Ho tepella ho tlōla ha DeltaFosB ho amahanngoa le ho tlosoa ha k'hok'heine e bakoang ke kokoana-hloko ea ho kenngoa ha saccharin ka litoeba. (2009)

THUTO E TLAHANG

Behav Neurosci. 2009 Apr; 123 (2): 397-407.

Freet CS, Steffen C, Nestler EJ, Grigson PS.

mohloli o moholo

Lefapha la Saense ea Neural le Boitšoaro, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. [imeile e sirelelitsoe]

inahaneloang

Liroto li hatella ho ja saccharin ha e penta ka moriana oa tlhekefetso (Goudie, Dickins, & Thornton, 1978; Risinger & Boyce, 2002). Ka tlaleho ea bangoli, ketsahalo ena eo ho thoeng e bapisoa le moputso, ho nahanoa hore e arotsoe ka ho lebella thepa e tlisang melemo ea lithethefatsi (PS Grigson, 1997; PS Grigson & CS Freet, 2000). Leha ho sa ntsane ho fumaneha ho hongata malebana le motheo oa neural oa moputso le bokhoba, ho tsejoa hore ho fetella ha ΔFosB ho amana le keketseho ea maikutlo le ts'usumetso ea lithethefatsi. Ka lebaka lena, bangoli ba ile ba beha lebaka la hore oxpxpression ea ΔFosB le eona e lokela ho ts'ehetsa phaello e kholo ea tlatsetso ea lithethefatsi ea moputso oa tlhaho. Ho leka taba ena, litoeba tsa NSE-tTA × TetOp-ΔFosB (Chen le al., 1998) e nang le osFosB e tloaelehileng kapa e nang le khatello ea matla holima striatum e ne e fuoa mokhoa oa ho sebelisa caccharin cue ebe e kenngoa ka letsoai, 10 mg / kg cocaine, kapa 20 mg / kg cocaine. Ho fapana le polelo ea pele, ho qojoa ha vereFosB ho ne ho amana le tšebeliso ea takatso ea koae ea cocaine. Ho tšelisoa hore ho phahamisoa ha ΔFosB ha ho eke feela boleng ba lithethefatsi, empa boleng ba moputso ba saccharin cue le bona.

Keywords: papiso ea moputso, meputso ea tlhaho, litoeba tsa transgenic, CTA, ho ja

ΔFosB ke setho sa lelapa la Fos la lintlha tse hatisitsoeng le amohetseng tlhokomelo e kholo e le phetoho ea limolek'hule bakeng sa polasetiki ea nako e telele ea neuronal e hlokometsoeng ts'ebelisong ea lithethefatsi (McClung et al., 2004; Nestler, Barrot, & Self, 2001; Nestler, Kelz, & Chen, 1999). ΔFosB e ka etsa hore homodimerize (Jorissen et al., 2007) kapa heterodimerize le JunD (le ka tekanyo e nyane, JunB; Hiroi et al., 1998; Perez-Otano, Mandelzys, & Morgan, 1998) ho etsa li-protein-1 complexes (Chen le al., 1995; Curran le Franza, 1988; Nestler et al., 2001). Protheine ea activator-1, ka hona, e sebetsa setsing sa tumellano ea "activator protein-1" (TGAC / GTCA) ho khothaletsa kapa ho thibela phetiso ea mefuta e fapaneng ho kenyeletsoa, ​​empa e sa felle ho, dynorphin, AMPA glutamate receptor subunit GluR2, cyclin-wate kinase 5 , and factor factor kappa B (Chen, Kelz, Hope, Nakabeppu, & Nestler, 1997; Dobrazanski et al., 1991; Nakabeppu & Nathans, 1991; Yen, Wisdom, Tratner, & Verma, 1991). Ho bokellane ba li-nucleus, ho phahamisoa ha osFosB ho thibela ho hatisoa ha dynorphin (McClung et al., 2004, empa bona Andersson, Westin, & Cenci, 2003) empa e khothalletsa ho hatisoa ha GluR2 (Kelz le Nestler, 2000), XXUMX e itšetlehileng ka cyclinMcClung le Nestler, 2003), le factor factor kappa B (Ang et al., 2001). Ho qhekella boholo ba mefuta ena (le / kapa lihlahisoa tsa bona) ho fumanoe ho susumetsa maikutlo a litlhare tsa tlhekefetso. Mohlala, overexpression ea GluR2 e sebelisa phetiso ea vaerase e kopantsoeng le litoeba, kapa blockade ea dynorphin ke mohanyetsi oa κ-receptor kapa-BNI ka litoeba, e eketsa litlamorao tse khahlisang tsa koae le morphine, ka ho latellana (Kelz et al., 1999; Zachariou et al., 2006).

Ho na le lintlha tse 'maloa tse ka phahamisang ΔFosB bokong,' me bophahamo e ka ba sebaka se ikhethileng. Matšoenyeho a sa feleng, lithethefatsi tsa antipsychotic, le lithethefatsi tsa tlhekefetso kaofela li phahamisa ΔFosB ka har'a dorsal (caudate-putamen) le ventral striatum (Atkins et al., 1999; Perrotti et al., 2004, 2008). Ho "ventral striatum" (ke hore, li-nucleus accumbens), leha ho le joalo, e 'ngoe le e' ngoe ea lintlha tsena e phahamisa phapang ea ΔFosB ka mefuta e ikhethang ea sele. Mohlala, khatello ea maikutlo e sa foleng e phahamisa ΔFosB ka har'a dynorphin + / ntho P + le enkephalin + li-subsets tsa li-neuropin tsa "spiny dopamine" tse fumanehang ho "" ventral striatum "Perrotti et al., 2004). Lithethefatsi tsa antipsychotic li phahamisa ΔFosB ho enkephalin + dopamine neurons ka har'a ventral striatum (Atkins et al., 1999; Hiroi le Graybiel, 1996), le lithethefatsi tsa tlhekefetso li phahamisa ΔFosB ka har'a dynorphin + / ntho P + dopamine neurons ka har'a ventral striatum (Moratalla, Elibol, Vallejo, & Graybiel, 1996; Nye, Hope, Kelz, Iadarola, & Nestler, 1995; Perrotti et al., 2008). Ke mokhoa ona oa ho qetela oa polelo ea ΔFosB ka har'a dorsal striatum le dynorphin + / ntho P + dopamine neurons ka har'a li-nucleus tsa "nucleus" tseo re buang ka tsona e le polelo ea "striatal" sengoloa sena (ntle le ha ho boletsoe se seng) hobane ke mokhoa ona oa polelo. e amana haholo le moputso oa tlhaho, lithethefatsi tsa tlhekefetso, le bokhoba ba tahi (Colby, Whisler, Steffen, Nestler, & Self, 2003; McClung et al., 2004; Olausson et al., 2006; Werme et al., 2002), mme ke mokhoa ona oa polelo o fumanoang ho litoeba tsa transgenic tse sebelisitsoeng lithutong tsa rona (Kelz et al., 1999).

Ho khahlisang, ho phahamisoa ha ΔFosB ke lithethefatsi tsa tlhekefetso ho hloka ho pepeseha ho fapana le ho pepeseha hampe (McClung et al., 2004; Nye et al., 1995; Nye & Nestler, 1996). Kahoo, le ha ho pepesetsoa lithethefatsi ka bongata ho potlaka ho eketsa liprotheine tse ngata tsa lelapa tsa Fos striatum, joalo ka c-Fos le FosB (Daunais le McGinty, 1994; B. Hope, Kosofsky, Hyman, & Nestler, 1992; Persico, Schindler, O'Hara, Brannock, & Uhl, 1993; Sheng & Greenberg, 1990), ho na le keketseho e nyane haholo ea ΔFosB (Nestler, 2001a; Nestler et al., 1999). Leha ho le joalo, hang ha e hlahisitsoe, ΔFosB e tsitsitse ebile e na le bophelo bo fetang halofo ea beke ea vNUMX ha e bapisoa le 1-10 hr liprotheine tse ling tsa Fos (Chen le al., 1997). Khokahano ena e lumella ho bokelloa ha ΔFosB butle butle ka lebaka la lithethefatsi. Liprotheine tse ling tsa Fos, ha li bapisoa, li bonts'a karabo e sa feleng ha nako e ntse e feta (Hope et al., 1992, 1994; Moratalla et al., 1996; Nye et al., 1995). Ho pepesehela lithethefatsi tse sa feleng, ka hona, ho lumella ΔFosB ho fihla maemong ao a ka amang mofuta oa gene le ho ba le boitshwaro bo nepahetseng.

Ho na le sengolo sa lingoliloeng se ntseng se hola se bonts'a hore bophahamo ba ΔFosB bo eketsa boleng ba moputso oa lithethefatsi tsa tlhekefetso. Mohlala, khetho ea libaka tse amanang le lithethefatsi, e hlahisoang ke maemo a khethiloeng a sebaka, e eketseha ho litoeba tse nang le ΔFosB e phahameng ho striatum (Kelz et al., 1999). Ho fumana le ho boloka boits'oaro ba ho sebelisa lithethefatsi, hammoho le tšusumetso ea ho fumana lithethefatsi, le tsona li eketseha ka tsela e tšoanang ka litoeba tse nang le ΔFosB e phahameng (Colby et al., 2003). Leha ho entsoe tsoelo-pele ho utloisiseng litlamorao tsa ΔFosB maemong a mangata a bokhoba ba lithethefatsi, sebaka se seng se sa kang sa botsoa ke phello ea ΔFosB ho kenyellelitsoeng tlasa lithethefatsi meputso ea tlhaho. Ho batho, ntho ena e bonahatsoa ka tšusumetso e fokotsehileng ea mosebetsi, metsoalle, lelapa, le phaello ea chelete (mohlala, Goldstein et al., 2006, 2008; Jones, Casswell, & Zhang, 1995; Nair et al., 1997; Santolaria-Fernandez et al., 1995).

Lintlha tsa rona li fana ka maikutlo a hore phello ena e bohloko ea bokhoba ba lithethefatsi ho batho e ka fetisoa ka litoeba ka ho sebelisa papiso ea paradigm (Grigson & Twining, 2002). Pararigming ena, ho fihlella sejo se fumanehang habonolo sa saccharin se lateloa ke ho fumana lithethefatsi tsa tlhekefetso, joalo ka morphine kapa cocaine. Tlas'a maemo ana, likhoto le litoeba li tla qoba ho jella mofuta oa tatso ka ho lebella taolo ea sethethefatsi (Grigson, 1997; Grigson & Twining, 2002; Risinger & Boyce, 2002). Ho latela hypothesis ea moputso, ho jella moroalo oa tlhaho oa moputso ho ka qojoa kamora ho roala joala le lithethefatsi tsa tlhekefetso, bonyane qalong (bona Wheeler et al., 2008), hobane boleng ba matla a tšusumetso ea matla a bokantle ha a bapisoa le thepa e matlafatsang ea lithethefatsi (Grigson, 1997). Maikutlo ana a fapana le ak'haonte ea nako e telele ea tatso e ratang tatso (ke hore, pono e fapana le tlhahiso ea hore likhoto li qobelle ho ja sejo sa tatso hobane se bolela esale pele thepa ea lithethefatsi e tlotsang) (Nachman, Lester, & Le Magnen, 1970; Riley & Tuck, 1985).

Haeba moputso oa tekanyo ea moputso o nepahetse, boemo bofe kapa bofe kapa bofe bo bonts'ang boleng ba moputso oa lithethefatsi bo lokela ho thusa ho qoba ho fokola ha sethethe sa saccharin. Ho latela litlolo tse amanang le lithethefatsi tsa Lewis tse senang lithethefatsi li bonts'a mokhoa o mongata oa ho qoba setlolo sa saccharin kamora li-coupcharin-cocaine ho fapana le likhoto tsa Fischer tse sa tsotelleng.Grigson & Freet, 2000). Likhoto tsa Sprague-Dawley le tsona li bonts'a phetoho e kholo ea tatso e tatsoang ka koae kapa sucrose kamora pale ea kalafo ea morphine e sa foleng.Grigson, Wheeler, Wheeler, & Ballard, 2001). Ho khahlisang ke hore likhoto ka bobeli tsa lewis tsa Lewis le litoeba tsa Sprague-Dawley tse nang le nalane ea kalafo ea morphine e sa foleng li phahamisitse ΔFosB ka har'a nucleus accumbens (Haile, Hiroi, Nestler, & Kosten, 2001; Nye & Nestler, 1996). Teko 1 e hlahlobisisa karolo ea ΔFosB ka tekanyo ea ts'usumetso e khothalletsoang ke lithethefatsi (CS) ka ho sekaseka khatello ea maikutlo ea cocaine e khothalletsang tšebeliso ea ckecharin cue ka litoeba tse tlatselletsang ntlha ena e ngotsoeng.

Leka 1

Liphuputso tse fetileng li bontšitse hore litoeba li hatella ho jella tatso ea tatso ha e pentiloe ka sethethefatsi sa tlhekefetso ka tsela e ts'oanang le e bonoang ho litoeba (Risinger & Boyce, 2002; Schroy, 2006). Haholo joalo ka lithuto tse kenyeletsang likhoto, lithuto tsena li sebelisitse thibelo ea ho kena metsing le tharollo e ratoang ea 0.15% saccharin joalo ka CS (Bachmanov, Tordoff, & Beauchamp, 2001; Tordoff & Bachmanov, 2003). Litekong tsena, ho jele setsi sa saccharin ho ile ha hatisoa ha ho fihlella saccharin ho lateloa ke ente ea 10 mg / kg cocaine (ho litoeba tsa DBA / 2) kapa 20 mg / kg cocaine (ho DBA / 2 le C57BL / 6 ) koae (Risinger & Boyce, 2002; Schroy, 2006). Ka hona, Teko ea 1 e ile ea lekola ho hatelloa hoa tšebeliso ea 0.15% saccharin cue ha e palangoe le saline, 10 mg / kg cocaine, kapa 20 mg / kg cocaine metsing a se nang metsi a NSE-tTA × TetOp-ΔFosB Line A litoeba. Litoeba tsena tse kholo tsa transgenic (SJL × C57BL / 6) li bonts'a ho khetha ho feteletseng ha ΔFosB ka har'a striatum mabapi le ho tlosoa hoa docycycline metsing (Chen le al., 1998). Motheong oa data e fumaneng litoebeng, re ile ra nahana hore ho phahamisoa ha ΔFosB ho litoeba tsena ho ka khothatsa litlamorao tse tlisoang ke lithethefatsi ka hona ho nolofalletsa khatello ea maikutlo e khothalletsoang ke tšebeliso ea saccharin cue e amanang le taolo e tloaelehileng ea ΔFosB.

Method

Lihlooho

Lithuto tseo e ne e le litoeba tsa 60 tsa banna NSE-tTA × TetOp-ΔFosB Line A bitransgenic litoeba. Litoeba li hlahisitsoe ke setsi sa liphoofolo Univesithing ea Texas Southwestern Medical Center e Dallas, Texas, 'me se hlokometsoe ho 100 μg doxycycline / ml metsing a nooang. Mokhoa ona o boloka khatello e felletseng ea polelo ea transgenic ΔFosB mme ka tsela eo e lumella kholo e tloaelehileng (joalo ka ha ho hlalositsoe ho Chen le al., 1998). Joale litoeba li ile tsa fetisetsoa setsing sa liphoofolo ho Pennsylvania State University College of Medicine e Hershey, Pennsylvania, 'me tsa beheloa likhoeli tsa 2 (litoeba tsohle li ne li bolokoa ho doxycycline nakong ea lipalangoang le nakong ea ho arola batho). Ha e lokolloa botlolong, halofo ea litoeba (n = 30) ho tlositsoe doxecycline, 'me ΔFosB overexpression e ne e lumelletsoe ho tsoella libeke tsa 8 pele ho liteko, nako e hlokahalang bakeng sa bohato bo boholo ba ΔFosB (McClung le Nestler, 2003). Limpho tse ling kaofela (n = 30) o ile a lula ho Doxycycline bakeng sa nako ea lithuto. Ho ile ha lekanngoa lipakeng tsa 31.2 g le 45.0 g qalong ea liteko mme li ne li behiloe ka mokhoa o le mong, liphaephe tse hlakileng tsa polasetiki sebakeng sa tlhokomelo ea liphoofolo se laoloang ke 21 ° C le 12-hr. ho 7: 00 am). Liphetoho tsohle tse entsoeng ka liteko li entsoe 2 hr (9: 00 am) le 7 hr (2: 00 pm) karolong e bobebe ea potoloho. Litoeba li ile tsa bolokoa ka mokhoa oa mahala oa ho ja li-jaort tsa Harlan Teklad rodent (W) 8604 le metsi, ntle le moo ho boletsoeng ka tsela e 'ngoe.

didirisiwa

Liphetoho tsohle tse entsoeng ka liteko li ne li etsoa mekotla ea malapeng. Ho ile ha sebelisoa lipeipi tse ntlafalitsoeng tsa Mohr ho fana ka dH2Ho fihlella le saccharin. Li-pipette li ile tsa fetoloa hore e be likhalase tsa khalase ka ho tlosa lipheletso tsa eona. Sethala sa rabara se nang le tšepe ea tšepe e kentsoeng ka har'a sethala se ne se kenngoa ka tlas'a moqomo, 'me sethala se tšoanang sa rabara (ho tlosa spout) se ile sa koala karolo e kaholimo ea moqomo. Tjello ea dH2O le saccharin li tlalehiloe ho 1 / 10 ml.

Tsamaiso

Lithuto tsohle li ne li lekantsoeha hang ka letsatsi thutong eohle. Kamora ho lokolloa botlolong, 'me joalo ka ha ho hlalositsoe, litoeba tsa ΔFosB overexpression (n = 30) li tlositsoe 100 μg / ml doxycycline. Litoeba tsena li amohetse dH e sa silafatsoang2Bakeng sa thuto e setseng, le halofo e 'ngoe ea litoeba (n = 30), lihlopha tse tloaelehileng tsa ΔFosB, li ile tsa tsoela pele ho doxycycline. Kamora libeke tsa 8 tsa ΔFosB overexpression, ts'ebetso ea metsi a mantlha e ile ea hlahlojoa. Bakeng sa litekanyo tsa motheo, litoeba tsohle li ile tsa beoa lenaneong la phokotso ea metsi le neng le kenyelletsa phihlello ea dH2O (e nang le kapa e se nang doxycycline ho latela sehlopha sa kalafo) bakeng sa 1 hr ho qala ka 9: 00 am le bakeng sa 2 hr ho qala ka 2: 00 pm Basake ula le boima ba 'mele li tlalehiloe bekeng ea 1. Nakong ea liteko, litoeba tsohle li amohetse phihlello ea 1 hr ho 0.15% saccharin hoseng e lateloang hang hang ke ente ea intine ea saline (e kenang ka hare)n = 10 / sele), 10 mg / kg cocaine (n = 10 / sele), kapa 20 mg / kg cocaine (n = 10 / sele). Takatso ea litatso-lithethefatsi li etsahetse ka linako tsohle tsa 48 hr bakeng sa liteko tse hlano. Ho boloka hydration, lithuto tsohle li fumane phihlello ea 2 hr ho dH2O kapa 100 μg / ml doxycycline thapama e 'ngoe le e' ngoe le 1 hr ho fihlella dH2O kapa 100 μg / ml doxycycline hoseng ho hong le ho hong pakeng tsa liteko tsa maemo, joalo ka ha ho boletsoe ke sehlopha sa sehlopha. Saccharin e fumanoe ho Sigma Chemical Company, St. Louis, MO, le HCl ea koae e fanoe ke Setsi sa Naha sa Ts'ebeliso e Mpe ea Lithethefatsi. Tharollo ea saccharin e ile ea hlahisoa ka mocheso oa kamore.

Liphetho le puisano

CS ula

Ts'ebetso le boima ba 'mele li ile tsa hlahlojoa ho sebelisoa li-2 x 3 × 5 li-processorial tse kopantsoeng tsa li-variances (ANOVA) kalafo e fapaneng (tloaelehileng vs. overexpression of ΔFosB), drug (saline, 10 mg / kg cocaine, kapa 20 mg / kg cocaine), le liteko (1-5). Ho ile ha etsoa liteko tsa post hoc, moo ho loketseng, ho sebelisa liteko tsa Neuman-Keuls ka alpha ea .05. Ho shebiloe Setšoantšo sa 1 e bonts'a hore overexpression ea ΔFosB seterekeng e amana le phokotso ho fapana le ho khothaletsoa ha khatello ea koae e khothalletsoang ho ja seccharin cue.

Setšoantšo sa 1 

Ho ja (± SEM) ho kenella (ml / 1 hr) ea 0.15% saccharin ho latela lipara tse hlano tse kenngoeng ka ente ea saline, 10 mg / kg cocaine, kapa 20 mg / kg cocaine ho NSE-tTA × TetOp-ΔFosB Line A litoeba ka tloaelehileng (phanele e lets'ehali) kapa e phahameng ...

Ts'ehetso ea tlhahlobo ena e fanoe ke tlhaiso ea post hoc ea ts'ebelisano e kholo ea kalafo ea Drug × Litlhare, F(8, 212) = 2.08, p <.04. Haholo-holo, liphetho tsa post hoc Newman-Keuls liteko li bonts'itse hore leha tekanyetso ea 10 mg / kg ea cocaine e ne e sa sebetse ho fokotsa ho kenella ha CS lihlopheng ka bobeli tsa kalafo (p > .05), tekanyetso ea 20 mg / kg e ne e sa sebetse hantle ho litoeba tse nang le polelo e phahameng ea ΔFosB (bona Setšoantšo sa 1, phanele e nepahetseng). Ka mantsoe a mang, leha kalafo e nang le tekanyetso ea 20 mg / kg ea koae e fokolitse haholo ts'ebeliso ea "saccharin cue" e amanang le taolo ea sehlopha ka seng sa saline e tšoaroang ka liteko tsa Trials 2-5 (ps <.05), litoeba tse nang le polelo e phahameng ea ΔFosB li jele haholo lesela la saccharin le neng le kopantsoe le k'hok'heine ea 20 mg / kg ho feta taolo e tloaelehileng ea ho hlahisa maikutlo. Mokhoa ona oa boitšoaro o ne o le bohlokoa litekong tsa 3-5 ( pS <.05).

Boima ba 'mele

Ha ho boima bo feteletseng ba BFosB boteng kapa ho pepesetsoa lithethefatsi ho fetotse boima ba 'mele haholo. Qeto ena e tšehelitsoe ke phello e seng ea bohlokoa ea kalafo, F <1, kapa sethethefatsi, F(2, 53) = 1.07, p = .35. Phello e kholo ea liteko e ne e le bohlokoa, F(5, 265) = 10.54, p <.0001, e bontšang hore boima ba 'mele bo fetohile ho feta liteko tse latellanang. Kamora nako, leha 2 × 3 × 6 mehato e phetoang ANOVA e senotse ts'ebelisano ea bohlokoa ea kalafo × Lithethefatsi × liteko tsa liteko, F(10, 265) = 4.35, p <.01, liphetho tsa liteko tsa post hoc li ne li sa makatse.

Ho ja metsi a hoseng

Tloaelo ea hoseng ea dH2O (ml / h) matsatsing a lipakeng tsa liteko tsa boemo bo tlase (basement, Trials W1-W4) e hlahisoa ho Setšoantšo sa 2 (holimo holimo le ka letsohong le letšehali).

Setšoantšo sa 2 

Ho bolela (± SEM) tšebeliso ea dH2O hoseng (ml / 1 hr; panels tse holimo) le thapama (ml / 2 hr; panels tse ka tlase) ho NSE-tTA × TetOp-ΔFosB Line litoeba tse nang le maemo a tloaelehileng (liphanele tse tsoang ka ho le letona) kapa li-panels tse phahameng (li-panels tse nepahetseng) tsa ΔFosB striatum ...

A 2 × 3 × 5 e kopaneng le thuto ea lithuto tsa ANOVA e senoletse hore maikutlo a ΔFosB ha a matla kapa ho pepesetsoa lithethefatsi ha a fetoloe haholo dH hoseng.2Ho ja ka bongata joalo ka ha ho bonts'oa ke ts'ebelisano e se nang mosola ea kalafoF <1). Ho phaella moo, leha e le phello e ka sehloohong ea kalafo, F <1, kapa sethethefatsi, F(2, 53) = 2.55, p = .09, kapa tšebelisano 'moho le lithethefatsi. F(8, 212) = 1.57, p = .14, e ne e bohlokoa.

Karolelano ea metsi motšeare

Tjello ea dH2O bakeng sa nako ea ho fihlella ea 2-hr thapama bakeng sa liteko tsohle ho hlahisoa Setšoantšo sa 2 (ka tlase letsohong le letšehali le ka ho le letona). Phello e ka sehloohong ea kalafo e ne e se bohlokoa (F <1), ho fana ka maikutlo a hore khatello e fetelletseng ea ΔFosB ha e amme thapama dH2Batla ka kakaretso Kameho e kholo ea lithethefatsi, leha ho le joalo e bile le bohlokoa ba lipalo, F(2, 53) = 7.95, p <.001, joalo ka kalafo ea kalafo × Lithethefatsi × Liteko, F(18, 477) = 2.12, p <.005. Teko ea poso ea ANOVA ena ea litsela tse tharo e senotse thapameng eo dH2Ho kenella ka bongata sehlopheng sa li-cocaine tsa 10 mg / kg ho ne ho sa fapana haholo le taolo ea saline (ps> .05). Leha ho le joalo, thapama dH2Ho kenella ka bongata ho ne ho eketsehile haholo lihlopheng tsa 20 mg / kg ha ho bapisoa le taolo ea bona ea saline, mme phello ena e ne e le bohlokoa litekong tse nang le maemo moo litoeba li neng li qoba ho jella saccharin cue hoseng (ke hore, Trials 3, 4, le 5 ho litoeba e na le ΔFosB e tloaelehileng le liteko tsa 4 le 5 ka litoeba tse nang le ΔFosB e phahameng, ps.. .05).

Leka 2

Liphetho tse fumanoeng ho Teko ea 1 li khahlano le tse boletsoeng esale pele motheong oa data e phatlalalitsoeng pele. Litoeba tse nang le polelo e phahameng ea ΔFosB e bonts'itsoeng hanyane, ho e-na le ho feta, ho qojoa ha serethe sa saccharin kamora ho pheta-phetoa ha li-saccharin-cocaine. Ho na le litlhaloso tse 'maloa bakeng sa data ena. Tse hlakileng haholo, tse fuoeng lingoliloeng, ke hore paradigm ena e tsotella batho ba iphapanyetsang, ho fapana le ho ruisa, thepa ea lithethefatsi (Nachman et al., 1970; Riley Tuck, 1985). ΔFosB e phahamisitsoeng, ka hona, e kanna ea seke ea eketsa karabelo ho thepa ea lithethefatsi e fanang ka moputso, empa hape e ka fokotsa ho arabela maemong a litheko tse fapaneng tsa lithethefatsi. Haeba ho joalo, litoeba tse nang le ΔFosB e phahameng li ka lebelloa le ho bontša li-CCA tse nyane tse hlahisitsoeng ke LiCl ho feta litoeba ka polelo e tloaelehileng ea ΔFosB. Ho etsa tlhahlobo ea maikutlo ana, litoeba tse tšoanang li ne li tsamaisoa ka mokhoa o tloaelehileng oa ho latsoa tatso eo ba e fumaneng 1 hr phihlello ea buka ea 0.1 M NaCl mme hang kamora moo, ba kenngoa kahare ka letsoai, 0.018 M LiCl, kapa 0.036 M LiCl.

Method

Lihlooho

Lithuto tsena e ne e le 58 (29 overexpression ΔFosB le 29 tloaelehileng ΔFosB) male NSE-tTA × TetOp-ΔFosB Line A litoeba tse sebelisitsoeng ho Teko ea 1. Lice li ile tsa hanyetsoa ka mokhoa o tšoanang ho tsamaisa boiphihlelo ba pele ba saccharin-saline kapa bo-saccharin-cocaine har'a lihlopha. Nakong ea liteko, litoeba sehlopheng sa liteko li bile le qoelopele ea ΔFosB seterekeng bakeng sa libeke tsa 17, le litoeba tsohle tse boima pakeng tsa 31.7 le 50.2 qalong ea liteko. Li ne li bolokoa ka bonngoe le ho hlokomeloa joalo ka ha ho hlalositsoe kaholimo.

didirisiwa

Sesebelisoa se ne se tšoana hantle le se hlalositseng Teko ea 1.

Tsamaiso

Lithuto tsohle li ne li lekantsoeha hang ka letsatsi thutong eohle. Bakeng sa litekanyo tsa motheo, litoeba tsohle li ne li behiloe lenaneong la ho fokotsa metsi le hlalositsoeng ka holimo (1 hr am le 2 pm), ka kapa ntle le doxycycline e le kabelo ea sehlopha. Ho ja lijo tsa motheo le boima ba 'mele li tlalehiloe bakeng sa beke ea 1. Nakong ea liteko, litoeba tsohle li amohetse phihlello ea 1 hr ho 0.1 M NaCl hoseng e lateloang hang hang ke ente ea intine ea saline (n = 9 / cell), 0.018 M LiCl (n = 10 / cell), kapa 0.036 M LiCl (n = 10 / sele). Ho litoeba, phello ea khatello ea 0.009 M lethal dose ea LiCl e tsamaelitsoe le ea 10 mg / kg tekanyetso ea koae (Grigson, 1997). Leha ho le joalo, ha ho fanoa ka boiphihlelo ba pele ba litoeba ho liteko tsa 1 le bopaki bo bonts'ang hore boiphihlelo bo joalo ba pele bo ka khutlisa nts'etsopele le / kapa polelo ea kamoso e latelang ea CS-unconditioned susumetsa (US) (Twining et al., 2005), re sebelisitse litekanyetso tse phahameng tsa LiCl (0.018 M le 0.036 M). Takatso ea litatso-lithethefatsi li etsahetse ka linako tsohle tsa 48 hr bakeng sa liteko tse hlano. Lithuto tsohle li fumane ho fihlella ha 2 hr ho dH2O kapa 100 μg / ml doxycycline thapama e 'ngoe le e' ngoe le 1 hr ho fihlella dH2O kapa 100 μg / ml doxycycline hoseng ho hong le ho hong pakeng tsa liteko tsa boemo. NaCl e fumanoe ho Fisher Chemical, Pittsburgh, PA; LiCl e fumanoe ho Sigma Chemical Company, St. Louis, MO. Tharollo ea NaCl e hlahisitsoe ka mocheso oa kamore.

Liphetho le puisano

CS ula

Intake e ile ea hlahlojoa ho sebelisoa mofuta oa 2 × 3 × 5 motsoako oa 'nete o kopantsoeng (mofuta o tloaelehileng oa ΔFosB), lithethefatsi (saline, 0.018 M LiCl, kapa 0.036 M LiCl), le liteko (1-5). Ho ile ha etsoa liteko tsa post hoc, moo ho loketseng, ho sebelisa liteko tsa Neuman-Keuls ka alpha ea .05. Kameho ea vereFosB ea ho ithuta ka LiCl CTA e bonts'oa Setšoantšo sa 3.

Setšoantšo sa 3 

Metsi a bolelang (± SEM) (ml / 1 hr) ea 0.1 M NaCl kamora li-pair tse hlano tse kenngoeng ka ente ea letsoai, 0.018 M LiCl, kapa 0.036 M LiCl ho NSE-tTA × TetOp-ΔFosB Line a litoeba tse tloaelehileng ) kapa e phahame ...

Liphetho tsa ANOVA li senotse tšebelisano e kholo ea Drug ×, F(8, 204) = 5.08, p <.001, e bonts'a litoeba tsohle, ho sa tsotelehe polelo ea ΔFosB, li qoba ho ja NaCl CS e neng e kopantsoe le moemeli ea hlohlelletsang bokuli LiCl mabapi le litaba tse tšoaroang ka letsoai. Ho fapana le tlhaiso-leseling ea cocaine e hlalositsoeng kaholimo, ANOVA ea litsela tse tharo ha ea ka ea atamela bohlokoa ba lipalo (F <1). Ntle le moo, ho ne ho se na phello e kholo ea kalafo (ke hore, doxy kapa metsi; F <1), Kalafo × Tšebelisano ea liteko (F <1), kapa Kalafo × Ho sebelisana le lithethefatsi (F <1). Leha ho le joalo, ho shebella lintlha tse bonts'itsoeng ho Setšoantšo sa 3 e fana ka maikutlo a hore phello ea khatello ea LiCl, joalo ka cocaine, e kanna ea ba e nyane ho litoeba tse feteletseng tsa ΔFosB. Ka hona, re ile ra nchafatsa lihlopha tsa kalafo ka thoko re sebelisa li-3 x 5 li-programorial tse tsoakaneng tsa li-ANOVA tse fapaneng tsa lithethefatsi le liteko. Liphetho tsa li-ANOVA tsena li netefalitse tšebelisano e kholo ea Drug × liteko bakeng sa bobeli bo tloaelehileng, F(8, 100) = 3.48, p <.001, le ba fetang tekano, F(8, 108) = 2.19, p <.033, litoeba tsa osBFosB. Liteko tsa Post hoc li bonts'itse phokotso e kholo ea ts'ebeliso ea CS ke tekanyetso e phahameng ea LiCl ho Liteko tsa 3-5 bakeng sa litoeba tse tloaelehileng le ho Liteko tsa 3 le 4 bakeng sa litoeba tse hatellang haholo (pS <.05).

Leha ho na le sampole e batlang e phahame haholo, datha tsa LiCl li fapane hofeta kamoo e neng e le data ea cocaine ho liteko tsa 1 Phapang e bontšitsoeng ho Setšoantšo sa 3 mohlomong e amana le nalane ea kalafo ea morara kapa oa koae ho Teko ea 1. Ha re leka ho hlahloba mohopolo ona, re ile ra ntlafatsa data ea LiCl CTA re sebelisa 2 × 2 × 3 × 5, 'nete ea' mino e tsoakiloeng (saline vs. cocaine), kalafo (tloaelo khahlanong le vereFosB). M LiCl, kapa 0.018 M LiCl), le liteko (0.036-1). Molemong oa bonolo, nalane ea cocaine e bonts'a kakaretso ea datha tse tsoang ho litoeba ka nalane ea boiphihlelo ka 5 mg / kg le cocaine ea 10 mg / kg. E ts'oanang le sephetho sa tlhahlobo ea pele, tšebelisano ea litsela tse 'ne le eona e sitiloe ho fumana bohlokoa ba lipalo, F(8, 180) = 1.34, p = .22. Nalane ea saccharin-saline kapa saccharin-cocaine, ka hona, e ka baka karohano ho datha, empa tšusumetso ha e ts'oane, mme ho kenyelletsa ntlha ea nalane ha ho na thuso ho senola phapang e kholo ea kholo ea LiCl- ho kenya CTA pakeng tsa litoeba tse tloaelehileng tsa ΔFosB le litoeba ka ho fetelletse hoa ΔFosB. Ka kakaretso, LiCl e hatella ho kenella ha NaCl CS, mme leha ho na le tšekamelo ea phello e fokotsehileng hanyane ho litoeba tse tebileng tsa ΔFosB, phapang lipakeng tsa lihlopha tsa kalafo ha e ea ka ea atamela bohlokoa ba lipalo.

Ha ho nahanoa ka litholoana tsa lipatlisiso tsa liteko tsa 1 le 2 li bonts'a litoeba tse nang le ΔFosB tse jang karolo ea CS ea charin ka mor'a li-coupcharin-cocaine, 'me li batla li sebelisa CSC ea NaCl kamora li-pair tsa NaCL-LiCl. Tloaelo ea ho sebelisa li-CS tse amanang le lithethefatsi haholo (haholo-holo ho Teko ea 1) e kanna ea ba sephetho sa keketseho ea kutloelo-bohloko ea thepa e ruisang molemo ea saccharin le / kapa NaCl CS hobane maemo a phahameng a ΔFosB a tsejoa a amana le keketseho ea ho arabela likarolong tse ling tsa tlhaho tsa meputso tse kang li-pellets tsa lijo (Olausson et al., 2006) le wheel wheel (Werme et al. 2002). Liteko tsa 3 tsa liteko tsa hore na litoeba tsena tse nang le litheko tse phahameng tsa ΔFosB li arabela haholo mehahong e khotsofatsang ea likhatiso tse fapaneng tsa sucrose le letsoai litekong tse peli tsa botlolo ea metsi.

Leka 3

Teko ea 3 e ne e etselitsoe ho hlahloba phepelo ea maikutlo hore khatello e fokotsitsoeng ea litheko tsa CS ke litoeba tse feteletseng tsa ΔFosB ho Teko ea 1 e bile sephetho sa ho phahamisa boleng ba moputso oa ho tseba eseng feela ts'ebeliso ea tlhekefetso, empa tlhaho ea moputso oa "saccharin" le. Ho hlahloba tšibollo ena, re sebelisitse tlhahlobo e le 'ngoe le tse peli tsa botlolo ho hlahloba hore na ΔFosB e tebile hakae ha ho etsoa tšusumetso e ntle. Ntle le moo, ha re nahana ka tšekamelo ea litoeba tsena tsa ho fetela ho ts'ebetso ea NaCl CS kamora hore ho be le li-pair tsa NaCl-LiCl ho Teko ea 2, re sebelisitse tlhahlobo ea botlolo e le 'ngoe le tse peli ho hlahloba ts'ebetso ea "ΔFosB e phahameng" ea tšebeliso ea mefuta e fapaneng ea lintho Liphetho tsa NaCl tse "sa nke lehlakore". Ho ile ha hlahlojoa lintlha tse tharo tsa NaCl (0.03 M, 0.1 M, le 0.3 M) le sucrose (0.01 M, 0.1 M, le 1.0 M). Ho ile ha nahanoa hore haeba bophahamo ba ΔFosB bo nyolla boleng bo khotsofatsang ba meputso ea tlhaho, ho ja sucrose ho lokela ho ba kholo ho litoeba tsa liteko ha li bapisoa le taolo.

Method

Lihlooho

Lithuto tsena e ne e le 28 (14 overexpression ΔFosB le 14 tloaelehileng ΔFosB) male NSE-tTA × TetOp-ΔFosB Line A litoeba tse sebelisitsoeng ho Teko ea 1. Ka nako ea liteko, litoeba sehlopheng sa liteko li ne li le ho feta ha ressionFosB ho striatum ka libeke tse ka bang 25. Ntle le moo, litoeba li bile le boiphihlelo ba pele ka li-coupcharin-sucrose ka tekong e sa atleheng ea tebello ea phapang (litekanyetso tse ts'ehetsang phapang e mabapi le litoeba li ntse li ntse li le lipatlisiso). Ho lekantsoe hantle pakeng tsa 31.5 le 54.5 g qalong ea liteko. Li ne li bolokoa le ho hlokomeloa joalo ka ha ho hlalositsoe pele.

didirisiwa

Lisebelisoa li ne li tšoana hantle le se hlalositsoeng ho Teko ea 1.

Tsamaiso

Lithuto tsohle li ne li imaloa hang ka letsatsi. Nako e fetang ea 4 ea matsatsi a bolulo, mouse e 'ngoe le e' ngoe e fumane phihlello ea 1 hr ho dH2O hoseng le ho fihlella ha 2 hr thapama. Ha u ntse u lekoa, litoeba tse nang le ΔFosB e phahameng (n = 14) e amohetse dH2O ho nchafatsa hape thapama e 'ngoe le e' ngoe, le litoeba ka ΔFosB e tloaelehilengn = 14) e amohetse 100 μg / ml doxycycline. Meetso e meraro ea NaCl (0.03 M, 0.1 M, le 0.3 M) le sucrose (0.01 M, 0.1 M, le 1.0 M) li sebelisitsoe joalo ka litoro. Khatello e 'ngoe le e' ngoe e hlahisitsoe ho litoeba nakong ea hoseng ea 1-hr bakeng sa matsatsi a 3 a latellanang. Matsatsi a pele a 2 e ne e le tlhahiso ea botlolo e le 'ngoe ea tastant mme letsatsi la 3rd le ne le fana ka tlhahiso ea botlolo ea tastant le dH tse peli.2O. Boemo ba libotlolo bo ne bo hanyetsoa, ​​ka ho le letšehali le ka ho le letona, ka har'a lihlopha le nakong ea liteko tsa libotlolo tse peli. Litharollo li hlahisitsoe ka tatellano e kholo, 'me tšebeliso ea NaCl e ile ea hlahlojoa pele ho sucrose. DH tse peli2Ho ile ha etsoa liteko tsa O-pakeng tsa NaCl le liteko tsa sucrose. Ho ja ho ne ho lekanyetsoa letsatsi le leng le le leng ho ea 1 / 10 ml e haufi.

Tlhahlobo ea lintlha

Lintlha li ne li hlahlojoa li sebelisoa t liteko ka alpha ea .05.

Liphetho le puisano

Lintlha tse tsoang litekong tsa libotlolo tse peli li ne li ruta haholo 'me, ka hona, li hlahisoa mona (bona Setšoantšo sa 4). Motheo oa metsi a botlolo ea botlolo ea botlolo ea metsi le ona o bonts'oa e le ntlha ea bohlokoa.

Setšoantšo sa 4 

Hlahloba (± SEM) mokelikeli (ml / 1 hr) ea mefuta e fapaneng ea likelello tsa NaCl (liphanele tse kaholimo) le sucrose (liphanele tse ka tlase) bapisoa le dH2O ho NSE-tTA × TetOp-ΔFosB Line litoeba tse nang le maemo a tloaelehileng (a leqeleng) kapa a maemo a phahameng (a matona a otlolohileng) a ΔFosB ...

Likhetho tsa NaCl

Ka kakaretso, nalane ea ho ithuta ka CTA ho tharollo ea 0.1 M NaCl kamora hore li-coupon tse nang le tekanyetso e tlase ea LiCl ha e a ka ea thibela polelo ea likhetho-mesebetsi ea ho hloea ho eketsa ho tsepamisoa ha NaCl ha ho hlahlojoa tlhahlobong ea ho ja. Ho litoeba tse nang le ΔFosB e tloaelehileng (sebaka se kaholimo sa leqele), litheko tse tlase tsa NaCl (0.03 M le 0.1 M) li ne li sa fapana le tšebeliso ea dH2O tlhatlhobong ea libotlolo tse peli (ps> .05). Khakanyo e phahameng ka ho fetisisa ea NaCl (0.3 M), leha ho le joalo, e ne e sa khethoe haholo ho feta dH2O (p <.0001), e tsamaellanang le boits'oaro ba mohopolo ona (Bachmanov, Beauchamp, & Tordoff, 2002). Ka litoeba tse nang le ΔFosB e phahameng (holimo ka lehlakoreng le letona), mokhoa o tšoanang o ile oa bonahala ka khatello ea 0.3 M ea NaCl (p <.01), e bonts'a hore bophahamo ba ΔFosB ha boa ka ba fetola karabelo ho tšusumetso ena e matla. Mohlala o fapaneng, o kile oa ba teng ka maemo a tlase a NaCl. Ka ho khetheha, likhoto tse nang le polelo e phahameng ea ΔFosB li bontšitse khetho bakeng sa likhakanyo tse tlase tsa 0.03 M le 0.1 M tsa NaCl tse amanang le dH2O tlhatlhobong ea libotlolo tse peli (ps.. .03). Bophahamo ba ΔFosB, ka hona, bo ka fetola khetho bakeng sa maemo a tlase a NaCl ho tloha ho se nke lehlakore ho ea ho a ratoang.

Ho rata khetho

E lekola ho sebelisa t Liteko tsa lisampole tse itšetlehileng li bonts'itse hore ho litoeba tse nang le ΔFosB e tloaelehileng, tšebeliso ea khatello e tlase ea sucrose (0.01 M) e ne e sa fapana haholo le dH2O (p = .82). Ho fapana le hoo, lintlha tsa sucrose tsa 0.1 M le 1.0 M li ne li khethiloe haholo ho dH2O (ps... .0001). Ho litoeba tse nang le ΔFosB e phahameng, sucrose e ne e ratoa haholo ho feta dH2Ho pholletsa le likhopolo tsohle tse lekiloeng (pS <.02). Tlhahiso ena e fana ka ts'ehetso bakeng sa qeto ea hore bophahamo ba ΔFosB bo eketsa khetho ea meputso ea tlhaho.

Puisano e akaretsang

Lintlha tse fumanoeng sengoloa sena li bonts'a hore bophahamo ba ΔFosB kahar'a setereke bo amahanngoa le tšebeliso ea takatso ea "cocaine" e khothalletsoang ke "saccharin". Ho fumana hona ho hanana le polelo ea rona ea pele ea hore maemo a holimo joalo a lokela ho tsamaisa litlamorao tsa koae. Ka ho khetheha, ho phahamisoa ha ΔFosB ho eketsa boleng bo khotsofatsang ba lithethefatsi tsa tlhekefetso (Colby et al., 2003; Kelz et al. 1999), le liphoofolo tse nang le tšusumetso ea tšenyo kapa tšibollo ea kalafo e nang le morphine e sa foleng (bobeli ba tsona li hlahisang maemo a phahameng a ΔFosB) li bonts'a khatello e matla ea tšebeliso ea lithethefatsi ea saccharin e amanang le taolo (Grigson & Freet, 2000; Grigson et al., 2001). Ho bohlokoa ho hlokomela, leha ho le joalo, hore lithuto litekong tse fetileng li ne li se na ΔFosB feela, empa le maemo a amanang le neuronal a hlahisoang ke ho pepesetsoa lithethefatsi tsa tlhekefetso kapa tšebeliso ea lithethefatsi tse lemalloang.Nestler, 1995, 2001b; Nestler le Aghajanian, 1997). Litokiso tsena tse ling ntle le pelaelo li bile le tšusumetso molemong oa boitsoaro 'me li hlahisa pherekano ha li leka ho fetolela karolo ea ΔFosB, ka sekhahla, ho khothalletsoang ke ts'ebeliso ea lithethefatsi tsa CS. Pherekano ena e ne e laoloa bakeng sa liteko tsena (ke hore, lithuto tsohle li ne li ts'oana ntle le lintlha tse phahameng ho ΔFosB), li lumella ho hlalosoa ka mokhoa o hlakileng mabapi le karolo ea ΔFosB ketsahalong eo. Joalokaha ho boletsoe kaholimo, datha ea hajoale e bonts'a hore khatello ea koae e khothalletsoang ke koae ka ho ba teng ha "striatal ΔFosB" empa phello e lumellana le taolo. Phahamiso ea ΔFosB ka har'a striatum, ka hona, e thusa ho fokotsa ho fapana le ho khothaletsa tšebeliso ea koae ea koae.

Ho na le litlhaloso tse 'maloa tsa phello e kenyellelitsoeng e ka khetholloang ka nepo kapele. Taba ea pele, ho ka etsahala hore maemo a phahameng a ΔFosB a fokotse boleng bo putsa ba koae. Sena se bonahala e le mokhoa o sa lebelloang o fuoeng lingoliloeng tse pharalletseng tse hokahanyang ΔFosB le keketseho ea boleng ba moputso oa cocaine le lithethefatsi tse ling tsa tlhekefetso (Colby et al., 2003; Kelz et al., 1999; McClung le Nestler, 2003; McClung et al., 2004; Nestler et al., 2001, 1999). Taba ea bobeli, ho kenella ho ka bonts'a phapang ea mefuta ea ho hatelloa ke lithethefatsi le litlamorao tsa boitšoaro ba ΔFosB. Hape, lingoliloeng ha li lumellane le monyetla ona hobane litoeba le litoeba li bonts'a mokhoa o tšoanang oa tšusumetso e khothalletsoang ke lithethefatsi tsa CS (Grigson, 1997; Grigson & Twining, 2002; Risinger & Boyce, 2002) boitšisiso ba boitšoaro ka ΔFosB (Kelz et al., 1999; Olausson et al., 2006; Werme et al., 2002; Zachariou et al., 2006). Kamora nako, ho ka etsahala hore ebe bophahamo ba BFosB bo ka baka khaello e kopanetsoeng e ka khethollang tšebeliso ea koae ea cocaine. Monyetla ona, le oona o hlaha o sa ratehe hobane tšitiso ea mofuta ona e sa bonoe thutong kapa liketsong tsa motho ea sebetsang (Colby et al., 2003), le ho fumana CTA e hlahisitsoeng ke LiCl ha hoa ka ha fapana, haholo, joalo ka ts'ebetso ea polelo ea ΔFosB ho liteko tsa 2. Litoeba tsa ΔFosB tse fetang tekano le tsona li phela ka tsela e tloaelehileng moahong oa metsi oa Morris le moo li ratang ho ba teng (Kelz et al., 1999).

Monyetla o mong o hlahisoa ke tlhaiso ea setso ea CTA ea data ho liteko tsa 1. Ka mantsoe a mang, haeba khokahano ea cocaine e hlohlellelitsoeng ea ho sebelisa caccharin cue e khannoa ke litheko tse matla tsa lithethefatsi, motho o ne a tla fihlela qeto ea hore ΔFosB e fokotsoe bonyane ka karolo ea eona, litlamorao tsa thepa ena e khelohang ea lithethefatsi. Ebile, ho na le bopaki ba hore lithethefatsi tsa tlhekefetso li na le thepa e khelohang. Cocaine e bontšitsoe hore e tšohe ka tsela e ka 'nang ea tšoana le likarabo tsa sefofane (Blanchard, Kaawaloa, Hebert, & Blanchard, 1999le boits'oaro bo itšireletsang (Blanchard le Blanchard, 1999) ka litoeba. Leha ho le joalo, bopaki bo bongata bo bontšitse hore lithethefatsi tsa tlhekefetso li hatella ho ja CS ka thepa ea lithethefatsi e nang le moputso (Grigson & Twining, 2002; Grigson, Twining, Freet, Wheeler, & Geddes, 2008). Mohlala, marang-rang a gustatory thalamus (Grigson, Lyuboslavsky, & Tanase, 2000; Reilly & Pritchard, 1996; Scalera, Grigson, & Norgren, 1997; Schroy et al., 2005), gustatory thalamocorticol loop (Geddes, Han, & Grigson, 2007), le "cortex" e kenelletsengGeddes, Han, Baldwin, Norgren, & Grigson, 2008; Mackey, Keller, & van der Kooy, 1986) ho sitisa khatello ea setlolo sa saccharin ka li-sucrose le lithethefatsi tsa tlhekefetso, empa eseng ka LiCl. Ka mokhoa o ts'oanang, litekanyetso tse khethiloeng li bonts'a khatello e fapaneng bakeng sa lithethefatsi tsa tlhekefetso kapa US, empa eseng bakeng la LiCl US (Glowa, Shaw, & Riley, 1994; Grigson & Freet, 2000). Ho arohana ho tšoanang ho bontšitsoe ka thetso ea naha ea bohloka (Grigson, Lyuboslavsky, Tanase, & Wheeler, 1999) le litlalehong tse nang le nalane e sa feleng ea morphine (Grigson et al., 2001). Ntle le moo, ho liteko tsa 3 le 2, ho phahamisoa ha ΔFosB ha ho na ho ba le phello ho karabelo e sa laoleheng kapa boemo bo lumellanang le bo susumetsang bo nyarosang. Kahoo, ka lebaka la litoeba tse tloaelehileng, litoeba tse nang le ΔFosB e bontšitse ho feto-fetoha ho tšoanang ha tharollo e matla ea 0.3 M NaCl ho Teko ea 3 le boiphetetso bo tšoanang bo tšoanang le CSC bo amanang le LiCl ho Teko ea 2.

Bopaki bona ka thoko, thutong ea morao-rao re fumane bopaki ba hore khatello ea ts'ebeliso ea koae e khothalletsoang ke koae e amana le ho qaleha ha boemo bo feto-fetohang (Wheeler et al., 2008). Re kholoa hore naha e khelohileng e arotsoe, ka karolo e kholo, ka nts'etsopele ea ho tlosa sepheo sa kholiseho (Grigson et al., 2008; Wheeler et al., 2008). Monyetla, ka hona, o kanna oa nkuoa hore keketseho ea ΔFosB kahar'a setereke e lebisa ho phelisong e fokolang ea cue e amanang le lithethefatsi hobane lithethefatsi li ts'ehetsa nts'etsopele ea ho khaotsa ho tlisoang ke cue. Le ha ho khoneha, sephetho sena se boetse se bonahala se le thata ho se amohela hobane ho litoeba, ho hloea ho eketsehileng CS (joalo ka ha ho lekantsoe ke keketseho ea boitšoaro bo fetolang tatso) ho amana le keketseho ea menahano e sa utloahaleng ea lithethefatsi (Wheeler et al., 2008). Kahoo, ka ho sebelisa mohopolo ona, re tla qobelloa ho etsa qeto ea hore litoeba tse nang le ΔFosB e arabela hantle meahong e khotsofatsang ea lithethefatsi, joalo ka ha ho bonts'itsoe, empa hape e bonts'a takatso e tlase kapa e tsoang ho eona. Sena se bonahala se sa ratehe.

Tlhaloso e matla haholoanyane bakeng sa sephetho se fumanehang data e teng hona joale ke hore le ha ho phahamisoa ha ΔFosB ho eketsehile melemo ea koae litapong tsena, e boetse e eketsa boleng bo ananeloang ba saccharin. Haeba ΔFosB e eketsa boleng bo felletseng ba moputso oa saccharin le cocaine ka mokhoa o ts'oanang, keketseho e lemohuoang ea boleng ba moputso oa saccharin e ne e tla ba kholo le ho feta (bapisoa le cocaine) joalo ka ha ho boletsoe ke molao oa Weber (ke hore, maikutlo a phetoho e nahanoang ka mokhoa o sa thekeseleng o ipapisitse le matla a felletseng a tšusumetso ; Weber, 1846). Keketseho e joalo ea bokhoni ba CS bo ka fokotsang phapang e lekanang lipakeng tsa meputso le ho bona sephetho sa papiso (Flaherty Rowan, 1986; Boreleli, Turovsky, & Krauss, 1994). Tlhaloso ena e tšehetsoa hape ke lingoliloeng tse bonts'ang hore bophahamo ba ΔFosB bo eketsa ho arabela bakeng sa meputso ea tlhaho. Mohlala, wheel wheel (Werme et al., 2002khothaletso ea li-pellets tsa lijo (Olausson et al., 2006) li eketsehile ka bobeli ka bophahamo ba ΔFosB. Ntle le moo, data e fumanoeng ho Teko ea 3 e boetse e bonts'a hore bophahamo ba ΔFosB bo eketsa khetho ea sucrose (0.03 M, 0.1 M, le 0.3 M) le likhatisong tse tlase tsa NaCl (0.01 le 0.1 M) litekong tse peli tsa botlolo ka metsi.

Morero oa teko ena e ne e le ho lekola phello ea ΔFosB ea maemo a holimo papisong le papiso ea meputso, e leng mokhoa o neng o nahana ho etsisa tšusumetso ea tlhotlheletso e tlisoang ke lithethefatsi ea meputso ea tlhaho ea batho ba lemaletseng (Grigson, 1997, 2000, 2002; Grigson & Twining, 2002; Grigson et al., 2008). Ho lemalla ho na le mokhoa o rarahaneng oa boits'oaro, 'me ho ameha lintlha tse ngata ponong ea boitšoaro. Leha ho le joalo, motheong oa lingoliloeng tsa hajoale, ho phahamisoa ha ΔFosB e hlahisoang ke ho pepesehela lithethefatsi tsa tlhekefetso ho bonahala ho bapala karolo ea ho susumetsa litlamorao tsa litlamorao tsa lithethefatsi (Colby et al., 2003; Kelz et al., 1999) le ho arabeleng ho eketsehileng bakeng sa meputso ea tlhaho (Olausson et al., 2006; Werme et al. 2002). Sengoliloeng sena se fana ka leseli mabapi le phello ea ΔFosB mabapi le ho sebelisana le moputso ona. Ho phahamisoa ha ΔFosB ha ho bonahale ho hlokahala bakeng sa ho theoleloa ha lithethefatsi ka sethethefatsi sa saccharin. Ebile, litoeba tsa taolo li hatelletse ho ja saccharin ka nepo. Ho fapana le moo, datha ea rona e fana ka maikutlo a hore bophahamo ba ΔFosB ka striatum bo ka hanyetsa taba ena ka ho fokotsa phapang e lemohuoang ea boleng ba moputso lipakeng tsa meputso ea tlhaho le lithethefatsi tsa tlhekefetso. Ka ho etsa joalo, litoeba tse nang le mofuta ona oa phenotype li kanna tsa sireletsoa hamolemo ho lithethefatsi ha li fuoa meputso e ntle ea tlhaho. Ka ts'ehetso, ho fihlella ha "saccharin blunts" nucleus e bokella karabelo ea dopamine ho jekeng ea pele ea morphine ho Sprague-Dawley rats (Grigson le Hajnal, 2007) le phihlello ea nakoana ea tharollo e fumanehang habonolo ea sucrose e fokotsa boikemisetso ba litoeba ho sebeletsa k'hok'heine pele e fumaneha (Twining, 2007) Kahoo, leha ho phahamisoa ha ΔFosB ho ka etsa hore litoeba le litoeba li sebetse ts'ebelisong ea lithethefatsi kamora hore li fumane meputso e meng, e ka sireletsa sehlooho hohang ka tšebeliso ea lithethefatsi ho na le moputso o mong o sebetsang oa tlhaho.

lumela hore baa fokola

Patlisiso ena e ne e tšehelitsoe ke Lits'ebeletso tsa Ts'ebeletso ea Bophelo ba Sechaba DA09815 le DA024519 le ke PA State Tobacco Settlement Fund 2006-07.

References

  1. Andersson M, Westin JE, Cenci MA. Nako ea nako ea kalafo ea striatal DeltaFosB-joalo le litekanyetso tsa mRNA tsa prodynorphin kamora ho khaotsa kalafo ea dopaminomimetic e sa foleng. Koranta ea Europe ea Neuroscience. 2003; 17: 661-666. [E fetotsoe]
  2. Ang E, Chen J, Zagouras P, Magna H, Holland J, Schaeffer E, et al. Ho hlahisoa ha nyutlelie-kappaB ho li-nucleus tse bokelloang ke tsamaiso ea cocaine e sa foleng. Tlaleho ea Neurochemistry. 2001; 79: 221-224. [E fetotsoe]
  3. Atkins JB, Chlan-Fourney J, Nye HE, Hiroi N, Carlezon WA, Jr, Nestler EJ. Ho kenella ka ho khetheha sebakeng sa deltaFosB ke taolo e pheta-pheto ea lithethefatsi tse tšoanang le tsa atypical antipsychotic. Synfall. 1999; 33: 118-128. [E fetotsoe]
  4. Bachmanov AA, Beauchamp GK, Tordoff MG. Tšebeliso ea boithaopo ea NaCl, KCl, CaCl2, le litharollo tsa NH4Cl ka 28 ea li-mouse. Liphatsa tsa lefutso. 2002; 32: 445-457. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  5. Bachmanov AA, Tordoff MG, Beauchamp GK. Monate oa monate oa C57BL / 6ByJ le 129P3 / J litoeba. Likelello tsa Lik'hemik'hale. 2001; 26: 905-913. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  6. Blanchard DC, Blanchard RJ. Cocaine e ka itšoara ka boits'ireletso e amanang le ts'abo le matšoenyeho Litlhahlobo tsa Neuroscience le Biobehaisheral. 1999; 23: 981-991. [E fetotsoe]
  7. Blanchard RJ, Kaawaloa JN, Hebert MA, Blanchard DC. Cocaine e hlahisa likarabo tse kang tsa ho fofa tse tšoanang le litoeba ka ho betere ea tlhahlobo ea tšireletso. Thutong ea limela 1999; 64: 523-528. [E fetotsoe]
  8. Chen J, Kelz MB, Hope BT, Nakabeppu Y, Nestler EJ. Li-antigen tse amanang le Fos tsa nako e telele: Mefuta e sa fetoheng ea deltaFosB e kentsoeng bokong ka kalafo e sa foleng. Tlaleho ea Neuroscience. 1997; 17: 4933-4941. [E fetotsoe]
  9. Chen J, Kelz MB, Zeng G, Sakai N, Steffen C, Shockett PE, et al. Liphoofolo tsa Transgenic tse nang le polelo e sa bonahaleng e lebisitsoeng ho mofuta oa bokong. Moarek'ii ea Molek'hule. 1998; 54: 495-503. [E fetotsoe]
  10. Chen J, Nye HE, Kelz MB, Hiroi N, Nakabeppu Y, Tšepo BT, et al. Taolo ea li-protein tsa delta FosB le tsa FosB ka ho ts'oaroa ke motlakase le kalafo ea koae. Moarek'ii ea Molek'hule. 1995; 48: 880-889. [E fetotsoe]
  11. Colby CR, Whisler K, Steffen C, Nestler EJ, Self DW. Striatal cell Type overexpression e khethehileng ea DeltaFosB e ntlafatsa ts'usumetso ea koae. Tlaleho ea Neuroscience. 2003; 23: 2488-2493. [E fetotsoe]
  12. Curran T, Franza BR., Jr Fos le Jun: Khokahano ea AP-1. Sele. 1988; 55: 395-397. [E fetotsoe]
  13. Daunais JB, McGinty JF. Tsamaiso e matla le e sa foleng ea cocaine e fapana ka tsela e fapaneng e fetolang li-striatal opioid le transcript ea nyutlelie ea nyutlelie ea nyutlelie. Synfall. 1994; 18: 35-45. [E fetotsoe]
  14. Dobrazanski P, Noguchi T, Kovary K, Rizzo CA, Lazo PS, Bravo R. Ka bobeli lihlahisoa tsa mofuta oa fosB, FosB le mofuta oa eona o mokhuts'oane, FosB / SF, ke li-activator tse sebetsang ka har'a transroblasts. Biology ea Limolek'hule le ea Cellular. 1991; 11: 5470-5478. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  15. Flaherty CF, Rowan GA. Phapanyetsano e atlehileng, ka nako e le 'ngoe le e lebelletsoeng ts'ebelisong ea tharollo ea saccharin. Tlaleho ea Psychology ea Tlhahlobo ea Ts'ebetso: Mekhoa ea Boitšoaro ba Liphoofolo. 1986; 12: 381-393. [E fetotsoe]
  16. Mofuta oa CF, Turovsky J, Krauss KL. Boleng ba hedonic bo amanang bo hlophisa phapang e lebelletsoeng. Physiology le Boitšoaro. 1994; 55: 1047-1054. [E fetotsoe]
  17. Geddes RI, Han L, Baldwin AE, Norgren R, Grigson PS. Liso tsa cortex tsa "gustatory insular cortex" li senya ts'ebetso ea lithethefatsi, empa ha li hlahisoe ke chloride e khothalletsang tšebeliso ea boemo bo khothalletsang tšusumetso. Neuroscience ea Boitšoaro. 2008; 122: 1038-1050. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  18. Geddes RI, Han L, Grigson PS. Manonyeletso a "gustatory thalamocorticol loop block" a khothalletsoang ke lithethefatsi ka tlhaho ea tlhaho ea saccharin, ha a ntse a tlohela tšebetso ea 'mele e le kannete. Takatso ea lijo. 2007; 49: 292-311.
  19. Glowa JR, Shaw AE, Riley AL. Litakatso tse nang le tatso ea cocoaine tse hlahisoang ke cocaine: Ho bapisoa lipakeng tsa litla-morao tsa LEW / N le F344 / N. Psychopharmacology (Berlin) 1994; 114: 229-232. [E fetotsoe]
  20. Goldstein RZ, Cottone LA, Jia Z, Maloney T, Volkow ND, squires NK. Litlamorao tsa moputso oa chelete o hlophisitsoeng holim'a bokhoni ba kelello bo amanang le liketsahalo le boitšoaro ho batho ba baholo ba phetseng hantle. Koranta ea Machaba ea Psychophysiology. 2006; 62: 272-279. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  21. Goldstein RZ, Parvaz MA, Maloney T, Alia-Klein N, Woicik PA, Telang F, et al. Kutloahalo e kopantsoeng ea moputso oa chelete ho basebelisi ba koae ba hona joale: Phuputso ea ERP. Psychology. 2008; 45: 705-713. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  22. Goudie AJ, Dickins DW, Thornton EW. Kokonate e hlahisoang ka mokhoa oa cocoaine e natefisang litakatso tsa likhoho. Thutong ea limela 1978; 8: 757-761. [E fetotsoe]
  23. Grigson PS. Maemo a hohelang tatso le lithethefatsi tsa tlhekefetso: Tlhaloso. Neuroscience ea Boitšoaro. 1997; 111: 129-136. [E fetotsoe]
  24. Grigson PS. Lithethefatsi tsa tlhekefetso le papiso ea moputso: Tlhahlobo e khuts'oane. Takatso ea lijo. 2000; 35: 89-91. [E fetotsoe]
  25. Grigson PES. Joalo ka lithethefatsi bakeng sa chokolete: Meputso e arohaneng e hlophisitsoeng ke mekhoa e tloaelehileng? Physiology le Boitšoaro. 2002; 76: 389-395. [E fetotsoe]
  26. Grigson PS, Freet CS. Litlamorao tse sithabetsang tsa sucrose le cocaine, empa eseng lithium chloride, li kholo ho Lewis ho feta ho litoeba tsa Fischer: Bopaki ba tlhaiso-leseling ea moputso. Neuroscience ea Boitšoaro. 2000; 114: 353-363. [E fetotsoe]
  27. Grigson PS, Hajnal A. Hang ha e se e le ngata haholo: Liphetoho tse etselitsoeng ho li-accumbens dopamine ka mor'a ho etsa mokokotlo o le mong oa saccharin-morphine. Neuroscience ea Boitšoaro. 2007; 121: 1234-1242. [E fetotsoe]
  28. Grigson PS, Lyuboslavsky P, Tanase D. Lits'oaetso tsa moea tse bohloko tsa "gustatory thalamus" li senya morphine- empa eseng LiCl-e hlohlellelitse ho kenella ho litheko: Bopaki bo khahlano le boemo bo khelohileng ba tatso ea maikutlo. Patlisiso ea Brain. 2000; 858: 327-337. [E fetotsoe]
  29. Grigson PS, Lyuboslavsky PN, Tanase D, Wheeler RA. Ho haelloa ke metsi ho thibela morphine-, empa eseng e bakoang ke LiCl, khatello ea phepelo ea sucrose. Physiology le Boitšoaro. 1999; 67: 277-286. [E fetotsoe]
  30. Grigson PS, ea Twining RC. Khatello e khothalletsoang ea Cocaine ea ho ja lijo tsa saccharin: Mohlala oa boitšisinyo bo tlisoang ke lithethefatsi meputso ea tlhaho. Neuroscience ea Boitšoaro. 2002; 116: 321-333. [E fetotsoe]
  31. Grigson PS, Twining RC, Freet CS, Wheeler RA, Geddes RI. Khatello e khothalletsoang ke lithethefatsi ea tšusumetso e nang le tšusumetso e matla: Moputso, ho hlohlona le ho lemalla. Ka: Reilly S, Schachtman T, bahlophisi. Maikutlo a khelohileng a tatso: Lits'ebetso tsa boitšoaro le tsa neural. New York: Oxford University Press; 2008. maq. 74-90.
  32. Grigson PS, Wheeler RA, Wheeler DS, Ballard SM. Phekolo ea morphine e sa foleng e eketsa litlamorao tse sithabetsang tsa sucrose le cocaine, empa eseng lithium chloride, ho sejoatho sa saccharin ho likhoto tsa Sprague-Dawley. Neuroscience ea Boitšoaro. 2001; 115: 403-416. [E fetotsoe]
  33. Haile CN, Hiroi N, Nestler EJ, Kosten TA. Likarabo tse fapaneng tsa boitšoaro mabapi le cocaine li amahanngoa le li-protein tsa mesolimbic dopamine ho likhoto tsa Lewis le Fischer 344. Synfall. 2001; 41: 179-190. [E fetotsoe]
  34. Hiroi N, Greybiel AM. Litlhare tsa kalafo tsa "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "Ancypical" "kalafo" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "T'asali" "" "" "" "" "" "" "" "" "" "" "" "" "Essipical" Tlaleho ea Nearology e Bapisang. 1996; 374: 70-83. [E fetotsoe]
  35. Hiroi N, Marek GJ, Brown JR, Ye H, Saudou F, Vaidya VA, et al. Karolo ea bohlokoa ea mofuta oa fosB molekong oa lisele tsa cellular, tsa cellular le boits'oaro ba ho ts'oaroa ka matla ho sa feleng ha motlakase. Tlaleho ea Neuroscience. 1998; 18: 6952-6962. [E fetotsoe]
  36. Tšepo B, Kosofsky B, Hyman SE, Nestler EJ. Taolo ea polelo ea pele ea liphatsa tsa lefutso le AP-1 e tlamang lenaneong la litekanyetso ke cocaine e sa foleng. Ts'ebetso ea National Academy of Science, USA. 1992; 89: 5764-5768. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  37. Tšepo BT, Nye HE, Kelz MB, Self DW, Iadarola MJ, Nakabeppu Y, et al. Tlhahiso ea motsoako oa AP-1 oa nako e telele o qapiloeng ke liprotheine tse kang Fos ka bokong ka cocaine e sa feleng le kalafo tse ling tse sa foleng. Neuron. 1994; 13: 1235-1244. [E fetotsoe]
  38. Jones S, Casswell S, Zhang JF. Litsenyehelo tsa moruo tsa ho ba sieo mosebetsing tse amanang le joala le ho fokotsa tlhahiso har'a baahi ba New Zealand. Ho lemalla. 1995; 90: 1455-1461. [E fetotsoe]
  39. Jorissen HJ, Ulery PG, Henry L, Gourneni S, Nestler EJ, Rudenko G. Matlafatso le DNA-tse tlamang thepa ea transcription factor DeltaFosB. Likokoana-hloko. 2007; 46: 8360-8372. [E fetotsoe]
  40. Kelz MB, Chen J, Carlezon WA, Jr, Whisler K, Gilden L, Beckmann AM, et al. Khopolo ea "transaction factor deltaFosB" bokong e laola maikutlo a cocaine. Tlhaho. 1999; 401: 272-276. [E fetotsoe]
  41. Kelz MB, Nestler EJ. DeltaFosB: Phetoho ea limolek'hule tlasa polasetiki e telele ea neural. Maikutlo a ha joale ho Neurology. 2000; 13: 715-720. [E fetotsoe]
  42. Mackey WB, Keller J, van der Kooy D. Visceral cortex lesions blockchaeling litakatso tsa maemo tse hlahisoang ke morphine. Thutong ea limela 1986; 24: 71-78. [E fetotsoe]
  43. McClung CA, Nestler EJ. Taolo ea polelo ea gene le moputso oa koae ka CREB le DeltaFosB. Neuroscience ea Tlhaho. 2003; 6: 1208-1215. [E fetotsoe]
  44. McClung CA, Ulery PG, Perrotti LI, Zachariou V, Berton O, Nestler EJ. DeltaFosB: Phetoho ea limolek'hule bakeng sa boikoetliso ba nako e telele bokong. Patlisiso ea Brain Research ea Mele. 2004; 132: 146-154. [E fetotsoe]
  45. Moratalla R, Elibol B, Vallejo M, Greybiel AM. Liphetoho tsa boemo ba sebaka sa marang-rang tse hlahisang liprotheine tse sa sebetseng tsa Fos-Jun ka har'a striatum nakong ea kalafo ea koae e sa foleng le ho ikhula. Neuron. 1996; 17: 147-156. [E fetotsoe]
  46. Nachman M, Lester D, Le Magnen J. Ho nyatsa joala ho rat: Tlhatlhobo ea boitšoaro mabapi le litla-morao tse seng kotsi. Mahlale. 1970 June 5; 168: 1244-1246. [E fetotsoe]
  47. Nka P, Black MM, Schuler M, Keane V, Snow L, Rigney BA, et al. Lisosa tsa kotsi ea ho sitisoa ha tlhokomelo ea mantlha hara masea a tlhekefetso ea basali. Tlhekefetso ea Bana le ho Hlokomoloha. 1997; 21: 1039-1051. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  48. Nakabeppu Y, Nathans D. Mofuta o hlahang oa tlhaho oa FosB o thibelang mosebetsi oa ho ngola oa Fos / Jun. Sele. 1991; 64: 751-759. [E fetotsoe]
  49. Nestler EJ. Motheo oa limolek'hule tsa linaha tse lemalloang. Neuroscientist. 1995; 1: 212-220.
  50. Nestler EJ. Motheo oa limolek'hule tsa polasetiki ea nako e telele e tlatsitsoeng. Tlhahlobo ea Tlhaho Neuroscience. 2001a; 2: 119-128. [E fetotsoe]
  51. Nestler EJ. Molek'hule ea moea oa ho lemalla. Koranta ea Amerika mabapi le Likhoka. 2001b; 10: 201-217. [E fetotsoe]
  52. Nestler EJ, Aghajanian GK. Molek'hule le selefounu ea ho lemalla. Mahlale. 1997 Mphalane 3; 278: 58-63. [E fetotsoe]
  53. Nestler EJ, Barrot M, Self DW. DeltaFosB: Phetoho e tsoetseng pele ea molek'hule ea ho lemalla. Ts'ebetso ea National Academy of Science, USA. 2001; 98: 11042-11046. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  54. Nestler EJ, Kelz MB, Chen J. DeltaFosB: Mokena-lipakeng oa molek'hule oa polasetiki e telele ea neural le ea boitšoaro. Patlisiso ea Brain. 1999; 835: 10-17. [E fetotsoe]
  55. Nye HE, Tšepo BT, Kelz MB, Iadarola M, Nestler EJ. Boithuto ba pharmacological ba taolo ea kalafo ea antigen e amanang le FOS ea nako e telele ka cocaine ho striatum le nucleus accumbens. Tlaleho ea Pharmacology le Therapeutics ea Tlhahlobo. 1995; 275: 1671-1680. [E fetotsoe]
  56. Nye HE, Nestler EJ. Ho hlahisoa ha li-antigen tse amanang le Fos bokong ba rat ka tsamaiso ea morphine e sa foleng. Mofuta oa 'mele 1996; 49: 636-645. [E fetotsoe]
  57. Olausson P, Jentsch JD, Tronson N, Neve RL, Nestler EJ, Taylor JR. DeltaFosB bokong ba nyutlelie e laola boitšoaro bo matlafalitsoeng ba sesebelisoa le ts'usumetso. Tlaleho ea Neuroscience. 2006; 26: 9196-9204. [E fetotsoe]
  58. Perez-Otano I, Mandelzys A, Morgan JI. MPTP-Parkinsonism e tsamaisana le polelo e phehellang ea protheine ea delta-FosB e tšoanang le dopaminergic pathways. Patlisiso ea Boko: Patlisiso ea Brain ea Mele. 1998; 53: 41-52. [E fetotsoe]
  59. Perrotti LI, Hadeishi Y, Ulery PG, Barrot M, Monteggia L, Duman RS, et al. Ho hlahisoa ha deltaFosB ka likarolo tsa boko tse amanang le moputso kamora khatello ea maikutlo e sa foleng. Tlaleho ea Neuroscience. 2004; 24: 10594-10602. [E fetotsoe]
  60. Perrotti LI, Weaver RR, Robison B, Renthal W, Maze I, Yazdani S, et al. Mekhoa e fapaneng ea tlhahiso ea DeltaFosB bokong ka lithethefatsi tsa tlhekefetso. Synfall. 2008; 62: 358-369. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  61. Persico AM, Schindler CW, O'Hara BF, Brannock MT, Uhl GR. Tlhaloso ea taba ea brain: Litlamorao tsa amphetamine e bohloko le e sa foleng le khatello ea maikutlo. Patlisiso ea Boko: Patlisiso ea Brain ea Mele. 1993; 20: 91-100. [E fetotsoe]
  62. Reilly S, Pritchard TC. Makhophoa a bohloko a ka morao a lere: II. Mofuta oa tatso e monate le e monate. Neuroscience ea Boitšoaro. 1996; 110: 746-759. [E fetotsoe]
  63. Riley AL, Tuck DL. Maemo a hohelang tatso: Boemo ba boitšoaro bo nang le chefo. Liphatlalatso tsa New York Academy of Science. 1985; 443: 272-292. [E fetotsoe]
  64. Risinger FO, Boyce JM. E boemong bo latsoang le ho fumaneha ha lithibelo tsa tatso e nang le maemo ho lithethefatsi tsa tlhekefetso ho litoeba tsa DBA / 2J. Psychopharmacology (Berlin) 2002; 160: 225-232. [E fetotsoe]
  65. Santolaria-Fernandez FJ, Gomez-Sirvent JL, Gonzalez-Reimers CE, Batista-Lopez JN, Jorge-Hernandez JA, Rodriguez-Moreno F, et al. Teko ea phepo e nepahetseng ea ba lemaletseng lithethefatsi. Ho Tebella Lithethefatsi le Joala. 1995; 38: 11-18. [E fetotsoe]
  66. Scalera G, Grigson PS, Norgren R. Mesebetsi e matla ea takatso ea lijo, sodium takatso ea lijo le mokhoa o monate oa tatso o pholohang ha o le teng lisekeng tsa tatso ea thalamic. Neuroscience ea Boitšoaro. 1997; 111: 633-645. [E fetotsoe]
  67. Schroy PL. Lintlha tse kenyang karohano ea motho ka mong karabelong ea koae le meputso ea tlhaho ho papiso ea papiso. Univesithi ea Pennsylvania State; Hershey: 2006.
  68. Schroy PL, Wheeler RA, Davidson C, Scalera G, Twining RC, Grigson PS. Karolo ea thalamus ea gustatory ka ho lebella le papiso ea meputso ho feta nako ka likhoto. American Journal ea Physiology Regulatory, integrated, and Comparative Physiology. 2005; 288: R966-R980. [E fetotsoe]
  69. Sheng M, Greenberg ME. Taolo le ts'ebetso ea li-c-fos le mefuta e meng ea pele ho ts'ebetso ea methapo. Neuron. 1990; 4: 477-485. [E fetotsoe]
  70. Tordoff MG, Bachmanov AA. Liteko tsa likhetho tsa tatso ea 'Mouse: Hobaneng ha ho entsoe libotlolo tse peli feela? Likelello tsa Lik'hemik'hale. 2003; 28: 315-324. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  71. RC. Nts'etsopele ea mofuta o mocha oa mokhoa oa lithethefatsi o hlohlelletsang menyetla ea meputso ea tlhaho le bohlokoa ba eona lits'ebetsong tsa bokhoba ba lithethefatsi. Univesithi ea Pennsylvania State; Hershey: 2007.
  72. Twining RC, Hajnal A, Han L, Bruno K, Hess EJ, Grigson PS. Methapo ea sebaka se kenang se sa sebetse hantle e senya litabatabelo tsa takatso ea lithethefatsi empa ho bapisoa ha moputso. Koranta ea Machabeng ea Psychology e Bapisang. 2005; 18: 372-396.
  73. Weber EH. Der Tastsinn und das Gemeingefuhl. Ka: Wagner R, mohlophisi. Handworterbuch der Physiologie [Handworterbuch physiology] Vol. 3. Braunschweig, Jeremane: Vieweg; 1846. maq. 481-588.pp. 709-728.
  74. Werme M, Messer C, Olson L, Gilden L, Thoren P, Nestler EJ, et al. Delta FosB e laola mabili a tsamaeang. Tlaleho ea Neuroscience. 2002; 22: 8133-8138. [E fetotsoe]
  75. Wheeler RA, Twining RC, Jones JL, Slater JM, Grigson PS, Carelli RM. Boitšoaro bo bobe le boitshwaro bo bobe bo amang matla a boitšoaro bo bobe bo ka ama bokamoso ba ho itaola. Neuron. 2008; 57: 774-785. [E fetotsoe]
  76. Yen J, RM ea Bohlale, Tratner I, Verma IM. Mofuta o mong o fetisitsoeng oa FosB ke taolo e mpe ea ts'ebetso ea phetisetso le phetoho ea liprotheine tsa Fos. Ts'ebetso ea National Academy of Science, USA. 1991; 88: 5077-5081. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  77. Zachariou V, Bolanos CA, Selley DE, Theobald D, Cassidy MP, Kelz MB, et al. Karolo ea bohlokoa ea DeltaFosB ho li-nucleus e bokellanang ketsong ea morphine. Neuroscience ea Tlhaho. 2006; 9: 205-211. [E fetotsoe]