I-Journal of Neuroscience, 15 March 2001, 21(6): I-2123-2130;
+ Ukubambisana Kwombhali
abstract
Ukudluliswa kwe-Dopamine ku-nucleus accumbens kungenziwa kusebenze izidakamizwa, ukucindezeleka, noma ukuziphatha okugqugquzelayo, futhi ukuvezwa ngokuphindaphindiwe kulezi zinkinga kungashukumisa impendulo ye-dopamine. Izinhloso zalolu cwaningo kwakuwukuthi ukuziphatha kobulili besifazane kuvuselela yini i-nucleus accumbens neurons nokuthi ngabe isipiliyoni esedlule socansi siwela-senza izimpendulo ze-neuronal ku-nucleus accumbens ku-amphetamine. Ukusebenzisa ukufakwa kwe-immunocytochemical, ukukhulunywa kwe-c-Fos emazweni angaphansi (igobolondo vs core emazingeni angama-rostral, maphakathi, kanye ne-caudal) we-nucleus accumbens yahlolwa kuma-hamsters wesifazane ayenamazinga ahlukahlukene wezobulili. Ama-hamster wesifazane, anikezwe amaviki e-6 okuhlangenwe nakho ngokocansi noma ahlale ehlukumezeka ngokobulili, ahlolwe ukuziphatha ngokocansi ngokuvezwa kwamadold omdala abesilisa. Okuhlangenwe nakho kocansi kwangaphambilini kwandise ukulayishwa kwe-c-Fos kumazinga we-rostral no caudal kodwa hhayi emazingeni aphakathi nucleus accumbens. Ukuvivinya ukuziphatha ngokocansi kwandise ukulayishwa emkhathini, kodwa hhayi igobolondo, ye-nucleus accumbens. Ukuze kuqinisekiswe ukuthi ukuziphatha ngokocansi kwabesifazane kungabangela ukuvuselela i-neurons endleleni ye-mesolimbic dopamine endleleni, izimpendulo zokuzithokozisa ngokobulili nabesifazane abangenayo ubulili ukuya kumjovo we-amphetamine bese ziqhathaniswa. I-Amphetamine yanda umsebenzi wokuqasha jikelele kubo bonke abesifazane. Kodwa-ke, izilwane ezitholakale ngokobulili zasabela ngokushesha ku-amphetamine kunezilwane ezingenaso ubulili. Le datha ibonisa ukuthi ukuziphatha kocansi kwesifazane kungenza kusebenze i-neurons ku-nucleus accumbens nokuthi isipiliyoni socansi singashukumisa izimpendulo ze-neuronal ku-amphetamine. Ngaphezu kwalokho, le miphumela inikeza ubufakazi obengeziwe bokungalingani kokusebenza phakathi kwegobolondo kanye nenhloko ye-nucleus accumbens nakwezinye izingxube zayo ze-anteroposterior.
I-dopamine neurons evela endaweni ye-ventral tegmental futhi iqhubekela phambili e-forebrain nuclei ehlukahlukene, kuhlanganise ne-nucleus accumbens, iyingxenye ye-mesolimbic dopamine system. Kuye kwaphakanyiswa ukuthi le nqubo ye-dopamine ibalulekile ekulawuleni ukuziphatha okuphazamisayo (UMitchell noGratton, i-1994; Salamone, 1994, 1996; I-Ikemoto ne-Panksepp, i-1999), kanye nokuziphathisa izidakamizwa zokuhlukunyezwa (U-Pierre noVezina, i-1998;I-Koob, i-1999; Lorrain et al., 1999; McKinzie et al., 1999; Abantu kanye al., 1999; I-Bradberry et al., I-2000). Ukuphatha ngendlela ehlukahlukene yezidakamizwa zokuhlukumeza (isib. Cocaine, amphetamine, ne-heroin) kusebenze izindlela ze-dopamine (I-Pontieri et al., 1995; Nisell et al., 1997; Pierce and Kalivas, 1997a; Tanda et al., 1997; UTanda noDi Chiara, i-1998; I-Barrot et al., I-1999; Cadoni noDi Chiara, i-1999), futhi ukuphindaphindiwe okuphindaphindiwe kulezi zimakhemikhali zezokwelapha kungakhuthaza lezi zinzwa ze-dopamine-responds (URobinson et al., 1988; Kalivas et al., 1992; Kalivas noDuffy, i-1993; Pierce and Kalivas, 1995; Kuczenski et al., 1997; Nisell et al., 1997; UBirll noBalfour, i-1998; U-Heidbreder no-Feldon, i-1998; Cadoni noDi Chiara, i-1999; Cadoni et al., 2000). Ucwaningo luhlinzekele ubufakazi bokuthi i-nucleus accumbens nayo isabela kwezinye izindawo ezihlobene nokulingana. Amazinga e-extracellular dopamine ekunyuseni kwe-nucleus accumbens ngesikhathi sokusebenzisana ngokocansi kumazingwane ezinsikazi (UMermelstein noBerker, i-1995; I-Pfaus et al., I-1995) kanye nama-hamsters (I-Meisel et al., I-1993; Kohlert et al., 1997; U-Kohlert noMeisel, i-1999). Ngokufana nokuphathwa kwezidakamizwa eziphindaphindiwe, ukuhlolwa okuningi kokuziphatha ngokobulili nakho kwandise ukwanda kwamazinga e-nucleus accumbens dopamine, okuphakamisa ukuthi isipiliyoni socansi singashukumisa i-neurons endleleni ye-dopamine (U-Kohlert noMeisel, i-1999).
I-nucleus accumbens iqukethe izinhlaka eziningi ezihlukene ezihlukene, okujwayele kakhulu ukuthi igobolondo kanye nenhloko. Ukuxhumeka kwe-anatomical yegobolondo kanye ne-core diverge, okuphakamisa ukuthi lezi zinsizakalo ezimbili zilawula imisebenzi ehlukene (Crawley et al., 1985a,b; I-Heimer et al., I-1991; UZahm noBrg, 1992; U-Brog et al., 1993;Kalivas noDuffy, i-1995; Maldonado-Irizarry et al., 1995; Pierce and Kalivas, 1995; I-Pontieri et al., 1995; I-Broening et al., I-1997; I-Heimer et al., I-1997; Kelley et al., 1997; IStratford noKelley, i-1997; U-Heidbreder no-Feldon, i-1998; I-Lanca et al., I-1998; Bassareo noDi Chiara, i-1999; I-Di Chiara et al., 1999b; Groenewegen et al., 1999; Kelley, 1999; McKinzie et al., 1999; I-Zahm, i-1999; Brown kanye noMolliver, i-2000). Ngenxa yokuthi i-nucleus accumbens iyi-nucleus eyingqayizivele, akucaci ukuthi izimpendulo zendlela yokuziphatha ngokocansi zendawo zendawo zendawo zingaphansi kwezindawo ezithile ze-nucleus accumbens noma zisakaze kulo lonke i-nucleus. Izindlela ezisetshenziswe ngaphambilini ukuphendula lo mbuzo (isib., Microdialysis) azikwenzeki ngokwanele ukuhlola ukuphathwa kwe-heterogeneity ye-accumbens. Ngokuphambene, ukucubungula kwe-immunocytochemical kwiprotheni ye-c-Fos inikeza indlela yokuhlola ukusebenza okusebenzayo kwamaselula phakathi kwezifunda ze-nucleus accumbens. Ngakho-ke, injongo yokuqala yalokhu kuhlola kwakuwukucacisa ukuthi ukusebenza kwamaselula emva kokuziphatha kobulili besifazane kutholakale ezindaweni ezithile ezingaphansi kwe-nucleus accumbens.
Impahla ethandekayo yalezi zindlela ze-dopamine i-cross-sensitization. Ngamanye amazwi, i-dopamine neurons ngaphambilini yazwela kumuthi owodwa izobonisa izimpendulo ezithintekayo kwenye imithi enikezwe okokuqala (Cunningham noKelley, i-1992; Pierce and Kalivas, 1997a; UBirll noBalfour, i-1998; U-Taylor no-Horger, i-1999). Ngaphandle kokunciphisa izidakamizwa phakathi kwezidakamizwa, izifundo eziningana ziye zabika ukukhwabanisa phakathi kokuchazwa okuphindaphindiwe kumakhemikhali ezemithi kanye nokuziphatha okugqugquzela emvelo (UMitchell noStewart, 1990a,b; I-Tidey noMiczek, i-1997; Fiorino noPhillips, i-1999). Ngakho-ke, sihlolisise ukuthi izilwane ezizibandakanya ngokocansi nezingazibandakanya ngokobulili zingasabela ngokuhlukile ekugqugquzelweni kwendabuko eyaziwa ukuthi kusebenze izindlela zokuhamba (okungukuthi, ukuzwela okukhulu), njenge-amphetamine. Uma ukuziphatha ngokobulili kwabesifazane kukhuthaza izindlela ze-dopamine, abesifazane abathintekayo ngokobulili kufanele babonise impendulo yokuziphatha engathandwa ngokungathandwa kwabangelwayo ku-injection eyodwa ye-amphetamine.
IZIMPAHLA NEZINDLELA
Izindlela ezijwayelekile
Izilwane. Amanster aseSyria nabesifazane aseSyria athululwa eCharles River Laboratories (Kingston, NY) e- ~60 d yobudala. Amadodakazi ayehlelwe ngabanye, futhi izilwane ezivusa amadoda zazihlala emaqenjini amathathu noma amane emaphoyiseni epulasitiki (50.8 × 40.6 × 20.3 cm). Ikamelo lezilwane lezilwane lagcinwa ngokushisa okuvamile (22 ° C) ngezibani ezivaliwe phakathi kwe-1: 30 ne-11: 30 PM (14 / 10 hr ukukhanya / umjikelezo omnyama). Ukudla namanzi kwakutholakala isikhangiso.
Izinqubo ezisetshenziswe kulolu vivinyo zihambisana nezikhungo zezempilo zikazwelonke Imihlahlandlela Yokunakekelwa Nokusetshenziswa Kwezilwane Zabasebenzi futhi ivunyiwe yi-Purdue Animal Care neKomidi Lokusebenzisa.
Ukwabelana ngocansi. Cishe ngeviki le-1 ngemuva kokuba abesifazane befike ebhokisithriyori, bebodwa be-ovariectomized ngaphansi kwe-sodium pentobarbital (Nembutal) anesthesia (8.5 mg nge-100 gm body weight, ip). Ngemuva kwe-ovariectomy, abesifazane baqale bahlukaniswa ngamaqembu amabili. Iqembu elilodwa labesifazane lathola amasonto e-6 okuhlangenwe nakho kobulili ngesilisa eshukumisayo; iqembu lesibili lahlala lingenalo ubulili. Zonke izinsikazi zazihlonishwa nge-hormonally kanye ngesonto isikhathi seviki le-6. Kuzo zombili i-48 ne-24 hr ngaphambi kokuhlangenwe nakho kocansi, abesifazane bajojowe ngaphansi kwe-10 μg ye-estradiol benzoate ku-0.1 ml yamafutha omnene. Ngosuku lokuhlola okuhlangenwe nakho, abesifazane bawathola i-500 μg ye-progesterone ku-0.1 ml yamafutha amancane (injection engaphansi). Abesifazane abangatholi isipiliyoni socansi babejova nge-hormone regimen futhi bahlala emakameleni abo ekhaya egumbini lekoloni. Ku-4-5 hr ngemuva kokuphathwa kwe-progesterone, i-hamster yindoda endala eyayithole isipiliyoni socansi ngokusebenzisa ezinye izifundo zokuziphatha ngokocansi ibekwe ekhayeni lasekhaya lomfazi ohlolayo. Ukuhleleka kwamakheji aqukethe la madoda kwakushintshwa ngesonto ngalinye ukuze kuncishiswe amathuba okuba owesilisa nowesifazane babebhanqiswe izikhathi ezingaphezu kweyodwa ngesikhathi samaviki e-6 okuhlangenwe nakho kocansi.
Immunocytochemistry. I-hamster yowesifazane, ebulawa ngokudlula ngokweqile kwe-sodium pentobarbital, yayingenakunyakaziswa nge-25 mm Isixazululo se-PBS, i-pH 7.5, ye-2 min (izinga lokugeleza, i-25 ml / min), ilandelwa i-4% paraformaldehyde ku-PBS ye-20 min. Ubuchopho buhlelwe emuva kwe-2 hr ku-paraformaldehyde futhi bugcinwe ku-10% i-sucrose PBS ngobusuku obubili ku-4 ° C.
I-40 ım izingxenye ezibandisiwe zithathwe kulo lonke i-nucleus accumbens. Ngemuva kwezinhlanzi ezintathu ze-10 ku-PBS, izigaba zazifakelwe ku-antibody oyinhloko ku-c-Fos (i-1: 6000 ku-PBS ne-0.3% Triton X-100; i-Santa Cruz Biotechnology, i-Santa Cruz, i-CA) noma ku-antibody oyinhloko ku-calbindin-D (28 kDa) (1: 6000 ku-PBS nge-0.3% Triton X-100; Chemicon I-International, Temecula, CA) ku-4 ° C nge-48 hr. Kokubili izingxenye ze-c-Fos ne-calbindin-D zishintshwa ngamaminithi we-45 ekamelweni lokushisa e-anti-rabbit anti-rabbit anti-rabbit yesibili (1: 200 ku-PBS; i-Elite Vectastain ABC kit; i-Vector Laboratories, Burlingame, CA), ilandelwe yi- ukuxubha nge-avidin-biotin horseradish i-peroxidase complex (1: 50 ku-PBS; i-Elite Vectastain ABC kit) ye-45 min ekamelweni lokushisa, enezinhlanzi ezintathu ze-10 ku-PBS ezandulela ukufakwa ngaphakathi. Ngemuva kwezinhlanzi ezimbili ku-PBS kanye ne-10 min rinse ku-0.1 m I-Tris buffer, i-pH 7.6, izigaba ze-c-Fos nezi-calbindin-D zifakwe i-5 ne-10 iminithi, ngokulandelana, ku-0.08% i-diaminobenzidine (DAB) (Aldrich, Milwaukee, WI) ku-Tris buffer ene-0.003% i-hydrogen peroxide ne-0.015% i-nickel chloride. Zonke izigaba zahlanjululwa futhi ku-Tris buffer kanye namanzi ahlanzekile futhi zanyuka kuma-slides aphethwe yi-chrom-alum. Ama-slides ayomile, aphelelwe amanzi, ahlanjululwe futhi ahlanganiswe esebenzisa i-Permount (Fisher Scientific, Pittsburgh, PA).
Ukuhlaziywa okuncane. Izicubu ze-neural zenzelwe i-calbindin-D, ehlukanisa igobolondo kanye nenhloko ye-nucleus accumbens (Jongen-Relo et al., 1994a; Johnson and Wood, 1999) isetshenziselwa ukukhomba ingxenye eyodwa ngayinye ezingeni le-rostral, eliphakathi, nelesilungisa le-nucleus accumbens. Izingxenye ezisuka ku-nucleus accumbens emazingeni angama-rostral, aphakathi, nama-caudal agwetshiwe nge-calbindin aboniswa ku-Figure 1 A-C. Kuye kwabikwa ukuthi kukhona ukungafani okuncane phakathi kwekhanda kanye negobolondo ku-calbindin-D engakwazi ukuzenza ngaphandle kwe-hamster yaseSiriya uma kuqhathaniswa nesilwane, kodwa ukukhishwa kwalesi peptide kusakwazi ukuhlukanisa izifundazwe ze-nucleus accumbens (Johnson and Wood, 1999). Ibhokisi elihlanganisa isifunda sesampula se-0.1 mm2 (I-0.2 × 0.5 mm) ibekwa phezu kwegobolondo le-dorsal kanye nenhloko ye-nucleus accumbens kwesigaba ngasinye. Isithombe saleso sigaba ngasinye sanyatheliswa ekukhanyeni ifilimu futhi izithombe zabekwa phezulu ezingxenyeni ezihambisanayo ze-c-Fos zesilwane ngasinye, ukuqinisekisa ukuthi ibhokisi lafakwa endaweni efanayo kuzo zonke izilwane. Umfanekiso 1, D futhi E, ibonisa isigaba esisodwa esiqaphile esilwaneni esitholile amaviki e-6 okuhlangenwe nakho kobulili futhi sahlolelwa ukuziphatha ngokocansi. Ibhokisi lafakwa emgodleni we-nucleus accumuls ku-Figure 1 Dfuthi kugobolondo leqoqo le-caudal ku-Figure1 E. Ibhokisi elinobukhulu obufanayo lalibekwe esigabeni esifanayo sezicubu ku-medial cingate cortex nangaphezulu kwe-medial kanye ne-lateral dorsal caudate nucleus ezingeni ngalinye lamathathu asampuliwe kuma-nucleus accumbens. Ngoba sicabange ukuthi kungahle kube nokuhlukahluka kwe-rostral – caudal emiphumeleni yokuhlangana ku-c-Fos, isigaba esisodwa kuphela ezingeni ngalinye sahlaziywa ukukhulisa ukunemba kwe-anatomical kwesampula sethu. Inani lamaseli we-c-Fos-immunoreactive endaweni ngayinye ekhethiwe libalwe ngosizo lwekhamera yevidiyo exhunywe ohlelweni lokuhlaziya isithombe lwekhompyutha (BioQuant MegM; R & M Biometrics, Nashville, TN).
I-Nucleus iqoqa izicucu zezicubu ezenzelwe i-calbindin-D ne-c-Fos. A-C yizigaba ezivela emgodleni (A), phakathi (B), nokuqapha (C) i-nucleus iqoqa ibala (i-midline iyona kwesokunxele) nge-calbindin, ebonisa ukuhlukaniswa phakathi kwegobolondo kanye nezinsizakalo eziyisisekelo (i-asterisks). Kukhona i-320 μm emkhatsini wesigaba se-rostral kanye nesiphakathi kanye ne-240 μm emkhatsini wesigaba esiphakathi nesikhombisa. Izithombe ezisezantsi (D, E) ziyizibonelo ze-c-Fos ukudonsa kusuka emgodini we-caudal (D) kanye negobolondo (E) we-nucleus accumbens (i-midline yiyona kwesokudla) wesifazane owaziwa ngokocansi abulawe ngemva kokuhlolwa kocansi. Iisikwele ibonisa indawo yesampuli (0.2 × 0.5 mm).
Zama i-1
Ukuhlolwa kokuqala kuphenye imiphumela yezobulili kanye nokuhlolwa kokungeniswa kwe-c-Fos ku-nucleus accumbens, i-dorsal caudate nucleus, ne-cingulate cortex. Umgomo wokuhlola wawuphindwe kabili. Umgomo wokuqala kwakuwukunquma ukuthi kukhona yini ukungafani ekusebenzeni kwamaselula kunoma yiziphi izifunda zobuchopho ngenxa yesipiliyoni sangaphambili socansi kanye / noma ukuhlolwa kokuziphatha. Uma ukukhulumisana kwe-c-Fos kushintshiwe, kwabe sekubekwe ukuthi ngabe izinguquko zingasetshenziswa yini ezindaweni ezingaphansi kwezingxenye ezintathu zobuchopho ezihlaziywe.
I-hamster yaseSyria yamaSulumane ithole amasonto e-6 okuhlangenwe nakho kobulili noma yahlala engavumelani nobulili. Ngesikhathi samaviki we-6, isikhathi esiningi sokuthi i-lordosis (ukungahambisani nokuhamba kwesimo sangemuva) ilinganiselwe iseshini ngasinye sokuhlolwa kweminithi ye-10. Azikho izinyathelo zokuziphatha kobulili zesilisa eziqoshiwe. Ngeviki 7, uchungechunge olufanayo lwe-estradiol benzoate kanye ne-progesterone injection zanikezwa. Ngalesikhathi, isigamu sezilwane ezizibandakanya ngokocansi nezingazizwa zihlolwe ukuziphatha ngokocansi ngokubeka umuntu omdala endodeni yabo. Amadodakazi asele ashiywe emakamelweni abo. E-60-90 min ngemuva kokudonswa kwendoda, abesifazane basebenze kabi, futhi ubuchopho babo busetshenziselwa ukukhuluma kwe-c-Fos. Labo besifazane abazange bahlolwe ukuziphatha ngokobulili baphonyiswa i-4 hr ngemuva kokuphatha kwe-progesterone.
Ukuhlaziywa kwedatha. Ngenxa yokuthi izibalo zamaseli azifani phakathi kwalabo besifazane abangahlolwe ukuziphatha ngokocansi phakathi neviki 7, kungakhathaliseki ukuthi kwenzeka kanjani ngokobulili obudlule (bheka ithebula1 isibonelo), abesifazane abahlolwayo ekugcineni bahlukaniswa ngamaqembu amathathu wokwelashwa ukuze bahlaziywe. Iqembu lokuqala lalinabesifazane abathola amaviki e-6 okuhlangenwe nakho kobulili futhi bahlolwe ukuziphatha ngokocansi (isipiliyoni / ukuhlolwa, n = 6). Iqembu lesibili lalihlanganisa labesifazane abangazange bathole noma yikuphi okuhlangenwe nakho, kodwa bahlolwe ukuziphatha ngokocansi (akukho okuhlangenwe nakho / ukuhlolwa,n = 8). Iqembu lokugcina laliqukethe wonke ama-hamster wesifazane awazange ahlolwe ukuziphatha ngokocansi, kungakhathaliseki ukuthi yikuphi okuhlangenwe nakho kocansi okwedlule (akukho mvavanyo, n = 13). Amaqembu amabili angatholi ukuhlolwa kokuziphatha ngokobulili ahlangene ukuze akhulise amandla amanani ekuhlaziyeni. Inombolo yamaseli e-c-Fos-stained kusuka ku-dorsal nucleus accumbens, i-dorsal caudate nucleus, ne-cingulate cortex yafaniswa phakathi kwamaqembu amathathu.
Ukuqhathaniswa kwenombolo ye-mean ± SEM yamaseli e-c-Fos-immunoreactive kugobolondo le-nucleus accumbens kanye nomgogodla phakathi kwamaqembu ayizokwelapha
Ukubala kwe-cell kwahlaziywa usebenzisa ama-ANOVAs amaningi. Ama-ANOVAs asebenzayo okubalulekile futhi i-post hoc Ukuhlolwa kwe-Newman-Keuls kwenziwa lapho kufanelekile. Idatha yokuziphatha (i-lordosis durations) yahlaziywa isebenzisa ama-tailed amabili t ukuhlolwa.
Zama i-2
Ukuhlolwa kwesibili kuqhathanisa ikhono le-stimulus inoveli, i-amphetamine, ukukhiqiza ukukhushulwa kokuziphatha kwabakwa-hamster abathintekayo ngokocansi abanolwazi ngokocansi. Ukuboniswa kwe-c-Fos ku-nucleus accumbens, i-dorsal caudate nucleus, ne-cingulate cortex yahlaziywa futhi ukuze inqume ukuthi iphethini lomsebenzi wamaselula lalifana nemiphumela etholakala ku-Isivivinyo 1.
Ama hamster aseSyria anikezwa amasonto e-6 okuhlangenwe nakho ngokobulili noma ahlale engavumelani nobulili. Ngesonto i-7, bonke abesifazane bathuthelwa emvelweni wenveli (okungukuthi, i-10 gallon glass aquarium ekamelweni elingajwayelekile) i-4 hr ngemuva kokuphathwa kwe-progesterone. Amantombazane abekwe ku-10 gallon glass aquarium ye-10 min, ngemva kwalokho isigamu samakhosikazi wesifazane ocansinga ngokocansi kanye nocansid-amphetamine sulfate (1 mg nge-1 kg isisindo somzimba ku-1.0 ml ye-0.9% NaCl; isipho esivela kuDkt. David Nichols, University of Purdue). Amantombazane asele ajojowe nge-0.9% NaCl (1 mg nge-1 kg isisindo somzimba). Amantombazane abuye abuyiselwe ku-10 gallon aquarium nge-60 min minye eyengeziwe. Izikhathi ze-70 min zenziwe ngevidiyo nge-video ukuze zihlaziywe umsebenzi wokukhiqiza jikelele wesifazane. Ngaphakathi kwe-30 min ngemva kokuhlolwa komsebenzi jikelele, abesifazane babengaphili kahle, kanti ubuchopho babo busetshenziselwa ukukhuluma kwe-c-Fos.
Ukuhlaziywa kwe-Videotape. Phakathi nesonto i-7, umsebenzi we-70 wokuhlolwa kokuhlola umsebenzi wokuvota wawufakelwe ngevidiyo. I-10 gallon glass aquariums zahlukaniswa ngezigaba ezintathu ezilinganayo esikrinini sevidiyo, futhi umsebenzi wokuzijabulisa wesifazane wabhalwa ngokwezinombolo zemigwaqo yendawo.
Ukuhlaziywa kwedatha. Umlando owedlule wobulili awuzange uthinte umsebenzi wezintambo zezintambo zezinsikazi ezijova nge-saline; Ngakho-ke, abesifazane abahlolwayo bahlukaniswa ngamaqembu amathathu wokwelashwa ukuze bahlaziywe. Iqembu lokuqala laliqukethe abesifazane abathola amasonto e-6 okuhlangenwe nakho kocansi futhi bajova nge-amphetamine (isipiliyoni / amphetamine, n = 8). Iqembu lesibili lalihlanganisa lalabo besifazane ababethweswa i-amphetamine kepha abazange bathole isipiliyoni socansi (akukho isipiliyoni / i-amphetamine,n = 8). Iqembu lokugcina laliqukethe onke ama-hamster ayenesifo esine-saline, kungakhathaliseki ukuthi yikuphi okuhlangenwe nakho kocansi okwedlule (usawoti, n = 15). Umsebenzi wokwenza umsebenzi wezinsikazi wawuqhathaniswa phakathi kwamaqembu amathathu wokwelapha kuwo wonke ama-70 wokuhlolwa (ku-10 amaminithi amaminithi) usebenzisa ama-ANOVA amabili. Ama-ANOVAs asebenzayo okubalulekile futhi i-post hoc Ukuhlolwa kwe-Newman-Keuls kwenziwa lapho kufanelekile.
Inombolo yamaseli agwetshiwe nge-c-Fos awazange ahluke phakathi kwalabo besifazane abajojowe nge-saline, kungakhathaliseki ukuthi babe nesipiliyoni esedlule socansi. Ngakho-ke, inani lamaseli e-c-Fos-stained from the dorsal nucleus accumbens, i-dorsal caudate nucleus, ne-cingulate cortex zaqhathaniswa phakathi kwamaqembu amathathu okwelashwa njengalokhu kuhlolwa kokuqala. Ukubala kwe-cell kwahlaziywa usebenzisa ama-ANOVAs amaningi. Ama-ANOVAs asebenzayo okubalulekile futhi i-post hoc Ukuhlolwa kwe-Newman-Keuls kwenziwa lapho kufanelekile.
IZIPHUMA
Zama i-1
Izindlela zokuziphatha ngokocansi
Iminyaka ye-lordosis phakathi nokuhlolwa kokuziphatha ngokobulili ngeviki i-7 yayiqhathaniswa phakathi kokuhlangenwe nakho / ukuvivinywa kanye namaqembu okuhlola / amavivinyo. Ubude be-lordosis obuphakathi ngesikhathi sokuhlolwa kweminye ye-10 kwaba yi-341 ± 53 isekhondi yeqembu lesipiliyoni / isivivinyo kanye ne-478 ± 20 isekhondi elingenalo iqembu le-experience / test. Abesifazane abangekho esigabeni sokuhlangenwe nakho / sokuhlola babecabanga ukuthi ubude bube bude isikhathi eside kunabesifazane besigaba sokuhlangenwe nakho / sokuhlola (t 6 = 5.131; p = 0.05). Ngaphezu kwalokho, isipiliyoni socansi asizange sithinte isikhathi eside. Ukuhlaziywa akubonisi ukuhluka okuphawulekayo phakathi kwama-average durations ngesonto 1 (399 ± 44 isekhondi) kanye neviki 7 (341 ± 53 isekhondi) yabesifazane esigabeni sokuhlangenwe nakho / sokuhlola.
I-c-Fos inkulumo ku-nucleus accumbens
I-ANOVA enendlela ezintathu zokwelashwa izikhathi zezinga le-rostral-caudal izikhathi ze-shell-core azikho imiphumela ephawulekayo yokwelapha futhi akukho ukusebenzisana kwezintathu phakathi kokwelashwa, ukuqoqa izinga, kanye negobolk core (Fig. 2); Nokho, izindlela ezimbili ezibalulekile zokuxhumana (izikhathi zokwelapha i-shell-core kanye nezikhathi zokwelapha ezingeni le-rostral-caudal level) zitholakale.
I-c-Fos iboniswa kugobolondo kanye nenhloko ye-nucleus accumbens emazingeni e-rostral, aphakathi nendawo okuqaphayo kuwo wonke amaqembu okwelapha. I-ANOVA enendlela ezintathu (izikhathi zokwelapha izikhathi zezinga lama-rostral-caudal izikhathi ze-shell-core) zisetshenziselwa ukuhlola imiphumela yezocansi kanye nokuziphatha ngenombolo ye-± SEM yezinhlamvu ze-c-Fos. Ayikho imiphumela ephawulekayo yokwelapha futhi akukho ukusebenzisana kwezintathu phakathi kokwelashwa, ukuqoqa izinga, kanye negobolk core.
Ukuqhathaniswa kwezikhathi zokwelapha i-shell-core interaction yembula imiphumela ephawulekayo enkulu yamaqembu wokwelapha kuphela engxenyeni ye-nucleus accumbens (Fig. 3). Ukuqhathanisa okuphindaphindiwe kokubili kubonisa ukuthi labo besifazane bahlolwe ukuziphatha ngokocansi ngesonto 7 (isipiliyoni / ukuvivinywa futhi akukho okuhlangenwe nakho / ukuvivinywa) kwakunezichungechunge ezingaphezulu kakhulu ze-Fos-core in the core of the nucleus accumbens kunalokho labesifazane abangazange bavivinywe (akukho ukuhlola) (Newman-Keuls, p <0.01). Ayikho imiphumela yokuhlolwa ebonwe kugobolondo lama-nucleus accumbens. Ngaphezu kwalokho, bekungekho miphumela ecacile yesipiliyoni socansi enanini lamaseli aveza i-c-Fos egobolondweni noma kumongo wama-accumbens.
Inkulumo ye-c-Fos kugobolondo kanye nenhloko ye-nucleus accumbens, yawela ngaphesheya kwezinga le-rostral-caudal. Indlela e-ANOVA enesithathu yembula ukuxhumana okuphakathi kokubili phakathi kokwelashwa kanye nenombolo ye-± SEM yezinhlamvu ze-c-Fos egobolondo kanye nenhloko ye-nucleus accumbens (izikhathi zokwelapha i-shell-core;F (2,24) = 4.243; p<0.026). I-ANOVA yendlela eyodwa ehlola lokhu kusebenzisana ithole imiphumela ebalulekile yamaqembu okwelashwa kuphela ku-nucleus accumbens core (F (2,24) = 7.341; p<0.003) hhayi egobolondweni lama-accumbens (F (2,24) = 1.271; p> 0.1). Izinhlamvu ezahlukene khombisa umehluko omkhulu phakathi kwamaqembu.
Ukuqhathaniswa kwezikhathi zokwelapha ukuxhumana kwezinga le-rostral-caudal kutholakale imiphumela ebalulekile emikhakheni yezokwelapha emazingeni ama-rostral no caudal kodwa hhayi ezingeni eliphakathi le-nucleus accumbens (Fig. 4). I-Newman-Keuls i-post hoc ukuhlolwa kwabonisa ukuthi abesifazane abaye bathola ama-6 amasonto okuhlangenwe nakho kobulili futhi bahlolwe ukuziphatha ngokocansi (isipiliyoni / ukuhlola) babe namaseli angaphezu kuka-F-a-nucleus accumcums kunama-femen ahlolwe kepha awazange amukele noma yikuphi ukulwa ngokocansi kwangaphambili (akukho okuhlangenwe nakho / ukuhlolwa; p <0.05) nalabo besifazane abangahlolelwanga ukusebenza kwezocansi (akukho vivinyo;p <0.01). I- i-post hoc ukuhlolwa kwembula imiphumela efanayo ye-nucleus caudal accumbens. Abesifazane besipiliyoni sesipiliyoni / ukuhlolwa babe nenani eliphakeme lamaseli abonisa c-Fos ku-nucleus caudal accumbens kunezinsikazi ku-no-group experience / test test (p <0.05) futhi alikho iqembu lokuhlola (p <0.01). Ngakho-ke, ukuhlolwa kokuziphatha kocansi phakathi neviki i-7 kwakwenyuse inani lamaseli anamabala e-c-Fos kuma-rostral nase-caudal nucleus aqoqelwa kuphela kulabo besifazane ababethole amaviki e-6 wesipiliyoni.
Ukusho kwe-c-Fos ngokusebenzisa ubukhulu be-rostral-caudal ye-nucleus accumbens, buwe ngaphesheya komgogodla negobolondo. Nakuba indlela e-ANOVA eneminyaka emithathu ibonisa ukuthi ukuxhumana okuphakathi kwamabili phakathi kwamaqembu wokwelapha kanye nenombolo yocingo ± SEM c-Fos amaseli ngamazinga we-rostral-caudal we-nucleus accumbens kuphela kubaluleke kakhulu (F (4,48) = 2.365; p <0.066), sihlolisise ileveli ngayinye ye-nucleus accumbens ngokuhlukile ngomphumela wokwelashwa ekubekweni kwe-c-Fos. I-ANOVA yendlela eyodwa iveze imiphumela ebalulekile yamaqembu okwelashwa ezingeni le-rostral (F (2,48) = 5.230; p<0.009) nezinga le-caudal (F (2,48) = 7.455; p <0.002) kepha hhayi ezingeni eliphakathi (F (2,48) = 1.744; p> 0.1) yama-nucleus accumbens. Izinhlamvu ezahlukenekhombisa umehluko omkhulu phakathi kwamaqembu.
Inkulumo ye-c-Fos ku-nucleus ye-caudate ne-cingulate cortex
I-cell ibalwa kusukela e-dorsal caudate nucleus nayo yahlaziywa ngokusebenzisa i-ANOVA enendlela ezintathu. Ukuhlaziywa kwembula kuphela ukusebenzisana phakathi kokwelapha kanye nokukhulumisana kwe-c-Fos ku-nucleus ephakathi nesikhombisa (medial and lateral caudate nucleus)F (2,24) = 3.514;p <0.046). Kodwa-ke, ukuhlaziywa okuhlukile kwe-medial kanye ne-lateral caudate nucleus ngendlela eyodwa ye-ANOVA kukhombise ukuthi akukho mehluko enanini lamaseli anamabala we-c-Fos phakathi kwesipiliyoni / isivivinyo, akukho lwazi / ukuhlolwa, futhi awekho amaqembu wokuhlola (Ithebula2). Ngaphezu kwalokho, akukho miphumela emikhulu yokuzizwa ngokobulili noma ukuziphatha ngenani lamaseli okuveza i-c-Fos, noma noma yikuphi ukusebenzisana, atholakale ku-cortex ye-cingulate (idatha engaboniswa).
Inombolo yesilinganiso engu-± SEM yamaseli e-c-Fos-immunoreactive e-nucleus ephakathi nesikhombisa
Zama i-2
Umsebenzi wokwenza indawo
Indlela ye-ANOVA emibili (izikhathi zokwelapha izikhathi zokuhlola), uma kuqhathaniswa nomsebenzi oshiwo wabesifazane ekuhlangenwe nakho / amphetamine, ayikho isipiliyoni / i-amphetamine, namaqembu okunakekelwa kosawoti kulo lonke i-70 min yokuhlolwa yembula ukuxhumana phakathi kweqembu lezokwelapha kanye nesikhathi sokuhlola. Ukuze uhlole lokhu kusebenzisana, amaqembu okwelashwa ngabanye ahlotshaniswa ngokwehlukile nge-ANOVA eyodwa. Ukuhlaziywa kubonise izinguquko eziphawulekayo kulo msebenzi ovamile ngesikhathi sokuhlolwa kwe-70 kwamacembu amabili ama-females ayejove nge-amphetamine (isipiliyoni / i-amphetamine futhi akukho nhlobo / i-amphetamine). Kodwa-ke, umsebenzi jikelele wezinsikazi ezitholile u-saline azishintshi kakhulu kwi-70 min (Fig.5). I-Newman-Keuls i-post hocizivivinyo zazisetshenziselwa ukunquma ukuthi yiziphi izinkathi zokuhlola ezincane ze-10. Ukuqhathaniswa okuphindwe kabili kwaveza ukuthi umsebenzi ojwayelekile wabesifazane abathintekayo ngokobulili wanikezwa i-amphetamine kakhulu kakhulu i-10 min ngemva kokujola (p <0.05). Ngaphezu kwalokho, uma kuqhathaniswa nemizuzu eyi-10 ngaphambi kokujova, abesifazane abaseqenjini lokwelashwa lesipiliyoni / i-amphetamine bahlala bekhuthele kakhulu i-20 min (p <0.05) nemizuzu engama-30 (p<0.05) ngemuva kokujova. Ngokuphambene nalokho, imiphumela ye-amphetamine kwabesifazane abanamahloni ngokocansi ayizange ibonakale kuze kube yi-20 min ngemuva kokujova. Ngalesi sikhathi, laba besifazane bebesebenza kakhulu ngokuqhathaniswa nemizuzu eyi-10 ngaphambi kokujova (p <0.05). Ngaphezu kwalokho, umsebenzi wabesifazane abangenabulili ocansini onikezwe i-amphetamine uhlala ukhule kakhulu kuma-30 min (p <0.05) nemizuzu engama-40 (p<0.01) ngemuva kokujova.
Imiphumela ye-amphetamine emisebenzini evamile ye-hamster yabesifazane abathintekayo ngokocansi kanye nocansi. Indlela ye-ANOVA emibili (izikhathi zokwelashwa izikhathi zokuhlola) yembula ukuxhumana phakathi kweqembu lezokwelapha kanye nesikhathi sokuhlola (F (12,150) = 2.288;p <0.011) yokubalwa kwenani lomsebenzi ± SEM. I-ANOVA yendlela eyodwa yokuhlola amaqembu okwelashwa ngamanye ikhombise ushintsho olukhulu emsebenzini ojwayelekile wabesifazane kulwazi / i-amphetamine (F (6,150) = 3.0468; p <0.008) futhi akukho okuhlangenwe nakho / amphetamine (F (6,150) = 3.893;p <0.001) amaqembu okwelashwa. Umsebenzi wabesifazane abajojowe ngosawoti awuzange ushintshe (F (6,150) = 1.619;p <0.1). Thumela i-hoc ukuhlolwa kwabonisa ukuthi abesifazane abathintekayo ngokobulili basabela ngokusheshisa kakhulu ku-amphetamine, kubonisa ukwanda komsebenzi ngaphakathi kwe-10 min yokuqala emva komjovo. Abesifazane abangazibandakanya ngokocansi abazange baphendule i-amphetamine kuze kube yi-20 min ngemva kokujova. *p <0.05 kuqhathaniswa nesikhathi ngaphambi kokuhlolwa.
inkulumo ye-c-Fos
I-ANOVA enendlela emithathu (izikhathi zokwelapha izikhathi zezinga lama-rostral-caudal izikhathi ze-shell-core) zisetshenziselwa ukuhlola imiphumela yesipiliyoni socansi kanye ne-amphetamine ekuboniseni c-Fos ku-nucleus accumbens. Ayikho imiphumela ephawulekayo yokwelapha futhi akukho ukusebenzisana kwezintathu phakathi kokwelashwa, ukuqoqa izinga, kanye negobolk core. Ngaphezu kwalokho, ukuhlaziywa akuzange kubonakalise ukusebenzisana phakathi kwamaqembu okwelapha kanye nokukhulumisana kwe-c-Fos kugobolondo kanye nomgogodla we-accumbens noma phakathi kwamaqembu wokwelapha kanye ne-c-Fos ekubhaleni emazingeni we-nucleus accumbens (rostral, middle and caudal) idatha ayibonisiwe).
I-cell ibalwa kusukela e-dorsal caudate nucleus nayo yahlaziywa ngokusebenzisa i-ANOVA enendlela ezintathu. Ukuhlaziywa kokuqala akuveze umphumela ophawulekayo wobulili obudlule noma i-amphetamine ngenani lama cell c-Fos-positive. Ngaphezu kwalokho, akukho mphumela wezolimo zangaphambilini zangaphambili zobulili noma i-amphetamine ngenani lamaseli okuveza i-c-Fos itholakala ku-cortex yecingulate esebenzisa i-ANOVA emibili (idatha engaboniswa).
UKUKHULUMA
Inhloso yalolu uphenyo yayinezimbili. Sasihlola kuqala imiphumela yezobulili ekusebenzeni kwamaselula ezindaweni ezihlukahlukene ze-nucleus accumbens. Ingqinamba yesibili, noma ngabe isipiliyoni sangaphambilini sezocansi singasondeza i-mesolimbic dopamine endleleni, siphenywe ngokuqhathanisa nezimpendulo zokuziphatha ezilwaneni ezitholakalayo ngokocansi kanye nesilwane esingenalutho kumjovo we-amphetamine. Ukuthola kwethu akubonisi nje ukuthi ukuziphatha kocansi besifazane kungenza i-neurons isebenze ku-nucleus accumbens kodwa futhi ukuthi isipiliyoni socansi singakwazi ukukhuthaza ukuphendula kwe-neuronal ku-amphetamine.
Imiphumela yokuziphatha ngokobulili ekuboniseni c-Fos kugobolondo kanye nenhloko ye-nucleus accumbens
Ukuhlolwa kokuziphatha ngokocansi kwandise ukukhulumisana kwe-c-Fos engqenqemeni, kodwa hhayi igobolondo, ye-nucleus accumbens, exhasa ukucwaninga kwangaphambilini okubonisa ukuthi ukuhlangana kocansi olulodwa kungenza kusebenze ama-neurons ku-nucleus accumbens kuma-rodents wesifazane (I-Meisel et al., I-1993; Joppa et al., 1995; UMermelstein noBerker, i-1995; I-Pfaus et al., I-1995; Kohlert et al., 1997; U-Kohlert noMeisel, i-1999). Izincwadi ezikhuluma nge-dichotomy esebenzayo ye-nucleus accumbens iqukethe imibiko eminingi yezinguquko ezihlukile ekudlulisweni kwe-dopamine ngaphakathi kwegobolondo kanye nenhloko ye-nucleus accumbens ekuphenduleni isimiso semithi nesimo semvelo. Ukuphathwa kwezidakamizwa eziningana zokuhlukunyezwa kubangela ukwanda okhethekile kumazinga e-extracellular dopamine kugobolondo le-nucleus accumbens (I-Pontieri et al., 1995; Nisell et al., 1997; Pierce and Kalivas, 1997a; Tanda et al., 1997; UTanda noDi Chiara, i-1998; I-Barrot et al., I-1999; Cadoni noDi Chiara, i-1999). Ngendlela efanayo, ukudla okunomusa kakhulu (UTanda noDi Chiara, i-1998; I-Di Chiara et al., 1999a; Kelley, 1999), ukucindezeleka okuncane (isb., ukushaywa ngonyawo) (Kalivas noDuffy, i-1995; I-Tidey noMiczek, i-1997; I-Bruijnzeel et al., 1999; I-Wu et al., 1999), kanye nokuhlelwa kwemvelo (Rebec et al., 1997;I-Rebec, i-1998) futhi ukwandisa ukwandisa i-dopamine ukudluliselwa kugobolondo le-nucleus accumbens.
Izinto esizifunayo zihambisana ne-hypothesis ukuthi igobolondo nomgogodla usebenza ngendlela ehlukile, nakuba sithole ingqikithi, hhayi igobolondo, ukuba isabele ekuziphatheni ngokobulili. Nokho, kungenzeka ukuthi kunezinguquko ku-c-Fos immunoreactivity kugobolondo le-nucleus accumbens, kodwa lezi zinguquko azitholakalanga. Igobolondo ihlelwe ngendlela eyinkimbinkimbi ezindaweni ezingezansi, igobolondo eliphakathi, eliyindilinga, nele-lateral, nezindawo ezingenalutho nezindlala zegobolondo eliphakathi okungenzeka libe yizifundazwe ezimbili ezihlukene (Groenewegen et al., 1999). Lezi zifundazwe zegobolondo, kanye nezingxenye eziphakathi nendawo ze-coreal, zithola inhlanganisela ehlukene yezimpendulo ezivela ezindaweni eziphathelene ne-cortical ne-subcortical (Groenewegen et al., 1999). Ngaphezu kwalokho, okukhona kulezi zingxenye zezifundazwe kukhona ama-esembles ahlukene e-neurons ahlelwe ngamakamelo ahlukahlukene ajwayelekile (Groenewegen et al., 1999). Ngenxa yokuthi ukuziphatha ngokobulili ekuboniseni c-Fos kulolu cwaningo kuhlolwe kuphela ngegobolondo elidabukisayo, kungenzeka ukuthi inani lamaseli c-Fos-positive empeleni lishintshiwe endaweni engaphansi kwegobolondo.
Naphezu kokubheka ukuthi iningi le-nucleus accumbens imisebenzi likhona endaweni yesigobolondo, kunengqondo ukucabangela ukuthi izifunda ezahlukene ze-neural ngaphakathi kwe-nucleus accumbens zixhumanisa izindawo eziqinisayo zokuziphatha okuhlukile. Carelli et al. (I-2000)ziye zabika kamuva ukuthi i-nucleus accumbens neurons emantwini ibonisa umsebenzi ofanayo we-neuronal ngesikhathi siphendula ngokusebenza ngokuvumelana nama-reinforcers amabili (okungukuthi, ukudla kanye namanzi) kodwa amaphethini ahlukene okudubula ngenkathi ephendula ngokuqiniswa kwemvelo ngokumelene ne-cocaine. Baqedile ukuthi izifunda ezihlukene ze-neural kwinqubo ye-nucleus accumbens ulwazi mayelana nokudla kanye nokuqiniswa kwamanzi nokuqiniswa kwe-cocaine (I-Carelli et al., 2000).
Imiphumela yezocansi ekuboniseni c-Fos ngokusebenzisa i-rostral-caudal i-nucleus accumbens
Izincwadi ezihlola inhlangano yenuzi enqamula i-rostral-caudal nucleus accumbens encane; Kodwa-ke, ukungafani okusebenzayo nokusabalalisa kuye kwaba khona. Izinto esizifunayo zihambisana nezifundo eziye zabika ukuhlukaniswa okungafaniyo kwezimpendulo ze-neurochemical kanye nezithuthuthu kuwo wonke ama-rostral-caudal we-accumbens. I-Cholecystokinin (CCK) ihlukanisa ngokuhlukile imithwalo eyenziwa yi-dopamine engxenyeni ye-rostral ne caudal accumbens (Crawley et al., 1985a,b), okubangelwa i-hyperlocomotion lapho ifaka khona i-caudal accumbens, isifunda esingasetshenziswa yi-CCK neurons egqamile nge-dopamine (Crawley et al., 1985a,b; I-Lanca et al., I-1998). Kodwa-ke, i-CCK ayisebenzisi kahle uma ijoqwe kwi-nucleus yesikhombandlela, isifunda esithola i-CCK ehlukile ne-dopamine (Crawley et al., 1985a,b; I-Lanca et al., I-1998). Kuye kwabikwa ukuthi ukumnika okuqondile kwe-amphetamine kugobolondo yama-rostral, igobolondo le-caudal, noma umgogodla oyinhloko kuthinta umsebenzi wokuziphatha kanye ne-extracellular dopamine namazinga e-serotonin (U-Heidbreder no-Feldon, i-1998). Ukulawulwa kwama-peptide opioid, i-substance P, i-dopamine i-D1 receptors (I-Voorn ne-Docter, i-1992; UJongen-Relo et al., 1994b; I-Voorn et al., I-1994), nokukhululwa kwe-acetylcholine (UJongen-Relo et al., 1995) nge-dopamine kanye ne-dopamine receptor agonists futhi ihluke phakathi kwezingxenye ze-rostral ne-caudal ze-accumbens, ne-rostral accumbens ezwela kakhulu ukuphulukiswa kwe-dopamine nokuphathwa. Nakuba lezi zohluko zomsebenzi eziphakathi kwe-nucleus accumbens ziye zabikwa, kungani lezi zingxabano zomsebenzi zikhona kodwa aziqondi kahle.
Imithwalo yemiphumela yocansi ngesenzo somkhiqizo owenzelwe i-amphetamine
Imiphumela ebikwe lapha futhi ocwaningweni yangaphambilini ibonisa ukuthi isipiliyoni sangaphambilini sezocansi sikhuthaza izimpendulo ze-neuronal ekuhlolweni kokuziphatha ngokocansi, okubonisa ukwanda okukhuthaziwe ekukhululweni kwe-dopamine (U-Kohlert noMeisel, i-1999) kanye nomsebenzi weselula ku-nucleus accumbens (lolu cwaningo). Nokho, ukukhathazeka okukodwa, ukuthi abesifazane abathintekayo esifundweni esedlule kungenzeka ukuthi basabela kokubili ukuhlolwa kokuziphatha ngokocansi kanye nokukhuluma kwemvelo ngenxa yokwaziswa kocansi nokuhlolwa okwenziwa egumbini elifanayo. Izigcawu zemvelo ezihambisana nokuziphatha okukhuthazayo zingathola izakhiwo zokukhuthaza futhi zandise izinga le-dopamine ku-nucleus accumbens (Reid et al., 1996, 1998; I-Watson ne-Little, i-1999). Okukhathazeka okwesibili ukuthi ngoba izinyathelo zokuziphatha ngokobulili ezingabhalwanga, aziwa ukuthi amaqembu amabili abesifazane ahlolwe ukuziphatha ngokocansi athola inani elilinganayo lokugqugquzelwa kwamagciwane. Kuye kwabikwa ukuthi ukugqugquzelwa kwe-vaginocervical kuyadingeka ukuze kukhululwe i-dopamine ku-nucleus accumbens ngesikhathi sokubeletha (Kohlert et al., 1997). Mhlawumbe abesifazane abathintekayo ngokobulili bathola ukugqugquzelwa kwamagincervical ngaphezulu (okungalinganiswa nalolu cwaningo), ngaleyo ndlela kwandisa ukufakwa kwe-c-Fos. Ngakho-ke, ukuqinisekisa ukuthi ukuziphatha ngokobulili kwabesilisa kuyashukumisa indlela ye-mesolimbic dopamine endleleni, siphenyisisa ukuthi ngabe abesifazane abathintekayo ngokocansi kanye nabesifazane abangazizwayo basabela ngendlela ehlukile kumjovo we-amphetamine, esinye isisusa esaziwa ukuxazulula imiphumela yaso nge-dopamine pathways. Ngaphezu kwalokho, ukuqinisekisa ukuthi izimpendulo ezithintekayo zibonwe ngenxa yokuziphatha okuphindaphindiwe ngokocansi hhayi ngenxa yokuxhumana okuhambisana nesimo sokuziphatha ngokocansi, izimpendulo zokuziphatha ze-hamsters kuya kwe-amphetamine zivivinyelwe endaweni yemoveli.
I-Amphetamine yanda umsebenzi jikelele kuwo wonke ama-hamster wesifazane. Kodwa-ke, abesifazane abathintekayo ngokobulili basabela ngokushesha ngaphambi kwe-amphetamine kunezintombikazi ezingenayo ubulili. Le miphumela igqugquzela ukucabanga ukuthi ukuziphatha okuphindaphindiwe ngokocansi kungashukumisa ama-neurons endleleni ye-mesolimbic dopamine futhi kuphakamisa ukuthi izinguquko endleleni ziveza izimpendulo zokuziphatha ezizwakalayo kokubili ukuziphatha okugqugquzela ukuguquka komzimba kanye nokuvuselela kwengqondo (ukuzwela okukhulu).
Lezi zitholakele zihambisana nenkolelo yokuthi kukhona izindlela eziguquguqukayo ze-neural ezixazulula izimpendulo eziphathelene nezidakamizwa nokuziphatha ngokobulili (I-Robinson ne-Berridge, i-1993; Pierce and Kalivas, 1997b). Ucwaningo oluthile oluthile luye lwabona ukunqamuzana okukhulu phakathi kokuchayeka kwezidakamizwa nokuphindaphindiwe kwemvelo. Ukucindezeleka komuntu ukuhlukunyezwa kunciphisa isikhathi sokuthola i-cocaine self-administration kumagundane (I-Tidey noMiczek, i-1997). Indawo ehlanganiswe nezijovo ze-morphine eziphindaphindiwe zingenza kube lula ukuziphatha ngokobulili kumagundane angamadoda (UMitchell noStewart, 1990a,b). I-Amphetamine pretreatment ibuye isebenzise ukuziphatha ngokocansi kumazinyane wesilisa angenayo ubulili futhi ihlotshaniswa nokukhululwa kwe-dopamine engathandwayo ku-nucleus accumbens (Fiorino noPhillips, i-1999).
Inkulumo ye-c-Fos yahlaziywa ku-nucleus accumbens ngemuva kokwelashwa kwe-amphetamine. Kwakucatshangelwa ngokuthi i-amphetamine izokwandisa ukukhulumisana kwe-c-Fos ku-nucleus accumbens, nakwezinga elikhulu kulabo abathintekayo ngokobulili. Kodwa-ke, akukho miphumela ye-amphetamine enani lamaseli okuveza i-c-Fos etholakala kunoma yiziphi izifundazwe ze-nucleus accumbens. Kubonakala kuThebula3 ukuthi izilwane zokulawula ekuhlolweni i-2 (ama-saline abesifazane) zinenani eliphakeme lamaseli a-c-Fos aqhathaniswa nezilwane zokulawula ekuhlolweni i-1 (ayikho abesifazane abahlola). Badiani et al. (I-1998) kubika ukuthi intsha yanda c-fos I-mRNA enomthamo we-nucleus accumbens, nokuthi lokhu kusebenza kwento entshac-fos okuqukethwe kwakunamandla ezindaweni eziningana zobuchopho ukuthi ukuphathwa kwe-amphetamine endaweni engumabonakude akuzange kuveze impendulo eyengeziwe eyengeziwe. Ngakho-ke, kubonakala sengathi ekutadisheni kwethu ukucindezeleka kokuthunyelwa emvelweni wenveli yegumbi lokuhlola kusetshenziselwa ukuhlanganiswa kweprotheyini ye-c-Fos, ngaleyo ndlela kuguqulwa izinguquko ekukhulumeni kwe-c-Fos okubangelwa i-amphetamine nesipiliyoni socansi.
Inombolo yesilinganiso esingu-± SEM ye-basal yamaseli we-c-Fos-immunoreactive kugobolondo le-nucleus accumbens kanye nomgomo wokulawula izilwane ekuhlolweni kwe-1 ne-2
Okubalulekile okungenzeka
Lezi zivivinyo zijoyina uhlu oluqhubekayo lwezifundo (UMitchell noStewart, i-1990b; Fiorino noPhillips, i-1999; Miczek et al., 1999) okubonisa ukuthi okuhlangenwe nakho kwesilwane kungashukumisa ukuphendula komzila we-mesolimbic dopamine kokubili ekuziphatheni okuyingxenye ye-repertoire yemvelo yesilwane nemithi ethile abantu abayaziwa ukuthi bayayisebenzisa kabi (Ohlakaniphile noBozarth, i-1987). Inkinga ebalulekile ekucwaningeni kokusebenzisa kabi izidakamizwa ukubhekelwa ngabanye emiphumeleni yezidakamizwa (I-Newcomb, i-1992; I-Robinson ne-Berridge, i-1993), futhi ngokubambisana lolu cwaningo lunganikeza ulwazi mayelana nentuthuko yokulutha umlutha kubantu.
Imibhalo yaphansi
- Yamukelwe Juni 8, 2000.
- Ukubuyekeza okutholiwe Disemba 12, 2000.
- Yamukelwe Disemba 20, 2000.
Lolu cwaningo lusekelwa yi-National Science Foundation Grant IBN-9723876. Siyabonga uMelissa Zila, uSannon McCanna, uMarchelle Baker, uMichael Huntington, noDeborah Shelley ngosizo lwabo lobuchwepheshe ngokuhlolwa kokuziphatha nokucutshungulwa kwe-c-Fos.
Ukuxhumana kufanele kuqondiswe kuDkt. Robert L. Meisel, uMnyango Wezezimo Zengqondo, I-Purdue University, West Lafayette, IN 47907-1364. Imeyili: [i-imeyili ivikelwe].
- I-copyright © 2001 Society for Neuroscience
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