzi 8 amasonyeza kuti gululo limatanthauza zambiri pa magawo awiriwa ndipo limasonyeza kuti gawoli likuwonetsa kuchepa kwakukulu kuchokera ku chizoloŵezi choyesa kuyesera. Choncho, kulandira jekeseni pa se (mwachitsanzo, kuyembekezera, kupanikizika) sikunapangitse kuti ogwira ntchito ayankhe.

 

Chithunzi 8. Yankho lokhazikika (SE) lovotor (chiwerengero cha mapulogalamu osokoneza bongo pa 90 min) pamapeto omaliza maphunziro osokoneza bongo a 3 ndi gawo lotsatira pambuyo pa jekeseni ya saline (ip, 1 ml / kg) m'magulu a Lewis makoswe (n = 8 / gulu) kale lomwe likuwonetsedwa ndi 15 masewera tsiku ndi tsiku ndi sucrose mphoto (10% yankho) yoperekedwa pansi pa 0, 25, 50, 75, kapena 100% ndandanda zosinthika. Chotsatiracho chinali chowala (120 s). Gulu 0 linalandira mphoto zomwezo monga gulu la 100 pokhapokha palibenso zokakamizidwa.

Zotsatira za 0.5 mg / kg AMPH.

Kutuluka kwa jekeseni koyamba. Gulu la 5 × 2 Gawo la ANOVA la kutuluka kwa jekeseni loyambitsa kupatsirana linapangitsa zotsatira zazikulu za Gawo, F_{(1, 35)} = 15.04, p <0.001, ndipo palibe zovuta zina, F_{(4, 35)} <1.19, p > 0.33. Zofanizira zomwe zidakonzedwa sizinapeze kusiyana kwakukulu pakati pa gulu 50 ndi gulu 0 kapena gulu 100 pamayeso aliwonse oyesera, t₍₇₀₎ <0.99, p > 0.30. Chifukwa chake, kusiyana koyambira koyambira koyambitsa jekeseni sikunayambitse kusiyana kwamagulu poyankha kwa 0.5 mg / kg AMPH. Kutanthauza (SE) kuphulika kwa gawo loyambilira jekeseni woyamba ndi wachiwiri (pambuyo pakulimbikitsa) magawo a 0.5 mg / kg anali 325 (25) ndi 473 (36).

Kupuma kwa jekeseni. Gulu la 5 × 2 Gawo la ANOVA lakumvera kwa 0.5 mg / makilogalamu a makilogalamu aperekedwa kale ndi pambuyo pake 1 mg / kg AMPH inapereka zotsatira zazikulu za Gawo, F_{(1, 34)} = 87.44, p <0.0001, ndipo palibe zovuta zina, F_{(4, 34)} <0.94, p > 0.45. Chithunzi 9 amachititsa kuti phindu likhale lothandiza pa gulu lirilonse ndi gawoli ndipo likuwonetsa kuti gawoli likuwonetsa kuwonjezereka kwachiwiri kwa kachiwiri ka 0.5 mg / kg mlingo, mogwirizana ndi kuwalimbikitsa. Chiwerengerochi chikuwonetsanso kuti maguluwo anachita mofananamo pa gawo la 1, koma gululi 50 linawonetsa ntchito zambiri zowonjezera kuposa magulu ena pa gawo 2. Kuyerekezera kwapadera poyankhidwa ndi chiwerengero choyamba cha 0.5 mg / kg sikuwonetsa kusiyana kwakukulu pakati pa gulu 50 ndi gulu 0 kapena gulu 100, t₍₃₅₎ <1.28, p > 0.20. Komabe, gulu la 50 likuwonetsa kuyankha kwakukulu kwa oyendetsa ku gawo lachiwiri la 0.5 mg / kg kuposa momwe gulu 0, t₍₃₅₎ = 4.32, p <0.001, kapena gulu 100, t₍₃₅₎ = 2.24, p <0.05.

 

Chithunzi 9. Yankho lokhazikika (SE) locomotor response (chiwerengero cha mapulogalamu ophatikizira pa 90 min) kwa 0.5 mg / kg d-amphetamine pa magawo osiyana asanayambe ndi pambuyo pa gawo la 5 kulimbikitsa mphamvu ya d-amphetamine (1.0 mg / kg; ip gawo lililonse) m'magulu a makoswe a Lewis (n = 8 / gulu) kale lomwe likuwonetsedwa ndi 15 masewera tsiku ndi tsiku ndi sucrose mphoto (10% yankho) yoperekedwa pansi pa 0, 25, 50, 75, kapena 100% ndandanda zosinthika. Chotsatiracho chinali chowala (120 s). Gulu 0 linalandira mphoto zomwezo monga gulu la 100 pokhapokha palibenso zokakamizidwa. *p <0.05 yamatanthauzidwe apakati pa gulu 50 ndi gulu 0 komanso gulu 100, kutengera kufananiza komwe kumakonzedwa.

Zotsatira za 1 mg / kg AMPH.

Kutuluka kwa jekeseni koyamba. Gulu la 5 × 5 Gawo la ANOVA la 30-min kupititsa patsogolo kwa magawo okhudzidwawo linapereka zotsatira zazikulu za Gawo, F_{(4, 140)} = 4.10, p = 0.004, ndipo palibe zotsatira zina zofunikira, F_{(4, 35)} = 1.25, p > 0.31. Kufanizira komwe kumapangidwira kunapeza kuti mitengo imaswa panthawi yopangira jekeseni (M; SE) inali yotsika kwambiri pagulu 50 (395; 62) kuposa gulu 100 (508; 62), t₍₁₇₅₎ = 2.58, p <0.01, koma osati gulu 0, t₍₁₇₅₎ <1.83, p > 0.10, pa 1 mg / kg AMPH gawo 1. Pachigawo chomaliza cha 1 mg / kg AMPH, kuyerekezera komwe kudakonzedweratu kunapezekanso kuti kutulutsa kwa jekeseni koyambirira mu gulu 50 (378; 60) kunali kotsika kwambiri kuposa gulu 100 (650; 75 ), t₍₁₇₅₎ = 6.17, p <0.001, koma osati pagulu 0, t₍₁₇₅₎ <1.84, p > 0.10. Momwe kuwongolera kwa magawidwe awa (gulu lowongolera = gulu 50) kunali kotsutsana ndi kapangidwe kake, kusiyana kwamagulu pakubwezeretsa pambuyo pobayira komwe kumagwirizana ndi malingaliro sikungachitike chifukwa cha magwiridwe anthawi yoyamba a jakisoni. Kutanthauza (SE) mitengo yonse yopumira mkati mwa gawo loyambirira la jakisoni wa Sessions 1 mpaka 5 anali: 442 (34), 452 (32), 542 (40), 411 (26), 504 (37).

Kupuma kwa jekeseni. Gulu la 5 × Masewero a 5 ANOVA wa mayankho ku 1 mg / kg Mlingo wafika pamsinkhu waukulu kwambiri wa Session, F_{(4, 140)} = 6.15, p <0.001, ndipo palibe zovuta zina, F_{(4, 35)} <0.57, p > 0.68. Kusanthula kwamachitidwe a Polynomial kuwulula njira yodziwika bwino, F_{(1, 35)} = 9.34, p = 0.004, ndi chikhalidwe cha cubic, F_{(1, 35)} = 5.08, p = 0.031, zotsatira zotsatilazi zikuimira maxima pa magawo 3 ndi 5. Chithunzi 10 amalinganiza zinthu izi ndipo amasonyeza kuti, ngakhale kuti panalibe kugwirizana kwakukulu kwa ANOVA, gulu la 50 linawonetsa kutentha kwakukulu kuposa magulu ena anayi poyankha chiwerengero chomaliza cha 1 mg / kg. Choncho, kuyerekezera komwe kunakonzedweratu kunabvumbulutsira zowonjezera zazikulu kwambiri pa gawo 5 mu gulu 50 kusiyana ndi magulu ena onse, t₍₃₅₎ > 3.68, p <0.001.

 

Chithunzi 10. Yankho lokhazikika (SE) lovotor (chiwerengero cha mapulogalamu a magetsi pa 90 min) kwa 1 mg / kg d-amphetamine (ip) pa magawo a 5 mlungu ndi mlungu mu magulu a Lewis (n = 8 / gulu) kale lomwe likuwonetsedwa ndi 15 masewera tsiku ndi tsiku ndi sucrose mphoto (10% yankho) yoperekedwa pansi pa 0, 25, 50, 75, kapena 100% ndandanda zosinthika. Chotsatiracho chinali chowala (120 s). Gulu 0 linalandira mphoto zomwezo monga gulu la 100 pokhapokha palibenso zokakamizidwa. *p <0.05 yamatanthauzidwe apakati pa gulu 50 ndi gulu 0 komanso gulu 100, kutengera kufananiza komwe kumakonzedwa.

Kusintha kwa kusintha kwa mphuno poke kuyankha pa maphunziro a sucrose

Gulu la 5 Gulu × 2 Gawo la ANCOVA la kuyanjanitsa kwa 0.5 mg / kg AMPH isanayambe ndi pambuyo poyambitsa chidziwitso, kuphatikizapo mphuno pa maphunziro a sucrose ndi CS panopa ndipo CS sakhala ngati covariate yosiyana, F_{(1, 32)} <0.44 p > 0.51. Magulu awiri a 5 × 5 Gawo la ANCOVAs poyankha oyendetsa 1 mg / kg AMPH panthawi yolimbikitsana yokhala ndi mphuno zonse (CS alipo, CS kulibe) popeza ma covariate osiyana sanabweretse zovuta za covariate pomwe CS analipo kapena kulibe, F_{(1, 33)} <0.14, p > 0.71. Chifukwa chake, kuyankha kosagwiritsa ntchito mankhwala osokoneza bongo sikunapangitse kusiyana kwamagulu pama mayankho a oyendetsa pamlingo uliwonse wa AMPH.

Kukambirana

Sensitization idayamba chifukwa chakubwereza 1.0 mg / kg amphetamine. Dongosolo lazozolowera komanso zamchere zimatsimikizira kuti izi sizinachitike chifukwa cha kusiyana komwe kunalipo kale, chiyembekezo, kapena mayankho okhudzana ndi kupsinjika kwa jakisoni. Ma ANCOVA okhala ndi zokopa pamphuno amatsimikizira kuti izi sizinachitike chifukwa chogwiritsa ntchito mankhwala osokoneza bongo. Dongosolo lamphuno lokha lidawonetsa kuti maguluwo adapeza mgwirizano pakati pa CS ndi chiyembekezo chopeza mphotho ya sucrose. Mulingo wamagulu amphuno omwe amayankha kumapeto kwa maphunziro amafanananso pafupipafupi pamalipiro osiyanasiyana kuchokera kumagulu apamwamba (gulu 100) mpaka otsika kwambiri (gulu 0), monga momwe amachitira poyesa 2. Zomwe zili zochepa kwambiri zimatanthauza Kutulutsa mphuno poyesa uku poyerekeza ndi kuyesa 1 ndi 2 kumatha kuwonetsa njira zina zoyankhira mphotho ya makoswe a Lewis (Kosten et al., 2007).

Dongosolo la 0.5 mg / kg la dozi linawonetsa kuti kuyankhidwa koyamba kwa AMPH mu makoswe a Lewis (Chithunzi 9) adasokonezedwa poyerekeza ndi makoswe a Sprague Dawley (yesani 2; Chithunzi 5), koma kuwonjezereka kwa gulu mkati mwachidziwitso kwa mlingo wachiwiri mu makoswe a Lewis kunali kwakukulu (pafupifupi kawiri kuyankha kwa mlingo woyamba 0.5 mg / kg) potsatira ndondomeko ya AMPH ya gawo la 5 Chodabwitsa kwambiri, gulu la 50 likuwonetsa yankho lalikulu la ogwira ntchito kuposa magulu onse kupatula gulu 25 mpaka lachiwiri (kutanthauza, pambuyo polimbikitsa) 0.5 mg / kg AMPH mlingo ndi yankho lalikulu kuposa magulu ena onse, kuphatikizapo gulu 25, mpaka ku 1 mg / kg AMPH dose (gawo lomaliza kulandirira) .

Kusanthula mwachidule za chiwerengero cha gulu kudutsa mayesero

Pofuna kudziwa kutsimikizika kwa kusiyana kwa magulu pakulimbikitsana, kusanthula kwapadera komweko kunayambitsa kusiyana pakati pa gulu ndi mtundu wa mayankho ogwira ntchito otanthauzira kwa wachiwiri (mankhwala osapitirira nthawi AMPH) 0.5 mg / kg mlingo komanso mapeto a 1.0 mg / kg a AMPH kuchokera ku ziyeso za 3. Kusanthula kunapangitsa chidwi kwambiri, φ = 0.986, p = 0.025, kusonyeza kuti gulu la 50 linayambira poyamba pa zonse koma zofananako. Gulu lapamwamba la gulu la 50 likuyerekeza ndi magulu ena onse poyankha yachiwiri (AMPH osasintha) AM 0.5 mg / kg mlingo akuwonetsedwa mu Chithunzi 5 (yesani 2) ndi Chithunzi 9 (yesani 3). Mtsogoleri wapamwamba wa gulu 50 wokhudzana ndi magulu ena potengera chiwerengero chomaliza cha 1.0 mg / kg mlingo akuwonetsedwa mu Chithunzi 2 (yesani 1) ndi Chithunzi 10 (yesani 3). Chinthu chokhacho pa chitsanzo ichi chinali kuyankhidwa kwa mlingo womaliza wa 1.0 mg / kg pamatsuko a Sprague-Dawley poyesera 2.

Kukambirana Kwambiri

Zochitika zamakono zatsopano zinayesa lingaliro loti nthawi zonse kuyang'ana njuga-monga ndondomeko ya mphotho kungalimbikitse ubongo DA njira zowonjezereka monga kusadziwika kwa mankhwala osokoneza bongo. Umboni wa zotsatira zoterozo zingasonyeze kuti ubongo wothandizira, womwewo umaganiziridwa kuti umathandizira kuledzeretsa, ungapangidwe ndi kupezeka kosatha kwa ndondomeko za mphotho zosadziŵika. Malinga ndi mabuku okhudzana ndi mankhwala osokoneza bongo, kuyankhidwa kwa osokoneza bongo ku 0.5 ndi 1.0 mg / makilogalamu a makilogalamu a AMPH omwe alembedwa ndi DA a reactivity, ndi kukwera kwakukulu pamayendedwe amtsogolo omwe amatha kufotokozera mphamvu (cf. Robinson ndi Berridge, 1993; Pierce ndi Kalivas, 1997; Vanderschuren ndi Kalivas, 2000).

Zonsezi, zotsatira zimagwirizana ndi maganizo athu. Komabe, amasonyezanso kusiyana kwakukulu kwa zotsatira zoyesayesa chifukwa chazifukwa. Zotsatira za kukhazikitsa nthawi zinali zosavuta koma zosasinthika, ndi gulu la 50 likuwonetsa kuyankha kwakukulu kusiyana ndi magulu ena anayi ku madera onse omwe akutsatira mayendedwe asanu. Ngakhale ambiri F-maganizidwe a zotsatira zokhudzana ndi magulu pamaganizo osiyana omwe nthawi zambiri anali osagwirizana, kusiyana kwa magulu akuluakulu kunatsimikiziridwa ndi kufanana kwapadera. Pachifukwa ichi tiyenera kukumbukira kuti, "Kuganizira tsopano, komabe, ndikofunika kwake [kwa F mu ANOVA] sikofunika. Choyamba, maganizo oyesedwa ndi mayesero onse ndi mayeso osiyana-siyana ndi osiyana, ndi mphamvu zosiyana. Mwachitsanzo, zonsezi F kwenikweni amapereka kusiyana pakati pa magulu kudutsa chiwerengero cha madigiri a ufulu kwa magulu. Izi zimakhala ndi zotsatira zochepetsera zonse F pamene ziwerengero zingapo zimatanthauza zofanana koma zosiyana ndi zina zotanthawuza "(Howell, 1992, p. 338). Izi ndizozimene zakhala zikugwiritsidwa ntchito panthawiyi, pamene gulu la 50 liyenera kuti likhale losiyana ndi gulu la 0 ndi gulu la 100 koma palibe kusiyana pakati pa magulu awa olamulira omwe ananenedweratu ku gulu la 25 kapena gulu la 75.

Deta ya mphuno ya mphuno inatsimikizira kuti, muyeso iliyonse, nyamazo zinapeza mgwirizano pakati pa CS ndi chiyembekezo cha sucrose mphotho. Malembo pakati pa mphuno ya mphuno ya phokoso la magulu osiyanasiyana ndifupipafupi ya mphotho pansi pa ndondomeko zawo za maphunziro amasonyeza kuti mlingo woyenera wa sucrose njira yowonongeka yopanda mankhwala yopanda mankhwala. Komabe, kusagwirizana kwa mphuno kumapangidwe ku mayankho ogwirizana ndi gulu ku AMPH mu ANCOVAs akusonyeza kuti njira zosiyana zimayendera makhalidwe awiri.

Nthawi zina, zotsatira za ndondomeko ya chikhalidwe zinkaonekera poyankha mlingo woyamba wa AMPH; Nthawi zina izi zinangowonjezera pambuyo poyerekeza mobwerezabwereza. Kusiyana kwa magulu pa kuyankhidwa kwa ogwira ntchito kumsonkhano woyamba wa AMPH kumasonyeza kuti kuwonetsa njuga-monga ndondomeko ya malipiro ndikwanira zokha kuti azilimbikitsa. Kusiyanasiyana kwa magulu pamtundu wotsatira kumayeso angapo a AMPH kumasonyeza zotsatira zowonongeka zomwe zingatchulidwe monga "kukhudzidwa," zomwe zimangowonekera ngati zimakhala zikudziwika ndi nthawi zonse (ie, amphetamine).

Kusiyanasiyana kwa kayendedwe ka mayesero kumasonyeza kuti nthawi yayitali pakati pa maphunziro ndi vuto loyamba la AMPH lingapangitse mpata kuti azindikire kuti thupi limakhala ndi mphamvu yochizira. Izi zikuwonetseratu kuti zotsatira za mphotho zowonjezereka zimatha kuwonjezereka pakapita nthawi, chinthu chowonetseratu chikuwonetsedwanso ndi mphamvu yolimbikitsa (Grimm et al., 2006). Mchitidwe wotsatira mazira awiri a amphetamine umasonyeza kuti 0.5 mg / kg mlingo ungakhale wogwira bwino powulula zotsatira za chikhalidwe cha mbiri. Izi zikuwonetseratu kuti zotsatira za chikhalidwe pansi pano zimakhala zovuta kwambiri ndipo zingayambidwe ndi zotsatira za denga pansi pa mlingo wa AMPH ndi zomwe zimapanga de novo kulimbikitsa.

Poyesera 3, njira ya biphasic yankho la 0.5 mg / makilogalamu ndi kuyambira kwapamwamba mu gulu 50 ndizogwirizana ndi maonekedwe a rats Lewis poyankha methamphetamine (Camp et al., 1994). Izi zimapereka chitsimikizo kuti zokhudzana ndi zomwe zilipo panopa zikugwirizana ndi zomwe zimachititsa kuti chiopsezo cha psychostimulant ndi kutchova njuga, monga ndondomeko ya malipiro.

Pakati pa mayesero, yankho lolimbikitsana posachedwa la gulu la 50 limapitirira kuposa la magulu ena omwe ali ndi mitundu yosiyana ya amphetamine ndi mitundu yosiyanasiyana ya zinyama. Komabe, chiwerengero cha anthu omwe ali pakati pa magulu osiyana-siyana amasonyeza kuti pali zinthu zina zomwe zimagwiritsidwa ntchito pa DA kuti zikhale ndi amphetamine potsatira ndondomeko zosiyanasiyana za mphotho ya sucrose. Ngakhale mayankho a DA kuti apereke malipiro angapereke chitsanzo chokhala ndi njuga (Fiorillo et al., 2003), monga zitsanzo zonse, pali kutayika kwa chidziwitso chifukwa cha kugonana-kutanthauza, kusonyeza njira yofunikira. Chotsatira chake, chitsanzo cha zotsatira m'ma CS-US mu chiyambi cha Fiorillo et al. Kuphunzira sikumapereka kwathunthu kuyankha kwa amphetamine. Kupitanso patsogolo kwa chitsanzochi kumafunidwa kuti agwire zonse za njuga zomwe zimagwira ntchito pa DA.

Kuphatikizidwa pamodzi, zotsatira za zowonongekazi zimapereka chithandizo panthawi yodziwika kuti kutchova njuga nthawi zonse-monga ndondomeko za mphotho zimapangitsa kuti reactivity ya ubongo wa DA ikwaniritsidwe ndi vuto la psychostimulant. Potero, amawonjezera zotsatira za Singer et al. (2012) amene amasonyeza kuti, potsata ndondomeko yeniyeni, asanafike panthawi yowonjezera yowonjezera pulogalamu yamagetsi imapangitsa kuti anthu apitirize kuyankha amphetamine. Zowonjezereka, zomwe zapeza tsopano zikuwonetsa kusatsimikizika kwa kuperekedwa kwa mphoto monga chinthu chachikulu chomwe chimayambitsa zotsatira za mphotho yosiyanasiyana. Kukula kwa zotsatira m'zochitika zogwirira ntchito kunali kwakukulu kwambiri kuposa zotsatira zomwe zakhala zikuchitika panopa. Izi zikhoza kukuwonetseratu kwambiri kutchova njuga-monga ntchito (55 vs. 15 masiku); Zikhoza kuwonetsa zotsatira za kufunikira kuyankhidwa kuti apereke mphotho (mwachitsanzo, udindo ku bungwe) kusiyana ndi kuwonetsetsa, ngati mukuphunzira pano. Kuwonjezeka kwa nthawi yophunzitsidwa mu paradigm yatsopano kungathandize kuthetsa mafunso awa.

Kutha kwa mphotho yosinthika ndi ndondomeko zowonjezereka monga zitsanzo za njuga sizingakhoze kusonkhanitsidwa kuchokera ku zoyeserazi. Kafukufuku wamtsogolo omwe amawunikira zotsatira za mbiri ya chikhalidwe pamayendedwe oopseza kuntchito zomwe zingathetsere vutoli. Mofananamo, makalata omwe alipo pakati pa khalidwe lachidziwitso omwe amapezeka pano ndi yankho lapamwamba loyankhidwa ndi DA kwa amphetamine posachedwapa omwe apeza anthu otchova njuga ayenera kuyembekezera kufufuza (Boileau et al., 2013). Micro-dialysis ingayankhe funso ili, ndipo maulosi okhudzana ndi chidziwitso cha umunthu ndikuti DA yowonjezera ku gulu la 50 "kutchova njuga phenotype" idzawonetsedwa momveka bwino pamtundu wothamanga (sensorimotor striatum) m'malo mojambulira (limbic) striatum . Kuvomereza kwa 50% kufotokoza kwa mphoto kwa CS + m'mabuku enawa kungathandizire ntchito yake monga chitsanzo chabwino cha PG.

Pomwe mitundu ina ya juga imakhudza kuyankha kwamphamvu (mwachitsanzo, makina olowetsa), munjira zina zamtundu wa juga (mwachitsanzo, lottery) kulumikizana pakati pa zomwe zikuchitika (kugula tikiti, kuyika kubetcha), njira zopezera mphotho (mwachitsanzo. , manambala a lottery) ndi mphotho yomwe (nambala yomwe yapambana komanso phindu) ikufalikira kwambiri. Komabe, kuyambitsidwa kwa DA mkati mwa nthawi ya CS-US kumatha kuchitika. Izi zitha kufotokozera chifukwa chake, pomwe "nambala yopambana" yalengezedwa, chidwi chimaperekedwa pamene mpira wa lottery aliyense umatsika motsatizana kuti apange manambala angapo a nambala yomwe yapambana. Ngakhale kuthekera kwa manambala omwe akupezeka kumatanthauzidwa ndi masamu, zotsatira zake pamiyeso yamiyeso yamunthu aliyense ndiyabinage- kugunda (kumagwirizana ndi nambala ya wosewera) kapena kuphonya (sikugwirizana ndi nambala ya wosewerayo) - ndipo zotsatira zake pakuyesedwa kulikonse sikudziwika. Zochitika zoterezi zitha kuwonetsa zomwe gulu la 50 likuchita m'mayesero apano, pomwe mphotho idaperekedwa mosagwirizana komanso mosayembekezereka ndipo CS imangowonetsa kuthekera kwa mphotho popanda kuwulula ngati zingachitike pamayeso ena. Makina oyeserera amalumikizidwa kwambiri ndi PG kuposa matikiti a lottery (Cox et al., 2000; Bakken et al., 2009), kusonyeza mbali yofunikira pazinthu zamagulu (ndi nthawi yomweyo) m'malo opindulitsa a njuga kwa anthuwa (Loba et al., 2001). Ngakhale zili choncho, njira ya Pavlovian yomwe imayesedwa panthawiyi (CS) + sichidziwika kuti ndi mphoto) ikuwoneka ngati yofunikira ngati chinthu chokwanira pachitchova njuga.

Kuphatikizidwa ndi kusowa kwa chida chofunikira, zingapo zina zomangamanga zingakhale zathandiza kuti pakhale zovuta zowonongeka. Maguluwa anali osiyana kwambiri ndi chiwonetsero cha asprose komanso chidziwitso pakati pa CS ndi sucrose mphotho. Ngakhale kuti izi zathandiza kuti magulu ena azikhala osiyana, sangathe kufotokoza mosavuta chifukwa chake zinyama zomwe zili ndi gulu lalikulu (group 100) zimawonetseratu kuchepa kusiyana ndi gulu la 50. Kuphatikizanso, gulu la 0 silinapezeko chotsitsimutsa musanayambe kutsogolo pamayesero alionse. Ngakhale kuti izi zinkasokoneza chiyembekezero cha mphotho, sizinathetsere kupezeka kwa mphotho asanabwezere malipiro, omwe analipo m'magulu ena onse. Pofuna kuthetsa vutoli, kafukufuku wamtsogolo ayenera kukhala ndi vuto pamene nyama zimalandira mphotho pamayesero aliwonse omwe amatsatira mwadzidzidzi kuti asatengere mbali zina (ie, kupezeka kwake sikukutanthauza mphotho ya mphotho).

Kupangidwanso kwina ndi njira yomwe ingayambitsire khalidwe labwino lomwe lingakhudze zotsatira za maphunziro. Poti sitingakayike, nyama zikhoza kukhala ndi zikhulupiriro zokhudzana ndi zikhulupiliro zomwe zimakonzedwa kuti zikhale ndi mphamvu zowonongeka ndi kuchepetsa kutsegulidwa kwa DA kosatsimikizika (cf. Harris et al., 2013). Motero n'zotheka kuti mbali zosawerengeka za zojambulazo zinathandiza zinyama kuthetsa zotsatira za chikhalidwe. Zotsatira zoterezi zingathandize kuti amphetamine ayambe kuyankha mwachidule m'gulu la 50 pambuyo pa CS + sucrose. Kafukufuku wamtsogolo ayenera kulemba khalidwe lokhazikika, pambali pa mphuno, panthawi yophunzitsa kuti athe kuyesa izi, komanso kuti aziwongolera. Chifukwa chakuti khalidwe limeneli liyenera kuyerekezera kapena kuchepetsa zotsatira za kusautsika kwa nthawi, kusankhidwa kwa amphetamine mu gulu la 50 kuyenera kulimbikitsidwa ngati likulamulidwa (njira kapena chiwerengero). Choncho, mawonekedwe amasiku ano (osadziletsa) amapereka mayeso oyenera a zotsatira za 50% CS + mphoto pa kuyamwitsidwa kwa amphetamine.

Pogwiritsa ntchito zowoneka kunja, kugwiritsa ntchito makoswe amphongo kumapangitsanso kuti chiwerengero cha zotsatira zake chikhazikitsidwe. Kulephera kwa chilango "chomveka" chowonekera kumasiyananso ndi njuga, komwe ndalama zambiri zimatayika ndipo zimakhala zovuta kwambiri (Nieuwenhuis et al., 2005; Singh ndi Khan, 2012). Kukwanitsa kupezerapo mphotho sikungakhalenso ndi paradigm yamakono komanso zopambana zomwe zikupezeka mu masewera a masewera amapezeka kuti zigwirizane ndi machitidwe a DA mu anthu (Tremblay et al., 2011; Smart et al., 2013). Mofananamo, mwayi wa jackpot ndi kusiyana kwakukulu pakati pa kachitidwe kameneka ndikutchova njuga.

Ngakhale zolepheretsa izi, zotsatira zake zikusonyeza kuti mphoto ya 50% yosiyana CS + ingagwiritse ntchito njira za DA zophatikizapo potchova njuga (Fiorillo et al., 2003; Anselme, 2013). Kuwongolera pamtunda kuyankha kwa AMPH potsatira kayendetsedwe ka juga monga ndondomeko ikugwirizana ndi ntchito yofunikira kwa DA mukutchova njuga ndi zotsatira za mankhwala (psychostimulant effects effects)Zack ndi Poulos, 2009), ndipo amapitiliza maphunziro oyambirira pa zokopa zowonongeka ndi AMPH mu masewera othamanga njuga (Zack ndi Poulos, 2004). Zotsatira zamakono zikuwonetseranso kuti njira zochepa za AMPH, zomwe sizingapangitse kuti thupi lachilengedwe likhale lopangidwa ndi DA, likhoza kukhala ndi ubwino wabwino wa ubongo chifukwa cha zizindikiro zapadera (mwachitsanzo, pachitchova njuga) kusiyana ndi kuthamanga kwapamwamba (mwachitsanzo, kubisala) Mlingo wa mankhwala osokoneza bongo (cf. Vanderschuren ndi Pierce, 2010). Thandizo lachindunji la kalata iyi lingachoke poyesa kuwomboledwa kwa DA poyankha ndondomeko ya 50% yosiyana ya CS-US ndi mlingo wosiyana wa AMPH pogwiritsa ntchito microdialysis.

Kuyambira kafukufuku, chitsanzo cha Pavlovian chomwe chilipo komanso njira yapitayi yomwe imagwiritsidwa ntchito posinthira mofanana, ikuwoneka kuti imachititsa kuti phenotype ikhale ngati munthu wotchova njuga. Momwemonso, amapereka zothandizira pazinthu zoyendetsa njuga zomwe zimatengera kutchova njuga (monga chiyeso chodalira) koma mpaka lero, amagwiritsa ntchito nyama zathanzi, zomwe zimakhala zofanana ndi anthu otchova njuga. Malingana ndi zolembedwazo, zinyama zomwe zimawululidwa kuti zingapangidwe mphoto zingakhale zosiyana pa ntchitozi, makamaka poyankha mankhwala osokoneza bongo a DA. Kuphatikizidwa ndi makoswe wotchova njuga wotchedwa phenotype ndi kutchova njuga kungalolere chitukuko choyenera cha mankhwala kuchiza PG, zomwe sizingatheke kukwaniritsidwa ndi nyama zathanzi zokha. Kuonjezeretsanso kusintha kwa kayendedwe ka kafukufuku ndi maphunziro, monga momwe tafotokozera pamwambapa, ziyenera kusintha malembo pakati pa zinyama zophunzitsidwa ndi pulogalamuyi ndi ochova njuga.

Kuchokera kuchipatala-chikhalidwe cha anthu, kupeza kuti kuwonetsedwa kwa 50% mphotho yosiyanasiyana ya CS +, yomwe imayenderana ndondomeko ya mphoto pamakina opanga malonda (Tremblay et al., 2011), amasintha njira ya ubongo ya DA mu njira zodalirika ndi zotsalira zikusonyeza kuti, nthawi zina, kuchita njuga, monga kugwiritsa ntchito mankhwala osokoneza bongo, kungakhale "tizilombo toyambitsa matenda" zomwe zingayambitse vutoli. Komabe, kuchepetsa kukula kwake kwakukulu ndi kusiyana kwakukulu poyankha mphoto ya 50% CS + kumasonyeza kuti, monga kugwiritsa ntchito mankhwala osokoneza bongo, chizoloŵezi chotchova njuga-monga ndondomeko ya mphotho kuti adzalitse chizoloŵezi chogonjera chidzadalira kwambiri payekha pangozi ya wotchova njuga. Komabe, kuti pakhale ngozi yaikulu kuti anthu adziwone zomwe zingakhale zovuta zokhudzana ndi juga, zikuwoneka kuti malamulo omwe akugwiritsidwa ntchito kuti athetse ntchito ndi kuchepetsa kuwonongeka kwa mankhwala osokoneza bongo angathenso kutchova njuga.

Kutsutsana kwa Chidwi

Olembawo akunena kuti kufufuza kunkachitika popanda mgwirizano uliwonse wa zamalonda kapena zachuma zomwe zingatengedwe kuti zingatheke kukangana.

Kuvomereza

Kafukufukuyu anagwiritsidwa ntchito ndi ndalama kuchokera ku Natural Sciences ndi Engineering Research Council ku Canada kwa Paul J. Fletcher. Tikuthokoza Madamu Djurdja Djordjevic poyamikira ziwerengerozo.

Zothandizira

Lolembedwa ndi:

Bryan F. Singer, University of Michigan, USA

Kuwunikira by:

Louk Vanderschuren, University of Utrecht, Netherlands
Ruud Van Den Bos, Radboud University Nijmegen, Netherlands
Patrick Anselme, University of Liège, Belgium