I-Journal ye-Neuroscience, I-15 ngo-Matshi 2001, 21(6): 2123-2130;
+ UkuBambisana noMbhali
Abstract
Ukuhanjiswa kwe-Dopamine kwi-nucleus accumbens kunokusebenza ngamachiza, ngoxinzelelo, okanye kukuziphatha okukhuthazayo, kwaye ukubhengeza okuphindaphindiweyo kwezi zinto zibangela ukuziva impendulo. Iinjongo zolu phononongo yayikukufumanisa ukuba ngaba indlela yokuziphatha kwabasetyhini ebangela ukuba i-nucleus iqokelele i-neurons kunye nokuba amava ezesondo abesemva kokuziphatha ngokwesondo aqonda iimpendulo ze-neuronal kwi-nucleus accumbens kwi-amphetamine. Usebenzisa iilebhile ye-immunocytochemical, i-c-Fos expression in sub subionsions (iqokobhe vs isiseko kumqolo we-rostral, embindini, kunye ne-caudal) ye-nucleus accumbens yavavanywa kwii-hamsters zabasetyhini ezazinamaxabiso ahlukeneyo kumava ezesondo. Ii hamsters zabasetyhini, ezinikezwe iiveki ze-6 zamava ezesondo okanye ezisele zingamakhoboka ngokwesondo, zavavanywa ekuziphatheni ngokwesondo ngokuchazwa kwabantu abadala abangamadoda. Amava ezesondo angaphambili anyuse i-c-Fos ilebheli kwimigangatho ye-rostral kunye ne-caudal kodwa hayi kumanqanaba aphakathi e-nucleus accumbens. Ukuvavanywa kokuziphatha ngokwesondo kwanda ukulebhelisha embindini, kodwa hayi iqokobhe, le-nucleus accumbens. Ukuqinisekisa ukuba isenzo sesondo sabasetyhini sinokuvuselela i-neurons kwindlela ye-mesolimbic dopamine, iimpendulo ze-locomotor zabasetyhini abanamava kunye nabasetyhini abathandanayo ngokwesondo kwi-amphetamine inaliti emva koko bathelekiswa. I-Amphetamine yonyusa umsebenzi we-locomotor kubo bonke abantu basetyhini. Nangona kunjalo, izilwanyana ezinolwazi ngesondo zaphendula kwangoko kwi-amphetamine kunezilwanyana ezithandwayo ngokwesini. Ezi datha zibonisa ukuba indlela yokuziphatha kwabasetyhini besondo inokuvula i-neurons kwi-nucleus accumbens kunye nokuba amava ezesondo anokuwela kwiimpendulo ze-neuronal kwi-amphetamine. Ukongeza, ezi ziphumo zinika ubungqina obengezelelweyo bokusebenza okwahlukileyo phakathi kweqokobhe kunye nengcambu yentsimbi eqokeleleneyo kunye nayo yonke intsimbi yayo ye-anteroposterior.
- yokuziphatha ngokwesondo kwabasetyhini
- nucleus accumbens
- iqokobhe
- umbilini
- I-c-Fos
- ku khuthazwa
- uvavanyo-mfanekiso
- amphetamine
intshayelelo
I-dopamine neurons evela kwindawo ye-midbrain ventral tegmental and projekt to a widebrain nuclei, kubandakanya i-nucleus accumbens, yinxalenye yenkqubo ye-mesolimbic dopamine. Kucetyiswe ukuba le nkqubo yeedopamine ibalulekile kulawulo lweendlela zokuziphatha ezithandekayo (UMitchell noGraton, i-1994; Salamone, 1994, 1996; I-Ikemoto nePanksepp, i-1999), kunye nokuzilawula ngokwamachiza okuphathwa gadalala (UPierre noVezina, 1998;I-Koob, i-1999; Lorrain et al., 1999; UMcKinzie et al., 1999; Abantu et al., 1999; Bradberry et al., 2000). Ukulawulwa kwenkqubo yeendlela ezahlukeneyo zeziyobisi zokuxhatshazwa (umzekelo, i-cocaine, amphetamine, kunye ne-heroin) kusebenze iindlela zedopamine (I-Pontieri et al., 1995; UNisell et al., 1997; UPierce noKalivas, 1997a; I-Tanda et al., 1997; I-Tanda kunye ne-Di Chiara, i-1998; Barrot et al., 1999; I-Cadoni kunye ne-Di Chiara, i-1999), kwaye ukuvezwa okuphindaphindiweyo kwezi arhente zekhemesti kunokubangela imvakalelo yokuphendula kwimpendulo ye-dopamine (URobinson et al., 1988; Kalivas et al., 1992; IKalivas kunye neDuffy, 1993; Pierce kunye neKalivas, i-1995; Kuczenski et al., 1997; UNisell et al., 1997; UBirrell kunye neBalfour, i-1998; UHeidbreder kunye noFeldon, 1998; I-Cadoni kunye ne-Di Chiara, i-1999; UCadoni et al., 2000). Uphando lubonelele ubungqina bokuba i-nucleus accumbens nayo iyaphendula kwiipropathi ezithile ezinxulumene nokukhula. Amanqanaba e-dopamine ye-extracellular kwi-nucleus accumbens inyuka ngexesha lokunxibelelana ngokwesondo kwimigundwane yabasetyhini (Mermelstein noBrakker, 1995; Pfaus et al., 1995) kunye ne-hamsters (Meisel et al., 1993; U-Kohlert et al., 1997; I-Kohlert kunye neMeisel, 1999). Okufanayo nokulawula iziyobisi okuphindaphindiweyo, iimvavanyo zokuziphatha ngokwesondo ezininzi zikwandisa ukunyuka kwamanqanaba e-dopamine, iphakamisa ukuba amava ezesondo anokuziva i-neurons kwindlela ye-dopamine (I-Kohlert kunye neMeisel, 1999).
I-nucleus accumbens idityaniswa ngamacandelwana amaninzi ahlukane ngokwendalo, eyona nto iqhelekileyo ziigobolondo kunye nomongo. Ukudityaniswa kweqokobhe kunye nokuphambuka kwengqondo, icebisa ukuba ezi ziqendwana zibini zilawula imisebenzi eyahlukileyo (UCrawley et al., 1985a,b; UHeimer et al., 1991; I-Zahm kunye ne-Brog, i-1992; Brog et al., 1993;IKalivas kunye neDuffy, 1995; Maldonado-Irizarry et al., 1995; Pierce kunye neKalivas, i-1995; I-Pontieri et al., 1995; I-Broening et al., 1997; UHeimer et al., 1997; Kelley et al., 1997; IStratford kunye neKelley, 1997; UHeidbreder kunye noFeldon, 1998; Lanca et al., 1998; I-Bassareo kunye ne-Di Chiara, i-1999; UDi Chiara et al., 1999b; IGroenewegen et al., 1999; Kelley, 1999; UMcKinzie et al., 1999; I-Zahm, 1999; UBrown noMolliver, 2000). Ngenxa yokuba i-nucleus accumbens yinyuksi ene-heterogenible, akucaci nokuba iimpendulo kwindlela yokuziphatha kwabasetyhini yenziwa kwalapha kwimimandla ethile ye-nucleus accumbens okanye yasasazeka kuyo yonke i-nucleus. Iindlela zobuchwephesha ezazisetyenziswa ngaphambili ukuphendula lo mbuzo (umzekelo, i-Microdialysis) azinabugcagazi ngokwaneleyo ngokwaneleyo ukuphonononga ukusebenza kwe heterogeneity ye-accumbens. Ngokwahlukileyo, ukuqhutywa kwe-immunocytochemical protein ye-c-Fos kubonelela ngendlela yokuvavanya ukusebenza kweeselfowuni phakathi kokuhanjiswa kwe-nucleus accumbens. Ke, injongo yokuqala yoluvavanyo yayikukufumanisa ukuba ingaba iselfowuni emva kwendlela yokuziphatha kwabasetyhini yenziwa kwindawo ethile yecandelo le-nucleus.
Ipropathi enomdla yezi ndlela dopamine kukuboniswa kweminqamlezo. Ngamanye amagama, i-dopamine neurons ngaphambili ibonakaliswe kwisichiza esinye iya kubonisa iimpendulo ezenziweyo kwelinye ichiza elinikwe okokuqala (ICunningham kunye neKelley, 1992; UPierce noKalivas, 1997a; UBirrell kunye neBalfour, i-1998; UTaylor noHorger, 1999). Ukongeza kwiimvakalelo ezinqamlezayo phakathi kweziyobisi, uphononongo oluninzi luxelile ubuntununtunu phakathi kokuchazwa okuphindaphindiweyo kubathengisi bezonyango nakwindlela yokuziphatha evuselelweyo yendalo (UMitchell noStewart, 1990a,b; Tidey noMiczek, 1997; UFiorino noPhillips, 1999). Ke ngoko, sivavanye ukuba izilwanyana ezinamava nezesondo zinokusabela ngendlela eyahlukileyo kwinkuthazo yenoveli eyaziwayo ukwenza ukuba kusebenze iindlela zedopamine (okt, imvakalelo yokuwela), njengeamphetamine. Ukuba indlela yokuziphatha kwabasetyhini iyaziveza iindlela zedopamine, ke abantu ababhinqileyo abanokwabelana ngesondo kufuneka babonise indlela yokuziphatha engqinisisekyo kwisitofu esinye se-amphetamine.
IMPAHLA NENKQUBO
Iindlela ngokubanzi
Izilwanyana. Ii hamsters ezingamadoda nabasetyhini baseSyria bahlangulwa kuCharles River Laboratories (eKingston, NY) kwi-∼60 d yobudala. Ezi zilwanyana zazigcinwa zodwa, kwaye izilwanyana ezivuselelayo zazigcinwa ngokwamaqela amathathu okanye amane kwiikhephe zeplastiki (50.8 × 40.6 × 20.3 cm). Igumbi le-colony yesilwanyana ligcinwe kwiqondo lokushisa rhoqo (i-22 ° C) kunye nezibane ezicinywe phakathi kwe-1: 30 kunye ne-11: I-30 PM (14 / 10 hr ukukhanya / umjikelezo omnyama). Ukutya namanzi ayefumaneka ad adum.
Iinkqubo ezisetyenzisiweyo koluvavanyo zihambelana namaZiko ezempilo kuZwelonke Izikhokelo zoKhathalelo kunye nokuSetyenziswa kwezilwanyana zaselebhu kwaye zivunyiwe yiKomiti yokuNakekela izilwanyana kunye neKomiti yokuThintela.
Amava ezesondo. Phantse iveki ye-1 kwiveki emva kokuba abafazi befika kwilebhu, babekwa ovariectomized phantsi kwe-sodium pentobarbital (Nembutal) anesthesia (8.5 mg nge-100 gm yomzimba, ip). Emva kwe-ovariectomy, iimazi zokuqala zahlulwa zangamaqela amabini. Iqela elinye labasetyhini lafumana iiveki ze-6 zamava ezesondo kunye nendoda yokuvuselela; Iqela lesibini lahlala linobuhlanga ngokwesini. Onke amanenekazi aye anyanzelwa ukuba abe yi-6 ngeveki ngexesha leveki. Kuzo zombini i-48 kunye ne-24 hr ngaphambi kwamava okwabelana ngesondo, amanenekazi afakwa ngenzakaliso nge-10 μg ye-estradiol benzoate kwi-0.1 ml yeoyile ye-cottonseed. Ngomhla wovavanyo lwamava, ababhinqileyo bafumana i-500 μg yeprogesterone kwi-0.1 ml yeoyile ye-cottonseed (inaliti engaphantsi). Abasetyhini abangafumani amava ezesondo bangenwe ngerimen ye-hormone kwaye bahlala ezindlini zabo kwigumbi lekholoni. Kwi-4-5 hr emva kolawulo lwe-progesterone, indoda endala eyomeleleyo Hamster eyayifumene amava ngokwesondo ngokusetyenziswa kwezinye izifundo zokuziphatha ngokwesondo yabekwa kwikheji yasekhaya yowesifazane olilingo. Ukulandelelana kweekheji ezibandakanya amadoda kujikelezwe veki nganye ukunciphisa amathuba okuba indoda eyindoda nebhinqileyo zibhangqulwe ngaphezulu kube kanye ngeveki ye6 yamava ezesondo.
I-immunocytochemistry. Ii-hamsters zabasetyhini, ezibulewe nge-overdose ye-sodium pentobarbital, zenziwa nge-intracard ngokukodwa nge-25 mm Isisombululo se-PBS, i-pH 7.5, ye-2 min (umda wokuhamba, i-25 ml / min), ilandelwa yi-4% paraformaldehyde kwi-PBS ye-20 min. Iibreyikhi zazithunyelwe ngaphambili nge-2 hr kwiparaformaldehyde kwaye zigcinwe kwi-10% sucrose PBS ngobusuku kwi-4 ° C.
Icandelo le-serial ye-coron ye-40 μm yathatyathwa kuyo yonke i-nucleus accumbens. Emva kwamawaka amathathu e-10 i-rinses kwi-PBS, amacandelo afakwa kwi-anti-antibody eyintloko ukuya kwi-c-Fos (1: 6000 kwi-PBS ene-0.3% iTriton X-100; iSanta Cruz Biotechnology, iSanta Cruz, CA) okanye kumachiza aphambili kwi-calbindin-D (28 kDa) (1: 6000 kwi-PBS nge0.3% iTriton X-100; Chemicon I-International, i-Temecula, CA) kwi-4 ° C ye-48 hr. Zombini amacandelo e-c-Fos kunye ne-calbindin-D emva koko afuduselwa i-45 ye-min kwiqondo lokushisa kwigumbi kwi-biotinylated anti-rabbit IgG yesibini antibody (1: 200 in PBS; Elite Vectastain ABC kit; Vector Laboratories, Burlingame, CA), and by an ukufaka inckeation kunye ne-avidin-biotin horseradish peroxidase tata (1: 50 in PBS; Elite Vectastain ABC kit) ye45 min kwiqondo lokushisa kwigumbi, kunye ne-10 min rinses kwi-PBS yangaphambi kokungenisa ngaphakathi. Emva kweerins ezimbini kwi-PBS kunye ne-10 min ukuhlamba kwi-0.1 m I-Tris buffer, pH 7.6, amacandelo e-c-Fos kunye ne-calbindin-D afakelwe i-5 kunye ne-10 min, ngokulandelanayo, kwi-0.08% diaminobenzidine (DAB) (Aldrich, Milwaukee, WI) kwi-Tris buffer equkethe i-0.003% hydrogen peroxide kunye ne-0.015% I-nickel chloride. Onke la macandelo ahlanjwa kwakhona kwi-Tris buffer kunye namanzi enziwe amanzi aza agalelwa kwi-chrom-alum-coated slides. Izilayidi zazomisiwe, zinamanzi, zacocwa, kwaye zigqunywe kusetyenziswa iphepha-mvume lokuloba (iFisher Science, Pittsburgh, PA).
Uhlalutyo lweMicroscopic. Izicubu ze-neural ezigcinwe kwi-calbindin-D, echaza igobolondo kunye nomxholo we-nucleus accumbens (UJongen-Relo et al., 1994a; UJohnson noWood, 1999) isetyenziselwe ukubonisa icandelo elinye kwinqanaba ngalinye le-rostral, embindini, kunye ne-caudal ye-dorsal nucleus accumbens. Amacandelo asuka kwi-nucleus eqokelela kwi-rostral, embindini, nakumanqanaba e-caudal egcinwe i-calbindin aboniswe kuMzobo. 1 A-C. Kuxelwe ukuba kukho umahluko omncinci ophakathi konobumba kunye neqokobhe kwi-calbindin-D immunoreactivity kwi-Syria hamster xa kuthelekiswa nomyinge, kodwa ukubekwa kwale peptide kusenako ukwahlulahlulahlula imihlathana ye-nucleus accumbens (UJohnson noWood, 1999). Ibhokisi ebandakanya ummandla wesampulu ye-0.1 mm2 (I-0.2 × 0.5 mm) yabekwa ngaphezulu kweqokobhe le-dorsal kunye nomxholo we-nucleus accumbens yecandelo ngalinye. Imifanekiso yecandelo ngalinye yayiprintwe kwifilim ebonakalayo kwaye imifanekiso yaze yafakwa kumacandelo e-c-F ehambelana nesilwanyana ngasinye, iqinisekisa ukuba ibhokisi ibekwe kwindawo enye kuzo zonke izilwanyana. Umzobo 1, D kwaye E, ibonisa icandelo elinye le-caudal kwisilwanyana esifumene iiveki ze-6 yamava esondo kwaye yavavanywa kwindlela yokuziphatha ngokwesondo. Ibhokisi ibekwe emanqindini we-caudal nucleuseba kwi-Figure 1 Dnakwigobolondo ye-caudal accumbens kwi-Figure1 E. Ibhokisi enobungakanani obufanayo ibekwe kwicandelo elifanayo leethishu kwi-medial cingate cortex kunye nangaphezulu kunye ne-lateral dorsal caudate nucleus kwinqanaba ngalinye lala manqanaba mathathu esampulu ye-nucleus accumbens. Kungenxa yokuba siye safumanisa ukuba kunokubakho ukwahluka kwe-rostral – caudal kwiziphumo zokutshatisa kwi-c-Fos, linye kuphela icandelo kwinqanaba ngalinye elahlalutyiweyo ukonyusa ukuchaneka kwe-anatomical yesampulu yethu. Inani leeseli ze-c-Fos-immunoreactive kwindawo nganye ekhethiweyo yabalwa ngoncedo lwekhamera yevidiyo eqhagamshelwe kwinkqubo yohlalutyo lomfanekiso wekhompyuter (iBioQuant MegM; R & M Biometrics, Nashville, TN).
Inuksi eqokelela iinxalenye zeethishu ezigcinwe i-calbindin-D kunye ne-c-Fos. A-C ngamacandelo avela kwi-rostral (A), phakathi (B), kunye ne-caudal (C) I-nucleus eqokelelweyo khohlo) ye-calbindin, ebonisa ukwahlula phakathi kweqokobhe kunye nokuhanjiswa okungaphantsi (i asterisks). Kukho i-320 μm phakathi kwamacandelo e-rostral kunye nephakathi kunye ne-240 μm phakathi kwamacandelo aphakathi kunye ne-caudal. Imifanekiso engezantsi (D, E) yimizekelo ye-c-Fos yokubekwa kwindawo engumbala we-caudal (D) kunye negobolondo (E) ye-nucleus accumbens (i-midline yi kunene) yowasetyhini onolwazi ngesondo wabulawa emva kovavanyo lokuziphatha ngokwesondo. Iunxantathu ibonisa indawo yesampulu (0.2 × 0.5 mm).
Uvavanyo lwe-1
Isilingo sokuqala saphanda ngemiphumo yamava esini kunye nokuvavanywa kwi-c-Fos induction kwi-nucleus accumbens, i-dorsal caudate nucleus, kunye ne-cingates cortex. Injongo yokuvavanywa yayikabini. Injongo yokuqala yayikukufumanisa ukuba ngaba kukho umahluko ekusebenzeni kweselula kuyo nayiphi na imimandla yobuchopho ngenxa yamava esondo kunye / okanye uvavanyo lokuziphatha. Ukuba intsingiselo ye-c-Fos yatshintshiwe, kwagqitywa ke ukuba ngaba utshintsho olo lungabekwa kwindawo ethile kumacandelo athile obuchopho obuhlaziyiweyo.
Ii-hamsters zaseSyria zabesifazane zifumene iiveki ze-6 zamava ezesondo okanye zihlala zifundisa ngokwesondo. Ngexesha leeveki ze-6 zamava, inani elongezelekayo lexesha lokuthathwa kwesetyhini ukuba yi-Lordosis (ukungasebenzi kunye ne-dorsoflexion yangasemva) ukulinganiswa kwiseshoni yovavanyo nganye ye-10 yemizuzu. Akukho zinyathelo zokuziphatha kwamadoda ngokwesini ezirekhodiweyo. Ngeveki i-7, uchungechunge olufanayo lwe-estradiol benzoate kunye nenaliti yeprogesterone yanikwa. Ngeli xesha, isiqingatha sabasetyhini abanamava kunye nabasetyhini abavavanyiyo bavavanywa ngokuziphatha ngokwesondo ngokubeka indoda endala kwikhaya labo. Amanenekazi ashiyekileyo kwizindlu zawo zasekhaya. Kwi-60-90 min emva kokuvezwa kwindoda, amabhinqa acocwa kakuhle, kwaye iingqondo zawo zaye zalungiswa ukuvakaliswa kwe-c-Fos. Abo basetyhini abangavavanywanga ekuziphatheni ngokwesondo baphulukiswa i-4 hr emva kolawulo lweprogesterone.
Uhlalutyo lwedatha. Kuba ukubalwa kweseli kwakungahlukanga phakathi kwento yokuba amabhinqa angavavanywa ekuziphatheni ngokwesondo phakathi kweveki ye-7, akukhathalekile kumava esini esidlulileyo1 umzekelo), iimazi ezivavanyayo ekugqibeleni zahlulwa zangamaqela amathathu onyango wohlalutyo. Iqela lokuqala liqulathe amabhinqa afumene iiveki ze-6 yamava ezesondo kwaye avavanywa kwindlela yokuziphatha ngokwesondo (amava / uvavanyo, n = 6). Iqela lesibini eliqulathe la mabhinqa angafumananga naliphi na amava angaphambili, kodwa avavanyelwa indlela yokuziphatha ngokwesondo (akukho mava / kuvavanyo,n = 8). Iqela lokugqibela liqulathe zonke ii hamsters zowesifazana ezazingavavanyelwanga ukuba ziziphatha njani ngokwesondo, kungajongwanga naluphi na amava okwabelana ngesondo (akukho luvavanyo n = 13). La maqela mabini angafumani kuvavanyo lokuziphatha ngokwesondo adityaniswa ukunyusa amandla ezibalo kuhlalutyo. Inani leeseli-ezinokufakwa kwi-c-Fos-st seli evela kwi-dorsal nucleuseba, i-dorsal caudate nucleus, kunye ne-cingrate cortex xa ithelekiswa phakathi kwamaqela amathathu.
Thelekisa intsingiselo ± I-SEM yenombolo ye-c-Fos-engafunekiyo kwi-nusus eqokelela iqokobhe kunye nesiseko phakathi kwamaqela onyango.
Amabala eseli ahlaziywe kusetyenziswa ii-ANOPA ze-multifactor. Isiphumo esibonakalayo esibonisa ii-ANOVA kunye iposi Uvavanyo lweNewman-Keuls lwenziwa apho kufanelekileyo. Idatha yokuziphatha (i-Lordosis durations) yahlaziywa kusetyenziswa i-ta-tiles ezimbini t vavanyo.
Uvavanyo lwe-2
Ukuvavanywa kwesibini kuthelekisa ubuchule bokuvuselela inoveli, i-amphetamine, ukuvelisa ubuntu ekuziphatheni ngokwesini kunye nama-hamsters abesetyhini abangenamava. Ukuchazwa kwe-c-Fos kwi-nucleus accumbens, i-dorsal caudate nucleus, kunye ne-cingrate cortex kwahlaziywa kwakhona ukufumanisa ukuba ipateni yemisebenzi yeselula iyafana kusini na kwiziphumo ezifunyenwe kwiNgcali 1.
Abafazi baseSyria abangama-hamsters banikwa iiveki ze-6 zamava esini okanye bahlala bekhohlakele ngokwesini. Ngeveki i-7, onke amanenekazi ahanjiswa kwindawo yenoveli (okt. I-aquarium yeglasi ye-10 yeglasi kwindawo yegumbi elingaziwayo) i-4 hr emva kolawulo lweprogesterone. Abasetyhini babekwa kwi-10 yeglasi ye-aquarium yeglasi ye-10 min, emva kwexesha apho isiqingatha sabasetyhini abanamava kunye nabasetyhini kunyed-amphetamine sulfate (1 mg nge-1 kg ubunzima bomzimba kwi-1.0 ml ye-0.9% NaCl; isipho esivela kuGqr David Nichols, Dyunivesithi yasePurdue). Amanenekazi aseleyo afakwa kwi-0.9% NaCl (1 mg nge-1 kg yomzimba). Iimazi ke emva koko zabuyiselwa kwi-10 gallon aquarium ngemizuzu eyongezelelweyo ye-60. Iiseshini ze-70 zemizuzu zavotelwa ukuba zihlalutywe ngokubanzi komsebenzi weenqanawa ezisetyhini. Ngaphakathi kwimizuzu ye-30 emva kovavanyo oluqhelekileyo lomsebenzi, amabhinqa acocwa ngobuchule, kwaye iingqondo zawo zaye zalungiswa ukuvakaliswa kwe-c-Fos.
Uhlalutyo lweVideotape. Ngeveki ye-7, iiseshini ze-70 zeeseshoni zokuvavanya umsebenzi we-locomotor zavota. I-aquariums zeglasi ye-10 yeglasi zahlukaniswa zaba zindawo ezintathu ezilinganayo kwiscreen sevidiyo, kwaye umsebenzi we-locomotor wabasetyhini wabhalwa phantsi kwenani leendawo ezinqamlezayo.
Uhlalutyo lwedatha. Imbali edlulileyo yezesondo ayizange ibe nefuthe kwimisebenzi ye-locomotor yee hamsters zowesifazane zifakwe kwisaline; ke ngoko, iimvavanyo zesetyhini zahlulwa zangamaqela amathathu onyango wohlalutyo. Iqela lokuqala laliqulathe amabhinqa afumene iiveki ze-6 zamava ezesondo kwaye afakwa kwi-amphetamine (amava / amphetamine, n = 8). Iqela lesibini libandakanya la mabhinqa ayelawulwa i-amphetamine kodwa engafumananga naluphi na amava okwabelana ngesondo (akukho mava / amphetamine,n = 8). Iqela lokugqibela liqulathe zonke ii hamsters zowesifazana ezazifakwe ngaphakathi ngealine, ngaphandle kwawo nawuphi na amava okwabelana ngesondo (saline, n = 15). Umsebenzi we-locomotor wabasetyhini wathelekiswa phakathi kwamaqela onyango amathathu kwi-70 min yeemvavanyo (kumaxesha e-10 min) usebenzisa ii-ANOVA ezimbini. Isiphumo esibonakalayo esibonisa ii-ANOVA kunye iposi Uvavanyo lweNewman-Keuls lwenziwa apho kufanelekileyo.
Inani leeseli ezigcinwe ngenxa ye-c-Fos alizange lahlukane phakathi kwabo basetyhini abachaphazelekileyo nge-saline, ngaphandle kokufumana amava okwabelana ngesondo kwangaphambili. Ke ngoko inani le-c-Fos-stain-seli ezivela kwi-dorsal nucleuseba, i-dorsal caudate nucleus, kunye ne-cingulate cortex yathelekiswa phakathi kwamaqela amathathu onyango njengakwilingo lokuqala. Amabala eseli ahlaziywe kusetyenziswa ii-ANOPA ze-multifactor. Isiphumo esibonakalayo esibonisa ii-ANOVA kunye iposi Uvavanyo lweNewman-Keuls lwenziwa apho kufanelekileyo.
IINKCUKACHA
Uvavanyo lwe-1
Amanyathelo okuziphatha ngokwesondo
I-Lordosis durations ngexesha lovavanyo lokuziphatha ngokwesondo ngeveki ye-7 yayithelekiswa phakathi kwamava / kuvavanyo kunye namava. Ixesha eliphakathi le-Lordososis ngexesha lokuvavanywa kwe-10 min yayiyi-341 ± 53 sec yamava / iqela lovavanyo kunye ne-478 ± 20 sec yeqela elingenamava / lovavanyo. Abantu ababhinqileyo abangenamava / iqela lokuvavanya lithathe i-Lordosis ixesha elide kakhulu kunokuba besetyhini kwiqela lamava / kuvavanyo (t 6 = 5.131; p = 0.05). Ngaphaya koko, amava ezesondo awachaphazelanga ixesha le-Lordosis. Uhlalutyo lubonise ukungafani okwahlukileyo phakathi kobude obuqhelekileyo beveki 1 (399 ± 44 sec) kunye neveki 7 (341 ± 53 sec) yabasetyhini kwiqela / kuvavanyo lweqela.
c-Fos intetho kwi-nucleus accumbens
Indlela ezintathu ze-ANOVA zamaxesha onyango i-rostral-caudal level times igobolondo-isiseko ayifumananga ziphumo zibalulekileyo zonyango kwaye akukho kuhlangana kwendlela phakathi kwonyango, inqanaba le-ascobs, kunye ne-shell-core (i-Fig. 2); nangona kunjalo, iindlela ezimbini zonxibelelwano ezibaluleke ezimbini (amaxesha okunyanga igobolondo-kunye namaxesha onyango inqanaba le-costral-caudal) lafunyanwa.
Ukuthetha kwe-c-Fos kwibhombu kunye nencindi ye-nucleus eqokelele kwinqanaba le-rostral, eliphakathi, kunye ne-caudal kwiqela ngalinye lonyango. I-ANOVA yendlela ezintathu (amaxesha onyango i-rostral-caudal level times shell-core) yayisetyenziselwa ukujonga iziphumo zamava ezesondo kunye nokuziphatha kwi-± SEM inani leeseli ze-c-Fos. Akukho ziphumo zibalulekileyo zonyango kwaye akukho kudibana ngeendlela ezintathu phakathi kwonyango, inqanaba le-accumbens, kunye ne-shell-core yafunyanwa.
Ukucinga ixesha lokunyanga igobolondo-nxibelelano olusisiseko lubonakalise iziphumo eziphambili zamaqela onyango kuphela kwincam ye-nucleuseba (Fig. 3). Ukuthelekisa okuninzi kwePairwise kwabonisa ukuba la mabhinqa avavanyelwe indlela yokuziphatha ngokwesondo phakathi kweveki ye-7 (amava / uvavanyo kwaye engenamava / kuvavanyo) ayeneeseli ezilinganayo ze-c-Fos kumbindi we-nucleus accumbens kunaleyo yamabhinqa angavavanywa (hayi uvavanyo) (Newman-Keuls, p <0.01). Akukho ziphumo zovavanyo zaqwalaselwa kwigobolondo ye-nucleus accumbens. Ngaphaya koko, kwakungekho miphumo icacileyo yamava ezesondo kwinani leeseli ezibonisa i-c-Fos kwigobolondo okanye kumbindi we-accumbens.
I-c-Fos expression "Kwibholam kunye nengcambu yentsimbi eqokeleleneyo, yawela kwinqanaba le-rostral-caudal. Iindlela ezintathu ze-ANOVA ziveze ukusebenzisana phakathi kweendlela ezimbini zonyango kunye nentsingiselo ye-SEM yenani leeseli ze-c-Fos kwiqokobhe kunye nomxholo we-nucleus accumbens (amaxesha okunyanga igobolondo-elingundoqo;F (2,24) = 4.243; p<0.026). Indlela yendlela i-ANOVA yokuvavanya olu nxibelelwano ifumene iimpembelelo eziphambili kumaqela onyango kuphela kwi-nucleus accumbens core (F (2,24) = 7.341; p<0.003) hayi kwiqokobhe le-accumbens (F (2,24) = 1.271; p> 0.1). Iileta ezahlukileyo bonakalisa umahluko obonakalayo phakathi kwamaqela.
Ukukhangelwa kwamaxesha okunyanga inqanaba lokudibana kwe-rostral-caudal lafumana iziphumo eziphambili zamaqela onyango kuwo omabini amanqanaba e-rostral kunye ne-caudal kodwa hayi kwinqanaba eliphakathi le-nucleus accumbens (Fig. 4). INewman-Keuls iposi Uvavanyo lubonise ukuba abasetyhini abafumene i-6 iiveki yamava ezesondo kwaye bavavanywa ngenxa yesimo sokuziphatha ngokwesondo (amava / uvavanyo) babene-c-Fos-positive cell kwi-rostral nucleus accumbens kunabasetyhini abavavanyiweyo kodwa abangazange bafumane naluphi na amava okwabelana ngesondo kwangaphambili (akukho mava / kuvavanyo; p <0.05) kunye nalawo mabhinqa angavavanyelwanga indlela yokuziphatha ngokwesondo (akukho vavanyo;p <0.01). Inkqubo ye- iposi Iimvavanyo ziveze iziphumo ezifanayo ze-caudal nucleus accumbens. Abantu ababhinqileyo kumava / kwiqela lokuvavanya belinenombolo ephezulu yeeseli eziveza i-c-Fos kwindawo ye-caudal nucleus eqokelelweyo kunabasetyhini kwiqela elingenamava / lovavanyop <0.05) kwaye akukho qela lovavanyo (p <0.01). Ke ngoko, ukuvavanywa kokuziphatha ngokwesondo phakathi kweveki ye-7 kwandise inani leeseli ezinamabala e-c-Fos kwi-rostral kunye ne-caudal nucleus eqokelelelela kuphela abo bafazi babefumene iiveki ze-6 zamava.
I-c-Fos expression ngokusebenzisa ubukhulu be-rostral-caudal ye-nucleus ye-nucleus, yawa ngaphaya komgangatho kunye neqokobhe. Nangona i-ANOVA enezindlela ezintathu ibonise ukuba ukuhlangana kwendlela ezimbini phakathi kwamaqela onyango kunye nentsingiselo ye-EM SEM inombolo ye-c-Fos iiseli ngokwamanqanaba e-rostral-caudal ye-nucleus accumbens yasondela ngokubaluleka kuphela (F (4,48) = 2.365; p <0.066), sivavanye inqanaba ngalinye le-nucleus eqokelelene ngokwahlukileyo kwisiphumo sonyango kumabala e-c-Fos. Indlela yendlela i-ANOVA ityhile imiphumo ephambili yamaqela onyango kuwo omabini amanqanaba e-rostral (F (2,48) = 5.230; p<0.009) kunye nenqanaba le-caudal (F (2,48) = 7.455; p <0.002) kodwa hayi kwinqanaba eliphakathi (F (2,48) = 1.744; p> 0.1) ye-nucleus accumbens. Iileta ezahlukileyobonakalisa umahluko obonakalayo phakathi kwamaqela.
I-c-Fos expression kwi-caudate nucleus kunye ne-cingulate cortex
Amabala eseli avela kwi-dorsal caudate nucleus nawo ahlalutywa kusetyenziswa indlela emithathu ye-ANOVA. Uhlalutyo lubonakalise kuphela intsebenziswano phakathi koncedo kunye nentetho ye-c-Fos kwi-medial kunye ne-lateral caudate nucleus (F (2,24) = 3.514;p <0.046). Nangona kunjalo, uhlalutyo olwahlukileyo lwe-medial kunye ne-lateral caudate nucleus yendlela enye ye-ANOVA ayibonisi mahluko kwinani le-c-Fos ezinamabala phakathi kwamava / uvavanyo, akukho mava / kuvavanyo, kwaye akukho maqela ovavanyo (Itheyibhile2). Ukongeza, akukho miphumo iphambili yamava ezesondo okanye yokuziphatha kwinani leeseli eziveza i-c-Fos, okanye naluphi na unxibelelwano, lwafunyanwa kwi-cingxe cortex (idatha ayiboniswanga).
Ithetha ukuba inani le-SEM ye-c-Fos-immunoreactive kwiseli kunye nasemva kwe-dorsal caudate nucleus
Uvavanyo lwe-2
Umsebenzi we-locomotor
I-ANOVA yendlela ezimbini (ixesha lokuvavanywa kwamaxesha onyango), thelekisa umsebenzi weentsini kumava / i-amphetamine, amava / amphetamine, kunye neqela lokunyanga i-saline kwimizuzu ye-70 yokuvavanya ukusebenzisana phakathi kweqela lonyango kunye nexesha lovavanyo. Ukuvavanya ukusebenzisana, amaqela onyango ngamnye ayevavanywa ngokwahlukeneyo kunye nee-ANOVA zendlela enye. Uhlalutyo lubonakalise utshintsho oluluqilima kwimisebenzi yokuthetha ngokubanzi ngexesha lemizuzu ye-70 yokuvavanywa kwamaqela amabini abesifazana afakwe ngaphakathi kwi-amphetamine (amava / amphetamine kwaye akukho mava / amphetamine). Nangona kunjalo, imisebenzi eqhelekileyo yabasetyhini abafumene i-saline ayitshintshanga kakhulu kwi-70 min (Fig.5). INewman-Keuls iposiIimvavanyo zaze zasetyenziswa ukufumanisa ukuba ngawaphi amaxesha ovavanyo lwe-10 imizuzu eyahlukileyo. Ukuthelekisa okuphakathi kwePairwise kubonise ukuba imisebenzi eqhelekileyo yabasetyhini abanolwazi ngesondo enikezwe i-amphetamine inyuse kakhulu i-10 min emva kokulimala (p <0.05). Ngaphaya koko, xa kuthelekiswa nemizuzu eyi-10 ngaphambi kwenaliti, abantu ababhinqileyo kumava / kwiqela lonyango lwe-amphetamine bahlala bekhuthele ngakumbi i-20 min (p <0.05) kunye nemizuzu engama-30 (p<0.05) emva kwenaliti. Ngokwahlukileyo, iimpembelelo ze-amphetamine kubantu ababhinqileyo ababhinqileyo ngokwesini zazingabonakali kude kube yi-20 min emva kwenaliti. Okwangoku, la mabhinqa ayesebenza kakhulu ngokuthelekisa i-10 min ngaphambi kwenaliti (p <0.05). Ukongeza, imisebenzi yabasetyhini abanesondo abanama-amphetamine yahlala inyuke kakhulu kwi-30 min (p <0.05) kunye nemizuzu engama-40 (p<0.01) emva kwenaliti.
Iziphumo ze-amphetamine kwimisebenzi ngokubanzi yabasetyhini abanamava kunye nabasetyhini abathobekileyo ngokwesini. I-ANOVA yendlela ezimbini (ixesha lokuvavanywa kwamaxesha onyango) iveza unxibelelwano phakathi kweqela lonyango kunye nexesha lokuvavanya (F (12,150) = 2.288;p <0.011) yeentsingiselo ± ukubalwa komsebenzi we-SEM. Indlela ye-ANOVA yokuvavanya amaqela onyango ngamnye ibonise utshintsho olukhulu kwimisebenzi ngokubanzi yabasetyhini kumava / amphetamine (F (6,150) = 3.0468; p <0.008) kwaye akukho amava / amphetamine (F (6,150) = 3.893;p <0.001) amaqela onyango. Umsebenzi wabasetyhini ojoyiweyo ngetyuwa awutshintshanga (F (6,150) = 1.619;p <0.1). Post post Uvavanyo lubonise ukuba abantu ababhinqileyo abanesondo baphendule ngokukhawuleza kwi-amphetamine, bebonisa ukwanda komsebenzi ngaphakathi kwemizuzu yokuqala ye-10 emva kwenaliti. Abasetyhini abathandanayo ngokwesondo abangaphendulanga kwi-amphetamine kude kube yi-20 min emva kokulimala. *p <0.05 xa ithelekiswa nexesha phambi kovavanyo.
intetho-ye-Fos
I-ANOVA yendlela ezintathu (amaxesha onyango i-rostral-caudal level times shell-core) yayisetyenziselwa ukujonga iziphumo zamava ezesondo kunye ne-amphetamine kwimbonakalo ye-c-Fos kwi-nucleus accumbens. Akukho ziphumo zibalulekileyo zonyango kwaye akukho kudibana ngeendlela ezintathu phakathi kwonyango, inqanaba le-accumbens, kunye ne-shell-core yafunyanwa. Ngapha koko, uhlalutyo aluzange luveze naluphi na unxibelelwano phakathi kwamaqela onyango kunye nentetho ye-c-Fos kwibholam kunye nomxholo we-accumbens okanye phakathi kwamaqela onyango kunye ne-c-Fos efakwe ilebheli kwindawo yomqolo, embindini, kunye nakwimimandla ye-caudal ye-nucleus accumbens ( idatha ayiboniswanga).
Amabala eseli avela kwi-dorsal caudate nucleus nawo ahlalutywa kusetyenziswa indlela emithathu ye-ANOVA. Uhlalutyo lokuqala alibonisanga mpembelelo ibalulekileyo kumava esini okanye kwi-amphetamine kwinani leeseli ze-c-Fos. Ukongeza, akukho siphumo samava esondo okanye i-amphetamine yenani leeseli eziveza i-c-Fos ifunyenwe kwi-cingxe cortex isebenzisa iindlela ezimbini ze-ANOVA (idatha engaboniswanga).
UKUQALA
Iinjongo zolu phando zazimbini. Siqale sivavanye iimpembelelo zamava ezesondo kwimisebenzi yeselula kwiindawo ezahlukeneyo zokuhanjiswa kwe-nucleus. Umcimbi wesibini, nokuba amava ezesondo angaphambili angayivisa indlela ye-mesolimbic dopamine, iphandwe ngokuthelekisa iimpendulo zokuziphatha kwezilwanyana ezinamava nezesondo kunye nesitofu se-amphetamine. Iziphumo zethu azibonisi nje ukuba umntu obhinqileyo ngokwesini unokusebenzisa i-neurons kwi-nucleuseba kodwa kunye namava ezesondo anokuwela iimpendulo ze-neuronal kwi-amphetamine.
Iziphumo zokuziphatha ngokwesondo ekubonakalisweni kwe-c-Fos kwigobolondo kunye nomxholo we-nucleus accumbens
Uvavanyo lokuziphatha ngokwesondo luyonyusa ukubonakaliswa kwe-c-Fos embindini, kodwa hayi iqokobhe, le-nucleus accumbens, exhasa uphando lwangaphambili olubonisa ukuba ukudibana okunye ngokwesini kunokusebenzisa i-neurons kwi-nucleus accumbens kwiintonga zabasetyhini (Meisel et al., 1993; UJoppa et al., 1995; Mermelstein noBrakker, 1995; Pfaus et al., 1995; U-Kohlert et al., 1997; I-Kohlert kunye neMeisel, 1999). Uncwadi oluchaza ukusebenza kwe-dichotomy yokusebenza kwe-nusus ye-nucleus yenziwe ngeengxelo ezininzi zenguqu eyahlukileyo ekuhanjisweni kwe-dopamine ngaphakathi kweqokobhe kunye nomxholo we-nucleus accumbens ekuphenduleni kwe-pharmacological kunye ne-physiological stimuli. Ukulawulwa kwamachiza amaninzi okuxhatshazwa kubangela ukunyuka okukhethiweyo kumanqanaba e-dopamine ye-extracellular kwiqokobhe le-nucleus accumbens (I-Pontieri et al., 1995; UNisell et al., 1997; UPierce noKalivas, 1997a; I-Tanda et al., 1997; I-Tanda kunye ne-Di Chiara, i-1998; Barrot et al., 1999; I-Cadoni kunye ne-Di Chiara, i-1999). Ngendlela efanayo, ukutya okutyebileyo kakhulu (I-Tanda kunye ne-Di Chiara, i-1998; UDi Chiara et al., 1999a; Kelley, 1999), Uxinzelelo olungezantsi (umzekelo, ukwethuka kweenyawo) (IKalivas kunye neDuffy, 1995; Tidey noMiczek, 1997; UBruijnzeel et al., 1999; Wu et al., 1999), kunye nobungendawo bendalo esingqongileyo (URebec et al., 1997;URebec, 1998) kwakhona ngokunyusa inyusa ukuhanjiswa kwe-dopamine kwigobolondo yenyukliya.
Iziphumo zethu ziyahambelana ne-hypothesis ethi iqokobhe kunye nengqiniba isebenza ngokuhlukileyo, nangona safumana eyona nto iphambili, hayi igobolondo, ukuba iphendule kwizenzo zesondo. Kuyenzeka, nangona kunjalo, ukuba kukho utshintsho kwi-c-Fos immunoreactivity kwigobolondo ye-nucleus accumbens, kodwa olu tshintsho alukhange lubonwe. Iqokobhe licwangciswe ngokudibeneyo labahlulahlulo abahlukeneyo, igobolondo yedial, yangaphakathi, neye-lateral, eneendawo ezingaphakathi kwendawo kunye ne-dorsal yeqokobhe loku medial kusenokwenzeka ukuba ibe ngamacandelwana amabini ahlukileyo (IGroenewegen et al., 1999). Oku kuhanjiswa kweqokobhe, kunye namalungu endalo kunye nawendawo esembindini, bafumana indibaniselwano eyahlukeneyo yegalelo elivela kwiindawo zecortical kunye ne-subcortical (IGroenewegen et al., 1999). Ngaphaya koko, ngaphakathi kwezi ziqendwana zi-ensembles zangaphakathi ezisebenzayo ezahlulwe ngokwamacandelo omzimba ahlukileyo (IGroenewegen et al., 1999). Ngenxa yokuba iimpembelelo zokuziphatha ngokwesondo ekubonakalisweni kwe-c-Fos kolu phononongo zavavanywa kuphela kwibholomisi e-dorsomedial, kunokwenzeka ukuba inani leeseli ze-c-Fos ezintle zitshintshile kwi-subregion eyahlukileyo yeqokobhe.
Ngaphandle kokuqaphela ukuba imisebenzi emininzi ye-nucleus eqokelelene yenziwa kwingingqi yeqokobhe, kusengqiqweni ukuqaphela ukuba imijikelezo eyahlukeneyo ye-neural ngaphakathi kwe-nucleus accumbens ilamla iipropathi zokuqinisa zokuziphatha ezahlukeneyo. UCarelli et al. (2000)baxelile kutsha nje ukuba i-nucleus iqokelela ii-neurons kwiigundane zibonisa imisebenzi efanayo ye-neuronal ngexesha lokusebenza iphendula iziqiniseko ezimbini zendalo (okt, ukutya namanzi) kodwa iipateni ezahlukeneyo zokudubula ngexesha lokuphendula kokuqiniswa kwendalo ngokuchasene necocaine. Baye bagqiba kwelokuba imijikelezo eyahlukeneyo ye-neural kwi-nucleus iqoqa ulwazi malunga nokutya kunye nokuqiniswa kwamanzi ngokuchaseneyo nomvuzo we-cocaine (Carelli et al., 2000).
Amava okwabelana ngesondo kwiziphumo ze-c-Fos expression ngokusebenzisa i-rostral-caudal axis ye-nucleus accumbens
Uncwadi oluvavanya umbutho wenyukliya ngokwendlela ye-rostral-caudal nucleus encinci; Nangona kunjalo, umahluko ocacileyo wokusebenza kunye neatomical ubekiwe. Iziphumo zethu ziyahambelana nezifundo ezixeliweyo ngommiselo we-neurochemical kunye neempendulo zeemoto kwi-rostral-caudal axis ye-accumbens. I-Cholecystokinin (CCK) imodareyitha ngokungafaniyo isiphumo se-dopamine kwi-rostral kunye ne-caudal nucleus accumbens (UCrawley et al., 1985a,b), i-hypoplocomotion ye-dopamine enokubangela ukuba ichukunyiswe kwi-caudal accumbens, ingingqi engafakwanga yi-CCK neurons colocalized nge-dopamine (UCrawley et al., 1985a,b; Lanca et al., 1998). Nangona kunjalo, i-CCK ayisebenzi ngokuziphatha xa itofwe kwi-rostral nucleus bokon, ingingqi efumana i-CCK eyahlukileyo kunye nengqikelelo ye-dopamine (UCrawley et al., 1985a,b; Lanca et al., 1998). Kukwachazwe nokuba kukungeniswa ngokuthe ngqo kwe-amphetamine kwigobolondo ye-rostral, iqokobhe le-caudal, okanye isiseko esingafaniyo sichaphazela imisebenzi yokuziphatha kunye ne-extracellular dopamine kunye namanqanaba e-serotonin (UHeidbreder kunye noFeldon, 1998). Ukulawulwa kwee-pioides ze-opioid, izinto P, dopamine D1 receptors (I-Voorn kunye neXwebhu, i-1992; UJongen-Relo et al., 1994b; UVoorn et al., 1994), kunye nokukhululwa kweacetylcholine (UJongen-Relo et al., 1995) Nge-dopamine kunye ne-dopamine receptor agonists ziyahluka phakathi kweendawo ze-rostral kunye ne-caudal ye-accumbens, kunye ne-rostral tarbens ikuthakazelela ngakumbi ukudodop dopamine kunye nolawulo. Nangona ezi zinto zisebenzayo phakathi kwe-rostral kunye ne-caudal nucleuseba zixeliwe, kutheni le nto umahluko wokusebenza ukhona ungakaqondwa ngokupheleleyo.
Iziphumo zesondo kwiziphumo zomsebenzi we-amphetamine
Iziphumo ezixelwe apha kunye nophando lwangaphambili lubonisa ukuba amava ezesondo zangaphambili eziva iimpendulo ze-neuronal kuvavanyo lokuziphatha ngokwesondo, zibonisa ukwanda kokukhululwa kwe-dopamine (I-Kohlert kunye neMeisel, 1999) kunye nomsebenzi weselula kwi-nucleus accumbens (kolu phando). Enye inkxalabo, nangona kunjalo, kukuba abantu ababhinqileyo abanolwazi kwisifundo esedlule banokuthi baphendule kuzo zombini iimvavanyo zokuziphatha ngokwesondo kunye neendlela zokusingqongileyo kuba amava ezesondo kunye novavanyo lwenziwa kwigumbi elinye. Iindawo zokusingqongileyo ngokwemeko enxulunyaniswa neendlela zokuziphatha eziqinisekileyo zinokufumana iipropathi zokukhuthaza kunye nokunyusa amanqanaba e-dopamine kwii-nucleus accumbens (Reid et al., 1996, 1998; UWatson kunye nomncinci, 1999). Inkxalabo yesibini kukuba ngenxa yokuba amanyathelo okuziphatha ngokwesini angamadoda engabhalwanga, akukaziwa ukuba la maqela mabini ababhinqileyo abavavanyiweyo malunga nokuziphatha ngokwesini bafumana izixa ezifanayo zokuvuselela ubuntu besini. Kuxelwe ukuba ukukhuthaza i-vaginocervical kuyimfuneko ukuze kukhutshwe i-dopamine kwi-nucleus accumbens ngexesha lokuzala (U-Kohlert et al., 1997). Mhlawumbi abantu ababhinqileyo abanolwazi ngesondo bafumene ukukhuthaza okungaphezulu kwe-vaginocervical (engalinganiswanga kolu phononongo), ke oko kukhulisa ukwenziwa kwe-c-Fos. Ke ngoko, ukuqinisekisa ukuba indlela yokuziphatha yesondo yabasetyhini ivisa indlela ye-mesolimbic dopamine, siphande ukuba ngaba abantu ababhinqileyo abanesini kunye nabasetyhini abathobekileyo baphendule ngokwahlukileyo kwi-injongos ye-amphetamine, esinye isikhuthazo esaziwayo sokulamla iziphumo zaso ngendlela ye-dopamine. Ngaphaya koko, ukuqinisekisa ukuba iimpendulo ezibonakalayo eziqwalaselweyo zibangelwe kukuziphatha okuphindaphindiweyo ngokwesini kwaye kungengenxa yomdibaniselwano onemeko yokusingqongileyo kwisimo sokuziphatha ngokwesini, iimpendulo zokuziphatha kwama-hamsters ukuba amphetamine ahlolwa kwimeko yenoveli.
I-Amphetamine yonyusa umsebenzi oqhelekileyo kuwo onke ama-hamsters abesifazana. Nangona kunjalo, abantu ababhinqileyo abanesondo baphendule kwakamsinya kwi-amphetamine kunokuba besenza abantu besini ababhinqileyo abasetyhini. Ezi ziphumo zenza ukuba u-hypothesis ophindaphindiweyo abe nokuziphatha ngokwesini unokuziva amandla e-neurons kwindlela ye-mesolimbic dopamine indlela kwaye ucebise ukuba utshintsho kwindlela yokuhamba luveze iimpendulo zendlela yokuziphatha eyimvakalelo kokubini kukuziphatha okukuko kwendalo kunye nasekuvuseleleni kwengqondo.
Ezi zinto zifunyanisiweyo ziyahambelana ne-hypothesis yokuba kukho iindlela eziguquliweyo eziguquguqukayo ze-neural reaction on drug and behaviour (URobinson noBerridge, i-1993; UPierce noKalivas, 1997b). Izifundo ezininzi zamva nje ziye zaphawula ukunxibelelana phakathi kweziyobisi eziphindaphindiweyo kunye nokuziphatha okukhuthazayo kwendalo. Uxinzelelo lokwahlula intlalontle kunciphisa ixesha lokufumana ukuzilawula kwe-cocaine kumagundane (Tidey noMiczek, 1997). Indawo ebhangqiwe ngenaliti ephindaphindiweyo ye-morphine inokuqhubekisa indlela yokuziphatha ngokwesondo kwiigundane zesilisa (UMitchell noStewart, 1990a,b). I-Amphetamine intsholongwane ikwakhokelela ekuziphatheni ngokwesondo kwiigundane zesini ezingenamntu kwaye zidityaniswa nokukhutshwa kwe-dopamine okwandisiweyo kwi-nucleus accumbens (UFiorino noPhillips, 1999).
Ukuchazwa kwe-c-Fos kwahlaziywa kwi-nucleus accumbens emva konyango lwe-amphetamine. Kwakucingelwa ukuba i-amphetamine iyonyusa ukubonakaliswa kwe-c-Fos kwi-nucleus accumbens, kunye nenqanaba elikhulu kubantu ababhinqileyo abanesondo. Nangona kunjalo, akukho miphumo ye-amphetamine kwinani leeseli eziveza i-c-Fos zifunyenwe kulo naluphi na ucwangco lwe-nucleus accumbens. Kuyabonakala kwiTafile3 ukuba izilwanyana ezilawulayo ekuzameni i-2 (i-saline females) yayinenani eliphezulu leeseli ze-c-Fos ezintle xa kuthelekiswa nezilwanyana ezilawulayo kwi-1 (akukho luhlolokazi). UBadiani et al. (1998) Yachaza ukuba ukunyuka kwamaxabiso kuyanda c-fos Umxholo we-mRNA kwi-nucleus accumbens, kunye nokuba isiphumo sokunqabile kokuc-fos Umxholo wawunamandla kwiindawo ezininzi zobuchopho kangangokuba ukulawulwa kwe-amphetamine kwindawo yenoveli akuvelisanga mpendulo yongezelelweyo. Ke ngoko, kubonakala kunokwenzeka ukuba kwisifundo sethu uxinzelelo lokuhanjiswa kwimeko yenoveli yegumbi lokuvavanya ukwenziwa kwe-c-Fos protein, apho ke utshintsho lwe-mas-expression kwi-c-Fos expression yenziwe ngu-amphetamine kunye namava ezesondo.
Ithetha ± Inombolo yesiseko se-SEM ye-c-Fos-immunoreactive kwi-nucleus accumbens iqokobhe kunye nesiseko sokulawula izilwanyana kwiimvavanyo ze-1 kunye ne-2
Ukubaluleka okunokubakho
Olu vavanyo lujoyina uluhlu olukhulayo lwezifundo (UMitchell noStewart, 1990b; UFiorino noPhillips, 1999; I-Miczek et al., 1999) Ukubonisa ukuba amava esilwanyana anokubangela ukuba impendulo yendlela ye-mesolimbic dopamine zombini ziziphathe eziyinxalenye yobuntu bendalo yesilwanyana kunye neziyobisi ezithile abantu abaziwa ukuba bayazisebenzisa (Ubulumko kunye no-Bozarth, 1987). Umcimbi ophambili kuphando ngokusetyenziswa gwenxa kweziyobisi kukuchaphazeleka komntu ngamnye kwiziphumo zamachiza (I-Newcomb, i-1992; URobinson noBerridge, i-1993), kwaye ngokudibeneyo olu phando lungabonelela ngokuqonda kuphuhliso lokwezobikhoboka ebantwini.
Imihlathi
- I funyenwe Juni 8, 2000.
- Uhlaziyo olufunyenweyo Disemba 12, 2000.
- Zamkelwa Disemba 20, 2000.
Olu phando luxhaswe yiNkxaso-mali yeSiseko seSizwe se-IBN-9723876. Sibulela uMelissa Zila, uShannon McCanna, uMarchelle Baker, uMichael Huntington, noDeborah Shelley ngoncedo lwabo lovavanyo ekuziphatheni uvavanyo kunye nokusebenza kwe-c-Fos.
Imbalelwano mayibhekiswe kuGqr Robert L. Meisel, iSebe lezeNzululwazi yezeengqondo, iYunivesithi yasePurdue, eWest Lafayette, kwi-47907-1364. I-imeyile: [imeyile ikhuselwe].
- Copyright © 2001 Society for Neuroscience
;