DeltaFosB: Heke ea Molecular ho Khothaletsoang Mekhoa ka hare ho Nucleus Accumbens? (2006)

Journal of Neuroscience, 15 November 2006, 26(46): 11809-11810; doi: 10.1523 / JNEUROSCI.4135-06.2006

  1. David Belin1 'me
  2. Molekane Rauscent2

+ Boikarabello ba Mongoli


  1. 1Lefapha la Psychology Psychology, Univesithi ea Cambridge, Cambridge CB2 3EB, United Kingdom, le

  2. 2Laboratoire de Physiologie et Physiopathologie de la Signalisation Cellulaire, Yunitus Remixte de Recherche 5543, Université Victor Segalen Bordeaux 2, 33076 Bordeaux Cedex, France

Selelekela

Li-nucleus accumbens (NAc) ke khale li bonoa e le khokahano lipakeng tsa li-limbic le motor motor (Mogenson et al., 1980) motheong oa lipehelo tsa eona tse fetolang glutamatergic tse tsoang mehahong e mengata ea li-cortical, joalo ka preortal cortex, le liphetho tsa eona ho likarolo tse amehang taolong ea makoloi, joalo ka pallidum. NAc e boetse e fumana dopaminergic innervation e kholo ho tsoa sebakeng sa ventral tegmental ka tsela ea mesolimbic e kenang haufi-ufi lits'ebetsong tse amanang le moputso le ho lemalla. Kahare ea NAc, litlatsetso tsa dopaminergic le glutamatergic li ka sebelisana ho laola boits'oaro bo tataisoang ke sepheo (mekhoa ea karabelo-sephetho) e khannoang ke meputso ea tlhaho (lijo, metsi, thobalano) kapa lithethefatsi tsa tlhekefetso, le maemo a hlahang a amanang le tsona.

Ho pepesetsoa lithethefatsi khafetsa ho etsa hore ho be le liphetoho tsa nako e telele tsa seleng le tsa limolek'hule kahare ho NAc eo ho nahanoang hore e kenya letsoho molemong oa boits'oaro bo phehellang bo amanang le ho lemalla. Har'a li-adaptation tse joalo, ho kenella ha transcript factor criptionFosB ka har'a dynorphin-medium kati spiny neurons ho ho hohela haholo. ΔFosB e bile molaoli oa pele oa bongoli ba nako e telele bo bonts'itsoeng ho nka karolo lits'ebetsong tsa polasetiki tse amanang le phetoho ea ho lemalla. Ehlile e bontša litlamorao tsa phello e matla le e susumetsang ea koae 'me e amahanngoa le mamello ho litlamorao tsa opiates. Leha ho le joalo, ho fihlela joale, ho ne ho tsejoa hanyane ka karolo ea ΔFosB phetolong ea boitšoaro bo susumetsoang ke meputso ea tlhaho.

Sengoliloeng sa bona se sa tsoa hatisoa ho Journal of Neuroscience, Olausson et al. ka botsitso potso ena ka ho bonts'a hore oxpxpression ea ΔFosB e tsoella le ho eketseha, ka ho latellana, bobeli phihlello ea boemo ba tšebetsong bakeng sa, le tšusumetso ea ho fumana, lijo.

Olausson et al. pele a sekaseka phello ea liente tse phetoang khafetsa, tlasa maemo a tsejoang ho hohela BFosB, ea lithethefatsi tse hlano tse fapaneng: cocaine, nicotine, (+) - 3,4-methylenedioxymethamphetamine (MDMA), le amphetamine, mabapi le phaello ea lever e hatellang bakeng sa lijana tsa lijo lijong- likhoto tse felisitsoeng. Ntle le MDMA, litlatsetso tsohle li hlohlelletsa maikutlo a boits'oaro 'me kaofela li ekelitse palo ea mechini e hatisang ea lever e hlahisitsoeng ke likhoto nakong ea maemo a sebelisang [Olausson et al. (2006), bona Feie. 1 (http://www.jneurosci.org/cgi/content/full/26/36/9196/F1)] le khothalletso ea ho fumana lijo joalo ka ha li lekantsoe ke sebaka se ntseng se eketseha sa kemiso e kholo (PR) [Olausson et al. (2006), Feiga. 2B (http://www.jneurosci.org/cgi/content/full/26/36/9196/F2)]. Kahoo, kalafo e tsejoang ho hohela ΔFosB ho NAc e ka eketsa karabelo ea bohlokoa bakeng sa lijo. Olausson et al. mme a leka ho bonts'a kamano e nang le lebaka lipakeng tsa NAc polelo ea ΔFosB le tlhoko e eketsehang ea tlhoko ea lijo. Bakeng sa sena, ba sebelisitse mefuta e 'meli ea induction ea maiketsetso ea ΔFosB ho NAc. Ba qalile ho ithuta litoeba tsa transgenic NSE-tTA-TetOP-ΔFosB, tse atisang protheine feela ho li-neuron tsa li-neurons tse ntle tsa "striatal tata" ha "doxcycline" (phetoho ea limolek'hule e hatellang ts'ebetso ea khothaletso ea TA) (Feie. 1A). Malome ana a bontšitse ΔFosB eseng feela ho NAc empa le ho dorsal striatum, e kenyelletsang ho ithuta tloaelo (Yin et al., 2004) (ke hore, mekhoa ea ho itšusumelletsa e ikatisang e tsejoang ka ho hloka botsitso ho fumana moputso ka mokhoa o hlakileng). Kahoo bangoli ba kenyellelitse ts'oaetso ea ΔFosB ka kotloloho mokokotlong oa NAc ba sebelisa phetiso ea bong bo kenelletseng ka har'a likokoana-hloko. Litekong tsena ka bobeli, polelo ea maiketsetso ea ΔFosB e etselitse phello e matla ea ho pepesetsoa hoa lithethefatsi khafetsa ho fumanoeng karabelo e matla [Olausson et al. (2006), Lekala la bona. 3 (http://www.jneurosci.org/cgi/content/full/26/36/9196/F3) le 5 (http://www.jneurosci.org/cgi/content/full/26/36/9196/F5)] le khothatso ea lijo [Olausson et al. (2006), Lekala la bona. 4A (http://www.jneurosci.org/cgi/content/full/26/36/9196/F4) le 7 (http://www.jneurosci.org/cgi/content/full/26/36/9196/F7)] ((Feie. 1B). Leha ho le joalo, ha ea ka ea fetola tšusumetso ea ho fumana lijo tlasa ad libitum maemo, ho fana ka maikutlo a hore mokhoa oa phenotype o bonoang o senoloa feela ha phoofolo e tobane le phephetso ea boits'oaro, e bonts'itsoeng e its'etleha ho dopaminergic neurons tse kenellang ho NAc (Salamone et al., 1994).

Setšoantšo sa 1. 

Ho hlaseloa haholo ha ΔFosB ka har'a nucleus e bokellanang ho eketsa karabelo ea lijo bakeng sa litoeba le likhoto: leseli le lecha bakeng sa hypothesis ea gating ea dopamine? A, Mohlala oa liteko. Liphoofolo tse laoloang (ka ho le letšehali) e ne e le litoeba tsa bitransgenic NSE-tTA-TetOP-ΔFosB kapa litoeba tse kentsoeng le LacZ-cDNA e nang le vaerase ea herpes. Ka bobeli ha ba a hlahisa ΔFosB. Ka ho le letona, litoeba tsa Bitransgenic NSE-tTA-TetOP-ΔFosB tse tlositsoeng ho doxycycline li hlalositsoe ΔFosB mohahong oa striatal, athe likhoto li kentsoe mantlha a NAc e nang le ΔFosB -cDNA e nang le vaerase ea herpes e hlahisitsoeng ka kotloloho ΔFosB. B, Kakaretso ea sephetho. Ha a qholotsoa ho fumana thepa ea boemo bo sebetsang (IC) (ke hore, ho tobetsa lever hore a fumane lijo) kapa nakong ea PR, liphoofolo tse hatellang ΔFosB li bonts'a karabelo e matla ea ho arabela ha li bapisoa le liphoofolo tse laolang. BP, sebaka sa ho phatloha. C, Pono ea theoretical. Tlas'a maemo a tloaelehileng (ka ho le letšehali), boits'oaro bo bontšitsoeng ke phoofolo bo tobaneng le phephetso ea ho fumana moputso bo laoloa ka bobeli ke tšitiso lipakeng tsa ketso ea bona le sephetho, le boleng bo susumetsang ba moputso. Ka har'a NAc, dopamine e ne e ka laola fensetere e sebetsang eo ho eona ho neng ho tla khethoa karabelo e nepahetseng lithutong tse susumetsang. Ha ΔFosB e tebelitsoe ka ho fetelletseng (ka ho le letona), fensetere ena e ne e tla atoloha, 'me sena se ka kenya letsoho karabong e matla ea boits'oaro ho susumetso e tšoanang.

Liphetho tse boneng li ne li sa hlahisoe ke ho eketseha hoa mosebetsi o sa ikhethang, hobane litekong tsohle tsa liteko le litoeba li ne li lebisitsoe ho manipulandum feela. Ntle le moo, ha ho na monyetla oa hore karabelo e ntlafalitsoeng e sebelisitsoeng boitekong ka bobeli e bile teng ka lebaka la ho ithuta ka tloaelo ea osFosB, hobane (1) lintlha tse hlahisitsoeng ke litoeba tsa transgenic overexpressing ΔFosB ho PR li ne li tsotella ho hloka matla ho matlafatsang, le (2) leha e le litekatsong tse tebileng tsa ΔFosB tse latelang thupelo e sebetsang, ka hona, ea thibela tšebelisano pakeng tsa maiketsetso le koetliso ea maiketsetso, e ile ea eketsa tšusumetso ea ho fumana lijo nakong ea PR e latelang.

Liphetho tsena li bontša ka ho hlaka hore oxpxpression ea ΔFosB ho NAc e ntlafatsa karabelo e matla ebile e eketsa ts'usumetso ea lijo (Feie. 1B). ΔFosB e khothalelitsoe ho ba phetoho ea limolek'hule tse akaretsang ho feto-fetoha hoa likarolo tsa tšusumetso tsa boitsoaro bo tataisoang ke sepheo. Ho hlakile hore pontsho ena ke ea mantlha kutloisisong ea lits'ebetso tse amanang le moputso, tse hlahisang lipotso tse khahlisang bakeng sa lipatlisiso tse eketsehileng.

Liphetho tsa Olausson et al. li ne li thehiloe ho kenyelletsoang ha ΔFosB ho NAc ke li-injotara tsa lithethefatsi tse sa tlisoang ke lithethefatsi kapa litheko tse matla tsa maiketsetso, mme e ne e sebetsana feela le boitsoaro bo tataisang sepheo mabapi le lijo. Mohato o latelang e tla ba ho sebetsana le karolo ea ΔFosB maemong a ho qobella ho batla lithethefatsi. Ho joalo, ha ho lemalla ho hlaha, boitšoaro bo qobelloang bo lebisoa ho moriana feela, athe meputso ea tlhaho e kang lijo e hlokomolohuoa. Kahoo ho tla ba bohlokoa haholo ho tseba, kamora nts'etsopele ea ho batla lithethefatsi ka mokhoa o qobelloang (Vanderschuren le Everitt, 2005), hore na ΔFosB e qobelletsoe ho NAc kapa likarolong tse ling tse tlase tsa striatum, e amehang boits'ebetsong bo bobebe bo its'epahallang le hore na e amana le khothaletso e ntlafalitsoeng kapa e fokotsoeng ea meputso ea tlhaho. Hypothesis ea bobeli e ka ananeloang lipatlisisong tsa nako e tlang e itšetleha ka pontšo ea hore li-subcopulsion tse fapaneng tsa NAc li arabela ka ho khetheha moputsong o fapaneng nakong ea boits'ebetso ba ts'ebetso (Carelli le al., 2000). Hobane ho bonahala eka ha ho na monyetla oa hore liente tse sa laoleheng tse sa hlahisoang kapa li-ovexpression tse ngata tsa ΔFosB li ka ikarabella bakeng sa karabelo ena e ikhethileng ea neuronal, polelo e ikhethileng ea marang-rang ea ΔFosB e kanna ea botsoa ka nepo. Ho joalo, haeba ho itaola ka nako e telele ha lithethefatsi ho amana le ho kenella ka ho khetheha ha osFosB ho NAc subnetwork mediating activutions for drug, karabelo e ntlafalitsoeng ea boitšoaro bakeng sa lithethefatsi, mme feela bakeng sa lithethefatsi, ho senya meputso ea tlhaho joalo ka lijo e ka lebelloa. Ka hona, ho ipapisitse le liphetho tsa hona joale, tse thabisang, hona joale ho bohlokoa ho sebelisa mefuta ea hona joale ea liphoofolo ea ho batla lithethefatsi, e thehiloeng ho boitaolo bo sa feleng. Ka tsela ena, re ka fumana leseli le tlatsetso mabapi le karolo ea ΔFosB nts'etsopele ea boitšoaro bo qobelloang ba ho batla lithethefatsi ho senya bophelo ba ho batla meputso ea tlhaho eo ho bonahalang e rata batho ba bang.Buka ea ho hlahloba le ea Statistical ea Mathata a kelello IVR).

Boemong ba theoretical haholoanyane, liphetho tsena li tsamaisana le phepo e matla ea tšebetso ea dopamine (Mosa, 2000). Ho ka etsoa tlhahiso ea hore, ka hara NAc, ΔFosB e ka holisa ts'ebetso ea ts'ebetso ea taolo ka dopamine ea sepheo sa boitšoaro se lebisitsoeng ho sepheo mabapi le tlhahiso ea tšusumetso e kholo (Feie. 1C). Ka hona ho ka pheha khang ea hore, le ntle le boleng bo phahameng ba tšusumetso, ts'usumetso e tšoanang e ka susumetsa karabelo e kholo ea boits'oaro ha osFosB e hatelloa ka mokhoa o fetelletseng.

Mongolo o botlaaseng ba leqephe

    • E amohetse September 21, 2006.
    • Tlhahlobo e amohetse September 28, 2006.
    • E amohetse September 28, 2006.
  • Mosebetsi ona o ne o tšehelitsoe ka lithuso ho tsoa Région Aquitaine-Center National de la Recherche Scientifique le Fyssen Foundation ho ea ho AR le DB, ka ho latellana.

  • Tsebiso ea Mohlophisi: Litlhahlobo tsena tse khuts'oane tsa pampiri ea morao tjena ho Journal, e ngotsoe feela ke liithuti tse abeloang mangolo kapa liithuti tse ling tsa postdoctoral, li etselitsoe ho etsisa lihlopha tsa likoranta tse leng teng mafapheng a hau kapa mekhatlong ea hau. Bakeng sa tlhaiso-leseling e batsi ka sebopeho le sepheo sa Sengoloa sa Borena, ka kopo bona http://www.jneurosci.org/misc/ifa_features.shtml.

  • Litaba li lokela ho lebisoa ho David Belin, Lefapha la Psychology Psychology, Univesithi ea Cambridge, Downing Street, Cambridge CB2 3EB, UK. [imeile e sirelelitsoe]

References

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