DeltaFosB na Nucleus Accumbens bụ Critical For Reminging Effects of Rewarding Sex. (2010)

IHE: Delta FosB bụ akara maka nrịba ahụ niile, ma omume ma na kemịkal. Dika molekul a na abawanye na ugwo olu ugwo dika omume ndi riri ahu. Ọ bụ otu n'ime ụmụ irighiri ihe na-emetụta mgbanwe ngbanwe. Nnwale a na-egosi na ọ na-abawanye site na ahụmịhe nke mmekọahụ, n'otu aka ahụ ka o si eme ya na ọgwụ ọjọọ riri ahụ. N’ime nnwale ahụ, ha were mkpụrụ ndụ ihe nketa iji mekwuo ogo ya karịa “nkịtị”. Nke a rụpụtara ọrụ dị mma nke inwe mmekọahụ. Anyị na-eche na nke a na-eme na ị addictionụ ọgwụ ọjọọ.

Ntụziaka dị mma

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

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

Ngalaba mmepụta ihe na usoro ọgwụ ndụ, Ụlọ akwụkwọ ọgwụ na Schulich na Dentistry, Mahadum Western Ontario, London, Ontario, Canada.

ABSTRACT

Mmekọahụ na oke ụmụ nwoke na-akwụ ụgwọ ma na-ewusi elu. Otú ọ dị, ọ bụ obere ihe a maara banyere usoro ihe omimi cellular na ngwongwo nke na-ekwusara ụgwọ ọrụ ego ma ọ bụ ihe na-eme ka ụgwọ ọrụ kwupụta na omume mmekọahụ. Ọmụmụ ihe a na-anwale nkwupụta ahụ bụ na ΔFosB, bụ nke a gosipụtara n'ụzọ doro anya FosB, na-arụ ọrụ dị oke mkpa n'ịkwalite omume mmekọahụ na mmemme nke ime ka mkpali na arụmọrụ nwee mmetụta.

A gosipụtara ahụmahụ mmekọahụ iji kpatara ΔFosB nchịkọta n'ọtụtụ ụbụrụ ụbụrụ na-agụnye ngwongwo ahụ (NAc), cortex nke dị na mbu, akụkụ nke akụkụ ahụ ma ọ bụ nke na-eme ka ọkpụkpụ ma ọ bụghị nke mbụ preoptic.

N'ikpeazụ, a na-atụle ntinye nke C-Fos, nke a na-eleba anya na ΔFosB, na anụ ọhịa na anụ ọhịa. Ọnụ ọgụgụ nke mkpụrụ ndụ c-Fos-immunoreactive na-emetụta ụbụrụ bụ nke dị ntakịrị na-ebelata na ụmụ anụmanụ na-enwe mmekọahụ ma e jiri ya tụnyere njikwa na-adịghị mma.

N'ikpeazụ, a na-ejikwa ihe ọmụmụ na-arụ ọrụ na NAC na-eme ihe iji mee ka ịmụta ọrụ ọ ga-arụ na mgbasa ozi gbasara ahụmahụ mmekọahụ na mmemme nke mmemme nke mmekorita. Ụmụ anụmanụ ndị nwere ΔFosB overexpression gosipụtara mmemme dị mma nke mmekorita nwoke na nwanyị na ahụmahụ mmekọahụ gbasara njikwa. N'ụzọ dị iche, okwu nke ΔJunD, bụ onye na - ejide onwe ya nke ΔFosB, ahụmahụ mmekọahụ na - emeghị ememe - na - eme ka mmemme nwee mmekorita ya ma jiri nlezianya na - emezi ihe na - eme ka a tụnyere protein fluorescence na ΔFosB overexpressing.

Otu n'ime ihe ndị a na-akwado ọrụ dị mkpa maka okwu ΔFosB na NAc maka mmetụta na-ewusi ike nke omume mmekọahụ na ahụmahụ mmekọahụ-na-ebute mmemme nke mmekorita nwoke.

OKWU

Mmekọahụ na-akwụ ụgwọ ma na-ewusi ndị na-eto eto ike (Coolen et al. 2004; Pfaus et al. 2001). Ọzọkwa, inwe mmekọahụ na-agbanwe àgwà omume mmekọahụ na ụgwọ ọrụ ọzọ (Tenk et al. 2009). Site n'ichekọ ahụmahụ ugboro ugboro, a na-emezi omume mmekọahụ ma ọ bụ "eme ka ọ dịkwuo ike," nke a na-egosi site na mgbada dị ala iji malite ịlụ na mmemme nke arụmọrụ mmekọahụ (Balfour et al. 2004; Pfaus et al. 2001). Otú ọ dị, a na-aghọtaghị usoro ihe omimi nke cellular na molecular nke ụgwọ ọrụ ego na nkwado. E gosipụtara omume mmekorita nwoke na nwanyị na-ekwu okwu banyere ịlụ nwanyị na-egosi na ha na-eme ka mkpụrụ ndụ c-fos na mbụ malitere na usoro mesolimbic nke oke oke (Balfour et al. 2004; Pfaus et al. 2001). Ọzọkwa, e gosipụtara na nso nso a na ahụmahụ mmekọahụ na-ebute neuroplasticity na-adịte aka na usoro oke usoro oke nke nwoke oke (Frohmader et al. 2009; Ndị na-akụ ụta et al. 2010). Na mgbakwunye, na oke nwoke, enwere mmekọahụ ka egosiputa ΔFosB, a Fos onye òtù ezinụlọ, na nucleus accumbens (NAc) (Wallace et al. 2008). ΔFosB, nke a na-edegharị ederede nke FosB, bụ onye pụrụ iche nke ezinụlọ Fos n'ihi na ọ kwụsiri ike karị (Carle et al. 2007; Ulery-Reynolds et al. 2008; Ulery et al. 2006) ma na-ekere òkè n'ime mkpali na nkwụghachi ụgwọ maka iji ọgwụ ike eme ihe na mmekorita ntanetị na-adị ogologo oge (Nestler et al. 2001). ΔFosB na-emepụta ihe mgbagwoju nke heteromeric (protein activator-1 (AP-1) na ndi na-edozi ndi Jun, nke kacha mma JunD (Chen et al. 1995; Hiroi et al. 1998). Site na ngosipụta nke ΔFosB, nke a na-ejedebe na striatum na-eji ụmụ anụ bi-transgenic eme ihe, a na-emepụta phenotype omume ọgwụ ọjọọ ma ọ bụ na enweghi ọgwụ mbụ (McClung et al. 2004). Njirimara omume a na-agụnye ihe omume nchịkọta locomotor nke cocaine (Kelz et al. 1999), ọganihu dị ukwuu maka cocaine (Kelz et al. 1999) na morphine (Zachariou et al. 2006), na ịba ụba cocaine dị ukwuu (Colby et al. 2003).

N'adịghị ka ụgwọ ọgwụ ọjọọ, a na-emezi ΔFosB site n'àgwà na-akwụghachi ụgwọ ma na-akwado usoro okwu ndị a. Ngosipụta nke ΔFosB na NAC site na iji ígwè mee ihe na-eme ka wheel ụkwụ na-agba ọsọ (Werme et al. 2002), ngwá ọrụ na-aza maka nri (Olausson et al. 2006), sugarrose oriri (Wallace et al. 2008), ma na-akwado nwoke (Wallace et al. 2008) na nwanyi (Bradley et al. 2005) omume mmekọahụ. Ya mere, ΔFosB nwere ike itinye aka n'ịgbasa mmetụta nke ahụmahụ na-akwụghachi ụgwọ. Tọmụmụ ihe ugbu a na-agbasawanye na ọmụmụ ihe gara aga site na nyochaa kpọmkwem ọrụ nke ΔFosB na NAc na ihe ndị na-eme ogologo oge nke ahụmahụ mmekọahụ na mmekọ ahụ na-agbaso na mmezigharị n'ime usoro mesolimbic.

  • Akpa, e guzobere ya nke mpaghara mpaghara ụbụrụ na-enwe na njem nleta na omume mmekọahụ gosipụtara ahụmahụ mmekọahụ - emetụta ΔFosB.
  • Ihe ọzọ, mmetụta nke ahụmahụ mmekọahụ - kpatara ΔFosB maka nkọwa nke mgbochi nke c-Fos, nke a na-echekarị site na ΔFosB (Na-akwụ ụgwọ et al. 2008), e nyochara ya.
  • N'ikpeazụ, mmetụta nke ịmepụta ΔFosB ọrụ na NAc (ntinye mkpụrụokwu na nkwupụta nke onye na-abaghị uru na-adịgide adịgide) na omume mmekọahụ na mmemme nke mmezi nke inwe mmekọahụ na arụmọrụ kpebisiri ike site na iji nkà na ụzụ na-ekesa ngwa ngwa.
Gaa:

METHODS

Animals

E nwetara ụmụ nwoke Sprague Dawley bụ okenye (200-225 grams) site na Charles River Laboratories (Senneville, QC, Canada). Ụmụ anụmanụ nọ na plexiglas cages na otu eriri tube n'otu ubu nwoke na nwanyi n'ime ule nile. Ụlọ ụlọ ahụ na-achịkwa ọnọdụ okpomọkụ-ma na-echekwa na 12 / 12 hr ìhè mgbagwoju anya na nri na mmiri dị ad libitum ma n'oge a na-anwale ule. Nwanyị na-ebugharị (210-220 gram) maka oge ngwongwo natara ntinye nke subcutaneous nke nwere 5% estradiol benzoate na 95% cholesterol nke na-esote ovariectomy nke ọkpụkpụ n'okpuru nhụjuanya miri emi (0.35g ketamine / 0.052g Xylazine). Nlekọta nke 500μg progesterone na 0.1 mL mmanụ nke Sesame dị ka awa 4 batara tupu nyocha. Usoro nhazi nile kwadoro usoro niile nke Kọmitii Na-elekọta Ụmụaka na Ndị Kọmitii nke Mahadum Western Ontario ma kwekọọ na ntụziaka CCAC ndị metụtara ụmụ anụmanụ vertebrate na nnyocha.

Àgwà Ọjọọ

Oge mmemme mere n'oge mbido oge (n'oge 2-6 awa mgbe mmalite nke oge ọchịchịrị) na-acha ọkụ ọkụ. Tupu enwee mmegharị ahụ, a na-ekewa ụmụ anụmanụ na mpaghara. Mgbe a na-enwe oge mkparịta ụka, a na-ekwe ka ụmụ nwoke nwee ike iṅomi ya ma ọ bụ oge 1, na ederede maka mmekorita nwoke na nwanyị: gụnyere eriri elu (ML, oge site na mmalite nke nwanyị ruo mgbe ugwu mbụ), nwanyị ahụ ruo mgbe ugwu mbụ ahụ na-abanye na mpempe mmiri), ọgbụgba ejaculation (EL, oge site na mbụ mgbochi ejaculation), na-etiti oge ejaculation (PEI, oge site na ejaculation na mbido nke mbụ), ọnụ ọgụgụ nke mbadamba (M pelvic ịbanye n'ime mmiri), ọnụ ọgụgụ nke mgbochi (IM; ugwu tinyere ntinye nke mmiri) na ike nrụpụta (CE = IM / (M + IM)) (Agmo 1997). E tinyeghị ọnụ ọgụgụ nke nkwụnye na ntinye aka na nyocha maka anụmanụ ndị na-adịghị egosipụta ejaculation. Ugwu na mkpochapu ihe na-egosi na ị na-enwe mmekọahụ, ebe ọ bụ na ịghaghị ịkwa iko, ọnụ ọgụgụ nke nkedo na ịrụ ọrụ mmanye gosipụtara arụmọrụ mmekọahụ (Hull 2002).

Ahụhụ 1: Nkwupụta nke ΔFosB

E kwere ka ụmụ nwoke na ụmụ nwoke na-enwe mmekọahụ na-achọ ịbanye n'ule nyocha dị ọcha (60 × 45 × 50 cm) maka 5 n'otu oge, ma ọ bụ nọgide na-enwe mmekọahụ. Nchịkọta Ntụkọ 1 akọwa ụdị omume nke otu n'ime ihe ndị na-eme nchọpụta: enweghi mmekọahụ (NNS; n = 5), enweghi mmekọahụ (NS; n = 5), enweghi mmekọahụ (ENS; n = 5) na inwe mmekọahụ ahụmahụ (ES; n = 4). NS na ES na-achụrụ anụmanụ 1 oge na-esonụ ejaculation na ụbọchị ikpeazụ nke mating iji nyochaa okwu na-emetụta c-Fos okwu. Ejiri anụmanụ NNS chụọ anụ na ENS anụ ọhịa 24 otu oge mgbe oge mgbakọ ikpeazụ gasịrị iji nyochaa ahụmahụ nwoke na nwanyị na-ebute ΔFosB. Ndị dị iche iche na-enwe mmekọahụ na-eme ka ha nwee mmekọahụ tupu a nwalee ha. Achọpụtaghi ọdịiche dị ịrịba ama n'etiti ndị otu maka ụdị omume ọ bụla n'ime oge gbasara ntụrụndụ kwesịrị ekwesị na inwe mmekọahụ - emee ka mmemme nke mmekorita na-egosipụta ma ọ bụ òtù abụọ ahụmahụ ahụ (Nchịkọta Ntụkọ 2). Njikwa gụnyere ụmụ nwoke na-enwe mmekọahụ na-ejikọta ya na ụmụ anụmanụ na-ejikọta ọnụ na-achọpụta na ọ dị mma na mmetụta nke nwanyi na-enweghi ihe jikọrọ ya na nwanyi.

Maka àjà, ụmụ anụmanụ na-ejikarị sodium pentobarbital (270mg / kg; ip) na 50 mL nke 0.9% saline, tinyere 500 mL nke 4% paraformaldehyde na 0.1 M phosphate buffer (PB). E wepụrụ ụbụrụ ma tinyezie ya maka 1 h na ọnụ ụlọ okpomọkụ n'otu nhazi ahụ, tinyezie ya na 20% sucrose na 0.01% sodium azide na 0.1 M PB wee debe ya na 4 ° C. Mpaghara nke coronal (35 μm) ka e jiri ya na microtome na-egbuke egbuke (H400R, Micron, Germany), na-agbakọta usoro anọ dị na nchịkwa cryoprotectant (30% sucrose na 30% ethylene glycol na 0.1 M PB) na echekwara na -20 ° C. Achachachasịrị ngalaba na-ese n'elu mmiri na salin (PBS; pH 0.1-7.3) n'etiti incubations. E gosipụtara akụkụ nke 7.4% H2O2 maka 10 min na ụlọ okpomọkụ iji bibie peroxidases endogenous, mgbe ahụ ka egbochiri na PBS + ihe ngwọta, nke bụ PBS nwere 0.1% bovine serum albumin (ihe dịka 005-000-121, ihe ntanetị ndị Jackson ImmunoResearch, West Grove, PA) na 0.4% Triton X -100 (ihe odide nke BP151-500; Sigma-Aldrich) maka 1 h. A na - atụgharị akụkụ ahụ n'otu ntabi anya na 4 Celsius C na ngwongwo polyclonal pan-FosB (1: 5K; sc-48 Santa Cruz Biotechnology, Santa Cruz, CA, USA). A na-ebulite mgbochi FosB ahụ na-adabere na mpaghara mpaghara nke FosB na ΔFosB nwere. Mkpụrụ ndụ ΔFosB-IR bụ kpọmkwem ΔFosB-nti n'ihi na n'oge oge post-stimulus (24 awa) ihe niile a na-emepụta bụ FosB nwere ike ịmepụta ihe niile (Perrotti et al. 2004; Perrotti et al. 2008). Tụkwasị na nke a, na nnwale a, anụ anụmanụ na ụbọchị ikpeazụ (NS, ES) na-achụ àjà 1 h mgbe mating, si otú ahụ tupu okwu FosB. Usoro ntinye nchịkọta nke Western blossen gosipụtara nchọpụta nke ΔFosB na ihe dịka 37 kD. Mgbe a na-eme ka a ghara ikpo ọkụ, a na-agbazi ngalaba maka 1 h na IgG Igwe mgbochi-rabbit conjugated (1: 500 na PBS +; Laboratories Vector, Burlingame, CA, USA) na 1 h na avidin-biotin-hoseradish peroxidase (ABC elite ; 1: 1K na PBS; Vector Laboratories, Burlingame, CA, USA). Ejichara ngalaba ndị a na-emegharị otu n'ime ụzọ ndị a:

1. Nkọwa aha peroxidase naanị

Akụkụ nke NNS na ENS anụ ọhịa ka e ji mee ihe maka nyocha ụbụrụ banyere ahụmahụ mmekọahụ-ebute ΔFosB nchịkọta. Mgbe a na - agbaso ABC, a na - ahụ anya peroxidase mgbagwoju anya na - eso ọgwụgwọ nke 10 nkeji na ngwanrọ chromogen nke nwere 0.02% 3,3'-diaminobenzidine tetrahydrochloride (DAB; Sigma-Aldrich, St. Louis, MO) ejiri 0.02% nickel sulfate mee na 0.1 M PB na hydrogen peroxide (0.015%). A na-asacha akụkụ dị iche iche na 0.1 M PB iji kwụsị mmeghachi omume ma tinye n'elu Superfrost coding tinyere ihe ngosi iko (Fisher, Pittsburgh, PA, USA) na 0.3% gelatin na ddH20. Mgbe mmiri gwụsịrị, ihe nkedo nile bu ihe mkpuchi - tinyere DPX (dibutyl phthalate xylene).

2. Abụọ immunofluorescence

A na-eji akụkụ anọ nke nyocha nke nwere NAC na MPFC mee ihe maka nyocha nke ΔFosB na c-Fos. N'esoro ABC incubation, a gbanyere ngalaba maka 10 min na biotinylated tyramide (BT; 1: 250 na PBS + 0.003% H2O2 Kọmitii Ngwá Ọrụ Nyocha nke Tyramid, NEN Life Sciences, Boston, MA) na maka 30 min na Alexa 488-conjugated strepavidin (1: 100; Jackson Immunoresearch Laboratories, West Grove, PA). Mgbe ahụ, a na-agbazi akụkụ ahụ na mgbochi polyclonal rabbit na-achọpụta kpọmkwem c-Fos (1: 150; sc-52, Santa Cruz Biotechnology, Santa Cruz, CA), tinyere 30 min incubation na ọrịa mgbochi Cy3-conjugated second antibody (1: 200; Jackson Immunoresearch Laboratories, West Grove, PA, USA). Mgbe nchara, a sachasịrị ngalaba ahụ na 0.1 M PB, na-etinye ya na slid slides na 0.3% gelatin na ddH20 na-ekpuchi ya na onye na-arịwanye elu na-arị elu (Gelvatol) nke na-agụnye 1,4-diazabicyclo (2,2) octane (DABCO; 50 mg / ml, Sigma-Aldrich, St. Louis, MO). Njigide ihe na-eme ka ọ bụrụ na ọ bụ ma ọ bụ maọbụ ma nje abụọ ahụ, na-akpata enweghị ntinye aha na ntụgharị ntụgharị kwesịrị ekwesị.

Nyocha data

Nyocha nke obi nke ΔFosB

Ndị nlele abụọ na-ahụ maka ọgwụgwọ mere ụbụrụ ka ọ na-achọpụta ngwa ngwa na eserese nzuzo. A na-enyocha mkpụrụ ndụ ΔFosB-immunoreactive (-IR) n'ime ụbụrụ iji jiri ọnụ ọgụgụ nke mkpụrụ ndụ ΔFosB-positive dị ka akọwapụtara na Isiokwu 1. Na mgbakwunye, dabere na nchọta nke nchịkọta, ọtụtụ mkpụrụ ndụ ΔFosB-IR na-eji usoro ntụle dị iche iche nke ụbụrụ na-etinye na nkwụghachi ụgwọ na omume mmekọahụ site na iji igwefụfụ na-emepụta ihe dị na Leica Microsystems GmbH, Wetzlar , Germany): A tụlere NAc (isi (C) na shea (S); 400 × 600μm) na ọkwa atọ nke rostral-caudal (Balfour et al. 2004); mpaghara nyocha (VTA; 1000 × 800μm) nyochachara na ọkwa atọ nke rostral-caudal (Balfour et al. 2004) na VTA ọdụ (Perrotti et al. 2005); (cor) nke mbụ (ACA), prelimbic cortex (PL), infralimbic cortex (IL); 600 × 800μm ọ bụla); klas caudate (CP; 800 × 800μm); na preoptic nucleus (MPN; 400 × 600 μm) (Ụdị ihe atụ 1-3). A gụrụ akụkụ abụọ na mpaghara mpaghara ọ bụla, na ọnụ ọgụgụ maka anụmanụ maka nchịkọta nke òtù ahụ pụtara. A na-eji ụbụrụ ΔFosB-IR mepụta ụbụrụ na enweghi ahụmahụ nke ọhụụ maka mpaghara nchịkwa ọ bụla site na iji t-ule a na-akwụghị ụgwọ.

Isiokwu 1    

Nchịkọta nke okwu ΔFosB na ụmụ anụmanụ na ụmụ anụmanụ nwere ahụmahụ
Nyocha nke ΔFosB na c-Fos

E weghaara foto site na iji kamera CCD nwere ume (Microfire, Optronics) nke ejikọtara na microscope Leica (DM5000B, Leica Microsystems, Wetzlar, Germany) na ngwanrọ Neurolucida (MicroBrightfield Inc) na ntọala igwefoto setịpụrụ maka isiokwu niile (iji ihe mgbaru ọsọ 10x). Ọnụ ọgụgụ nke mkpụrụ ndụ na-egosipụta c-Fos-IR ma ọ bụ ΔFosB-IR na mpaghara ntụle nke analysis na isi NA shea (400 × 600μm ọ bụla; Ihe atụ 1) na ACA nke mPFC (600 × 800μm; Ihe atụ 3) onye na-ekiri ihe na-eme nchọpụta na-ejide onwe ya n'ìgwè ahụ, na mpaghara 2 maka anụ ọ bụla na-eji software Neurolucida (MBF Bioscience, Williston, VT) na ụgwọ maka anụmanụ. A na-eji ọnụ ọgụgụ nke C-Fos ma ọ bụ sel ΔFOSB eme ihe site na iji ANOVA ụzọ abụọ (Ihe kpatara: ahụmahụ mmekọahụ na ọrụ mmekọahụ) na Fisher LSD maka njirimara post na nke 0.05 dị mkpa.

Nlekọta 2: Ntughari okwu ΔFosB

Gbanwee Gbanwee Ọkụ Vector-Mediated

A na-ekewa ụmụ nwoke Sprague Dawley nke na-enwe mmekọahụ na-enwe mmekọahụ ma ọ bụrụ na ha enweghi ike ịwa ahụ. Ụmụ anụmanụ niile na - ejikọta GFP (njikwa; n = 12), ụdị anụ ọhịa ΔFosB (n = 11) ma ọ bụ onye na - ejide onwe ya na - adịgide adịgide nke ΔFosB a na - akpọ ΔJunD (n = 9) n'ime NAc. ΔJunD na - ebelata nsụgharị ΔFosB nke a na - agbasa site na ịsọpụrụ heterodimerizing na ΔFosB tupu ejikọta mpaghara AP-1 n'ime ndị na -Winstanley et al. 2007). Achọpụtara nje virus site na qPCR ma nyochaa ya na vivo tupu ọmụmụ amalite. Titer bụ 1-2 × 1011 ihe na-efe efe kwa mL. A na-agbanye vekAV nke a na-akpọ 1.5 μL / n'akụkụ na 7 nkeji (nchịkọta: AP + 1.5, ML +/- 1.2 si Bregma; DV -7.6 si na mbara ala aka dị ka Paxinos na Watson, 1998) na-ejiri syringe Hamilton (5μL Harvard Apparatus, Holliston, MA, USA). Ihe na-emepụta ihe anaghị eme ka mmadụ ghara ịṅụbiga mmanya ókè karịa ka ọ na -Winstanley et al, 2007; maka nkọwa gbasara nkwadebe AAV, lee Hommel et al., 2003). Nchọpụta ịba ụbụrụ malitere na 3 n'izu mgbe ịchọrọ ịchọta ahụ na-enye ohere maka ịrịa ọrịa zuru oke na nke siri ike (Wallace et al. 2008). Okwu nke transgene na umu oke ugbua na 10 ụbọchị ma ka ebuli elu ma ọ dịkarịa ala ọnwa 6 (Winstanley et al. 2007). Na njedebe nke nnwale ahụ, a na-emegharị anụmanụ ndị a na-ebugharị ma na ngalaba nke NAc na-edozizi maka GFP (1: 20K, antibody GFP antibody; Mkpụrụ Igwe Mkpụrụ) na-eji mmeghachi ABC-peroxidase-DAB (dịka akọwapụtara n'elu) na histologically nyochaa ogwu ogwu site na iji GFP dika ihe akara (Ihe atụ 4). ΔFosB na ΔJunD vectors nwekwara mpaghara nke na-akọwa GFP nke site na saịtị ntinye nke ribosomal, na-enye ohere iji nweta nkwenye site na GFP na anụ ọhịa niile. Naanị ụmụ anụmanụ na saịtị na-egbu ogbugba ma gbasaa nje na-egbochi NAC gụnyere nyocha nchịkọta akụkọ. A na-ejidekarị nje virus na akụkụ nke NAC ma ghara ịgbasa ọkpụkpụ na-eme ka ọkpụkpụ ahụ pụta. Ọzọkwa, nje virus pụtara na ọ bụ nanị ma ọ bụ shea ma ọ bụ isi. Otú ọ dị, mgbanwe nke saịtị ndị na-egbu ma gbasaa n'ime NAc adịghị emetụta mmetụta na omume. N'ikpeazụ, mmechi nke GFP emetụtaghị omume mmekọahụ ma ọ bụ mmemme na-eme ka ndị mmadụ nwee mmekọahụ ma e jiri ya tụnyere ụmụ anụmanụ na-abụghị ndị na-awa ahụ site na ọmụmụ ihe gara aga (Balfour et al. 2004).

Àgwà Ọjọọ

Izu atọ na - esochi ngwa ngwa nke vetila, ụmụ anụmanụ na - ejikọta otu ejaculation (ma ọ bụ maka 1 hour) maka 4 n'otu oge, na-enwe kwa ụbọchị iji nweta ahụmahụ mmekọahụ (oge nleta) ma wee mesịa nyochaa maka okwu ogologo oge nke ahụmịhe nke mmemme mmemme nke 1 na 2 izu (oge nyocha 1 na 2) mgbe ikpe ikpeazụ. Edere mmegharịrị mmekorita nwoke na nwanyị na oge niile na-agwakọta dị ka akọwara n'elu. A na-atụle esemokwu statistical for all sorts during each session mating in and between groups using a double-frequency measurements ANOVAs (Ihe: ọgwụgwọ na mkparịta ụka mgbochi) ma ọ bụ otu ụzọ ANOVAs (mkparịta ụka ejaculation, ọnụ ọgụgụ nke nkedo na intromission; nnọkọ) na-esote nkuzi Fisher LSD ma ọ bụ Newman-Keuls maka nyochaa post-hoc na 0.05 dị mkpa. N'ụzọ doro anya, a na-atụle mmemme mmemme nke ahụmahụ mmekọahụ na mpaghara alụlụlụ dị n'etiti nhụkọ ahụmahụ 1 (naịve) ma nwee ahụmahụ 2, 3, ma ọ bụ 4 ọ bụla, nakwa n'etiti otu nchọpụta n'ime oge nlekọta ọ bụla. Ọzọkwa, iji nyochaa mmetụta nke ọgwụgwọ (vek) na mmezi oge nke omume mmekọahụ, a na-ejikọta akụkụ elekere anya n'etiti nnọkọ ahụmahụ 4 na oge nyocha 1 na 2 n'ime otu usoro ọgwụgwọ, ma tụnyere ha n'etiti otu nchọpụta n'ime oge nlele ọ bụla.

Gaa:

IHE

Ahụmahụ mmekọahụ na-akpata ΔFosB mkpokọta

Na mbido, nchọpụta nchịkọta nke nchịkwa ΔFosB n'ozuzu ụbụrụ ka ụmụ nwoke na-enwe mmekọahụ na-atụle nchịkwa nwoke na nwanyị. Nchịkọta nke nchoputa zuru ezu ka enyere Isiokwu 1. A nyere aka nyochaa ΔFosB-IR site na ịchọpụta ọnụọgụ nke mkpụrụ ndụ ΔFosB-IR n'ọtụtụ ụbụrụ ụbụrụ ejikọtara na-eji mpaghara nke nyocha. Nyocha 1 egosiputa ihe ngosi nke DAB-Ni na-achoputa NAC nke anu aru na ndi nwere ahuhu. Achọpụtara ụkpụrụ iwu ΔFosB dị ịrịba ama na mpaghara mPFC subregions (Nyocha 2A), Nac na shea (2B), ihe na-eme ka ọ bụrụ (2B) na VTA (2C). Na NAc, ọdịiche dịgasị iche dị na ọkwa nile nke rostral-caudal na isi NAc na shea, na data egosiri na Nyocha 2 bụ ọnụ ọgụgụ karịa ọkwa niile nke rostro-caudal. N'ụzọ dị iche, enweghi ọganihu dị ukwuu na ΔFosB-IR na hypothalamic medial preoptic nucleus (NNS: Avg 1.8 +/- 0.26; ENS: Avg 6.0 +/- 1.86).

Nyocha 1    

 

Ihe ngosi ndi ozo nke na-egosi ΔFosB-IR (nwa) na NAc nke nwaghi nwoke (A) ma enweghi otu nwoke (B). aco: nsụgharị akaebe N'uba mmanya na-egosi 100 μm.
Nyocha 2     

Ọnụ ọgụgụ nke mkpụrụ ndụ ΔFosB-IR na: A. infralimbic (IL), prelimbic (PL) na okpukpu ụbụrụ cingulate cortex (ACA) nke na-ahụ maka prefrontal corlyx; B. Ụdị isi na shei na-eme ka ọ bụrụ ihe na-adịghị mma, na kọmitii na-arụ ọrụ (CP); C. Rostral, n'etiti, caudal na ọdụ ...

Ahụmahụ mmekọahụ na-eme ka c-Fọd na-emetụta ya

E gosipụtara mmetụta nke ahụmahụ mmekọahụ na ọkwa ΔFosB na NAc site na iji usoro ntanetị ọkụ. Tụkwasị na nke ahụ, a na-enyocha mmetụta nke ahụmahụ mmekọahụ na nkwupụta nke C-Fos. Nyocha 3 egosiputa ihe oyiyi nke ΔFosB- (green) na c-Fos (red) -IR na sel nile n'ime otu nnwale (A, NNS; B, NS; C, ENS; D, ES). Ahụmahụ mmekọahụ na-esiwanyewanye ΔFosB okwu na NAc isi (Nyocha 4A: F1,15 = 12.0; p = 0.003) na shei (Nyocha 4C: F1,15 = 9.3; p = 0.008). N'ụzọ dị iche, oge 1 na-agwakọta tupu oge nsị, enweghị mmetụta na okwu ΔFosB (Nyocha 4A, C) na enweghi mmekorita di n'etiti nmekorita nwoke na nwanyi na ngwongwu ozugbo enwere ike ichota. E nwere mmetụta zuru oke nke ngwongwo tupu ịmịnye ihe na c-Fos okwu ma na NAc isi (Nyocha 4B: F1,15 = 27.4; p <0.001) na shei (Nyocha 4D: F1,15 = 39.4; p <0.001). Ọzọkwa, a chọpụtara mmetụta zuru oke nke ahụmịhe nke mmekọahụ na isi NAc (Nyocha 4B: F1,15 = 6.1; p = 0.026) na shei (Nyocha 4D: F1,15 = 1.7; p = 0.211) na mmekọrịta dị n'etiti ahụmahụ nwoke na nwanyị na ngwongwu tupu ịmịọpụ achọpụtara na NAc (F1,15 = 6.5; p = 0.022), na-emekarị na shei (F1,15 = 1.7; p = 0.211; F1,15 = 3.4; p = 0.084). Ihe nyocha nke hoc gosiputara igosi okwu c-Fos na-eme ka ihe na-emetụta ya na-emetụta ya na isi nke ụmụ nwoke na-enwe mmekọahụ (Nyocha 4B, D). Otú ọ dị, n'ime ụmụ nwoke na-enwe mmekọahụ, c-Fos adịghị arịwanye elu na NAc isi (Nyocha 4B) na eleba anya nke ukwuu na shea (Nyocha 4D). N'ihi ya, ahụmahụ mmekọahụ kpatara mbelata nke okwu C-Fọd na-emetụta ya. Ụkpụrụ P na-ejikọta ọnụ ọgụgụ dị iche iche na-atụle akụkọ akụkọ.

Nyocha 3     

Ihe ngosi ndị nnọchiteanya na-egosipụta ΔFosB (green) na c-Fos (ọbara ọbara) na NAc maka otu ọhụụ ọ bụla. Ogwe osisi na-egosi 100 μm.
Nyocha 4     

Mmekọrịta ahụmahụ nke mmekọahụ nwere ΔFosB na c-Fid na-emetụta ya. Ọnụ ọgụgụ nke ΔFosB (Core, A; Shell, C; ACA, E) ma ọ bụ C-Fos (Core, B; Shell, D; ACA, F) mkpụrụ ndụ immunoreactive maka otu ọ bụla: NNS (n = 5), NS (n = 5), ENS (n = 5) ma ọ bụ ES (n = 4). A na-egosipụta data ...

Mmetụta nke ahụmahụ mmekọahụ na ọkwa c-Fọd na-emetụta ụbụrụ abụghị nanị na NAc. Ejiri ihe yiri nke C-Fos dị na ACA na ụmụ anụmanụ nwere mmekọahụ ma e jiri ya tụnyere njikwa na-enwe mmekọahụ. Ahụmahụ mmekọahụ nwere mmetụta dị ịrịba ama na okwu ΔFosB na ACA (Nyocha 4E: F1,15 = 154.2; p <0.001). Atinggụ tupu ịmalite perfusion enweghị mmetụta na okwu ΔFosB (Nyocha 4C) ma budata ụba c-Fos (Nyocha 4F: F1,15 = 203.4; p <0.001) na ACA. Ọzọkwa, mmekorita c-Fos na-ekwu okwu na ACA belatara nke ukwuu site na ahụmịhe mmekọahụ (Nyocha 4F: F1,15 = 15.8; p = 0.001). Achọpụtara ụzọ abụọ ụzọ dị n'etiti ahụmahụ mmekọahụ na ngwongwu tupu ịmịnye ahụ maka c-Fos expression (Nyocha 4F: F1,15 = 15.1; p <0.001). -Kpụrụ P maka nkọwa doro anya dị iche iche dị na akụkọ ifo. N'ikpeazụ, enweghị mbelata dị ukwuu na ntinye okwu nke c-Fos na-atụgharị uche na ntọala preoptic medial (NS: Avg 63.5 +/− 4.0; ES: Avg 41.4 +/− 10.09), mpaghara ebe ahụmahụ mating adịghị eme ka ọ dị mkpa abawanye na okwu ΔFosB, na-egosi na emetụtaghị okwu c-Fos na-emetụta mating na mpaghara ụbụrụ niile.

ΔFosB na NAc na-akwado nkwado nke omume mmekọahụ

Iji nyochaa usoro ihe omuma nke nwere ike ime ka mmekorita nwoke na nwanyi nwee mmekorita dika ndi egosiputara site na mmekorita nke nwoke na nwanyi, enwere ike imeghari ihe nke ΔFosB na ihe edere ya. Ahụmahụ mmekọahụ na oge ọmụmụ ihe anọ dị iche iche nwere mmetụta dị ịrịba ama na mgbago ugwu (Nyocha 5A: F1,23 = 13.8; p = 0.001), nkwụsị ụbụrụ (Nyocha 5B: F1,23 = 18.1; p <0.001), na ejaculation latency (Nyocha 5C: GFP, F11,45 = 3.8; p = 0.006). GFP na-achịkwa ụmụ anụmanụ gosipụtara ahụmahụ a tụrụ anya ya-ịmebata mmemme nke inwe mmekọahụ ma gosipụta ụda nta nke nta ka obosara mbụ, mbido mbụ na ejaculation n'oge nnọkọ ahụ 4 na-atụnyere na oge nhọta 1 (Dee 5A-C; lee akụkọ ihe atụ maka p-uru). A hụkwara mmemme a na-akpali akpali nke inwe mmekọahụ na ìgwè ΔFosB maka ugwu na mgbochi ndị na-emepụta ihe, ma enweghi ihe dị ịrịba ama a chọpụtara na ụkọ ejaculation (Dee 5A-C). N'ụzọ dị iche, ụmụ anụmanụ ΔJunD gosipụtara mmemme nkwụsịtụ; ọ bụ ezie na ụlọ ọgwụ maka ndọtị, njigide, na ejaculations egbusara ya na oge ugboro ugboro, ọ dịghị nke ọ bụla n'ime ihe ndị a ga - aba uru dịka ọnụ ọgụgụ mgbe e jiri ya tụnyere oge mmemme 1 na 4 (Dee 5A-C). N'etiti ngọngọ nke otu maka ahụmịhe ọhụụ ọ bụla gosiri na ΔJunD nwere ụlọnga dị ogologo karịa ka ọ dị elu, na-ebute ma na-ejaculate n'oge oge nlebara anya tụnyere ΔFosB na GFP (Dee 5A-C). Tụkwasị na nke ahụ, ahụmahụ mmekọahụ na ọgwụgwọ nwere mmetụta dị ịrịba ama na arụmọrụ ịṅụ ọgwụ (Nyocha 5F: ahụmahụ mmekọahụ, F1,12 = 22.5; p <0.001; ọgwụgwọ, F1,12 = 3.3; p = 0.049). Ụmụ nwoke BΔBB nwere ụba na-arụ ọrụ na oge 4 na-ahụmahụ ma e jiri ya tụnyere oge nnọkọ 1 (Nyocha 5F). Tụkwasị na nke a, anụmanụ ΔFosB nwere ntakịrị ihe ntanculation bu ụzọ tupu ụbọchị 4 ahụmahụ, ma e jiri ya tụnyere oge nhọta 1 (Nyocha 5D: F10,43 = 4.1; p = 0.004), nakwa na ụmụ nwoke ndị AJunD nwere ụba na-arịwanye elu karịa ejaculation, si otú a mee ka ọnụ ọgụgụ dị mma karịa ka nke abụọ ndị ọzọ (Dee 5D na F). Ya mere, GFP na anụmanụ ΔFosB gosipụtara mmalite ahụmahụ na-eweta mmemme nke ịmalite ịkwa iko na omume mmekọahụ, ebe ọ bụ na ụmụ anụmanụ nke AJND adịghị.

Nyocha 5     

Mmekọahụ nke GFP (n = 12), ΔFosB (n = 11) na ΔJunD (n = 9) ụmụ anụmanụ: mgbaba ugwu (A), nkwụsị ụbụrụ (B), mgbachi ejaculation (C), ọnụ ọgụgụ nke mgbago (D), ọnụ ọgụgụ ndị na-emepụta ihe na-emepụta (E) na ịrụpụta ọgwụ (F). A na-egosipụta data ...

Iji nwalee echiche bụ na okwu ΔFosB dị oké mkpa maka okwu ogologo oge nke mmemme nke mmekorita nke omume mmekọahụ, a nwalere ụmụ anụmanụ nyocha 1 (oge nyocha 1) na izu 2 (oge nyocha 2) mgbe oge ikpe ikpeazụ. N'ezie, a nọgidere na-enwe mmekọahụ n'etiti ìgwè GFP na ìgwè ΔFosB ka ọ dịghị nke ọ bụla n'ime akpa àgwà dị iche n'etiti nyocha 1 ma ọ bụ 2 na nnọkọ ikpeazụ 4, n'ime GFP na ìgwè ΔFosB (Dee 5A-C; ọ gwụla ma ọ bụrụ na e nwere ike imepụta ejaculation na ike ịrụ ọrụ n'ime oge 1 nyocha maka anụmanụ ΔFosB). Esere dị iche n'etiti anụmanụ ΔJunD na GFP ma ọ bụ ìgwè ΔFosB ka a hụrụ na nyocha abụọ ahụ maka mmemme niile nke mmekọahụ (Nyocha 5A-F). Enweghị ọdịiche dị n'etiti ma ọ bụ n'ime ndị ọzọ mgbe ị na-atụle ọnụọgụ abụọ nke mberede, PEI, ma ọ bụ percentages nke ụmụ anụmanụ ndị ejikọtara (100% nke ụmụ nwoke na mpaghara niile ejaculated n'oge ikpeazụ anọ na ngwongwo sessions).

Gaa:

NKWASỊTA

Nnyocha a na-amụ ugbu a gosipụtara na ahụmahụ mmekọahụ na-akpata nchịkọta nke ΔFosB n'ọtụtụ mpaghara ụbụrụ na-ejikọta ọnụ, gụnyere nke NAc na shea, mPFC, VTA na caudate. Tụkwasị na nke ahụ, ahụmahụ mmekọahụ na-eme ka okwu c-Fos dị na mating depụtara na NAc na ACA. N'ikpeazụ, a gosipụtara ΔFosB na NAc dị ka ihe dị oké mkpa n'ịgbasa mmemme nke ịlụ di na nwunye mgbe ị na-enweta ahụmahụ mmekọahụ na okwu dị ogologo oge nke mmemme nke mmekorita nke inwe mmekọahụ. N'ụzọ doro anya, ịbelata įFosB na-eme ka a sụgharịrị ihe ọmụma na-eme ka a sụgharịa ya na-eme ka ọ bụrụ ihe na-akpali agụụ mmekọahụ na arụmọrụ, mgbe ihe ngosi nke ΔFosB na NAC mere ka enwee mmezi nke mmekorita nwoke na nwanyi, n'inwekwu mmekorita nwoke na nwanyi na enweghi mmuta. Otu n'ime ihe ndị a dị ugbu a na-akwado nkwenye ahụ bụ na ΔFosB bụ onye mgbasa ozi dị egwu nke dị egwu maka usoro ntanetị nke na-adịte aka na nke omume na-emetụta site na ahụmahụ mmekọahụ.

Ihe nchọpụta ndị a na-eme ugbu a na-egosi ihe ọmụmụ gara aga na-egosi ahụmahụ mmekọahụ - ΔFosB na-eduga na NAc na oke oke oke (Wallace et al. 2008) na nwanyi hamsters (Ogo et al. 2009). Wallace et al. (2008) gosiri na rAAV-Ngosiputa ΔFosB na omume nwoke na nwanyi na-enwe mmekọahụ na mbụ na nke NAc n'oge mbụ na-aga n'ihu, dị ka ihe àmà na-egosi na ọnweghị mkparịta ụka na mkparịta ụka dị mkpirikpi, ma enweghị mmetụta ọ bụla na ụmụ nwoke nwere mmekọahụ (Wallace et al. 2008).

N'ụzọ dị iche, nchọpụta a dị ugbu a gosipụtara mmetụta ọ bụla nke ΔFosB na-apụtaghị na ụmụ nwoke na-enwe mmekọahụ na-esote n'oge ule mbụ ahụ, mana n'oge na ịchụso ahụmahụ mmekọahụ. Ndị na-egosipụta nkwupụta ụda ΔFBB gosipụtara ọganihu nke mmekorita nwoke na nwanyị (mmụba nke nrụpụta) ka e jiri ya tụnyere anụmanụ GFP.

Tụkwasị na nke ahụ, nnyocha a na-amụ ugbu a nwalere ọrụ nke ΔFosB site na igbochi transcription mgbasa ozi ΔFosB site na iji ΔJunD-ekwupụta ngwa ngwa viral. Mgbochi nke mmụba ahụmahụ na-emetụta okwu nke ΔFosB emechibidoro mmemme nke mmekorita nke inwe mmekọahụ (ọnụ ọgụgụ ndị na-arịwanye elu na ndị na-eme ka ndị mmadụ ghara ịmalite ime ihe ike) nakwa dị ka mmekorita nke nwanyị (ụba ejaculation na ọnụ ọgụgụ nke nkedo) na okwu ogologo oge nke ime ka enwe mmekọahụ.

N'ihi ya, data ndị a bụ nke mbụ na-egosi ọrụ dị mkpa maka ΔFosB na inweta nnweta mmemme nke mmekorita nke mmekọahụ. Ọzọkwa, data ndị a na-egosi na ΔFosB na-emetụkwa aka na okwu ogologo oge nke mmemme nwere mmemme. Anyị na-ekwu na okwu a nke ogologo oge na-egosi ụdị nkwụsị maka ụgwọ ọrụ ziri ezi, ya mere ΔFosB na NAc bụ onye ogbugbo maka nchekwa ọrụ. Ahụmahụ mmekọahụ na-arịwanye elu ΔFosB ọkwa na VTA na MPFC, ebe a na-etinye na ụgwọ ọrụ na ebe nchekwa (Balfour et al. 2004; Phillips et al. 2008). A choro ichoputa ihe omumu ka ichoputa iwu nke ΔFosB n'elu ebe ndi a maka maka nchekwa.

Okwu nke ΔFosB siri ike, ya mere, o nwere ike dị ukwuu dịka onye ogbugbo nke na-agbanwe agbanwe mgbe ụbụrụ na -Nestler et al. 2001). A gosipụtara ΔFosB nwayọọ nwayọọ na NAc n'elu ọnụọgụ cocaine ọtụtụ na ịnọgide na-anọ ruo izu ole na ole (olileanya na et al. 1992; olileanya na et al. 1994). Mgbanwe ndị a na okwu NAC ΔFosB na-ejikọta na nkwụnye ụgwọ ọgwụ na ịṅụ ọgwụ ọjọọ (Chao & Nestler 2004; McClung & Nestler 2003; McClung et al. 2004; Nestler 2004, 2005, 2008; Nestler et al. 2001; Zachariou et al. 2006). N'ụzọ dị iche, arụ ọrụ nke ΔFosB na mgbasa ozi maka ụgwọ ọrụ nkịtị ka edozila. Ihe ndi ozo gosiri na ntinye nke ΔFosB na NAc bu ihe ugwo. Ụdị ΔFosB na-arịwanye elu na NAC na-esote nri sucrose na wiil na-agba ọsọ. Ngosipụta nke ΔFosB na striatum n'iji bitransgenic ụmụ oke ma ọ bụ ndị nje nje na-ebute mmụba na oriri nke sucrose, akpali akpali maka nri na ụba wheel na-agba ọsọ (Olausson et al. 2006; Wallace et al. 2008; Werme et al. 2002). Ihe data dị ugbu a na-agbakwụnye na akụkọ ndị a ma na-akwado nkwenkwe ahụ na ΔFosB bụ onye nkwekọrịta dị oke egwu iji nweta nkwado na ụgwọ ọrụ ụgwọ ọrụ.

ΔFosB nwere ike ịkọwa nkwado nke mmekorita nke mmekorita site na ime ka plasticity na usoro mesolimbic. N'ezie, ahụmahụ mmekọahụ na-eweta ọtụtụ mgbanwe dị ogologo na usoro mesolimbic (Bradley & Meisel 2001; Frohmader et al. 2009; Ndị na-akụ ụta et al. 2010). An'omume omume, nzaghachi nke locomotor na amphetamine na nrite amphetamine mepere emepe egosiputala na oke ụmụ nwoke nwere mmekọahụ (Ndị na-akụ ụta et al. 2010); a hụkwara usoro amị ụmụ na-eme ka amphetamine gbanwee na ụmụ nwanyị na -Bradley & Meisel 2001). Ọzọkwa, a na - achọta ọnụọgụ nke nrịba dendritic na mgbagwoju anya nke arbors dendritic mgbe ọ na - esote oge abstinence site na inwe mmekọahụ na oke nwoke (Ndị na-akụ ụta et al. 2010). Ihe omumu a na-egosi na ΔFosB nwere ike ịbụ onye ogbugbo kpomkwem nke ihe omimi nke ihe omimi. Na nkwekọrịta, a gosipụtara ΔFosB na nso nso a na ọ dị mkpa maka ịmalite mgbanwe mgbanwe ntụgharị dendritic iji zaghachi nchịkwa cocaine na-adịghị ala ala (Dietz et al. 2009; maze et al. 2010).

O doro anya na ndị na-ahụ maka ntanetransite (s) na-ebute ΔFosB na NAc, ma a gwala ya ka ọ bụrụ onye na -Nye et al. 1995). Ihe fọrọ nke nta ka ọ bụrụ ọgwụ ọjọọ nile, gụnyere cocaine, amphetamine, opiates, cannabinoids, na ethanol, yana ụgwọ ọrụ nkịtị, na-amụba ΔFosB na NAc (Perrotti et al. 2005; Wallace et al. 2008; Werme et al. 2002). Abụọ ọgwụ ọjọọ na ụgwọ ọrụ nkịtị na-eme ka synaptic DA concentration na NAc (Damsma et al. 1992; Hernandez & Hoebel 1988a, b; Jenkins & Becker 2003). E gosipụtara ọgwụ ọjọọ ΔFosB iji mee ihe n'ụzọ na-ezighị ezi na DA onye ntinye aka nwere sel na cocaine-akpagharị ΔFosB na-egbochi site na D1 DA receptor antagonist (Nye et al. 1995). N'ihi ya, a tọhapụrụ DA nkwupụta iji kpalie okwu ΔFosB ma si otú a gbasaa neuroplasticity. Na-akwado nkwenkwe na ΔFosB ọkwa bụ DA-dabere bụ ịchọpụta na ebe ụbụrụ ebe enwere mmekọahụ na-agbanwe ΔFosB ọkwa na-enweta ike dopaminergic ndenye si VTA, gụnyere medial prefrontal cortex na amọla amygdala.

Otú ọ dị, n'ụzọ dị iche, a naghị amụba ΔFosB na mpaghara preoptic na-ahụ anya ọ bụ ezie na mpaghara a na-enweta ntinye aka dopaminergic, ọ bụ ezie na isi mmalite hypothalamic (Miller & Lonstein 2009). Achọpụta ọmụmụ ihe n'ọdịnihu iji nwalee ma ọ bụrụ na nkwupụta ΔFosB na-emetụta ụbụrụ na mmetụta nke inwe mmekọahụ na mkpali na arụmọrụ na-adabere na arụmọrụ DA. Ọrụ nke DA na ụgwọ ọrụ ego na oke ụmụ nwoke adịghị ugbu a kpamkpam (Agmo & Berenfeld 1990; Pfaus 2009). E nwere ọtụtụ ihe àmà na-ahapụ DN na NAC mgbe ọ na - ekpughe nwanyị ma ọ bụ na -Damsma et al. 1992) na a na-ejikwa DA neurons rụọ ọrụ mgbe ha na-enwe mmekọahụ (Balfour et al. 2004). Otú ọ dị, nhazi usoro nke onye na-anabata onye na-anabata onye na-anabata ozi ọma anaghị egbochi ịlụ nwanyị na -Agmo & Berenfeld 1990) na nkwenye nke DA dị oké mkpa maka nkwado nke ahụmahụ na-emetụtaghị ya.

O dokwara anya banyere ihe ndị na-ekwusi olu ike banyere ΔFosB mmetụta gbasara omume mmekọahụ. A gosipụtara ΔFosB iji rụọ ọrụ dịka ma onye na-arụ ọrụ na transressal site na usoro AP-1 (McClung & Nestler 2003; Peakman et al. 2003). A matawo ọtụtụ mkpụrụ ndụ ihe nketa dị iche iche, gụnyere usoro mmalite c-fos n'oge mbụ (olileanya na et al. 1992; olileanya na et al. 1994; Morgan & Curran 1989; Na-akwụ ụgwọ et al. 2008; Zhang et al. 2006), cdk5 (Azu et al. 2001), dynorphin (Zachariou et al. 2006), sirtuin-1 (Na-akwụ ụgwọ et al. 2009), NFBB subunits (Ang et al. 2001), aenwe ihe nkwụnye ngwanrọ AMPA glutamate GluR2 (Kelz et al. 1999). Ihe ndị dị ugbu a na-egosi na enwere mmekọrịta mmekọahụ na ụbụrụ c-Fos na-eme ka ụbụrụ na-adaba na ụbụrụ na-arịwanye elu ΔFosB (NAc na ACA). Ntuchi nke c-Fos na-egosi dabere na oge ebe ọ bụ na nkwonkwo ikpeazụ na ugboro ugboro, dị ka ọ dị na ọmụmụ ihe gara aga, a chọpụtaghị ọnụ ọgụgụ nke c-Fos na oke ụmụ nwoke a nwalere 1 n'izu mgbe ịmechara mgbakọ ikpeazụ (Balfour et al. 2004) ma ọ bụ mgbe enwere mmekọahụ na-agụnye nanị otu nnọkọ ntụrụndụ (Lopez & Ettenberg 2002). Ọzọkwa, nchọpụta a na-achọta ugbu a kwekọrọ na ihe àmà na-egosi na ΔFosB na-agbapụta mkpụrụ ndụ c-fos mgbe ụbụrụ amphetamine na-adịghị ala ala (Na-akwụ ụgwọ et al. 2008). N'ikwekọ na nchoputa ndị a, a na - ebelata mmepụta nke ọtụtụ mRNA (mmalite oge, mgbochi), c-fos, fosB, c-jun, junB, na zif268 mgbe ha na - emechi cocaine ugboro ugboro ma e jiri ya tụnyere ọgwụ na -olileanya na et al. 1992; olileanya na et al. 1994), etinyere c-fos amphetamine na-esote mgbe a na-ewepụ ya site n'ọchịchị amphetamine na-adịghị ala ala (Jaber et al. 1995; Na-akwụ ụgwọ et al. 2008). Mmetụta dị irè nke usoro iwu nke okwu C-Fos mgbe ọgwụgwọ ọgwụ na-adịghị ala ala ma ọ bụ ahụmahụ mmekọahụ na-anọgide na-edoghị anya, a kwadoro ka ọ bụrụ ụzọ dị mkpa nke homeostatic iji chekwaa ihe ụmụ anụmanụ na-eme iji nweta ụgwọ ọrụ ugboro ugboro (Na-akwụ ụgwọ et al. 2008).

N'ikpeazụ, nchọpụta nke ugbu a na-egosi na ΔFosB na NAc na-arụ ọrụ dị mkpa na nchekwa ego na-arụ ọrụ, na-akwado na o nwere ike ịbụ na ΔFosB dị mkpa maka nweliteghachi na mgbake na ụgwọ. Ihe nchoputa site na omumu nke ugbua na-eme ka anyi gh ota ihe omuma banyere usoro ihe omumu na nke di omimi nke na-eme ka ndi mmadu nwee ike ime ka ndi mmadu nwee ihe ndi ozo na-eme ka o doo anya na ΔFosB bu ihe di mkpa n'inwe mmekorita, site n'igosi ΔFOSB maka ugwo olu nkwenye.

Gaa:

Ihe ndi ozo

Tụlee Fig S1-S4 & Isiokwu S1-S2

Gaa:

Acknowledgements

A na-akwado nyocha a site na enyemaka site n'aka Ụlọ Ọrụ Na-ahụ Maka Ahụ Ike Kanada na LMC, National Institute of Healthental Mental Health na EJN, na Nkà Na-ahụ Maka Nkà na Nkà Injinịa Canada nke KKP na LMC.

Gaa:

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