Synapse. 2008 May;62(5):358-69.
Perrotti LI, Weaver RR, Robison B, Renthal W, Maze I, Yazdani S, Elmore RG, Knapp DJ, Selley DE, Martin BR, Sim-Selley L, Bachtell RK, Self DW, Nestler EJ.
mohloli o moholo
Lefapha la Psychiatry, Setsi sa Bongaka sa Texas Southwestern Medical, Dallas, Texas 75390-9070, USA.
inahaneloang
Ntho ea transcription DeltaFosB ea bokellana le ho phehella mohopolong ka karabelo ea ho tsosoa ho sa feleng. Keketseho ena kamora ho pepesehela lithethefatsi tsa tlhekefetso e bonts'itsoe pejana ke sebaka sa Bophirimela se ikhethang haholo libakeng tse literekeng, ho kenyeletsoa dorsal striatum (caudate / putamen) le nucleus accumbens. Thutong ea hona joale, re sebelisitse immunohistochemistry ho hlalosa ka mokhoa o nepahetseng haholoanyane ho kenella ha DeltaFosB ho pholletsa le kelello ea methapo ka mora kalafo e sa foleng ea lithethefatsi. Re boetse re atolositse lipatlisiso tse fetileng tse amang cocaine, morphine, le nikotine ho lithethefatsi tse ling tse peli tsa tlhekefetso, ethanol le Delta (9) -tetrahydrocannabinol (Delta (9) -THC, motsoako o sebetsang oa matekoane. Re bonts'a mona hore taolo ea e 'ngoe le e' ngoe ea lithethefatsi tse mpe tsa koae, cocaine, morphine, ethanol, le Delta (9) -THC, e tsitsitseng ka matla DeltaFosB ka har'a li-sublocation tsa khetla le khetla. tsa nuk'hu e ne e bonahala ka litlhare tse fapaneng. Lithethefatsi li ne li boetse li fapana ka tekanyo ea tlhahiso ea DeltaFosB ho dorsal striatum. Ntle le moo, lithethefatsi tsohle tse 'ne li ile tsa kenya DeltaFosB ka pele ho cortex ea pele, ka litlamorao tse kholo tse bonoang ka koae le ethanol, le lithethefatsi tsohle li kentse DeltaFosB tekanyo e nyane ho amygdala. Ntle le moo, lithethefatsi tsohle li ile tsa kenya DeltaFosB hippocampus, ntle le ethanol, boholo ba tlhahiso ena bo bonoa meno. Maemo a tlase a DeltaFosB a ile a bonoa libakeng tse ling tsa boko ho arabela kalafo e itseng ea lithethefatsi. Liphumano tsena li fana ka bopaki bo bong ba hore ho kenngoa ha DeltaFosB ka har'a nucleus ke ketso e tloaelehileng ea hoo e batlang e le lithethefatsi tsohle tsa tlhekefetso le hore, ntle le li-nucleus kukusanya, setheo se seng le se seng se etsa DeltaFosB ka mokhoa o ikhethileng sebakeng sa bokong..
SELELEKELA
Ho pepeseha ka har'a cocaine ho bakoa haholo ke ho kenella hoa nakoana hoa lingoloa tsa c-Fos le FosB libakeng tsa straatal (Graybiel et al., 1990; Hope et al., 1992; Young et al., 1991) ka har'a bokella li-isoforms tse tsitsitseng tsa ΔFosB, mofuta oa splice o fapaneng oa mofuta oa fosB (Hiroi et al., 1997; Hope et al., 1994; Moratalla et al., 1996; Nye et al., 1995). Ha e hlohlellelitsoe, ΔFosB e phehella libakeng tsena libeke tse 'maloa ka lebaka la botsitso bo sa tloaelehang ba protheine. Patlisiso ea morao-rao e bonts'itse hore botsitso ba ΔFosB bo kopantsoe le ho se be teng hoa libaka tse senyehileng tse fumanehang C-termini ea FosB e felletseng le liprotheine tsohle tsa malapa tsa Fos (Carle et al., 2007) le phosphorylation ea ΔFosB ho N ea eona -terminus (Ulery et al., 2006). Ho fapana le hoo, taolo ea lithethefatsi e sa foleng ha e fetole ho petsoha ha fosB premRNA ho ΔfosB mRNA kapa botsitso ba mRNA (Alibhai et al., 2007), bo bonts'ang hape hore ho bokellana ha protheine ea ΔFosB ke mokhoa o ka sehloohong o amehang.
Bopaki bo ntseng bo hola bo bonts'a hore ho kenngoa ha ΔFosB libakeng tsa striatal, haholo-holo, ventral striatum kapa nucleus bokella, ho bohlokoa molemong oa ho loants'anya likarolo tsa bokhoba. Ho hlaseloa ka ho feteletseng ha theseFosB libakeng tsena tsa litoeba tse sa sebetseng tsa bitransgenic, kapa ka phetiso ea vaerase e kenang ka bongata, ho eketsa maikutlo a phoofolo molemong oa ts'ebetso le ts'ebetso e ntle ea cocaine le morphine, athe polelo ea mohanyetsi ea matla oa "cocaine" le eona e bitsoa "Δc-" Jun) e na le litlamorao tse fapaneng (Kelz et al., 1999; McClung le Nestler, 2003; Peakman et al., 2003; Zachariou et al., 2006). ΔFosB overexpression e boetse e bontšitsoe ho eketsa tšusumetso ea khothalletso bakeng sa koae (Colby et al., 2003). Ho feta moo, ΔFosB e susumetsoa ke koae ka ho khetheha liphoofolong, e leng se ka bakang tlokotsing ea bona ea ho lemalla (Ehrlich et al., 2002).
Ntle le bopaki bona, lipotso tsa bohlokoa li ntse li le teng. Leha tsamaiso e sa foleng ea lithethefatsi tse ling tse 'maloa tsa tlhekefetso, ho kenyelletsa amphetamine, methamphetamine, morphine, nikotine, le phencyclidine, ho tlalehiloe hore li susumetsa ΔFosB libakeng tsa striatal (Atkins et al., 1999; Ehrlich et al., 2002; McDaid et al. 2006b; Muller and Unterwald, 2005; Nye et al., 1995; Nye le Nestler, 1996; Pich et al. 1997; Zachariou et al., 2006), tlhaiso-leselinyana kapa ha e na letho mabapi le liketso tsa ethanol le Δ9-tetrahydrocannabinol (Δ9-THC, motsoako o sebetsang oa matekoane). Liphuputso tse peli tsa pele li bontšitse hore FosB-like immunoreactivity e kenngoa hippocampus le libakeng tse ling tsa boko nakong ea ho tlosoa ha ethanol, empa ho lula ho sa tsejoe hore na ts'ireletso ena e emela osFosB kapa FosB ea bolelele bo felletseng (Bachtell et al., 1999; Beckmann et al., 1997 ). Boithuto ba ethanol le (Δ9-THC bo bohlokoa haholo, hobane tsena ke lithethefatsi tse peli tse sebelisoang haholo ho tlhekefetso ho la US kajeno (SAMHSA, 2005) Ho feta moo, le ha lithethefatsi tse hlasimollang kapa tse opangate tsa tlhekefetso li bonts'itsoe ho kenya ΔFosB ka likarolo tse ling tse ikhethileng tsa boko, tseo, ho kenyelletsa le li-bokellane tsa nucleus le dorsal striatum, li kenyelletsa cortex ea pele, amygdala, ventral pallidum, sebaka sa ventral tegmental, le hippocampus (Liu et al., 2007; McDaid et al., 2006a, 2006b; Nye et al., 1995; Perrotti et al., 2005), ha ho e-so be le 'mapa o hlophisitsoeng oa ho kenella ha ΔFosB bokong ka lebaka la ho pepesetsoa ha lithethefatsi nako e telele.
Morero oa thuto ea morao-rao e ne e le ho sebelisa mekhoa ea immunohistochemical ho hlahisa ts'ebetso ea ΔFosB bokong bohle ka mor'a ts'ebetso e sa feleng ea lithethefatsi tse 'ne tsa tšebeliso e mpe: cocaine, morphine, ethanol, le Δ9-THC.
LISEBELISOA LE MEKHOA
Animals
Liteko tsohle li ile tsa etsoa ho sebelisoa likhoto tsa banna ba Sprague Dawley (Charles River, Kingston, 250-275 g). Liphoofolo li ne li beoa habeli ntlong e ngoe le e 'ngoe ebe li lula maemong a phaposi ea beke bakeng sa beke pele ho qala liteko. Ba ne ba ka fumana lijo le metsi mahala. Liteko li entsoe ho latela liprotheine tse hlahlojoang ke Institutional Animal Care and Use Use Committee ho The University of Texas Southwestern Medical Center ho Dallas.
Phekolo ea lithethefatsi
Cocaine e sa foleng
Likhoto (n = 6 ka sehlopha ka seng) li fumane liente tse habeli ka letsatsi tsa cocaine hydrochloride (15 mg / kg ip; National Institute on Drug Abuse, Bethesda, MD) e felisitsoe ka saline ea 0.9% bakeng sa matsatsi a 14. Likhoto tsa taolo (n = 6 ka sehlopha ka seng) li fumane liente tsa IP tsa saline ea 0.9% tlasa ts'ebetso e tšoanang ea nako e telele. Liente tsohle li ne li fanoa ka har'a matloana a liphoofolo. Regimen ena ea kalafo e bontšitsoe ho hlahisa mekhoa e metle ea boits'oaro le biochemical (bona Hope et al., 1994).
Ts'ebetso ea cocoaine
Liphoofolo (n = 6 ka sehlopha ka seng) li ile tsa koetlisetsoa ho tobetsa lever bakeng sa 45 mg sucrose pellet. Kamora thupelo ena, liphoofolo li ile tsa feptjoa libb mme tsa kenngoa ka mokhoa o tlatselletsang tlasa pentobarbital anesthesia e nang le catheter e sa foleng (Silastic tubing, Green Rubber, Woburn, MA) joalo ka ha ho hlalositsoe pejana (Sutton et al., 2000). Catheter e ile ea feta ka kotloloho e le hore e tsoe ka mokotleng ka 22-gauge cannula (Plastics One, Roanoke, VA), e kenelle ka samente ea cranioplastic, 'me e sirellelitsoe ka mesifa ea ho buoa ea Marlex (Bard, Cranston, RI). Boitlhokomelo bo ile ba etsoa ka likamoreng tsa liteko tsa liteko (Med Associates, St. Alban, VT) tse neng li fapane hole le phoofolo ea lapeng ea liphoofolo le e ka kamoreng e fapaneng. Kamore e 'ngoe le e' ngoe e ne e kentsoe khubung e nang le molumo e nang le molumo o nang le pokello ea pompo e kenyang pompo ea Razel Model A (Stamford, CT) le seratsoana sa khalase sa 10 ml se hokahantsoeng le mothapo o tsoang ka mokelikeli (Instech, Plymouth Assembly, PA) ka Teflon tubing . Tubgon ea Tygon e ile ea hokahanya swivel le kopano ea catheter ea phoofolo mme e kentsoe ke seliba sa tšepe. Kamore e 'ngoe le e' ngoe ea tšebetso e ne e e-na le levers tse peli (4 × 2 cm2, e leng 2 cm ka tlase). Nakong ea boikoetliso ba ho itaola, mochine o le mong oa 20 g lever-Press o neng o sebetsa o ile a tlisa infusion ea cocaine (0.5 mg / kg ka ho kenella ka 0.1 ml ka nako e fetang ea 5-s infusion. Ts'oaetso e ile ea lateloa ke nako ea ho tsoa ha 10, eo ka nako eo leseli la ntlo le neng le tima 'me ho araba ho sa hlahise litholoana. Leseli la leseli la ntlo le ne le supa pheletso ea nako ea ho tsoa. Tobetsa ea lever ho lairing e sa sebetseng ha e hlahise litholoana. Liphoofolo tse ikatisang cocaine nakong ea liteko tsa 14 tsa letsatsi le letsatsi tsa 4-h (6 matsatsi / beke) nakong ea potoloho ea bona e lefifi; karolelano ea karolelano ea letsatsi le letsatsi e ne e le ~ 50 mg / kg. Sehlopha sa liphoofolo tse kopantsoeng joko se ne se sebetsoa ka mokhoa o ts'oanang feela ba amohela infusions ea koae ha balekane ba bona ba ikemetseng ba amohela lithethefatsi. Sehlopha sa liphoofolo tse laolang letsoai se ile sa lumelloa ho hatella mochini bakeng sa infusions ea letsoai. Regimen ena ea kalafo e bontšitsoe ho hlahisa mekhoa e matla ea boitšoaro le biochemical (bona Sutton et al., 2000).
Morphine e sa foleng
Li-pellets tsa Morphine (e 'ngoe le e' ngoe e nang le 75 mg ea morphine; Setsi sa Naha sa Ts'ebeliso ea Lithethefatsi) se ne se kenngoa hang ka letsatsi bakeng sa matsatsi a 5 (n = 6). Laola likhoto tse buuoeng pelepele ka sham bakeng sa matsatsi a 5 a latellanang (n = 6). Regimen ena ea kalafo e bontšitsoe ho hlahisa mekhoa e matla ea boitšoaro le biochemical (bona Nye le Nestler, 1996).
Δ9-THC
Δ9-THC e felisitsoe ho 1: 1: Tharollo ea 18 ea ethanol, emulphor le saline. Lice li ile tsa kenngoa ka kotloloho ka makhetlo a mabeli ka letsatsi le Δ9-THC, kapa koloi bakeng sa matsatsi a 15. Motsoako oa pele oa Δ9-THC e ne e le 10 mg / kg mme lethalinyana le ile la imena habeli ka matsatsi a mararo ho fumana tekanyetso ea ho qetela ea 160 mg / kg. Re sebelisitse litoeba bakeng sa Δ9-THC, hobane regimen ena ea kalafo e bonts'itsoe ho hlahisa mekhoa e matla ea boitšoaro le biochemical ho mofuta ona (Sim-Selley le Martin, 2002).
Ethanol
Ethanol (ho tloha 95% stock; Aaper, Shelbyville, KY) e ne e tsamaisoa ka mokhoa oa phepelo e lekaneng ea phepo e metsi. Ts'ebetso ena e tloaelehileng ea "ethanol" ea lijo e kenyelletsa ho tsamaisoa ha 7% [boima / bophahamo (vol)] ethanol ka har'a lijo tse thehiloeng ho lactalbumin / dextrose bakeng sa matsatsi a 17, ka nako eo likhoto li jang ka tloaelo ethanol ka 8-12 g / kg / letsatsi le fihlella maemo a ethanol a mali ho fihlela ho 200 mg / dl (Criswell le Breese, 1993; Frye et al., 1981; Knapp et al., 1998). Lijo li ne li phethehile ka phepo e nepahetseng (e na le livithamini, liminerale le limatlafatsi tse ling tse tsoang ho ICN Research Diets le khalori e nang le "dextrose") ho likhoto tse tšoaroang ke ethanol le likhoto. palo ea lijo tse lekanang le karolelano ea karolelano ea likhoto tsa phepelo ea phepo ea letsatsi ea letsatsi le letsatsi. Lihlopheng tsena ka bobeli li ile tsa nona habonolo ka nako ea tlhahlobo ea ethanol (e sa bonts'ang) Mokhoa ona oa kalafo o bontšitsoe ho hlahisa tloaelo ea boits'oaro bo kopanetsoeng le biochemical (bona Knapp et al., 1998).
Immunohistochemistry
Leshome le robeli ho 24 h kamora kalafo ea bona ea hoqetela, liphoofolo li ile tsa khahloa haholo ke chloral hydrate (Sigma, St. Louis, MO) mme tsa hlatsuoa ka bongata ka 200 ml ea 10 mM phosphate-buffered saline (PBS) e lateloa ke 400 ml ea 4% paraformaldehyde ho PBS. Li-brains li tlositsoe mme li bolokiloe bosiu ho 4% paraformaldehyde ho 4 ° C. Hoseng ho latelang, masapo a kelello a fetiselitsoe 20% glycerol ho 0.1 M PBS tharollo ea cryoprotection. Likarolo tsa Coronal (40 µm) li ile tsa rengoa ka microtome ea leqhoa (Leica, Bannockburn, IL) ebe li sebetsoa bakeng sa immunohistochemistry. Li-immunoreactivities tsa ΔFosB le FosB li fumanoe li sebelisa antisera tse peli tse fapaneng tsa polyclonal antisera. Antiserum e le 'ngoe, e phahamisitsoeng khahlanong le FosB C-terminus e sieo ho ΔFosB (aa 317-334) e amohela FosB ea bolelele bo felletseng, empa eseng ΔFosB (Perrotti et al., 2004). Antiserum e 'ngoe, e leng "pan-FosB" antibody, e phahamisitsoe khahlanong le sebaka se kahare sa FosB mme e amohela FosB le ΔFosB (sc − 48; Santa Cruz Biotechnology, Santa Cruz, CA).
Merafo e kang ea FosB e ile ea senoloa ka tšebeliso ea mokhoa o rarahaneng oa avidin-biotin peroxidase. Bakeng sa ts'ebetso ena, likarolo tsa bokong li ile tsa phekoloa pele ka 0.3% H2O2 ho senya li-endoxidases tsa endoid ebe li fufuleloa bakeng sa 1 h ho 0.3% Triton X-100 le 3% serum ea poli e tloaelehileng ho fokotsa ho ngoloa ha nonspecific. Likarolo tsa mesifa li ile tsa kenngoa bosiu ka bongata mocheso oa kamoreng ho 1% serum poli e tloaelehileng, 0.3% Triton X-100 le anti-pan-FosB (1: 5000). Likarolo li ile tsa hlatsuoa, tsa beoa bakeng sa 1.5 h ho 1: 200 dilution of biotinylated goat-antirabbit immunoglobulin (DakoCytomation, Carpinteria, CA), e hlatsoitsoe, 'me e beiloe 1.5 h ho 1: 200 dilution of avidin-biotin complex from the Elite kit Laboratories, Burlingame, CA). Ts'ebetso ea Peroxidase e bonts'itsoe ke karabelo le diaminobenzidine (Vector Laboratories). Ho ne ho sebelisoa li-slide tsa "coded" ho bala palo ea lisele tsa FosB-immunoreactive. Khoutu ha ea ka ea robeha ho fihlela tlhahlobo ea teko ea motho ka mong e phethehile.
Hang ha ts'ebeliso ea thibelo ea mafu a FosB joalo ka ha e fumanoe, ho ngola habeli fluorescent ka FosB-e itseng (C-terminus; 1: 500) antibody le pan-FosB antibody (sc − 48; 1: 200) e entsoe ho bona hore na protheine e hlohlellelitsoeng e hlile e hlile e teng. ΔFosB. Ho sebelisitsoe protocol e phatlalalitsoeng (Perrotti et al., 2005). Liprotheine li ile tsa bonoa li sebelisoa CY2 le CY3 fluorophore-labels ea bobeli antibodies (Jackson ImmunoResearch Laboratories, West Grove, PA). Localization ea polelo ea protheine e entsoe ka microscope e poteletseng (Axiovert 100; LSM 510 e nang le META emission wavelength of 488, 543, and 633; Zeiss, Thornwood, NY). Litšoantšo tse hlahisitsoeng mona li hapuoe ka sistimi ena mme li emela karolo e kholo ea 1 µm ka sefofane sa Z-sefofane.
Tlhahlobo ea statistical
Ho kenella hoa bohlokoa ha lisele tsa ΔFosB + ho ile ha hlahlojoa ho sebelisoa t-liteko kapa li-ANOVA tsa tsela e le 'ngoe tse lateloang ke teko ea Newman-Keuls joalo ka tlhahlobo ea poso. Litlhahlobo tsohle li ile tsa lokisoa bakeng sa papiso e mengata. Lintlha li hlahisoa e le tse mpe ± SEM. Bohlokoa ba lipalo-palo bo hlalositsoe e le P <0.05.
LIPOTSO
Ho hlahisoa ha ΔFosB bokong
Ho bapisa ka kotloloho mekhoa ea ΔFosB ho kenella bokong ka karabelo ea mefuta e fapaneng ea lithethefatsi tsa tlhekefetso, re ile ra fana ka lithethefatsi tse 'ne tsa prototypical, cocaine, morphine, ethanol, le Δ9-THC,' me ra hlahloba polelo ea ΔFosB 18-24 h kamora ho pepeseha ha lithethefatsi tsa ho qetela . Re sebelisitse litekanyetso tse tloaelehileng tsa kalafo ea lithethefatsi, tse bonts'itsoeng libukeng ho hlahisa boitšoaro le litekanyetso tsa biochemical tsa phello e sa feleng ea lithethefatsi (bona karolo ea Lisebelisoa le Mekhoa). Maemo a ΔFosB a ne a emisitsoe ke immunohistochemistry, ka ho shebana haholo le libaka tsa bongoana le bokapele ba kelello bo kenelletseng moputsong oa lithethefatsi le ho lemalla. 'Mapa ona o motle oa tlhahiso ea ΔFosB o entsoe ka anti-pan-FosB, e amohelang ΔFosB le FosB ea bolelele bo felletseng. Leha ho le joalo, rea tseba hore ts'oaetso eohle e thibelitsoeng, bakeng sa sehlahisoa ka seng, e tlameha feela ho ΔFosB, kaha antibody e khethang FosB ea bolelele bo felletseng (bona Karolo ea Matali le Mekhoa) ha e fumane lisele tse ntle. Ntle le moo, ts'ebetso eohle e thibelang bokhachane e fumanoeng ke anti-pan-FosB e ile ea lahleha ka litoeba tsa fosB, tse netefatsang 'mele oa motho enoa bakeng sa lihlahisoa tsa mofuta oa fosB ho fapana le liprotheine tse ling tsa lelapa la Fos. Litaolo tsena li bonts'oa k'hok'heine ho Setšoantšo sa 1, empa e ile ea bonoa bakeng sa lithethefatsi tse ling kaofela (le eona ha e bontšoe). Liphumano tsena ha li makatse, hobane ntlheng ea nako ea 18-24 h e sebelisitsoeng thutong ena tsohle FosB e bolelele bo felletseng, e lebelletsoeng ke taolo ea ho qetela ea lithethefatsi, e ka lebelloa ho nyenyefatsa, e siea ΔFosB e tsitsitseng haholoanyane e le mofuta o le mong oa fosB sehlahisoa se setseng (bona Chen et al., 1995; Hope et al., 1994).
Feie. 1
Ho tšoaea habeli ha fluorescence immunohistochemistry ho sebelisa anti-FosB (pan-FosB, Santa-Cruz) kapa anti-FosB (C-terminus) antibody ka li-nucleus accumbens tsa liphoofolo tse tšoaroang ka k'hok'heine e matla kapa e sa foleng le rat ea taolo. Lits'oants'o tsa antibody ea pan-FosB (More…)
Kakaretso ea lipatlisiso tse felletseng tsa phuputso ena e fanoa ho Tafole ea pele. E 'ngoe le e' ngoe ea lithethefatsi tsena tse 'ne e fumanoe e le ho kenya ΔFosB bokong, leha e le ka litekanyetso tse ikhethileng tsa ts'ebetso e bonoeng bakeng sa sehlahisoa ka seng.
Lethathamo I
Tlhahiso ea ΔFosB bokong ka lithethefatsi tsa tlhekefetso
Ho hlahisoa ha ΔFosB libakeng tsa litereke
Ho kenella ka mokhoa o tsotehang oa ΔFosB ho ile ha bonoa bokong ba nyutlelie le dorsal striatum (caudate / putamen), moo lithethefatsi tsohle tse 'ne li hlohlelletsang protheine (Fig. 2-Fig. 4). Sena se bontšoa ka bongata ho Figure 5. Induction ea ΔFosB e ile ea bonoa maemong a mantlha le a khetla e tlatselletsang kahare ho lithethefatsi tse ngata. Ho kenella ka matla ho ΔFosB ho ile ha boela ha bonoa dorsal striatum bakeng sa lithethefatsi tse ngata. Mokhelo e ne e le Δ9-THC, e sa kang ea qobella ΔFosB ka sekhahla sa "nucleus accumbens shell" kapa "dorsal striatum" ntle le mekhoa e matla (bona sa feiga. 4; Lethathamo I). Ho khahlisang, ethanol e hlahisitse induction e kholo ka ho fetisisa ea ΔFosB bokong ba methapo ea methapo e bapisoa le kalafo e meng.
Feie. 2
Ho qhekelloa ha ΔFosB mokokotlong oa likhoto o bokellaneng ho rat (A) kapa kamora kalafo e sa foleng ea ethanol (B), morphine (C), kapa cocaine (D). Methati ea ho itšireletsa mafung e kang FosB e ile ea hlahlojoa ke immunohistochemistry e sebelisa lesole la pan-FosB. (Hape …)
Feie. 4
Ho qhekelloa ha ΔFosB bokong ba toeba kamora kalafo e sa foleng ea Δ9-THC. Methati ea ho itšireletsa mafung e kang ea FosB e ile ea hlahlojoa ke immunohistochemistry e sebelisa lesole la pan-FosB le laolang (A, C, E) le liphoofolo tse sa foleng tsa Δ9-THC (B, D, F). Ela hloko (more…)
Feie. 5
Quantification ea ΔFosB induction libakeng tse striatal kamora morphine e sa foleng, Δ9-THC, ethanol le kalafo ea cocaine. Li-graph li bontša palo e bolelang ea lisele tsa osBFosB + tse laolang liphoofolo le liphoofolong tse nang le morphine e sa foleng, (more…)
Ho hlahisoa ha ΔFosB ke ho pepesetsoa lithethefatsi ka mokhoa o ikemetseng
Ha re fuoa ts'ebetso e makatsang ea ΔFosB libakeng tsa literekeng, re ne re thahasella ho tseba hore na matla a lithethefatsi ho kenya protheine libakeng tsena a fapana joaloka tšebeliso ea lithethefatsi ka mokhoa o ikemetseng. Ho araba potso ena, re ithutile sehlopha sa likhoto tse iphekoletsang koae ka matsatsi a 14 mme re bapisa ho kenngoa ha ΔFosB ka har'a liphoofolo tsena le ba ileng ba amohela infusions ea koae le e amohelang saline feela. Joalokaha ho bontsitsoe ho Setšoantšo sa 6, k'hok'heine ea koae e ipabotseng robFosB ka har'a methapo ea mali (likarolo tsa mantlha le likarolo tse tlase) le dorsal striatum, ka litekanyo tse lekanang tsa tlhahiso e bonoang bakeng sa moriana o ikemetseng o kopantsoeng le joala. Tekanyetso ea ΔFosB e bonoang lihlopheng tsena tse peli tsa liphoofolo e ne e le kholo ho feta e bonoeng ka ente ea cocaine (bona Fig. 5), ka mohlomong ka lebaka la bongata bo boholo ba koae boitekong ba ho ipusa (litekanyetso tsa letsatsi le letsatsi: 50 mg / kg iv vs. 30 mg / kg ip).
Feie. 6
Quantification ea ΔFosB induction libakeng tsa striatal kamora ho ipusa ho sa foleng ha cocaine. Li-graph li bontša palo e bolelang ea lisele tsa osBFosB + tse laolang liphoofolo le liphoofolong tse sebelisang kalafo ea k'hok'heine, mokokotlong le (more…)
Ho hlahisoa ha ΔFosB libakeng tse ling tsa boko
Ka n the'ane ho moaho o tsoaloang, taolo e sa foleng ea lithethefatsi tsa tlhekefetso e bakiloe ke osBFosB libakeng tse ling tse ngata tsa boko (bona Tafole I). Re lokela ho totobatsa hore tlhaiso-leseling e hlahisitsoeng ho Tafole I ke ea bohlokoa, 'me ha e emele palo e nepahetseng ea ho qalisoa ha osBFosB, joalo ka ha e etsoa libakeng tsa striatal (Setšoantšo sa 5 le sa feiga. 6). Leha ho le joalo, re na le ts'epo ea hore ΔFosB e kenella libakeng tsena tse sa tsoaloeng: ΔFosB ha e bonahale libakeng tsena tlasa maemo a tlase, joalo ka hore phumano e ts'oanang ea ΔFosB kamora ho pepeseha ha lithethefatsi tse sa foleng e bohlokoa haholo (P <0.05 ke χ2).
Ho kenella ka matla ho lithethefatsi tsohle ho ile ha bonoa ho cortex ea pele, ka morphine le ethanol li bonahala li hlahisa litlamorao tse matla ka ho fetisisa ho li-layers tse ngata (sa feiga. 4 le Fig. 7). Lithethefatsi tsena tse 'ne li boetse li bakile ΔFosB ea ho kenella mokokotlong oa "stria terminalis" (BNST), mokokotlo oa karolo e ka morao ea leoto le ka morao ho mokokotlo (anterior commissure (IPAC)), le ho pholletsa le mochine oa amygdala (Fig. 8). Litlamorao tse ling, tse amanang le lithethefatsi tse itseng, le tsona li ile tsa bonoa. Cocaine le ethanol, empa eseng morphine kapa Δ9-THC, li hlahile li hohela maemo a tlase a ΔFosB ka septum ea morao, ntle le ts'ebetso e bonoang ho medial septum. Lithethefatsi tsohle tse hlohlelletsang ΔFosB ka hippocampus, ntle le ethanol, boholo ba tlhahiso ena bo bonoa ka har'a gyrus ea meno (Tafole I le Fig. 9). Ho fapana le moo, ethanol e ile ea qobella osFosB e nyane haholo ka meno 'me ea hloesetsa liprotheine tse ngata makaleng a mahareng a CA3-CA1. Cocaine, morphine, le ethanol, empa eseng Δ9-THC, e hlahisitse litekanyetso tse tlase tsa ho kenella ha ΔFosB ka har'a boea bo potelletseng, athe cocaine feela e qobelletseng ΔFosB sebakeng sa likarolo tse kenang ka hare, empa ho sena ts'ebetso e boneng ho sub-stantia nigra (bona Lethathamo I ).
Feie. 7
Ho qhekelloa ha ΔFosB karolong e ka pele ea cortex ka rat ea taolo (A) kapa kamora kalafo e sa foleng ea ethanol (B), morphine (C), kapa cocaine (D). Methati ea ho itšireletsa mafung e kang FosB e ile ea hlahlojoa ke immunohistochemistry e sebelisa lesole la pan-FosB. Ho ngola (More…)
Feie. 8
Ho qhekelloa ha ΔFosB ho basal lateral le bohareng ba medial nuclei ea amygdala ea rat rat (A) kapa likhoto tse fuoeng kalafo e sa foleng ea ethanol (B), morphine (C), kapa cocaine (D). Methati ea ho itšireletsa mafung e kang ea FosB e ile ea hlahlojoa ke immunohistochemistry (More…)
Feie. 9
Ho qhekelloa ha ΔFosB ho hippocampus ea rat rat (A) kapa likhoto tse fuoeng kalafo e sa foleng ea ethanol (B), morphine (C), kapa cocaine (D). Methati ea ho itšireletsa mafung e kang FosB e ile ea hlahlojoa ke immunohistochemistry e sebelisa lesole la pan-FosB. Ho ngola (More…)
TŠOHLOA
Liphuputso tse ngata li bontšitse hore tsamaiso e sa foleng ea mefuta e mengata ea lithethefatsi tsa tlhekefetso, ho kenyelletsa cocaine, amphetamine, methamphetamine, morphine, nicotine le phencyclidine, e etsa hore taba ea ho ngola e be, ΔFosB, ka li-nucleus accumbens le dorsal striatum. (sheba Selelekela karolo ea litšupiso; e hlahlobetsoe ho McClung et al., 2004; Nestler et al., 2001). Ho hlahisoa ha ΔFosB libakeng tse phahameng ho boetse ho bonoe kamora tšebeliso e sa feleng ea meputso ea tlhaho, joalo ka boits'oaro bo tsamaeang ka mabili. (Werme et al., 2002). Ntle le moo, ho bile le litlaleho tse 'maloa tsa maemo a tlase a ΔFosB ho kenella libakeng tse ling tsa boko, ho kenyelletsa preortal cortex, amygdala, ventral pallidum, sebaka sa ventral tegmental, le hippocampus (Liu et al., 2007; McDaid et al., 2006a, 2006b; Nye et al., 1996; Perrotti et al., 2005), ha a araba a mang a lithethefatsi tsena tsa tlhekefetso, leha ho le joalo ha ho mohla ho kileng ha ba le 'mapa oa tsamaiso ea lithethefatsi tsa ΔFosB bokong. Ntle le moo, leha ho na le lipatlisiso tsa lithethefatsi tse ngata tsa tlhekefetso, lintho tse peli tse hlekefelitsoeng ka ho fetisisa, ethanol le Δ9-THC, ha li e-so hlahlobeloe bokhoni ba tsona ba ho susumetsa ΔFosB. Morero oa thuto ea hona joale e ne e le ho etsa 'mapa oa ΔFosB bokong ka lebaka la ts'ebetso e sa fetoheng ea lithethefatsi tse' ne tsa tšebeliso e mpe: cocaine, morphine, ethanol, le Δ9-THC.
Liphetho tse kholo tsa boithuto ba rona ke hore ethanol le Δ9-THC, joalo ka lithethefatsi tse ling tsohle tsa tlhekefetso, li kenya maemo a phahameng a ΔFosB haholo ka har'a mochini oa striatal. Liphetho tsena li boetse li hlahisa induction ea ΔFosB libakeng tsena e le tloaelo e tloaelehileng, e sa fetoheng ea lithethefatsi tsohle tsa tlhekefetso (McClung et al., 2004). Mokhoa oa ho itlhahisa ka har'a mochini oa striatal o fapane ka tsela e itseng bakeng sa lithethefatsi tse fapaneng. Tsohle tse hlohlellelitseng ΔFosB ka sehlohlolong li bokellana mantlha, athe lithethefatsi kaofela-ntle le Δ9-THC-e kenyellelitseng inFosB haholo ka har'a nucleus accumbens shell le dorsal striatum, hape ho bile le mekhoa e matla ea Δ9-THC ho hlahisa litlamorao tse tšoanang ho libaka tsena tsa morao-rao. Li-nucleus li bokella mantlha le khetla ke libaka tsa moputso oa bohlokoa oa boko, tse bonts'itsoeng e le babuelli ba bohlokoa ba ketso tse khotsofatsang tsa lithethefatsi tsa tlhekefetso. Ka mokhoa o ts'oanang, dorsal striatum e amana le mofuta oa ts'ebeliso ea lithethefatsi kapa tloaelo-joaloka (Vanderschuren et al., 2005). Ka 'nete, ho kenella ka ΔFosB libakeng tsena ho bontšitsoe ho eketsa likarabo tse khotsofatsang tsa koae le morphine, le ho eketsa likarabo ho meputso ea tlhaho e kang boits'oaro ba ho matha ka lebelo la mokokotlo le takatso ea lijo, joalo ka (Colby et al., 2003; Kelz et al., 1999; Olausson et al., 2006; Peakman et al., 2003; Werme et al., 2003; Zachariou et al., 2006). Ho hlokahala mosebetsi o eketsehileng ho tseba hore na ho kenella ha ΔFosB libakeng tsena ho sebetsana le maemo a tšoanang a amanang le kutloisiso ea motho litlamorao tsa lithethefatsi tse ling tsa tlhekefetso.
Ho hlahisoa ha ΔFosB libakeng tse nang le litheko ha se mosebetsi oa tšebeliso ea lithethefatsi ka mokhoa o itseng. Kahoo, re bonts'a hore boitlhokomelo ba koae bo kenyelletsa tekanyo e lekanang ea ΔFosB maemong a bokellanang le li-dorsal striatum joalo ka ha ho bonoa liphoofolong tse fumaneng liente tse lekanang, tsa joko ea joala. Liphetho tsena li bonts'a hore ΔFosB induction in striatum e bonts'a ts'ebetso ea pharmacologic ea lithethefatsi tsa tlhekefetso, ntle le taolo ea phoofolo holim 'a ponaletso ea lithethefatsi. Ka lehlakoreng le leng le ikhethang, re bonts'itse morao tjena hore boikoetliso ba koae bo etsa hore maemo a mangata a phahameng a ΔFosB ho cortex ea orbitofrontal e bapisoa le tsamaiso ea koae ea joala (Winstanley et al., 2007). Phello ena e ne e khethehile bakeng sa cortex ea orbitof Pambal, hobane litekanyetso tse lekanang tsa indFosB li ile tsa bonoa ho cortex ea pele ho tlasa maemo ana a mabeli a kalafo. Kahoo, leha induction ea ΔFosB e sa amane le taolo e lekanyelitsoeng ea tšebeliso ea lithethefatsi libakeng tsa litereke, e bonahala e susumetsoa ke mabaka a susumetsang libakeng tse ling tse phahameng tsa cortical.
Re fana ka tlhahisoleseling e tlatselletsang ea hore lithethefatsi tsohle tse 'ne tsa tlhekefetso li hlohlelletsa ΔFosB libakeng tse' maloa tsa boko kantle ho mohopolo oa bongaka, leha e le ka kakaretso ho isa tekanyong e nyane. Libaka tsena tse ling tsa boko li kenyelletsa cortex ea pele, amygdala, IPAC, BNST, le hippocampus. Tlhahiso ea lithethefatsi ea ΔFosB ka pele ho cortex le hippocampus li ka amana le tse ling tsa litlamorao tsa lithethefatsi tsa tlhekefetso ts'ebetsong ea kelello, leha sena se sa ntse se lokela ho hlahlojoa ka kotloloho. Amygdala, IPAC le BNST kaofela li bile le tšusumetso ho laola likarabo tsa motho ka mong tse susumetsang maikutlo. Sena se hlahisa monyetla oa hore indFosB e kenngoe libakeng tsena kamora hore taolo e mpe ea ts'ebeliso ea lithethefatsi e sebelisane le litekanyetso tsa lithethefatsi tsa boitšoaro ba maikutlo bo fetang bo fuoang moputso. Ho tla ba monate ho hlahloba menyetla ena lipatlisisong tse tlang.
Lithethefatsi tse 'ne tsa tlhekefetso tse ithutoang mona li boetse li hlahisitse litlamorao tse itseng mabapi le lithethefatsi. Cocaine e ile ea susumetsa ΔFosB ka mokhoa o ikhethileng sebakeng se potolohileng ka hare, joalo ka ha ho tlalehiloe pejana (Perrotti et al., 2005). Ka mokhoa o ts'oanang, cocaine le ethanol ka mokhoa o ikhethileng li theola maemo a tlase a ΔFosB ho septum ea morao. Δ9-THC e ne e ikhethile bakeng sa litlamorao tse fokolang ho ΔFosB, ha e bapisoa le lithethefatsi tse ling tsa tlhekefetso, ka har'a nucleus accumbens shell le dorsal striatum, joalo ka ha ho boletsoe pejana. Δ9-THC le eona e ne e ikhethile ho pepeseng lithethefatsi ka mokhoa o sa feleng, ho fapana le ba bang kaofela, ha e ea ka ea hohela maemo a tlase a ΔFosB ka bohloeki ba pherekano. Ka lebaka la karolo ea hippocampus le septum ts'ebetsong ea kelello, le karolo ea libaka tsena hammoho le bohlooho ba ho lekola likarabo tsa phoofolo maemong a sithabetsang, ho kenella ka kotloloho ho lithethefatsi tsa ΔFosB literekeng tsena ho ka nka likarolo tsa bohlokoa tsa ketso ea lithethefatsi bokong.
Ka kakaretso, ho kenyelletsoa ha "osFosB libakeng tsa moputso oa boko ho bontšitsoe ka mokhoa o sa fetoheng tloaelo ea lithethefatsi tsa tlhekefetso. Re atolositse mohopolo ona ka ho bonts'a mona hore lithethefatsi tse peli tse eketsang le tse hlekefelitsoeng hohle, ethanol le Δ9-THC, le tsona li kenya letsoho ΔFosB libakeng tsena tsa boko. Re boetse re supa likarolo tse ling tsa boko, tse amehang ts'ebetsong ea kelello le likarabo tsa khatello ea maikutlo, tse bonts'ang maemo a fapaneng a ho itlhahisa ha ΔFosB ka karabelo ea tšebeliso e mpe ea lithethefatsi. Tse ling tsa likarabo tsena, joalo ka ho kenngoa ha ΔFosB libakeng tse phahameng, li tloaelehile ho lithethefatsi tsohle tsa tlhekefetso tse ithutoang mona, athe likarabo likarolong tse ling tsa boko li bua haholo ka lithethefatsi. Liphumano tsena li tla tataisa lipatlisiso tsa nako e tlang ho bonahatsa karolo ea ho kenella ha ΔFosB libakeng tsena tse ling tsa boko. Ba boetse ba thusa ho hlalosa ts'ebeliso e ka bang teng ea bahanyetsi ba ΔFosB e le kalafo e tloaelehileng bakeng sa li-syndromes tsa bokhoba ba lithethefatsi.
Feie. 3
Ho qhekelloa ha ΔFosB ho rat caudate putamen ka rat rat (A) kapa kamora kalafo e sa foleng ea ethanol (B), morphine (C), kapa cocaine (D). Methati ea ho itšireletsa mafung e kang ea FosB e ile ea hlahlojoa ke immunohistochemistry e sebelisa lesole la pan-FosB. (Hape …)
lumela hore baa fokola
Mofani oa liphallelo oa konteraka: Setsi sa Naha sa Tlhekefetso ea Lithethefatsi.
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