DeltaFosB ee Xaaladaha Nucleus waa mid Ba'an oo Lagu Xoojinayo Saamaynta Abaalmarinta Galmada. (2010)

Faallooyin: Delta FosB waa calaamad u leh dhammaan balwadaha, habdhaqanka iyo kiimikada labadaba. Maaddaama moleculekani uu ku sii kordhayo wareegga abaalmarinta sidaas oo kale dabeecadaha balwadda leh. Waa mid ka mid ah moleculeyaasha ku lug leh isbeddelada neuroplastic. Tijaabadani waxay muujineysaa inay ku sii kordheyso waayo-aragnimada galmada, si la mid ah sida ay u sameyso daroogada daroogada. Tijaabada waxay ku shaqaaleeyeen injineernimada hidaha si ay u kordhiyaan heerarkooda ka baxsan “caadiga”. Tani waxay keentay fududeynta fududeynta howlaha galmada. Waxaan u maleyneynaa inay taasi ku dhacdo qabatinka galmada.

WAXBARASHADA DHAQAALAHA

Pitchers KK, Frohmader KS, Vialou V, Mouzon E, Nestler EJ, Lehman MN, Coolen LM.

Genes Brain Behav. 2010 Oct; 9 (7): 831-40 doi: 10.1111 / j.1601-183X.2010.00621.x. Epub 2010 Aug 16.

Department of Anatomy and Cell Biology, Schulich School of Medicine iyo Dentistry, Jaamacada Western Ontario, London, Ontario, Canada.

aan la taaban karin

Dabeecada galmada ee jiirka labka ah waa abaalmarin iyo xoojin. Si kastaba ha noqotee, wax yar ayaa laga yaqaanaa qaababka gaarka ah ee cellular iyo molecular oo dhexdhexaadinaya abaalmarinta jinsiga ama saameynta sii kordhinta abaalmarinta ku saabsan muujinta dabeecadaha galmada. Daraasadani waxay tijaabinaysaa falsafadda ah in ΔFosB, qaabka la isku halleyn karo ee FosB, uu kaalin muhiim ah ka ciyaaro xoojinta habdhaqanka jinsiga iyo waayo-aragnimada ku-siman ee dhiirrigelinta jinsiga iyo waxqabadka.

Dhibaatada galmada waxaa loo muujiyey in ay keento isdhexgalka ΔFOSB ee dhowr gobol oo maskaxda ah oo ay ku jiraan nucleus accumens (NAc), kortex celcelis ee isbaarada, aagagga ventral tegmental iyo caudate putamen laakiin ma ah nuuca daaweynta preoptic.

Marka xigta, soo-saarka c-Fos, bartilmaameedka (tarbiyadda) ee ΔFosB, ayaa lagu qiyaasey jinsi ahaan khibrad iyo xayawaanba. Tirada xubnaha unugyada c-fos-immunoreactive-ka ah ayaa si aad ah hoos ugu dhacay xayawaannada qibrada leh ee galmada marka loo eego kantaroolka galmada.

Ugu dambeyntii, heerarka ΔFOSB iyo waxqabadkeeda NAc ayaa lagu maamuley iyadoo la adeegsanayo wareejinta hiddesidaha fayruuska ah si loo barto doorka ay ka qaadan karto dhexdhexaadinta waayo-aragnimada jinsiga iyo khibrad-u-sahlanaanta waxqabadka galmada. Xayawaanada leh ΔFosB dulucda ayaa soo bandhigay fududeynta waxqabadka jinsiga ah ee la xidhiidha galmada khibradda ku saabsan xakamaynta. Taas bedelkeeda, muujinta ΔJunD, oo ah wada-xuduud aan caadi ahayn ee ka dhaxeeya ΔFosB, ku-takri-fal galmo-ku-ool ah oo fududeynaya waxqabadka jinsiga iyo hagaajinta dayactirka muddada-dheer ee fududeeya marka la barbardhigo borotiinka cagaaran iyo ΔFOSB kooxo fara badan.

Si wadajir ah, natiijooyinkani waxay taageeraan doorka muhiimka ah ee ΔFosB ee faahfaahinta NAc ee loogu talagalay saameynta sii xoojinta dabeecadaha galmoodka iyo waayo-aragnimada jinsiga-ku-sahlanaanta waxqabadka galmada.

HORDHAC

Dabeecadda galmada waa mid si fiican u abaal-marinaysa lana xoojiyo jiirka yaryar (Coolen et al. 2004; Pfaus et al. 2001). Waxaa intaa dheer, waayo-aragnimada galmada waxay bedeshaa habdhaqanka galmada iyo abaalmarinta dambe (Tenk et al. 2009). Iyadoo la raacayo waayo-aragnimo labiska ah, dabeecadda jinsiga ayaa la fududeeyay ama "la xoojiyay", oo muujinaysa hoos u dhaca latights si loo bilaabo isku darka iyo fududeynta waxqabadka galmada (Balfour et al. 2004; Pfaus et al. 2001). Si kastaba ha noqotee, qaababka maskaxda iyo hababka molecular ee abaalmarinta jinsiga iyo xoojinta ayaa si xun loo fahmay. Dabeecadaha galmada iyo calaamadaha calaamadaha ah ee saadaaliya isu-geyntu waxay muujineysaa inay si cad u muujinayso muujinta hidda-hiddaha degdegga ah ee hidda-caanaha ee nidaamka mesolimbic ee jiirka (Balfour et al. 2004; Pfaus et al. 2001). Waxaa intaa dheer, waxaa dhawaan lagu soo bandhigay in khibrad jinsi ah ay keento nuroblastic joogta ah oo ku jira habka ragga ee gabdhaha mesolimbic (Frohmader et al. 2009; Pitchers et al. 2010). Intaa waxa dheer, jiirka labka ah, waayo-aragnimada galmoodka ayaa loo muujiyay in ay soo afjarto ΔFosB, a Xubin qoyska ka mid ah, oo ku yaala nucleus accumens (NAc) (Wallace et al. 2008). ΔFosB, oo ah kala duwanaansho kala duwan ee FosB, waa xubin ka mid ah qoyska Fos sababtoo ah xasillooni weyn (Carle et al. 2007; Ulery-Reynolds et al. 2008; Ulery et al. 2006) oo ka ciyaara doorka dhiirigelinta iyo abaal-marinta daroogada xadgudubka iyo cidhibnaanta neuraliska ee dhexdhexaadinta maandooriye (Nestler et al. 2001). ΔFosB waxay ka kooban tahay isku-dhafdhaqaaqa heteromerik ah (protein activator-1 (AP-1)) oo leh jimicsiyo Jun, oo doorbidaya JunD (Chen et al. 1995; Hiroi et al. 1998). Iyada oo la adeegsanayo muujin la'aanta isdhexgalka ee ΔFOSB, oo inta badan ku xaddidan qallalka oo isticmaalaya jiirarka bi-transgenic, waxaa la soo saaraa daroogo sumad u eg sida dabeecadda dabiiciga ah, (McClung et al. 2004). Fikraddan dabeecadeed waxaa ka mid ah jawaab-celinta dareemayaasha ah ee dareemayaasha ah ee cocaine (Kelz et al. 1999), kordhinta doorbididda kookeynta (Kelz et al. 1999) iyo morphine (Zachariou et al. 2006), iyo isweydaarsiga cocaine-ga ee kordhay (Colby et al. 2003).

Si la mid ah abaalmarinta daroogada, ΔFosB waxaa lagu hagaajiyaa dabeecadaha dabiiciga ah ee dabiiciga ah iyo dhexdhexaadinta muujinta dabeecadahaas. Falanqaynta dheeraadka ah ee ΔFosB ee NAc iyadoo la adeegsanayo qaababka jilicsan ayaa kordhiya socodka gawaarida tabaruca ah (Werme et al. 2002), qalab wax ka qabashada cuntada (Olausson et al. 2006), qaadashada sukrose (Wallace et al. 2008), waxayna sahlaysaa labka (Wallace et al. 2008) iyo haween (Bradley et al. 2005) dhaqanka galmada. Sidaas awgeed, ΔFOSB waxaa laga yaabaa inay lug ku yeeshaan dhexdhexaadinta saameynta khibradaha dabiiciga ah ee dabiiciga ah. Twuxuu daraasaddan cilmi-baarisku sii ballaarinaysaa daraasadihii hore iyadoo si gaar ah u baaraysa doorka ΔFosB ee NAc ee natiijooyinka muddada dheer ee khibradda galmada ee habdhaqanka nacaybka ee dambe iyo habdhaqaajinta neerfurka ee habka mesolimbic.

  • Ugu horreyntii, waxaa la aasaasay gobollada maskaxda ku lug leh wareegga abaal-marinta iyo hab-dhaqanka galmada, oo muujinaya waayo-aragnimada jinsiga ee ΔFosB.
  • Marka xigta, saameynta sinjiyada jinsiga ah ee loo yaqaan "ΔFosB" ee ku salaysan mawduucyada kala duwan ee c-Fos, oo ah bartilmaameed hoos-u-deyn ah oo lagu baddalayo ΔFosB (Kirada et al. 2008), ayaa la baaray.
  • Ugu dambeyntii, saameynta dhaqdhaqaaqa howlaha ΔFosB ee NAc (hiddaha badan ee muujinta iyo muujinta lamaanaha xun ee kufsiga ah) ee ku saabsan dabeecada galmada iyo fududaynta khibrad-u-qaadista dhiirigelinta iyo waxqabadka galmada waxaa lagu go'aamiyey iyadoo la adeegsanayo farsamooyinka farsamooyinka viral vectors.
Tag:

FARSAMADA

Xayawaanka

Maydhayaasha Sprague Dawley (200-225 grams) waxaa laga helay Charles River Laboratories (Senneville, QC, Canada). Xayawaanada waxaa lagu hayaa baqshadaha Plexiglas oo leh tuubo tunnel ah isla jinsi isku mid ah oo tijaabo ah. Qolka xaafadda ayaa ahaa heer-kulayliye oo lagu hayo 12 / 12 saacad madow khafiif ah oo leh cunto iyo biyo ad libitum marka laga reebo inta lagu jiro baaritaanka habdhaqanka. Dumarka Stimulus (210-220 Grams) oo lagu daray miisaaniyada ayaa la siiyay maqaar-galaha subcutaneous oo ay ku jiraan 5% estradiol benzoate iyo 95% kolestaroolka ka dib marka loo eego sambabada caadiga ah ka dib suuxdinta qoto dheer (0.35g ketamine / 0.052g Xylazine). Dhiirrigelinta galmada waxaa sababay maamulka 500mg progesterone ee saliidda 0.1 maadada xNUMX qiyaastii saacadaha 4 ka hor inta aan la baarin. Dhammaan nidaamyada waxaa ansixiyay Daryeelka Xoolaha iyo Isticmaalka ee Jaamacada Western Ontario iyo u hoggaansamaan xeerarka CCAC ee ku lug leh xayawaannada xayawaanka ee cilmi-baarista.

Habdhaqanka Galmada

Kulamada materiga ayaa dhacay intii lagu jiray marxaladda hore ee mugdiga (inta u dhexeysa saacadaha 2-6 ka dib bilawga xilliga madoobaadka) oo hoos imaanaya iftiin guduudan. Ka hor inta aan la tijaabin bilawga, xayawaanka ayaa si aan kala sooc lahayn loo qaybin kooxo. Inta lagu guda jiro kulammada materiga waxaa loo ogolaaday inay kaashadaan xayiraad ama saacad 1, iyo xuduudaha habdhaqanka galmada waxaa lagu duubay oo ay ka mid yihiin: qulqulka buuraha (ML), waqtiga laga bilaabo haweenka dhererka illaa buurta ugu horeysa), latency intrusion (IL; haweenka ilaa koollada ugu horeysa ee la galmoodo galmada siilka), marin-biyoodka (kolka laga bilaabo galmada ugu horreysa), dib-u-deynta dhalmada (PEI; waqtiga laga bilaabo ejaculation illaa horraantii isdaba-joog), tirada garaacista (M; isugeynta), tirada isdhexgalka (IM-ga oo ay ka mid yihiin galitaanka siilka) iyo waxtarka wareegga (CE = IM / (M + IM))Agmo 1997). Tirooyinka dhejinta iyo qulqulatooyinka laguma darin falanqaynta xayawaanka aan muujin shahwada. Miisaanka iyo xarigaha lafdhabarta ayaa ah calaamado muujinaya dhiirigelinta jinsiga, halka qulqulatada ejaculation, tirada macaamilada iyo waxtarka copulation ay ka tarjumayaan waxqabadka galmada (Hull 2002).

Tijaabo 1: Sifeynta ΔFosB

Xubno jinsi ah oo jinsi ah ayaa loo ogolaaday in ay ku duubaan baqshiinka tijaabada ah ee nadiifka ah (60 × 45 × 50 cm) loogu talagalay 5 oo isku xiga, fadhiyada moodooyinka maalinlaha ah ama sii jinsiga galmada. Jaantuska dhammeystiran 1 (NNS; n = 5), jinsiga (NS; n = 5), aan khibrad lahayn jinsi (ENS; n = 5) iyo galmo khibrad leh (ES; n = 4). Xayawaanka NS iyo Xayawaanka ESPS ayaa la bixiyay saacad 1 ka dib markii la naqdiyay maalintii ugu dambeysay ee la isku dardar-galiyay si loo baaro calaamadda c. Xayawaannada NNS ayaa la siidaayay isla marxaladda xayawaanka ENS ee 24 ka dib markii ay dhammaystiraan kulankooda ugu dambeeya si ay u baaraan ΔFosB waayo-aragnimo galmo. Kooxaha galmada ee khibrada u leh ayaa loo sameeyay habdhaqan galmo ka hor imtixaanka kaddib. Ma jiro farqi weyn oo dhexmara kooxo tallaabooyinka habdhaqanka ee ku lug leh fadhiga mawduucyada saxda ah iyo khibradda galmada ee ku-sahlanaanta dhaqanka galmada waxaa soo bandhigay kooxo khibrad leh (labadaba)Jaantuska dhammeystiran 2). Xakamaynta waxaa ka mid ah galmoodka naagaha la wada shaqeeyey si joogta ah xayawaanka xoolaha si loo hubiyo in lagu soo bandhigo urka haweenka iyo dhawaaqyada aan lahayn haween toos ah.

Xayawaanka, xayawaanka ayaa si qoto dheer loo suuxiyey iyada oo la isticmaalayo sodium pentobarbital (270mg / kg; ip) oo si fiican u gudubta 50 mL ee 0.9% saline, oo ay ku xigto 500 mL of 4% paraformaldehyde ee 0.1 M fosfat buffer (PB). Xanuunada ayaa la saarey kadibna dib loo dhigey 1 h heerkulka qolka isla xajmiga, ka dibna wuxuu ku dhuftay 20% sukrose iyo 0.01% sodium azide 0.1 M PB oo lagu kaydiyey 4 ° C. Qeybta Coronal (35 μm) ayaa la jaray microtome (H400R, Micron, Jarmalka), oo lagu soo ururiyey afar taxane ah oo isku xigta oo loo yaqaan 'cryoprotectant solution' (30% sukrose iyo 30% ethylene glycol in 0.1 M PB) oo lagu kaydiyey -20 ° C. Qeybaha bilaashka ah ayaa la dhaqay si aad u badan oo leh 0.1 M fosfat-dawo dabacsan (PBS; pH 7.3-7.4) inta udhaxeysa. Qeybaha waxaa loo soo gudbiyey 1% H2O2 10 min heerkulka qolka si ay u burburiso peroxidase-da qolalka, ka dibna lagu xakameynayo xalka PBS + xoojinta, kaas oo ah PBS oo ay ku jirto 0.1% serum albumin ah (Qeybta buugga 005-000-121; Jackson ImmunoResearch Laboratories, West Grove, PA) iyo 0.4% Triton X -100 (shayada buugga BP151-500; Sigma-Aldrich) ee 1 h. Qeybaha ayaa markaa lagu dabooli jiray habeenkii 4 ° C ee ka hortagga dabiiciga ah ee bakteeriyada FosB ah (1: 5K; sc-48 Santa Cruz Biotechnology, Santa Cruz, CA, USA). Antibio-fosB-ga waxaa lagu kiciyey dawlad goboleed oo ay wadaagaan FosB iyo ΔFosB. Unugyada ΔFosB-IR ayaa si gaar ah u ahaa ΔFosB-positive sababtoo ah xilligii kicinta kaddib (saacadaha 24) dhammaan FosB-stimulus-stimulus-kicin leh ayaa hoos u dhacay (Perrotti et al. 2004; Perrotti et al. 2008). Intaa waxaa dheer, in tijaabadan, xayawaanka la cunay maalinta ugu dambaysa (NS, ES) ayaa la siiyay 1 h ka dib markii laysku daray, ka hor intaan la soo bandhigin FosB. Falanqaynta maqaarka reer galbeedka ayaa xaqiijiyay ogaanshaha ΔFosB qiyaasta xNUMX kD. Ka dib markii kuleylka koowaad ee asaasiga ah, qaybaha ayaa lagu kululeeyay 37 h ee biotin-adheecat adhidhka ka hortagga ah ee IgG (1: 1 ee PBS +, Shaybaarada Wareega, Burlingame, CA, USA) kadibna 500 h ee avidin-biotin-hoseradish peroxidase (ABC elite ; 1: 1K ee PBS; Shaybaarada Waalidka, Burlingame, CA, USA). Ka dib qaybaha isugeynta waxaa lagu baari jiray mid ka mid ah siyaabahan soo socda:

1. Calaamadaha peroxidase oo keliya

Qaybaha NNS iyo xayawaanka ENS ayaa loo isticmaalay falanqaynta maskaxda ee xajmiga ΔFOSB ee khibrad u leh. Ka dib markii loo baahdo in lagu daro ABC, kakoobka peroxidase waxaa lagu sawirey daaweynta 10 daqiiqado si loogu xaliyo chromogen oo ay ku jiraan 0.02% 3,3'-diaminobenzidine tetrahydrochloride (DAB; Sigma-Aldrich, St. Louis, MO) oo lagu daray 0.02% nikel sulfate ee 0.1 M PB hydrogen peroxide (0.015%). Qeybaha waxaa lagu dhaqay si buuxda 0.1 M PB si loo joojiyo dareen-celinta oo lagu rakibay midka lagu magacaabo "Supercrost plus" iyo "slides" (Fisher, Pittsburgh, PA, USA) oo leh 0.3% gelatin ddH20. Ka dib marka fuuqbaxa, dhammaan bogagga ayaa la daboolay - la jiiday DPX (dibutil fthalate xylene).

2. Dual immunofluorescence

Qaybaha afar kooxood oo tijaabo ah oo ay ku jiraan NAc iyo mPFC ayaa loo isticmaalay falanqaynta ΔFosB iyo c-Fos. Ka dib markii kuleylka ABC, qaybaha ayaa lagu kululeeyay 10 min oo leh tyramide biyotinylated biotinylated (BT; 1: 250 ee PBS + 0.003% H2O2 Tennamid Signal Amplification Kit, NEN Life Sciences, Boston, MA) iyo 30 min oo leh Alexa 488-conjugated strepavidin (1; Shaybaarada Immunoresearch Search, West Grove, PA). Qeybaha ayaa markaa lagu daboolay habka difaaca jirka ee bakteeriyada ah oo si gaar ah u aqoonsaday c-Fos (100: 1; sc-150; Santa Cruz Biotechnology, Santa Cruz, CA), oo ay ku xigto 52 min qaboojin kulul oo la yiraahdo anti-antibacterial anti-baked anti-baked Cy30 (3: 1; Sheybaarka Jackson Immunoresearch Laboratories, West Grove, PA, USA). Ka dib markii la xoqay, qaybaha waxaa lagu dhaqay si buuxda 200 M PB, oo lagu rakibay lakabyo muraayad leh oo leh 0.1% jelatin ee ddH20 oo daboolay-dhexdhexaad ah dhexdhexaad ah oo dhexdhexaad ah (Gelvatol) oo ku jira wakiil ka hortagaya anti-fading 1,4-diazabicyclo (2,2) octane (DABCO; 50 mg / ml, Sigma-Aldrich, St. Louis, MO). Xakamaynta Immunohistochemical waxaa ka mid ah ka takhaluska labada ama labada jeermis ee asaasiga ah, taas oo keentay maqnaansho calaamadeyn ah oo ku xiran mawjada ku habboon.

Falanqaynta Xogta

Falanqaynta maskaxda ee ΔFosB

Laba tijaabo oo indho indhaynaya daaweyn ayaa ku samaysay sawirrada maskaxda ee xayeysiisyada. Unugyada difaaca jirka ee "ΔFosB-immunoreactive (-IR) ee maskaxda oo dhan maskax ahaan ayaa lagu falanqeynayaa iyadoo la adeegsanayo cabir loo adeegsado tirada unugyada 'ΔFosB-positive' sida lagu xusay Shaxda 1. Intaa waxaa dheer, iyadoo ku saleysan natiijooyinka nus-naqshadeed, tirada unugyada ΔFosB-IR waxaa lagu tiriyaa iyadoo la isticmaalayo meelaha laga soo xigtay meelaha falanqaynta goobaha maskaxda ee ku lug leh abaalmarinta iyo habdhaqanka galmada iyadoo la isticmaalayo tuubo sawir leh oo ku xiran Leica DMRD microscope (Leica Microsystems GmbH, Wetzlar , Jarmalka): NAc (asaasiga (C) iyo qolof (S); 400 × 600μm) lagu falanqeeyay sadexda heerarka dabiiciga ah (Balfour et al. 2004); (VTA; 1000 × 800μm) oo lagu falanqeeyay heerarka sadexda rostral-caudal (Balfour et al. 2004) iyo daboolka VTA (Perrotti et al. 2005); kortex galka hore (ACA), kortelka prelimbic (PL), kortex-kicinta (IL); 600 800mm kasta); CAYAAD (CP; 800 800μm); iyo medial preoptic nucleus (MPN; 400 × 600 μm) (Xogta dheeraadka ah 1-3). Laba qaybood ayaa loo tiriyey hoosba, iyo celcelis ahaan xayawaan loogu talagalay xisaabinta kooxda. Isku-dhafka galmada iyo celceliska kooxaha khibrada ee ΔFosB-IR ayaa loo barbardhigay subag walba iyada oo la adeegsanayo baaritaanada aan la socon.

Shaxda 1    

Soo koobida ereyada ΔFosB ee kufsiga galmada iyo xayawaanka khibrad leh
Falanqaynta ΔFosB iyo c-Fos

Sawirada waxaa lagu qabtay kamarad CCD oo la qaboojiyey (Microfire, Optronics) oo ku xiran Leica Microscope (DM5000B, Leica Microsystems; Wetzlar, Jarmalka) iyo software Neurolucida (MicroBrightfield Inc) oo leh goobo kamarad xaddidan oo loogu talagalay dhammaan maadooyinka (iyadoo la adeegsanayo ujeedooyinka 10x). Tirada unugyada muujinaya c-Fos-IR ama ΔFosB-IR ee meelaha caadiga ah ee falanqaynta NAc core iyo qolof (400 × 600mm kasta; Jaantuska dhammeystiran 1) iyo ACA ee mPFC (600 800μm; Jaantuska dhammeystiran 3) ayaa manhajka lagu tiriyay indho indheyn kooxo tijaabo ah, qaybaha 2 xayawaan isticmaalaya software Neurolucida (MBF Bioscience, Williston, VT) iyo celceliska xayawaanka. Isugeyntii celceliska kooxda c-Fos ama unugyada ΔFosB waxaa loo barbar dhigey iyadoo la isticmaalayo labo hab oo ANOVA ah (Caadooyinka: waayo-aragnimada jinsiga iyo dhaqdhaqaaqa jinsiga) iyo Fisher LSD marka la barbardhigo isbarbardhigga heerarka muhiimka ah ee 0.05.

Tijaabo 2: Dhexdhexaadinta ΔFOSB

Kala-wareegga Gawaarida Viral-Dhex-dhexaadinta

Jiirka jinsiga ah ee Sprague Dawley ayaa si aan kala sooc lahayn loogu kala qaybiyay kooxo ka hor qalliinka stereotaxic. Dhammaan xayawaanku waxay heleen isugeyn dheeri ah oo isku dhafan oo lagu magacaabo 'vaginal' adeno-associated viral (rAAV) codsiyada GFP (xakamaynta; n = 12), nooc caan ah ΔFosB (n = 11) ama lammaanaha isku-dhafan ee ΔFosB ΔJunD (n = 9) galay NAc. ΔJunD waxay hoos u dhigtaa ΔFosB dhexdhexaadin ah oo ay si xeeladeysan u hirgeliso ΔFosB ka hor inta aanay ku dhicin gobolka AP-1 ee ka dhexjirta hiddaha hiddaha (Winstanley et al. 2007). Qalabka Virus waxaa qeexay qPCR oo la qiimeeyey in vivo ka hor inta aanad bilaabin waxbarashada. Titer wuxuu ahaa 1-2 × 1011 qaybaha faafa ee mL. Wareegayaasha RAAV ayaa lagu duray miisaanka 1.5 μL / dhinac ka badan saacadaha 7 (iskudubarid: AP + 1.5, ML +/- 1.2 oo ka yimid Bregma; DV-7.6 oo ka soo baxa maskaxda sida Paxinos iyo Watson, 1998) iyadoo la adeegsanayo sirinjeerka Hamilton (5XL ; Harvard Apparatus, Holliston, MA, USA). Qaybaha yaryar waxay keenaan wax sarreysa oo ka weyn xakamaynta fedraalka oo keliya (Winstanley et al, 2007; Faahfaahinta diyaarinta AAV, arag Hommel et al., 2003). Dhibaatooyinka dabeecadda waxay bilaabeen todobaadka toddobaad kadib duritaanka vektorka oo u oggolaanaya infakshanka fayruska ee habboon iyo degganaanshoWallace et al. 2008). Tixgelinta transgene ee noocyada murqaha ayaa ka soo baxa maalmaha 10 oo wali kor u kacaya bilaha ugu yar ee 6 (Winstanley et al. 2007). Dhammaadka tijaabooyinka, xayawaanka ayaa loo gudbiyay si kaamil ah, qaybaha NAckuna waxay ahaayeen kuwo lagu talaalay GFP (1: 20K; bakteeriyada anti-GFP; Precursions Molecular) iyadoo la adeegsanayo fal-celinta ABC-peroxidase-DAB (sida kor lagu sharaxay) si histologically xaqiijin goobaha cirbadaha adoo isticmaalaya GFP sida calaamad (Jaantuska dhammeystiran 4). Walxaha ΔFosB iyo ΔJunD waxay sidoo kale ku jiraan qaybo muujinaya GFP oo ay kala soocaan goobaha ribosomal gudaha ah, taas oo u oggolaanaysa xaqiijinta goobta lagu durayo sawirada GFP ee xayawaanka oo idil. Kaliya xayawaanka leh goobaha cirbadaha iyo faafinta fayraska xaddidan NAc ayaa lagu daray falanqaynta tirakoobka. Faafidda fayruusku guud ahaan waxay ku koobnayd qayb ka mid ah NAc oo aan ku faafin nambarrada-nudleuska oo dhan. Intaa waxaa dheer, faafidda fayrasku waxay inta badan ku xaddidan tahay xayawaanka ama asaasiga. Si kastaba ha ahaatee, isbeddelka goobaha cirbadaha lagu faafiyo gudaha NAc saameyn kuma yeelan saameynta dabeecadda. Ugu dambeyntii, cirbadaha GFP ma saameynayaan dabeecada galmada ama fududeynta habdhaqanka galmada ee khibrad leh marka la barbar dhigo xayawaanka aan qaliinka ahayn ee daraasadihii hore (Balfour et al. 2004).

Habdhaqanka Galmada

Saddex wiig ka dib markii la bixiyay feyruuska viral, xayawaanka ayaa loo ruqeeyaa hal xayiraad (ama saacad 1) oo loogu talagalay 4 fadhiyo isku xigxig ah, si ay u helaan waayo-aragnimo jinsi ah (kulanno waayo-aragnimo), kadibna waxaa lagu tijaabiyey muujinta muddada dheer ee khibrad ku sahlanaanta habdhaqanka galmada 1 iyo toddobaadyada 2 (kulamada imtixaanka 1 iyo 2) kadib kaddib khibraddii ugu dambeysay. Xeerarka habdhaqanka galmada ayaa la duubay intii lagu jiray kalfadhiyo isku dhafan sida kor ku xusan. Qiyaasta tirakoobka ee dhammaan xaddidaadyada inta lagu jiro kulan kasta oo macaawin ayaa lagu barbardhigay gudaha iyo kooxaha dhexdooda iyadoo la adeegsanayo tallaabooyinka laba-jeer ee lagu celiyo ANOVAs (Caadooyinka: daaweynta iyo kalfadhi dhiska) ama hal dhinac oo ANOVAs ah (waayeelka xajinta, tirada mushaarka iyo isdhexgalka; fadhiga) waxaa ku xiga Fisher LSD ama Newman-Keuls oo tijaabo ah oo lagu barbardhigo isbarbardhig ku saabsan heerarka muhiimka ah ee 0.05. Gaar ahaan, saameynta sahlan ee khibrada jinsiga ah ee ku saabsan maadooyinka xakamaynta waxaa lagu barbar dhigay inta udhaxaysa waayo-aragnimada 1 (naïve) iyo waayo-aragnimada kulamada 2, 3, ama 4 kasta, iyo sidoo kale inta u dhaxaysa kooxaha tijaabada ah ee ku jira fadhiga khibrad kasta. Waxaa intaa dheer, si loo falanqeeyo saameynta daaweynta (vector) fududeynta dhaqdhaqaaqyada galmada ee mudada dheer, isbarbardhiga maadiga ah waxaa lagu barbar dhigaa xeeladda 4 iyo casharka 1 iyo 2 gudaha koox kasta oo daaweyn ah, oo marka la barbardhigo kooxaha tijaabada ah ee ka jira kulan kasta oo imtixaan ah.

Tag:

Natiijooyinka

Waayo-aragnimada galmadu waxay sababtaa isdhaafka ΔFOSB

Ugu horreyntii, baaritaan nusqaan ah oo ku saabsan xakamaynta ΔFOSB maskaxda oo dhan maskaxda ku jirta raga galmoodka khibrada leh marka la barbardhigo kantaroolka galmada. Soo koobidda guud ee natiijooyinka ayaa la bixiyaa Shaxda 1. Falanqaynta ΔFosB-IR ayaa sii kordhisay iyada oo la go'aaminayo tirada nambarada ΔFosB-IR ee dhowr gobol oo maskaxda ku xiran oo la isticmaalayo iyadoo la adeegsanayo falanqayn heerar ah ee falanqaynta. Jaantuska 1 waxay muujinaysaa sawirrada wakiil ee DAB-Ni kaas oo dhali kara NAc ee xayawaanka galmada iyo xayawaanka khibrad leh. Qawaaniinta is-beddelka ee "ΔFosB" oo muhiim ah ayaa laga helay qaybaha mPFC (Jaantus 2A), Saldhigga NAc iyo qolofka (2B), caudate putamen (2B) iyo VTA (2C). In NAc, faraqa udhexaadka ah ayaa ka dhexjiray heerarka rostral-caudal ee NAc core iyo qolof, iyo xogta lagu muujiyay Jaantuska 2 waa celceliska dhammaan heerarka rostro-caudal. Taas bedelkeeda, ma jirin wax isbeddel ah oo ku yimid ΔFosB-IR oo ku jira nudleerka hore ee maqaarka ee hypothalamic (NNS: Avg 1.8 +/- 0.26; ENS: Avg 6.0 +/- 1.86).

Jaantuska 1    

 

Sawirrada wakiilada oo muujinaya ΔFosB-IR unug (madow) ee NAc ee na soo jiid jinsi (A) oo aan waayo-aragnimo lahayn kooxo galmo (B). aco: bareebka qiiqa Miisaanka cabbirka wuxuu muujinayaa 100 μm.
Jaantuska 2     

Tirada ΔFosB-IR unugyada: A. infralimbic (IL), prelimbic (PL) iyo kore-kortex-kortex (ACA) qaybo ka mid ah kiliyaha hore ee hore; B. Nucleus waxay soo saartaa asalka iyo qolofka, iyo xarigga caudate (CP); C. Rostral, dhexe, caudal iyo dabo ...

Dhibaatada galmada waxay isku daydaa inay ceshato c-fosho

Saameynta khibradda galmada ee heerarka ΔFOSB ee NAc ayaa la xaqiijiyay iyada oo la isticmaalayo farsamooyinka dhuxusha. Intaa waxaa dheer, saameynta jimicsiga galmada ee muujinta c-Fos ayaa la falanqeeyay. Jaantuska 3 waxay muujinaysaa sawirrada wakiil ee ΔFosB- (cagaaran) iyo c-Fos (casaan) - unugyada dhammaan tijaabada (A, NNS, B, NS, C, ENS, D, ES). Khibradaha galmada waxay si weyn u kordhiyeen ereyada ΔFosB ee NAc core (Jaantus 4A: F1,15 = 12.0; p = 0.003) iyo qolof (Jaantus 4C: F1,15 = 9.3; p = 0.008). Marka la barbardhigo, isweydaarsiga Saacid 1 ka hor intaanan dhamaystirneyn, saameyn kuma laheyn ereyada ΔFosB (Jaantus 4A, C) iyo wax wada-xaajood ah oo udhaxeeya waayo-aragnimada jinsiga iyo isu-takrifsiga isla markiiba ka hor inta aan la nadiifin. Waxaa jiray saameyn guud oo la xidhiidha isweydaarsiga kahor inta aan la dhajin c-Fos ee labadaba NAc labadaba (Jaantus 4B: F1,15 = 27.4; p <0.001) iyo qolof (Jaantus 4D: F1,15 = 39.4; p <0.001). Intaa waxaa dheer, saameynta guud ee waayo-aragnimada galmada waxaa lagu ogaadey NAc core (Jaantus 4B: F1,15 = 6.1; p = 0.026) iyo qolof (Jaantus 4D: F1,15 = 1.7; p = 0.211) iyo isdhexgalka ka dhexeeya khibradda jinsiga iyo isweydaarsiga ka hor inta aaney fiyoobin ayaa lagu ogaaday asaaska NAc (F1,15 = 6.5; p = 0.022), oo isbeddel ku ah qolofka (F1,15 = 1.7; p = 0.211; F1,15 = 3.4; p = 0.084). Falanqaynta natiijada baadhitaanka ayaa muujisay qeexitaan c-fosho ah oo ku salaysan mabaadi'da iyo qolada labka ama dheddig-laboodka raga (Jaantus 4B, D). Si kastaba ha noqotee, ragga ragga ah ee khibradda leh, c-Fos si weyn uguma kordhin astaamaha NAc (Jaantus 4B) iyo si weyn u xejistay qolofka (Jaantus 4D). Sidaa awgeed, waayo-aragnimada galmada waxay sababtay hoos u dhigida c-fosho-ku-celinta cf. Qiimayaasha P-qiimaha isbarbardhiga ee qaaska ah waxay ku jiraan sheekooyinka sawirka.

Jaantuska 3     

Sawirrada wakiilada oo muujinaya ΔFosB (cagaaran) iyo c-Fos (casaan) ee NAc koox kasta oo tijaabo ah. Maydhka iskeelka wuxuu muujinayaa 100 μm.
Jaantuska 4     

ΔFosB-da waayo-aragnimada jinsiga ah iyo c-fos-cirfiidka. Nambarada ΔFosB (Core, A, Shell, C, ACA, E) ama c-Fos (Core, B, Shell, D, ACA, F) Unugyada difaaca jirka ee koox kasta: NNS (n = 5), NS (n = 5), ENS (n = 5) ama ES (n = 4). Xogta ayaa la muujiyey ...

Saamaynta khibradda galmada ee ku saabsan heerarka c-cabitaanka c-Fosigu ma ahayn mid xaddidan NAc. Dareenka isku midka ah ee c-Fos-ka ayaa lagu arkay ACA-ga xayawaanka la-xiirta marka la barbardhigo kontoroolka galmada. Khibrada galmada waxay saameyn weyn ku yeelatay ereyada ΔFosB ee ACA (Jaantus 4E: F1,15 = 154.2; p <0.001). Naas nuujinta kahor foosha wax saameyn ah kuma laheyn muujinta ΔFosB (Jaantus 4C) laakiin si wayn ayaa loo kordhiyay c-Fos (Jaantus 4F: F1,15 = 203.4; p <0.001) ee ACA. Intaa waxaa sii dheer, muujinta c-Fos ee ku saabsan ACA ayaa si weyn hoos ugu dhacay khibradda galmada (Jaantus 4F: F1,15 = 15.8; p = 0.001). Labada hab ee isdhexgalka ee udhaxeeya waayo-aragnimada jinsiga iyo isweydaarsiga ka hor inta aan la naqsheynin ayaa lagu ogaaday c-Fos (Jaantus 4F: F1,15 = 15.1; p <0.001). Qiimaynta P ee isbarbardhigga laba-caqliga leh ee gaarka ah waxay ku jiraan halyeeyada shaxanka. Ugu dambeyntiina, ma jirin hoos u dhac weyn oo ku yimid muujinta c-Fos ee ku saabsan isku-dheelitirka 'nucleus preoptic nucleus' (NS: Avg 63.5 +/− 4.0; ES: Avg 41.4 +/− 10.09), oo ah aag aan khibrad u lahayn isku-dheelitirnaan aysan keenin wax weyn kororka muujinta 'osFosB', oo muujinaya in muujinta c-Fos ee isku-dhafan aan saameyn ku yeelan dhammaan aagagga maskaxda.

ΔFosB ee NAc waxay dhexdhexaadineysaa xoojinta dhaqanka galmada

Si loo raadiyo habdhaqaaqa jimicsiga ee xoojinta dabeecadaha galmada sida lagu muujiyey fududeynta khibrad ku salaysan habdhaqanka jinsiga, saameynta dhaqdhaqaaqa maxalliga ah ee heerarka ΔFOSB iyo waxqabadyada isbeddelka ayaa la go'aamiyey. Khibrada galmada inta lagu guda jiro afar aragnimada khibrad ee isku xigta waxay saameyn weyn ku yeelatay latent mount (Jaantus 5A: F1,23 = 13.8; p = 0.001), latency intramination (Jaantus 5B: F1,23 = 18.1; p <0.001), iyo daahitaanka shahwada (Jaantus 5C: GFP, F11,45 = 3.8; p = 0.006). Xayawaanka xayiraadda GFP waxay soo bandhigeen khibradda la filayo inay fududeeyso dabeecada galmada waxayna muujineysaa dhibka hooseeya ee ugu horeysa ee la galo, marka hore iyo hawo-qaadista inta lagu guda jiro mudada tababarka 4 marka la barbardhigo xiisadda khibrada 1 (Jaantuska 5A-C; fiiri tusaalaha halyeeyada ee qiimayaasha p-da). Dhibaatada waayo-aragnimada leh ee hab-dhaqanka jinsiga ayaa sidoo kale lagu arkay kooxda ΔFosB ee meelaha lafa-goyska iyo hareeraha, lakiin ma jirin farqi weyn oo lagu ogaaday qulqulka wakhti yaraanta (Jaantuska 5A-C). Taa bedelkeeda, xayawaanka ΔJunD wuxuu soo bandhigay fududeyn la taaban karo; xitaa haddii latencies ee dhismaha, xayawaanka, iyo cabsida ay hoos u dhigtay kulanno isku dhafan oo soo noqnoqonaya, mid ka mid ah xuduudahaani waxay gaareen muhiimadda tirakoobka marka la barbardhigo kulannada waayo-aragnimada 1 iyo 4 (Jaantuska 5A-C). Intii u dhaxaysay isbarbardhig kooxeed ee khibrad kasta, waxay muujinaysaa in ΔJunD ay si weyn u dheereynayaan cagajugleynta, kaadimareenka iyo ejaculate inta lagu jiro kulannada waayo-aragnimada marka la barbar dhigo ΔFosB iyo GFP (Jaantuska 5A-C). Intaa waxa dheer, khibradda galmada iyo daaweynta labadaba waxay saameyn weyn ku yeelatay waxtarka copulation (Jaantus 5F: khibradda galmada, F1,12 = 22.5; p <0.001; daaweynta, F1,12 = 3.3; p = 0.049). Dumarka ΔFosB waxay kordhiyeen waxtarka ruqsadaha mudadii lagu guda jiray tababarka 4 marka la barbardhigo kulankan khibrada 1 (Jaantus 5F). Intaa waxaa dheer, xayawaanka ΔFosB ayaa si aad ah u yaraaday xayawaanka ka hor inta aan la saarin intii lagu guda jiray tababarka 4, marka la barbardhigo xiisadda khibrada 1 (Jaantus 5D: F10,43 = 4.1; p = 0.004), iyo in ragga ragga ΔJunD ay si weyn u dhaleen ka hor intaanay hawada la saarin, taas oo si weyn u yaraatay waxtarka copulation, marka loo eego labada kooxood ee kale (Jaantus 5D iyo F). Sidaa awgeed, xoolaha GFP iyo ΔFosB waxay soo bandhigeen fududaynta waayo-aragnimada ku-saleysnaanta dabeecada galmada iyo waxqabadka jinsiga, halka xayawaanka ΔJunD aysan sameynin.

Jaantuska 5     

Xayawaanka galmada ee GFP (n = 12), ΔFosB (n = 11) iyo ΔJunD (n = 9) xayawaanka dhererka (A), latency intrusion (B), latency ejaculation (C), tirada qiimaha (D) tirada ka-qaybgalayaasha (E) iyo waxtarka ruqsadaha (F). Xogta ayaa la muujiyey ...

Si loo tijaabiyo sharraxa ah in ereyga ΔFosB uu muhiim u yahay sharaxaadda muddada-dheer ee fududeynta khibrad-galinta dabeecadda galmada, xayawaanka waxaa la baari doonaa toddobaadka 1 (Xilliga imtixaanka 1) iyo toddobaadka 2 (Xulashada tijaabada 2) kadib kaddib khibradihii ugu dambeeyay. Xaqiiqdii, habdhaqanka galmada ee sahlan waxaa lagu hayaa labada kooxood ee GFP iyo ΔFOSB labadaba ma jiro mid ka mid ah xuduudaha habdhaqanka midkoodna u dhexeynin 1 ama 2 iyo kulankii ugu dambeeyey ee 4, oo ka tirsan kooxaha GFP iyo ΔFOSB (Jaantuska 5A-C; marka laga reebo jiritaanka quudinta xayawaanka iyo waxtarka wareegga xaddiga xiga 1 xayawaanka ΔFosB). Faraqa udhexeeya ee udhexeeya xayawaanka ΔJunD iyo GFP ama kooxaha ΔFOSB ayaa lagu arkay labadii imtixaan ee dhammaan hababka habdhaqanka galmada (Jaantuska 5A-F). Ma jiraan farqi u dhexeeya kooxo ama kooxo dhexdooda marka la barbardhigo tirada isdhexgalka, PEI, ama boqolkiiba xayawaanka la nuugay (100% dadka raga ah ee dhammaan kooxahii la afduubay muddadii afarta af-duubasho).

Tag:

DHIBAATOOYINKA

Daraasadani waxay muujisay in waayo-aragnimada jinsigu ay sabab u tahay isku-dhafka ΔFosB ee dhowr gobol oo maskaxda ku xiran, oo ay ka mid yihiin NAc core iyo shell, mPFC, VTA iyo caudate putamen. Waxaa intaa dheer, waayo-aragnimada galmoodka ayaa lagu soo bandhigay muujinta casho-ficil ah ee c-Fos ee NAc iyo ACA. Ugu dambeyntii, ΔFosB ee NAc ayaa lagu muujiyay in ay muhiim u tahay dhexdhexaadinta fududaynta macaamilka inta lagu guda jiro helitaanka khibradda jinsiga iyo muujinta muddada dheer ee fududeynta khibrad-u-helidda dhaqanka jinsiga. Gaar ahaan, hoos u dhigista wargalinta ΔFosB-dhexdhexaadin ah ayaa loo siman yahay fududeynta khibrad ku salaysan dhiirigelinta iyo waxqabadka jinsiga, iyada oo inta badan lagu tilmaamo ΔFosB NAc waxay keentay fududeyn dheellitiran ee dhaqanka jinsiga, marka loo eego waxqabadka jinsiga oo kordhay khibrad yar. Wadajir ahaan, natiijooyinka iminka taagan waxay taageertaa falsafadda in ΔFosB ay tahay dhexdhexaadiyaha muhiimka ah ee qummanaanta dabiiciga ah iyo dabeecadda aadaabta ee ay sababto khibradda galmada.

Natiijooyinka xaadirka ah waxay kordhiyaan baadhitaano hore oo muujinaya ΔFosB waayo-aragnimada jinsiga ee NAc ee jiirka labka (Wallace et al. 2008) iyo dumarka naasaha (Dabka et al. 2009). Wallace et al. (2008) waxay muujisay in rAAV-ΔFosB dulucda badan ee NAc kobcinta dabeecadaha galmada ee xayawaanka galmada kufilan inta lagu jiro fadhiga ugu horeeya, sida caddayn yar oo ka soo horjeeda huruufaha iyo waqtiyada gaaban ejaculatory-ka, laakiin wax saameyn ah kuma yeelan ragga ragga ee khibradda leh (Wallace et al. 2008).

Taa bedelkeeda, daraasadani waxay muujisay wax saameyn ah oo aan ka helin ereyada 'ΔFosB' ee ragga kufsiga galmada inta lagu guda jiro tijaabada ugu horeysa, laakiin intii lagu jiray iyo ka dib markii la helo khibrad jinsi. ΔFosB-dhaafsiis-bixiyeyaashu waxay muujiyeen waxqabadka jinsiga (korodhka waxtarka bilowga) marka la barbar dhigo xayawaanka GFP.

Intaa waxa dheer, daraasaddan hadda baaray doorka ΔFosB iyadoo xannibeysa waraaqaha ΔFosB-dhexdhexaadinta iyadoo la adeegsanayo vector viral viral ΔJunD. Ka hortagga khibradaha ka soo kordhay ee ΔFosB ayaa la xayiray khibrad u sahlaysa dhiirigelinta jinsiga (kororka buuraha iyo leexashada) iyo sidoo kale waxqabadka galmada (dhererka xajinta ejaculation iyo tirada jaranjarada) iyo muujinta mustaqbalka fog ee habdhaqanka galmada ee fudud.

Sidaa daraadeed, xogtan ayaa ah kuwa ugu horreeya ee muujiya doorka waajibka ah ee ΔFosB ee helitaanka fududeynta khibrad-u-helidda dhaqanka galmada. Intaa waxaa dheer, xogtaasi waxay muujinayaan in ΔFOSB ay sidoo kale si weyn ugu lug leedahay qaab-dhismeedka mudada dheer ee dabeecadda sahlan ee khibrad u leh. Waxaan soo jeedineynaa in mudnaanta muddada dheer ee habdhaqanka suurtogalka ah uu yahay qaab xusuus ah abaalmarinta dabiiciga ah, sidaas awgeed ΔFosB ee NAc waa dhexdhexaadiye xasuuseed abaalmarin. Khibrada galmada sidoo kale waxay kordhisay heerarka ΔFOSB ee VTA iyo mPFC, meelaha ay ku jiraan abaalmarinta iyo xusuusta (Balfour et al. 2004; Phillips et al. 2008). Daraasadaha mustaqbalka waxaa looga baahan yahay in ay caddeeyaan muhiimadda ay leedahay xakamaynta ΔFosB ee degaankaa si loogu abaalmariyo xusuusta.

Faahfaahinta ΔFosB waa mid aad u deggan, sidaas darteed waxa uu leeyahay awood weyn oo dhexdhexaadiye ah oo ah dhexdhexaadiyaha joogtada ah ee maskaxda oo la socda qalabyada dabadheeraadka ah (Nestler et al. 2001). ΔFosB ayaa lagu muujiyey in si tartiib tartiib ah loogu kordhiyo NAc oo ku saabsan irbado badan oo cocaine ah oo ay sii socoto illaa dhowr toddobaad (Rajaynaynaa et al. 1992; Rajaynaynaa et al. 1994). Isbeddeladaan ku jira NAc-ga ΔFosB waxay la xiriiraan dareenka daroogada iyo daroogada (Chao & Nestler 2004; McClung & Nestler 2003; McClung et al. 2004; Nestler 2004, 2005, 2008; Nestler et al. 2001; Zachariou et al. 2006). Taa bedelkeeda, doorka ΔFOSB ee dhexdhexaadinta abaalmarinta dabiiciga ah ayaa la fahmay. Cadaymihii dhowaa ayaa soo baxay oo tilmaamaya in ΔFOSB soo afjaraan NAc ay ku lug leeyihiin abaalgudka dabiiciga ah. Heerarka ΔFOSB ayaa sidoo kale la kordhiyay NAc ka dib qaadashada sukrose iyo gawaarida. Falanqaynta xad dhaafka ah ee ΔFosB ee qallalka ah iyadoo la isticmaalayo jiirka jooniska ah ama fayraska viral ee jiirka ayaa keena kororka qaadashada sukrose, dhiirigelinta dhiirrigelinta cuntada iyo kor u kaca gawaarida istiraatiijiga ah (Olausson et al. 2006; Wallace et al. 2008; Werme et al. 2002). Xogta hadda jirta ayaa si weyn ugu sii dareysa warbixinnadaas oo ay sii taageerayaan fikradda ah in ΔFosB ay tahay dhexdhexaadiye muhiim u ah abaalmarinta abaalmarinta iyo xusuusta dabiiciga ah.

ΔFosB waxay dhexdhexaadin kartaa khibrad soo jiidashada dabeecadaha jinsiga ah iyada oo loo marayo xayiraad ku xirnaanta nidaamka mesolimbic. Runtii, waayo-aragnimada galmadu waxay sababtaa isbeddelo dheer oo isdaba-joog ah oo ku yimaada nidaamka mesolimbic (Bradley & Meisel 2001; Frohmader et al. 2009; Pitchers et al. 2010). At heerka dabeecadda, jawaab-celin xeeldheer oo laga helo amphetamine iyo abaal-marin amfi ah oo la xoojiyey ayaa lagu muujiyay jinsiyada lab ahPitchers et al. 2010); Jawaabta isbedelka ah ee lafdhabarta ee amphetamine ayaa sidoo kale lagu arkay dumarka naasku (Bradley & Meisel 2001). Intaas waxaa sii dheer, kordhinta tirooyinka dendritic iyo kakanaanta qashinka dendritic ayaa la helay ka dib markii muddo dheer laga soocay waayo-aragnimada jinsiga ee jinsiyada lab (Pitchers et al. 2010). Daraasadda hadda waxay soo jeedineysaa ΔFOSB inay noqon karto dhexdhexaadiye gaar ah oo ka mid ah natiijooyinka muddada fog ee khibradda jinsiga. Heshiiska, ΔFosB ayaa dhowaan lagu muujiyey inuu muhiim u yahay soo bandhigida isbeddelka isbeddelka dendritic ee ka jawaab celinta maamulka cocaine-da (Dietz et al. 2009; xabaasha et al. 2010).

Ma cadda cidda maskaxda gaaban (neurotransmitter) inay mas'uul ka tahay soo-saarka ΔFosB ee NAc, laakiin DA ayaa loo soo bandhigay musharax (Nye et al. 1995). Dhamaanba daroogooyinka xadgudubka, oo ay ku jiraan kookeynta, amphetamine, opiates, cannabinoids iyo etanol, iyo sidoo kale abaalmarin dabiici ah, waxay kordhiyaan ΔFosB ee NAc (Perrotti et al. 2005; Wallace et al. 2008; Werme et al. 2002). Labada daroogo ee xadgudubka iyo abaalmarinta dabiiciga ah waxay kordhiyaan diiradda 'DA "ee NAc (Damsma et al. 1992; Hernandez & Hoebel 1988a, b; Jenkins & Becker 2003). Soo-saarista ΔFOSB ee daroogada xadgudubka ayaa lagu muujiyay ogtariistaha DA oo leh unugyo iyo ΔFosB-kooke-ku-oogista ayaa xannibay D1 DA antagonistt (Nye et al. 1995). Sidaa awgeed, DA sii-deynta ayaa lagu qiimeynayaa in lagu dhiirrigeliyo ereyga ΔFosB oo sidaas darteed dhexdhexaadin kara neuroplastic. Dheeraad ah oo taageera fikradda ah in heerarka ΔFOSB ay tahay DA-ku-tiirsane waa ogaanshaha meelaha maskaxda ee khibradda galmada ay bedeleen heerarka ΔFOSB helayaan talobixin xoog leh oo dopaminergic ah oo laga helo VTA, oo ay ka mid yihiin kortex celinta hore ee dhexdhexaadka ah iyo amygdala.

Si kastaba ha ahaatee, marka la barbardhigo, ΔFOSB looma kordho aagga hore ee daawada ah inkastoo aaggu helo dopaminergic, inkastoo uu ka yimid ilaha hypothalamic (Miller & Lonstein 2009). Daraasado mustaqbalka ayaa loo baahan yahay si loo baaro haddii ficil-celinta ΔFosB iyo saameynta jismiga galmada ku saabsan dhiirigelinta iyo waxqabadka galmada ay ku xiran tahay ficilka DA. Doorka DA ee ku saabsan abaalmarinta jinsiga ee jinsiyada lab ama dhedig maahan mid gebi ahaanba cad (Agmo & Berenfeld 1990; Pfaus 2009). Waxaa jira caddaymo dhab ah in DA lagu sii daayo NAc inta lagu guda jiro kufsiga dumarka ama wadaagista (Damsma et al. 1992) iyo DA neuro-yada waxaa lagu dhaqmaa inta lagu jiro dhaqanka galmada (Balfour et al. 2004). Si kastaba ha noqotee, cirbadaha kudka ah ee antagonist-ka DA-da ayaa ka hortagaya doorbidista booska ku habboon ee jinsiga ah (Agmo & Berenfeld 1990) iyo aragtida ah in DA uu muhiim u yahay waayo-aragnimada laysku daro ee isu-duubnaanta mate waa mid aan la tijaabin.

Sidoo kale ma cadda sida ay tahay dhexdhexaadiyeyaasha hoose ee saameynta ΔFOSB ee ku saabsan dabeecada galmada. ΔFosB ayaa lagu muujiyay in ay u dhaqmaan sidii dhaqdhaqaaqe-rogaal celiye iyo caaqil-celiye iyada oo loo marayo nidaam ku-meelgaar ah AP-1 (McClung & Nestler 2003; Peakman et al. 2003). Cilmi-baadhisyo badan oo la bartilmaameedsan ayaa la ogaadey, oo ay ku jiraan hiddesid hore loo yaqaan 'c-phos (Rajaynaynaa et al. 1992; Rajaynaynaa et al. 1994; Morgan & Curran 1989; Kirada et al. 2008; Zhang et al. 2006), cdk5 (Bibb et al. 2001), dynorphin (Zachariou et al. 2006), sirtuin-1 (Kirada et al. 2009), Qaybaha NFBB (Ang et al. 2001), Aiyo AMPA AMP glutamate GheR2 garsooraha (Kelz et al. 1999). Natiijooyinka iminka socda waxay muujinayaan in heerarka c-cabirta loo yaqaan 'c-Fos' ay hoos u dhigeen waayo-aragnimada jinsiga ee meelaha maskaxda ah oo ay kordheen ΔFosB (NAc iyo ACA). Diidmada c-Fosku waxay u muuqaneysaa inay ku xiran tahay muddadaas tan iyo markii la isku daro miisaankii hore iyo marxaladaha soo noqnoqda, sida daraasadihii hore, sida hoos u dhaca c-Fos oo aan la ogaanin faruuryaha labka ah ayaa tijaabiyay usbuuc 1 ka dib fadhiga ugu dambeeyay (Balfour et al. 2004) ama waayo-aragnimo galmo kadib oo ka kooban hal fadhiga oo keliyaLopez & Ettenberg 2002). Waxaa intaa dheer, helitaanka hadda waa mid la socota caddeynta ah in ΔFosB ay soo gebogabeyso hiddawada c-fos-yada ka dib soo-qaadista amfitamiin joogta ah (Kirada et al. 2008). Iyadoo loo eegayo natiijooyinkan, soo-qaadista dhowr hiddesid hore oo hiddaha ah ee mRNAs (c-fos, fosB, c-jun, junB, iyo zif268) ayaa la yareeyay ka dib markii lagu soo rogay cocaine-ka soo noqnoqda marka la barbardhigo cirbadaha daroogada ba'an (Rajaynaynaa et al. 1992; Rajaynaynaa et al. 1994), iyo amphetamine-ku-soo-ceshad c-fosos waxaa lagu xakameynayey ka dib markii laga reebay maamulka amfitamiin joogtada ah (Jaber et al. 1995; Kirada et al. 2008). Faa'iidada waxqabadka ee hoos-u-dhigidda qeexitaanka c-Fos ka dib daaweynta daawada dabadheerta ama waayo-aragnimada jinsiga weli lama caddeyn, waxaana loo soo jeediyay inay noqoto qalab guri-guri oo muhiim ah oo lagu xakamaynayo dareenka xayawaanka ee ku-soo-celinta abaal-marinta (Kirada et al. 2008).

Gebogebadii, daraasaddan hadda waxay muujineysaa in ΔFosB NAc ay ka ciyaaraan door muhiim ah xusuusta galmada, taageeraya suurtagalnimada in ΔFosB muhiim u tahay abaalmarinta guud ee xoojinta iyo xasuusta. Natiijooyinka ka soo baxa daraasaddan hadda waxay sii sharraxayaan fahamkayaga ku saabsan qaababka cellular iyo molecular kuwaas oo dhexdhexaadiya abaalmarinta jinsiga iyo dhiirigelinta, iyo ku darida qaababka suugaanta oo muujinaya in ΔFosB uu yahay ciyaaryahan muhiim u ah horumarka takoorka, isagoo muujinaya doorka ΔFosB ee abaalmarinta dabiiciga ah xoojinta.

Tag:

Qalabka Dheeraadka ah

Bixi Sawirka S1-S4 & Shaxda S1-S2

Tag:

Mahadnaq

Cilmi-baaristaan ​​waxaa taageero ka heley hay'adaha Kanada ee Cilmi-baarista Caafimaadka ee LMC, Machadka Qaranka ee Caafimaadka Maskaxda ee EJN, iyo Golaha Cilmi-baarista Isku-dhafka ee Kanada ee KKP iyo LMC.

Tag:

tixraacyada

  • Agmo A. Dhaqanka galmada ee lab ah. Daaweynta Maskaxda Maskaxda. 1997;1: 203-209. [PubMed]
  • Agmo A, Berenfeld R. Xoojinta sifooyinka shubanka ragga: doorka opioids iyo dopamine. Behav Neurosci. 1990;104: 177-182. [PubMed]
  • Ang E, Chen J, Zagouras P, Magna H, Holland J, Schaeffer E, Nestler EJ. Kicinta calaamadaha nukliyeerka-kappaB ee nucleus waxa soo galaya maamulka cocaine-da. J Neurochem. 2001;79: 221-224. [PubMed]
  • Balfour ME, Yu L, Coolen LM. Dabeecada galmada iyo calaamadaha bay'ada la xidhiidha jinsiga waxay u dhaqmaan nidaamka mesolimbic ee jiirka labka. Neuropsychopharmacology. 2004;29: 718-730. [PubMed]
  • Bibb JA, Chen J, Taylor JR, Svenningsson P, Nishi A, Snyder GL, Yan Z, Sagawa ZK, Ouimet CC, Nairn AC, Nestler EJ, Greengard P. Waxyeelooyinka saameynta joogtada ah ee cocaine-ka waxaa lagu xakumay Cdk5 borotiin ah. Dabeecadda. 2001;410: 376-380. [PubMed]
  • Bradley KC, Haas AR, Meisel RL. Dhaawacyada 6-Hydroxytopamine ee haweenka dumarka ah (Mesocricetus auratus) waxay baabi'iyaan saamaynta dareenka ah ee khibradda jinsiga ah ee isdhexgalka ka dhexeeya ragga. Behav Neurosci. 2005;119: 224-232. [PubMed]
  • Bradley KC, Meisel RL. Cudurka dabeecadda galmada ee c-Fos ee nambarada xuubka iyo dhaqdhaqaaqa amphetamine-stimulated lumomotor ayaa dareensiiyey waayo-aragnimo galmo hore ee haweenka reer Syria ee xamaasadda. J Neurosci. 2001;21: 2123-2130. [PubMed]
  • Carle TL, Ohnishi YN, Ohnishi YH, Alibhai IN, Wilkinson MB, Kumar A, Nestler EJ. Nidaamyada hormoodka ah ee ku-xidhan iyo habka madax-bannaan ee loogu talogal-galin la'aanta FosB: aqoonsiga FosB wuxuu ku salaysan yahay domains iyo saameyn ku yeelashada degganaanshaha DeltaFosB. Eur Jar Neurosci. 2007;25: 3009-3019. [PubMed]
  • Chao J, Nestler EJ. Cudurka neerobika ee miyir-qabka ah ee daroogada daroogada. Annu Rev Med. 2004;55: 113-132. [PubMed]
  • Chen J, Nye HE, Kelz MB, Hiroi N, Nakabeppu Y, Hope BT, Nestler EJ. Nidaaminta delta FosB iyo FosB-la midka ah borotiinka iyadoo la adeegsanayo qalabka elektaroonigga ah iyo daaweynta cocaine. Faytamoolka Molecular. 1995;48: 880-889. [PubMed]
  • Colby CR, Whisler K, Steffen C, Nestler EJ, Self DW. Cadaadiska nacaybka ee 'DeltaFosB' ee unugyada Striatal-ga ah wuxuu kor u qaadayaa dhiirrigelinta kookeynta. J Neurosci. 2003;23: 2488-2493. [PubMed]
  • Coolen LM, Allard J, Truitt WA, Mckenna KE. Xeer-dejinta dhexe ee quudinta. Physiol Behav. 2004;83: 203-215. [PubMed]
  • Damsma G, Pfaus JG, Wenkstern D, Phillips AG, Fibiger HC. Akhlaaqda galmada waxay kordhisaa gudbinta dopamine ee naasaha nukleus iyo calaamadaha jiirka labka: marka la barbardhigo casriga iyo qadarinta. Behav Neurosci. 1992;106: 181-191. [PubMed]
  • Dietz DM, Maze I, Mechanic M, Vialou V, Dietz KC, Iniguez SD, Laplant Q, Russo SJ, Ferguson D, Nestler EJ. Doorka muhiimka ah ee ΔFosB ee qawaaniinta cocaine ee qanjidhada dendritic ee nucleus waxay ku dhacdaa qanjidhada. Bulsho loogu talagalay Cudurka Neuroscience Abstract. 2009
  • Frohmader KS, Pitchers KK, Balfour Me, Coolen LM. Isku dayaayo raaxeysiga: Dib u eegista saameynta daroogada ku saabsan dabeecada galmada ee dadka iyo noocyada xayawaanka. Horm Behav. 2009 Saxaafadda.
  • Hedges VL, Chakravarty S, Nestler EJ, Meisel RL. Delta FosB Xilliga Fikradda ee Nucleus wuxuu hirgeliyaa abaalmarinta jinsiga ah ee haweenka reer Suuriya ah. Genes Brain Behav. 2009;8: 442-449. [Maqaallo bilaash ah PMC] [PubMed]
  • Hernandez L, Hoebel BG. Quudinta iyo kicinta hypothalamic waxay kordhisaa wareegga dopamine ee calaamadaha. Physiol Behav. 1988a;44: 599-606. [PubMed]
  • Hernandez L, Hoebel BG. Abaalmarinta cuntada iyo kookeynta ayaa kordhiya dopamine-ka ka baxsan ee nucleus accumens sida lagu qiyaaso microdialysis. Life Sci. 1988b;42: 1705-1712. [PubMed]
  • Hiroi N, Marek GJ, Brown JR, Ye H, Saudou F, Vaidya VA, Duman RS, Greenberg ME, Nestler EJ. Doorka muhiimka ah ee hiddaha fosB ee waxqabadyada molecular, cellular, iyo habdhaqanka ee suuxdinta joogtada ah ee korontada ku shaqeeya. J Neurosci. 1998;18: 6952-6962. [PubMed]
  • Hommel JD, Sears RM, Georgescu D, Simmons DL, DiLeone RJ. Gene-ga gudaha ah ee ku dhaca maskaxda iyadoo la adeegsanayo faragelinta RNA-dhexdhexaadinta. Nat Med. 2003;9: 1539-1544. [PubMed]
  • Hope B, Kosofsky B, Hyman SE, Nestler EJ. Nidaamka xayiraadda hore ee hidda-wakhti hore iyo AP-1 ee ku xiran faraska nukleus waxa soo galaya kookayn joogto ah. Proc Natl Acad Sci US A. 1992;89: 5764-5768. [Maqaallo bilaash ah PMC] [PubMed]
  • Hope BT, Nye HE, Kelz MB, Iskuday DW, Iadarola MJ, Nakabeppu Y, Duman RS, Nestler EJ. Kicinta qulqulka AP-1 oo dheer oo ka kooban borotiinka Fos-la midka ah oo maskaxda ku jira oo maskaxda ku leh kookayn joogto ah iyo daaweyn kale oo dabadheeraad ah. Neuron. 1994;13: 1235-1244. [PubMed]
  • Hull EM, Meisel RL, Sachs BD. Lab Dhaqanka Galmada. Horm Behav. 2002;1: 1-139.
  • Jaber M, Cador M, Dumartin B, Normand E, Stinus L, Bloch B. Daawooyinka amfitamin ee xasaasiga ah oo dabadheeraad ah ayaa si gooni ah u xakameynaya heerarka ragga RNA ee neuropeptide iyo Fos immunoreactivity ee nuucyada rat striatal. Neuroscience 1995;65: 1041-1050. [PubMed]
  • Jenkins WJ, Becker JB. Isbeddelku wuxuu kordhiyaa dopamine inta lagu guda jiro nuucista haweenka ee feerka dumarka. Eur Jar Neurosci. 2003;18: 1997-2001. [PubMed]
  • Kelz MB, Chen J, Carlezon WA, Jr, Whitler K, Gilden L, Beckmann AM, Steffen C, Zhang YJ, Marotti L, Is DW, Tkatch T, Baranauskas G, Surmeier DJ, Neve RL, Duman RS, Picciotto MR, Nestler EJ. Muujinta calaamadaha gawaarida la yiraahdo deltaFosB ee maskaxda ayaa xakameynaya xasaasiyadda kookaynta. Dabeecadda. 1999;401: 272-276. [PubMed]
  • Lopez HH, Ettenberg A. Cudurka jinsiga dumarku wuxuu soo saaraa kala duwanaanshaha c-fos indhaha oo u dhexeeya jinsi-jilicsan iyo jinsi lab ah. Maskaxda. 2002;947: 57-66. [PubMed]
  • Qeybta 3aad, Xeerka I, Xiisada, Dietz DM, LaPlant Q, Renthal W, Russo SJ, Mechanic M, Mouzon E, Neve RL, Haggarty SJ, Ren Y, Sampath SC, Hurd YL, Greengard P, Tarakhovsky A, Schaefer A, Nestler EJ. Doorka muhiimka ah ee methyltransferase G3a ee bucshirada cocaine-induced. Sayniska. 2010;327: 213-216. [Maqaallo bilaash ah PMC] [PubMed]
  • McClung CA, Nestler EJ. Xeerarka hiddaha hidaha iyo abaalmarinta cocaine ee CREB iyo DeltaFosB. Nat Neurosci. 2003;6: 1208-1215. [PubMed]
  • McClung CA, Ulery PG, Perrotti LI, Zachariou V, Berton O, Nestler EJ. DeltaFosB: waa qalab molekular ah oo loogu talo galay maskaxda. Brain Res Mol Brain Res. 2004;132: 146-154. [PubMed]
  • Miller SM, Lonstein JS. Saadaasha dopaminergic-ga ee qaybta hore ee maqaarka ee jiirka dhalmada ka dib. Neuroscience 2009;159: 1384-1396. [Maqaallo bilaash ah PMC] [PubMed]
  • Morgan JI, Curran T. Stimulus-kudhawaaqida isu-duubida qanjidhada: doorka dhaliyaha degdega ah ee degdega ah. Isbedelada Neurosci. 1989;12: 459-462. [PubMed]
  • Nestler EJ. Nidaamyada maadiga ah ee mukhaadaraadka daroogada. Neuropharmacology. 2004;47 Qalabka 1: 24-32. [PubMed]
  • Nestler EJ. Cudurka neurobiology ee xanuunka cocaine. Sci Imtixaan ah. 2005;3: 4-10. [Maqaallo bilaash ah PMC] [PubMed]
  • Nestler EJ. Dib u eegid. Hababka isdabajooga ee maandooriyaha: doorka DeltaFosB. Philos Trans R Soc London B Biol Sci. 2008;363: 3245-3255. [Maqaallo bilaash ah PMC] [PubMed]
  • Nestler EJ, Barrot M, Isku DW. DeltaFosB: Waa qaab beddelaadda maadada loo yaqaan 'mastitis'. Proc Natl Acad Sci US A. 2001;98: 11042-11046. [Maqaallo bilaash ah PMC] [PubMed]
  • Nye HE, Hope BT, Kelz MB, Iadarola M, Nestler EJ. Baaritaanka dawooyinka xayawaanka ee qawaaniinta indho-indheysiga ee FOS-ku xiran ee kobcinta kookeynta ee striatum iyo nucleus accumens. J. Pharmacol Exp Ther. 1995;275: 1671-1680. [PubMed]
  • Olausson P, Jentsch JD, Tronson N, Neve RL, Nestler EJ, Taylor JR. DeltaFosB ee ku-xigeenka nucleus wuxuu xakameeyaa dabeecadaha qalabka korontada iyo dhiirigelinta. J Neurosci. 2006;26: 9196-9204. [PubMed]
  • Peakman MC, Colby C, Perrotti LI, Tekumalla P, Carle T, Ulery P, Chao J, Duman C, Steffen C, Monteggia L, Allen MR, Stock JL, Duman RS, McNeish JD, Barrot M, Self DW, Nestler EJ , Schaeffer E. Maqnaanshaha, muujinta qaybta maskaxda ee gobolka ee mutaysiga xun ee c-Jun ee jiirarka transgenic ayaa hoos u dhigaya xasaasiyadda kookaynta. Maskaxda. 2003;970: 73-86. [PubMed]
  • Perrotti LI, Bolanos CA, Choi KH, Russo SJ, Edwards S, Ulery PG, Wallace DL, Self DW, Nestler EJ, Barrot M. DeltaFosB waxay ku urursan yihiin unugyada GABAergic ee ku yaala dusha sare ee qaybta hawada ka dib markii daaweynta nafsaaniga ah. Eur Jar Neurosci. 2005;21: 2817-2824. [PubMed]
  • Perrotti LI, Hadeishi Y, Ulery PG, Barrot M, Monteggia L, Duman RS, Nestler EJ. Kicinta deltaFosB ee qaababka abaal-marinta abaal-marinta ee maskaxda ka dib duuf dabadheeraad ah. J Neurosci. 2004;24: 10594-10602. [PubMed]
  • Perrotti LI, Weaver RR, Robison B, Kirada W, Maze I, Yazdani S, Elmore RG, Knapp DJ, Selley DE, Martin Br, Sim-Selley L, Bachtell RK, Iskuday DW, Nestler EJ. Qaababka kala-duwan ee DeltaFosB induction in maskaxda by daroogooyinka xadgudubka. Dhexdhexaad. 2008;62: 358-369. [Maqaallo bilaash ah PMC] [PubMed]
  • Pfaus JG. Wadiiqooyinka rabitaanka galmada. J Caafimaadka Med. 2009;6: 1506-1533. [PubMed]
  • Pfaus JG, Kippin TE, Centeno S. Xaaladda iyo dhaqanka galmada: dib u eegis. Horm Behav. 2001;40: 291-321. [PubMed]
  • Phillips AG, Vacc G, Ahn S. Muuqaalka sare ee dopamine, dhiirigelinta iyo xasuusta. Pharmacol Biochem Behav. 2008;90: 236-249. [PubMed]
  • Darajooyinka KK, Balfour ME, Lehman MN, Richtand NM, Yu L, Coolen LM. Neuroplasticity ee nidaamka mesolimbic ee lagu soo bandhigay abaalmarin dabiiciga ah iyo abaalmarinta xiga. Cilmi-nafsiyeedka Biol 2010;67: 872-879. [Maqaallo bilaash ah PMC] [PubMed]
  • Renthal W, Carle TL, Maze I, Covington HE, 3rd, Truong HT, Alibhai I, Kumar A, Montgomery RL, Olson EN, Nestler EJ. Delta FosB waxay dhexdhexaadinaysaa epigenetic desensitization ee hiddaha c-foska ka dib soo-gaadhista amfitamiin joogta ah. J Neurosci. 2008;28: 7344-7349. [Maqaallo bilaash ah PMC] [PubMed]
  • Rental W, Kumar A, Xiao G, Wilkinson M, Covington HE, 3rd, Maze I, Sikder D, Robison AJ, LaPlant Q, Dietz DM, Russo SJ, Vialou V, Chakravarty S, Kodadek TJ, Stack A, Kabbaj M, Nestler EJ. Falanqaynta genome-wide ee xeerka chromatin by kookayn ayaa muujinaya doorka sirtuins. Neuron. 2009;62: 335-348. [Maqaallo bilaash ah PMC] [PubMed]
  • Tenk CM, Wilson H, Zhang Q, Pitchers KK, Coolen LM. Abaalmarinta jinsiga ee jiirka labka ah: Saamaynta khibradda galmada ee ku saabsan doorbidka booska leh ee la xidhiidha xayawaanka iyo ka hortagga. Horm Behav. 2009;55: 93-97. [Maqaallo bilaash ah PMC] [PubMed]
  • Ulery-Reynolds PG, Castillo MA, Vialou V, Russo SJ, Nestler EJ. Fosforyaalka DeltaFosB wuxuu dhexdhexaadiyaa xasiloonida gudaha. Neuroscience 2008
  • Ulery PG, Rudenko G, Nestler EJ. Xeerka dejinta DeltaFosB by phosphorylation. J Neurosci. 2006;26: 5131-5142. [PubMed]
  • Wallace DL, Vialou V, Rios L, Carle-Florence TL, Chakravarty S, Kumar A, Graham DL, Green TA, Kirk A, Iniguez SD, Perrotti LI, Barrot M, DiLeone RJ, Nestler EJ, Bolanos-Guzman CA. Saamaynta DeltaFosB ee nucleus waxay ku dhacdaa dabeecadaha abaal-marinta dabiiciga ah. J Neurosci. 2008;28: 10272-10277. [Maqaallo bilaash ah PMC] [PubMed]
  • Werme M, Messer C, Olson L, Gilden L, Thoren P, Nestler EJ, Brene S. Delta FosB waxay xakameysaa socodka gawaarida. J Neurosci. 2002;22: 8133-8138. [PubMed]
  • Winstanley CA, LaPlant Q, Theobald DE, Green Ta, Bachtell RK, Perrotti LI, DiLeone RJ, Russo SJ, Garth WJ, Iskuday DW, Nestler EJ. Qabitaanka DeltaFosB ee kortex orbitofrontal wuxuu dhexdhexaad u yahay dulqaadka maqnaashaha cocaine-sababtoo ah. J Neurosci. 2007;27: 10497-10507. [PubMed]
  • Zachariou V, Bolanos CA, Selley DE, Theobald D, Cassidy MP, Kelz MB, Shaw-Lutchman T, Berton O, Sim-Selley LJ, Dileone RJ, Kumar A, Nestler EJ. Doorka muhiimka ah ee DeltaFosB ee nucleus waxay ku dhacdaa falalka morphine. Nat Neurosci. 2006;9: 205-211. [PubMed]
  • Zhang J, Zhang L, Jiao H, Zhang Q, Zhang D, Lou D, Katz JL, Xu M. C-Fos wuxuu fududeeyaa helitaanka iyo burburinta isbeddellada joogtada ah ee kookaynta. J Neurosci. 2006;26: 13287-13296. [PubMed]