Prefrontal / accumbal catecholamine tsamaiso e na le boikutlo bo matla ba ho susumetsa (2012)

Pele Behav Neurosci. 2012; 6: 31. Epub 2012 Jun 27.

Keywords: tšusumetso, maikutlo, sebete, norepinephrine, dopamine, prefrontal cortex, mesoaccumbens

Tšusumetso tsusumetso le mesoaccumbens

Lilemong tse mashome a mabeli tse fetileng, khopolo ea khothatso e fihletse lintlheng tsa bohlokoa ka ho fetisisa bakeng sa lisebello tsa kelello le lisebelisoa tsa maikutlo. Tšusumetso ea khopolo ea tšusumetso e ne e le litsela tsa bohlokoa tse neng li lebisa lintlheng tse joalo tsa bohlokoa. Khothatso ea likhopolo tse susumetsang li ile tsa hlaha ho 1960s ha lipatlisiso tse ngata tse ncha ka boko le tšusumetso li entse hore litsebi tse ngata tsa kelello le bo-rasaense ba boitšoaro bo hlephileng ba lahle koloi e bonolo le ho fokotsa likhopolo. Litsebi tse ling tse khethehileng li ile tsa hlahisoa ka mokhoa oa ho khothatsa likhopolo tsa khothatso (Bolles, 1972;; Bindra, 1978;; Li-toate, 1986, 1994;; Panksepp, 1998;; Berridge, 2001). Litsebi tse tharo tsa biopsychologists li entse monehelo o moholo ho ntlafatso ea eona. Bolles (1972) o ile a etsa tlhahiso ea hore batho ba susumetsoe ke ho khothalletsa maemo a ho lebella, eseng ka ho khanna kapa ho fokotseha ha koloi. Ho susumetsa mehopolo, hore Bolles e bitse S-S^* mekhatlo, e ne e le litebello tse ithutoang tsa moputso oa hedonic, o sa tsejoeng ke lipolelo tsa ts'oaetso. Ka lebaka leo, tlhahiso ea pele ea ho se nke lehlakore (S), e kang leseli kapa molumo, e ile ea amahanngoa le ho kopanya khafetsa le moputso oa hedonic o latelang (S^*), tse kang lijo tse monate. S o entse hore ho be le nako ea S^*. S, e ne e le ka mokhoa oa ho ithuta oa Pavlovia, e leng sepheo se ts'oanelang (CS kapa CS +), le S^* boikutlo bo sa amoheleheng (UCS).

Bindra (1974, 1978) o ile a lumela hore litebello li ka 'na tsa e-ba tsa bohlokoa ho mekhoa ea ho utloisisa ho fumana moputso, empa a fana ka maikutlo a hore CS bakeng sa moputso e hlile e hlahisa khothatso e ts'oanang le naha e susumelletsoang ka tloaelo e bakoang ke moputso ka boeona, ka lebaka la boemo ba khale ba khale. Mokhatlo o hlophisitsoeng ha o bake feela tebello ea moputso. E boetse e etsa hore motho e mong a lemohe CS e le moputso oa hedonic, mme o lumella CS ho susumelletsa mo susumelletso feela joalo ka moputso oa pele oa hedonic. Seo se bolela hore CS e nka thepa e ikhethileng eo e leng ea S^* ka boeona, 'me lintho tsena tse susumelletsoang ke ho susumetsa ka ho khetheha thepa. Hlokomela hore sena e ne e se nnete feela bakeng sa moputso S^*, empa le bakeng sa S ea utloisang bohloko^* tšusumetso, e neng e tla thehoa matlong a tšabo kapa a kotlo. Toates (1986) e fetotse maikutlo a Bolles-Bindra a fanang ka maikutlo a hore ho felloa ke matla ha 'mele ho ka ntlafatsa boleng ba tšusumetso ea sepheo sa bona sa sepheo. Sena se lebisa tšebelisanong e ngata pakeng tsa bofokoli ba mmele le tšusumetso ea kantle, e leng se bontshitseng boleng ba khothatso. Leha ho le joalo, matšoao a khaello ea mmele ha a khanne boits'oaro bo susumetsang ka kotloloho, empa a khona ho holisa tšusumetso ea boleng ba matla le tšusumetso ea moputso oa nnete (S^*), hape e na le bohlokoa bo ts'oanelang ho susumetsa mohopolo (CSs). Hoo e ka bang 1990 moelelo oa boikhothamoso o ile oa etsoa (Berridge et al., 1989;; Berridge le Valenstein, 1991) e neng e latela melao ea Bindra-toates bakeng sa ho khothatsa maemo empa e tsebahatsa likarolo tse arohaneng tsa boko "bakeng sa" ho rata "moputso ho latela" ho batla "moputso o tšoanang. "Ho rata" ke tšusumetso e matla ea maikutlo-boko bo sebetsanang le menyaka e tsotehang-e bakoang ke ho fumana moputso kapele, ka mohlala, tatso e monate (e sa amoheleheng "ea ratang").

"Ho batla," kapa ts'ehetso ea ts'usumetso, ke ts'usumetso e khothatsang ea moputso o tšoanang (Berridge le Robinson, 1998), ts'usumetso ea ts'ebeliso ea ts'ebeliso ea mohopolo, eseng phetoho ea eona ea hedonic. Ntlha ea bohlokoa ke hore "ho rata" le "ho batla" hangata ba tsamaea hammoho, empa ba ka arohanngoa maemong a itseng, haholo-holo ka bokooa bo itseng. "Ho rata" ntle le "ho batla" ho ka hlahisoa, 'me kahoo ho ka "batla" ntle ho "ho rata."

Tšusumetso e ka hlalosoa ka mokhoa o nahanang e le ts'ebetso e ts'oanang e ka matlafatsang kapa e otlang likarabo ho tse ling tse tsosang takatso. Boits'oaro, ts'ebetso e matlafatsang e bitsoa ho putsa le ba otlang ho hlasela (Skinner, 1953). Meputso le ho tsitlella ho hlahisa tšusumetso ho susumetsa boitšoaro, 'me ho fanoe ka litšobotsi tse susumetsang, kahoo ho khoneha ho etsa hore ho be le tšusumetso e matla ea ho susumetsa.

Mokhoa oa ho susumetsa batho ba nang le boikutlo bo matla o ile oa hatisa karolo e ka sehloohong ea mosebetsi oa dopamine (DA) e le mokhoa oa boko bo sebetsang. Ka sebele ho tlosoa ha DA ho tlohela batho ka bomong ho se na tšusumetso leha e le efe e khothatsang ho hang: lijo, thobalano, lithethefatsi, joalo-joalo, (Ikemoto le Panksepp, 1999;; Naranjo et al., 2001;; Berridge, 2004;; Salamone et al., 2005). Ka hona, ho ferekanya ha litšebeletso tsa DA ka mahlaseli a metsoako ea litsela tsa tsela ea DA e sebetsang ho nucleus accumbens (NAc) kapa ka lithethefatsi tse thibelang mokelikeli, ho fokotsa ka ho tsotehang matla a khothatsang kapa ho "batla" ho ja moputso o monate, empa ha ho fokotsa lipolelo tsa sefahleho ea "ho rata" bakeng sa moputso o tšoanang (Pecina et al., 1997;; Berridge le Robinson, 1998).

DA e na le karolo ea bohlokoa mosebetsing oa ho laola maikutlo. Mofuta o mong oa DA neuron o kenyelletsa bohlokoa ba ho susumetsa, ho thabisoa ke liketsahalo tse khotsofatsang le ho thibeloa ke liketsahalo tse sithabetsang kapa tse sithabetsang (Bromberg-Martin et al., 2010;; Cabib le Puglisi-Allegra, 2012, bakeng sa litlhahlobo). Li-neurons tsena li tšehetsa mekhoa ea boko ba ho batla lipakane, ho hlahloba liphello, le ho ithuta bohlokoa. Ha e le hantle, boholo ba li-neurone tsa DA bo kenyelitsoe ke moputso-o bolela esale pele meputso ea mekhoa ea boipheliso le mekhoa ea boipheliso ea moputso (e leng, ho molemo ho feta ho lebeletsoe / ho feta ho lebeletsoe) ho batho, litšoene le likhoto (Ikemoto le Panksepp, 1999;; Ikemoto, 2007;; Schultz, 2007). Le hoja boitsebiso bo sa utloahaleng bo kang boikutlo ba moferefere oa moea, letsoalo la hypertonic le tšabo ea motlakase ho etsa hore likarabo tse sebetsang li be le likarabo tse fokolang tsa li-neurone tsa DA liphoofolong tse tsohileng (Guarraci le Kapp, 1999;; Joshua et al., 2008;; Matsumoto le Hikosaka, 2009), boholo ba li-neurone tsa DA li tepeletse maikutlo ka lebaka la tšusumetso e mpe (Ungless et al., 2004;; Jhou et al., 2009). Karabo e fapaneng ea karabo e bontša hore lisele tse tlalehiloeng li karolo ea lipotoloho tse fapaneng, tse ikemetseng (Margolis et al., 2006;; Ikemoto, 2007;; Bromberg-Martin le al., 2010). Mofuta oa bobeli oa neuron ea DA o kenyelletsa matla a ho susumetsa, a khahloa ke liketsahalo tse peli tse thabisang le tse hlollang (Bromberg-Martin et al., 2010).

Bopaki bo bontša hore lihlopha tse fapaneng tsa li-neurone tsa DA li fetisa lipontšo tse susumetsang ka mekhoa e fapaneng (Matsumoto le Hikosaka, 2009) 'me tsamaiso ea DA ea mesocorticolimbic e ka ba le lipotoloho tse fapaneng, e' ngoe le e 'ngoe e fetotsoe ke likarolo tse fapaneng tsa tšusumetso e susumetsang, ho itšetlehile ka litekanyetso tsa DA ho NAC e kopanetsoeng ho sebetsana le tšusumetso e nepahetseng, ts'ebetsong ea DA ho mpFC e anngoeng ke tšusumetso e mpe, le litekanyetso ho NAc lateral khetla e anngoeng ke lintho tse peli tse thabisang le tse tsosang takatso, ho ka etsahala hore li bonahale hantle (Lammel et al., 2011). Ho bonts'itsoe kamoo VTA DA neurons e ka sebelisang leano la ho bokellana la convergent bakeng sa ho sebetsana le liphihlelo tse ntle le tse mpe, ho kopanya ka botlalo le lintlha le maemo a tikoloho (Wang le Tsien, 2011).

Mokhoa oa maolimbic dopaminergic, oo merero e tsoang sebakeng sa ventral tegmental (VTA) neuronal cell bodies ka mofuthu ho NAc, ke mohokahanyo oa mantlha tseleng ea moputso (Bohlale, 1996, 2004). Leha ho le joalo, ho lokolloa ha DA ha ho hlokahale hore mefuta eohle ea moputso e ithute 'me e ka' na ea se ke ea "khahloa" ka kutloisiso ea ho etsa hore motho a thabe, empa ke habohlokoa ho etsa hore lipakane li "batloe" ka kutloisiso ea liketso ho li finyella ( Robinson le Berridge, 1993, 2003;; Berridge le Robinson, 1998;; Setlama sa lipalesa, 2008).

Lintlha tsa bopaki bo tšehetsang karolo ea ts'ebetsong bakeng sa ts'ebeliso ea ts'ebeliso ea ts'ebeliso ea ts'ebeliso ea ts'oaetso ho tsoa ho sebaka sa boemo bo botle ba boemo bo botle (Mucha le Iversen, 1984;; van der Kooy, 1987;; Carr et al., 1989). Paradigm ena e sebetsana le keketseho ea nako e sebelisitsoeng tikolohong e kopantsoeng le UCS (ekaba lithethefatsi kapa matlafatso a tlhaho) joalo ka lethathamo la meputso ea tšusumetso. Ka lehlakoreng le leng, haeba liphoofolo li pepesetsoa khafetsa tikolohong e kopantsoeng le tšusumetso e matla e tla qoba tikoloho. Tabeng ea pele re bua ka khetho ea sebaka se hlophisitsoeng (CPP), karolong ea bobeli ea boemo bo hlohlontšang sebaka (CPA). Bahanyetsi ba DA ba ne ba tsamaisoa pele ho setlhopha se seng le se seng sa maemo a nang le amphetamine block amphetamine-conditioned place preferences (Nader et al., 1997 bakeng sa tlhahlobo). Liphello tsena ha li hlalosoe ka mokhoa o tloaelehileng oa ho ithuta hobane liphoofolo li bontšitsoe hore li khone ho theha mekhatlo e tloaelehileng ea CS-US sebakeng sa boemo bo itseng le ba bang ba US (Shippenberg le Herz, 1988). Liphuputso tsena li fana ka maikutlo a hore phetisetso e tloaelehileng ea DA e hlokahala bakeng sa matlotlo a khotsofatsang a ho susumelletseha ho etsahala.

Haeba litsela tsa dopaminergic tse tsoang VTA ho ea NAc ke lihlopha tse ka sehloohong litseleng tse tsamaisanang le litšusumetso tsa ts'oaetso (Tsai et al., 2009;; Adamantidis et al., 2011), joale mehlala ea moputso oa DA o ikemetseng ha oa lokela ho ba teng. Ho na le mehlala e 'maloa, leha ho le joalo, ea litšusumetso tse nang le thepa ea ho matlafatsa thepa e ikemetseng ea DA. Ka hona, liteko tsa boipheliso tsa meriana li bontša hore le hoja phetisetso ea DA e eketseha ka ho eketseha ha eona e phetha karolo ea bohlokoa ho matlafatsang liphello tsa lithethefatsi tse hlekefetsoeng, ho boetse ho na le mekhoa e ikemetseng ea DA e tlatsetsang haholo ho matlafatsa liphello tsa lik'hemik'hale tsena (Joseph et al., 2003;; Pierce le Kumaresan, 2006 bakeng sa tlhahlobo). Ka mohlala, ho ba le tšusumetso e matla ea mangeloi ea DA kapa 6-OHDA ea litsi tsa NAC ho tlalehiloe hore ha e na phello ho morphine kapa heroin ea botho (Ettenberg et al., 1982;; Pettit et al., 1984;; Dworkin et al., 1988), le ka boipheliso ba molumo oa ethanol (Rassnick et al., 1993). Ho hloka letsoho la dopaminergic libakeng tsa cocaine (Spyraki et al., 1982;; Mackey le van der Kooy, 1985) e tlalehiloe ka mor'a tsamaiso ea systemic kapa intra-accumbens (Koob le Bloom, 1988;; Hemby et al., 1992;; Caine le Koob, 1993). Maemong a mang, ho khetholloa ho khethiloe ha DA-opiate sebaka (Mackey le van der Kooy, 1985;; Bechara et al., 1992;; Nader le al., 1994). Ho feta moo, litoeba tse senyehileng tsa DA li bonts'a sebaka se setle sa morphine sebakeng se itseng sa liteko (Hnasko et al., 2005), le DA ha e amehe mmuso o se nang boikemisetso (Laviolette et al., 2004;; Vargas-Perez et al., 2009). Ho na le mokhoa o bontšang mefuta e meng ea mefuta ea boipheliso ea DA bakeng sa caffeine (Sturgess et al., 2010).

Dopamine D2 moeeng oa ho kokota ho thothomela ho C57BL / 6 litoeba li ile tsa hlōleha ho thibela lithahasello tsa sebaka sa ethanol ka litoeba tse itšetlehileng ka ethanol le litoeba tse tlohang (Ting-A-Kee et al., 2009). Ka maemo a mangata a "tlhaho" a sebetsang sebakeng se sebetsang ka banna ba chemo-pontšo ka litoeba tsa basali ha lia ka tsa angoa ke bahanyetsi ba D1 kapa ba D2 (Agustin-Pavon et al., 2007). Ke habohlokoa ho hlokomela hore VTA-mediated but le ts'ebeliso e ntle ea DA e ikemetseng e bontšitsoe (Fields et al., 2007).

Mehlala ena ea boitšoaro bo susumetsang ba DA bo ikemetseng ka botlalo bo botsa potso ea DA ea pele e neng e re DA ke tsela e tloaelehileng e tloaelehileng mekhoeng e kopanetsoeng ho matlafatsa.

Prefrontal-accumbal catecholamine system

Hoo e ka bang lilemong tse leshome tse fetileng, lipatlisiso li lebisitse ho prefrontal catecholamine (CA) taolo ea phetoho ea mesoaccumbens ea DA ka lebaka la tšusumetso e ntle kapa e nang le tšusumetso e matla (Le Moal le Simon, 1991). Ka ho khetheha, phetiso ea DA mehahong e meholo, e kang NAc, e bonahala e hlophisitsoe ke tsamaiso ea DA mesocortical ka tsela e thibelang (Ventura et al., 2004, bakeng sa tlhahlobo), kahoo e fana ka maikutlo a matla a hore ho arabela ha karabo ea DA ho hlile ho amana le karabo ea mesocortical ea DA.

Mesoaccumbens ea phetisetso ea DA e reretsoe ho laoloa ke tšebetso ea prefrontal ka li-glutamatergic projections (Carr le Sesack, 2000, bakeng sa ho hlahloba), ka ho ts'ebetswa ha sekhetho sa prefrontal-cortical ho VTA (Sesack le Pickel, 1990), le / kapa ka ho sebelisoa ha marticoaccumbens glutamatergic projection (Taber le Fibiger, 1995). Ka hona, ntle le moo ho ka khonehang ho potoloha cortico-accumbal circuit, cortico ((VTA) - setša sa marang-rang sa DA se nang le libaka tse fapaneng tsa boko, tse kang amygdala (Jackson le Moghaddam, 2001;; Mahler le Berridge, 2011), ho 'nile ha etsoa tlhahiso ea hore e be le karolo ea bohlokoa bakeng sa ho feto-fetoha ha DA.

Ho ella bofelong ba lilemo tse mashome a mararo, thuto ea Sefora (Darracq et al., 1998) o ile a bontša hore prefrontal cortical norepinephrine (NE) e bile le karolo ea bohlokoa ho lokolloa ha DA ka lebaka la tsamaiso ea tsamaiso ea amphetamine. Ho fihlela motsotsong oo, boko ba mekhoa ea boko le tsamaiso ea boitšoaro bo ne bo lebisitsoe ho mesebetsi ea Locus Coeruleus (LC) (Aston-Jones et al., 1999) kapa ka khopolong ea maikutlo a maikutlo ka amygdala (McGaugh, 2006). Mosebetsi oa bo-pula-maliboho oa Darracq le basebetsi-'moho le eena, o ile a fana ka tlhahiso e tiileng ea hore phetoho ea DA e NAc e ka laoloa ke ka ho toba e amanang le NE mofuteng oa likamorete (mpFC). Pono ena, hammoho le ts'ebetso e thibelitsoeng ea ho khetholla DA ea prefrontal mosebetsing oa dopaminergic ho accumbens, e fana ka tlhahiso ea hore mohato o ka khonehang oa li-amine tse peli sebakeng sa prefrontal cortex ka phetoho ea DA e fokolang.

Bopaki bo hlakileng ba laboratory ea rona ka litoeba tsa C57BL / 6 (C57) le DBA / 2 (DBA) tse nang le mathata a sa tšoaneng a tšehetsa khopolo ena. Lipatlisiso tsa ho bapisa le ho itšoara ka mefuta e fapaneng ea liphatsa tsa lefutso li etsa hore ho be le leano le leholo la ho hlahloba motheo oa neural oa liphello tsa lithethefatsi tse amanang le liphapang tsa batho ka bomong. Litoeba tsa DBA tsa morao-rao li bontšitsoe hore ha li amohele habonolo DA ea extracellular e bakoang ke psychostimulant ka NAc (shell) hammoho le liphello tse susumetsang / tse matlafatsang tsa amphetamine, tse itšetlehileng ka ho eketseha ha DA ho kenyelletsoa. Ntho e fapaneng e etsahala likarolong tsa C57, tse bontšitsoeng hore li amoheleha haholo ho susumetsa / ho matlafatsa liphello tsa amphetamine, joalo ka ha ho bontšoa ke mesebetsi e eketsehileng ea ho etsa lintho kapa ea CPP e entsoeng ke amphotamine (Zocchi et al., 1998;; Cabib et al., 2000). Ka C57, Amphetanine e hlahisa DA e tlaase ea mpFC le DA e phahameng ho NAc, e fapaneng le eona e hlahisa litoeba tsa DBA tse bontšang mesebetsi e tlaase ho feta C57s le CPP kapa CPA. Ho phaella moo, ho khetholla ha DA ho mpFC ea litoeba tsa DBA ho etsa hore bothata bona bo tšoane le litoeba tsa C57 tse holimo tse lebisang ho DA e phahameng ho tsoa ho NAc le ho theoha ha metsi. Leha ho le joalo, ha ho na phapang pakeng tsa moqapi oa DA ho NAc pakeng tsa mathata a C57 le DBA ho tlalehiloe (Womer et al., 1994). Liphello tsena li bonts'a hore liphello tse fapaneng tsa amphetamine ho tsoa ha lekhetho la DA maemong a mabeli ha li itšetlehe ka phapang pakeng tsa mekhoa e amanang le DAT. Leha ho le joalo, liteko tsa microdialysis li bontšitse hore amphetamine e eketsehile NE le DA e tsoa ka mpFC ea litoeba tsa C57 le DBA ka tsela e fapaneng. Le hoja C57 e bontšitse hore keketseho e phahameng ho feta ea DA, litoeba tsa DBA li fana ka mokhoa o fapaneng, kahoo li bontša hore karolo ea NE / DA e bakoang ke amphetamine e phahame ho C57 ho ea ho DBA. Ho tloha ha DA e thibela DA NAc, ha NE e ne e khothalletsoa ho thusa (Darracq et al., 1998), re nahana hore ho se lekane ha NE / DA ho mpFC e laoloang ke DA ho NAc le liphello tse amanang le boitšoaro, ho etsa hore mathata a C57 a amohelehe ho feta DBA. Maikutlo a joalo a tiisitsoe ke liteko tse latelang tse bontšang hore khetho ea prefrontal cortical NE e felisoe ke liphello tsa amphetamine ho DA ha e bokella le CPP ho litoeba tsa C57 (Ventura et al., 2003), le hoja ho khetholla khetho ea DA ea ho khetholla (sparing NE) ho ile ha etsa hore DA e tsoele pele ho NAC le liphello tsa boitšoaro maemong a DBA a tšoanang le a C57 (Ventura et al., 2004, 2005).

Litlaleho tsena li khothalletsa ka tieo hore DA e NAC e laoloa ke prefrontal cortical NE e e nolofalletsang, le DA e e thibelang. Ho feta moo, dintlha tsa rona li bonts'a hore prefrontal NE ho fetisa boits'oaro bakeng sa ho fuoa matla a ho susumetsa, joalokaha ho bontšoa ke ho senyeha ha CPP e entsoeng ka amphetamine ho mpFC NE litoeba tsa C57 tse seng li felile (Ventura et al., 2003).

Leha ho le joalo, bopaki bo bukeng (Ventura et al., 2002 bakeng sa tlhahlobo) le liphello tsa khatello ea kelello e fumanoang ka laborateng ea rona ho CICNUMX le litoeba tsa DBA li bontšitse hore sena se ne se le 'nete le ka liphihlelo tse hlollang (ho thibela, ho qobella ho sesa), bonyane ho laola pele ho DA ho laola DA ho NAC. Ha e le hantle, re fumane khatello ea khatello e hlahisoang ke thibelo ea mesoaccumbens DA release e tsamaeang le ho sebetsa ka potlako le ho matla ka metabolism ea DA mesocortical ho C57 litoeba, le ho fapana le litoeba tsa khatello ea DBA, ho bonts'a liphatsa tsa lefutso pakeng tsa mesocortical and mesoaccumbens DA e arabela khatellong ea maikutlo (Ventura et al., 2001). Ho feta moo, litoeba tsa C57 empa e se litoeba tsa khatello ea DBA li bontšitse boemo bo phahameng ka ho fetisisa ba ho tsamaea ka lekhetlo la pele ka tlhahlobo ea ho sesa (FST) hammoho le ts'ebetso e potlakileng le e matla ea mesocortical DA metabolism le ho thibela metabolism ea DA le ho lokoloha. Ho phaella moo, boitšoaro le litlhahiso tsa DA li arabela FST ho C57 litoeba li fokotsoe 'me li fetoleloa, ka ho latellana, ka ho khetholla dopamine DA ts'ebetso ho mpFC (Ventura et al., 2002).

Prefrontal NE e fetisetsoa ho ba le karolo ea bohlokoa ho laola mesebetsi e mengata ea cortical, ho kenyeletsa ho tsosoa, ho ela hloko, ho susumetsa, ho ithuta, ho hopola le ho fetoha ha boitšoaro (Sara le Segal, 1991;; Tassin, 1998;; Feenstra et al., 1999;; Arnsten, 2000;; Robbins, 2000;; Bouret le Sara, 2004;; Dalley le al., 2004;; Mingote et al., 2004;; Tronel et al., 2004;; Aston-Jones le Cohen, 2005;; Rossetti le Carboni, 2005;; Lapiz le Morilak, 2006;; van der Meulen et al., 2007;; Robbins le Arnsten, 2009). Ho feta moo, ho bontšitsoe hore lintho tse peli tse khotsofatsang / tse matlafatsang le tse matlafatsang li eketseha HA ho lokolloa pFC (Finlay et al., 1995;; Dalley le al., 1996;; Goldstein et al., 1996;; Jedema et al., 1999;; Kawahara et al., 1999;; McQuade et al., 1999;; Feenstra et al., 2000;; Leqephe le Lucki, 2002;; Morilak et al., 2005;; Feenstra, 2007). Bopaki bona bo boletse hore CA prefrontal phetiso e ka khona ho laola DA ha e bokella hape maemong a sithabetsang, khopolo-taba e lokelang ho hlahlojoa. Sena se entsoe ke li-laboratories tse peli tse ikemetseng tse hatisitsoeng ka 2007. Liphuputso tsena li bontšitse hore libuka tse hatellang liphihlelo li eketsa DA ho lokolloa ho NAc ka ho ts'oaroa ha prefrontal cortical alpha-1 adrenergic receptors (ARs) ka maemo a phahameng a lokolloa NE (Nicniocaill le Gratton, 2007;; Pascucci le al., 2007). Ka sebele, phihlelo e nang le khatello ea morao-rao e khothalletsa keketseho e potlakileng, e kholo le e fokolang nakong ea ho lokolloa ha mpFC e bapisoang le ho ntlafatsa mesoaccumbens DA release (Pascucci et al., 2007). Ho tlosoa ha khetho ea prefrontal cortical ha ho lumelle hore ho na le likarabo le likarolo tse eketsehileng tsa DA, ho tlohella ts'ebetso ea khatello ea prefrontal cortical DA hammoho le maemo a basal a CAs a sa ameheng (Pascucci et al., 2007). Ho feta moo, lik'ebetsong tsa alpha-1 AR tse khethollang benoxathian ho mpFC e thibela khatello ea DA e bakoang ke khatello ea kelello ka NAc-e itšetlehile ka eona (Nicniocaill le Gratton, 2007). Pascucci le al. (2007) e boetse e netefalitse hore khatello e bakoang ke khatello ea kelello ea NAc DA e thibetsoe ke ho kenyelletsa mpFC DA. Ha e le hantle, e ka 'na eaba DA e senyeha (Deutch et al., 1990;; Doherty le Gratton, 1996;; King et al., 1997;; Pascucci le al., 2007) kapa ho thibeloa ha li-D1 receptors ka ho kenngoa ha mohanyetsi ea khethollang mpFC (Doherty le Gratton, 1996) ho eketsa ts'oaetso ea DA ea khatello ea kelello NAC. Hoa tsebahala hore DA ea mpFC e na le tsusumetso e thibelang ho lokolloa ha DA ho NAC le ho felisoa ha DA mesocortical ho thusa ho ts'enyeletsa khatello ea khatello ea mesoaccumbens DA release (Deutch et al., 1990;; Doherty le Gratton, 1996;; King et al., 1997). Leha ho le joalo, liphello tsa rona li bontšitse hore nakong ea liphihlelo tse ts'oanang tsa khatello mpFC e etsa hore likarabo tsa DA li sebetsane le mekhoa e khahlanong le NE le DA. Dintlha tsa rona li ka hlalosetsa hore na ke hobane'ng ha khatello ea kelello e ka ameha maemong a fapaneng a bophelo. Ka sebele, ketso e leka-lekaneng ea li-CA tse peli ka mpFC e ka hlokeha bakeng sa ho sebetsana ka katleho le bophelo bo botle, empa liketso tse sa tsitsang li ka khothalletsa batho hore ba se ke ba e-ba le maikutlo a boikaketsi kapa ba li arabelang ka mesoaccumbens DA, e leng se lebisang litšitiso tse sa tšoaneng le tse sa tšoaneng.

Tšusumetso e fapaneng e sebelisoang ke mpFC NE le DA mabapi le phetiso ea DA ho NAc nakong ea liphihlelo tse sithabetsang tse hlalosang hore ho ka khoneha ho fapana le ho feto-fetoha ha li-cortuum glutamate (GLU) ka li-CA tse peli. Kaha ho thibeloa ha mpFC alpha-1 AR kapa li-receptor tsa D1 li na le liphello tse fapaneng ho eketseha ha GLU e bakoang ke khatello ea kelello (Lupinsky et al., 2010), ho ka etsahala hore frontal cortical NE le DA li hlahisa liphello tse sa tšoaneng ho mpFC e hlahisoang, mohlomong ka ho tsosoa ha glutamatergic ea li-interneurons tsa GABA mpFC (Del Arco le Mora, 1999;; Homayoun le Moghaddam, 2007).

Ho kenella ha li-alpha1-ARs prefrontal NE ho laola ho lokolloa ha DA nakong ea khatello ea kelello ho lumellana le bopaki ba hore keketseho e tsitsitseng ea prefrontal cortical NE (e bakoang ke khatello ea kelello) e khona ho etsa hore li-low-affinity receptors subtypes, ha keketseho e bonolo e khona ho etsa hore ho be le kamano e phahameng ea Alpha2- kapa beta1-AR (Ramos le Arnsten, 2007). Leha ho le joalo, karolo e ka sehloohong ea alpha1-ARs ha e etsoa ka matla a ts'ebetso ea DA ka khatello kapa ke amphetamine (Darracq et al., 1998;; Ventura et al., 2003;; Nicniocaill le Gratton, 2007), le boikarabelo bo bohlokoa ba prefrontal NE ho fana ka matla a susumetsang a susumetsang maikutlo ho amphetamine, joalokaha ho bontšoa ke CPP tlhahlobo ea mouse (Ventura et al., 2003), supa karolo e kholo ea li-receptors tsena ka boitšoaro bo susumetsang le ho sebetsana le boemo. mpFC le NAc ba fumana DA afferents ho tsoa ho batho ba sa tšoaneng ba lisele tsa VTA DA mme li laoloa ke lipotoloho tse fapaneng (Joel le Weiner, 1997;; Carr le Sesack, 2000; Lewis le O'Donnell, 2000;; Margolis le al., 2006;; Lammel et al., 2008;; Tierney et al., 2008). VTA e boetse e amohela li-afferents ho tloha karolong e ka hare ea amygdala (CeA); ho thibela ha CeA, ka lebaka leo ho kenya letsoho ho VTA, ho lebisa hoketseho ea NAC DA (Ahn le Phillips, 2003;; Phillips le al., 2003a), ho fana ka maikutlo a hore tlhahiso ena ke karolo ea mekhoa e metso e 'meli ea ho thibela tšoaetso (Fudge le Haber, 2000;; Ahn le Phillips, 2002;; Floresco et al., 2003;; Fudge le Emiliano, 2003). NE afferents mpFC e tsoa ho sehlopha se senyenyane sa lisele tsa LC (Aston-Jones et al., 1999;; Valentino le van Bockstaele, 2001;; Berridge le Waterhouse, 2003). LC e fumana litebelisuoa tse matla tsa convergent tse tsoang ho orbito-frontal le cingulate cortex, tse ileng tsa khothalletsoa ho khanna liphetoho pakeng tsa phasic le tonic modes tse NE neurons ho lumellana le litsebo tsa boitšoaro / tsebo le maemo a tikoloho (Aston-Jones le Cohen, 2005). Mosebetsi oa LC o boetse o sebelisoa ke CeA (Curtis et al., 2002) ka ho hloekisa sebaka sa pericoerulear (Berridge le Waterhouse, 2003) le ka hormone e hlahisang corticotropin-release (Van Bockstaele et al., 2001;; Bouret et al., 2003;; Jedema le Grace, 2004). NE e na le liphello tse fapaneng libakeng tse lebisitsoeng ho cortical ho itšetlehile ka ho tsepamisa mohopolo le ho ajoa ha alpha1 le li-receptors tsa alpha2 (Briand et al., 2007;; Arnsten, 2009). Ka sebele, litsela tse fapaneng tsa tonic neuromodulator ho lokolloa li ama li-receptors tse khethollohileng ka har'a likarolo tsa cortical, e le hore mochine oa neuromodulator a ka ama ka tsela e fapaneng lihlopha tsa oona tse hlalositsoeng ho ea ka li-receptor tseo li li sebelisang.

Bopaki bo nkiloeng ho fihlela hona joale bo bontša hore tsamaiso ea CA ea prefrontal e laola ho lokolloa ha DA ho NAc, sebaka se tlase sa likorinthe tse tsejoang e le se amehang boitšoarong bohle bo susumelletsoeng, ho sa itšetlehe ka valence ea sephetho kapa phihlelo. Ka hona, molao-motheo o tšoanang oa sekhetho o bontšitsoe bakeng sa ho putsa (amphetamine) kapa khatello ea kelello (khatello ea kelello). Liphuputso tse ling li ile tsa fana ka ts'ehetso e kholo ponong ena, ka bopaki ba liteko tsa hore prefrontal cortical NE e bohlokoa haholo liphellong tsa lithethefatsi tse ling tsa lithethefatsi, tsa lijo tse monate, le tsa tšusumetso e matla ea phekolo ea meriana kapa ea tlhaho. Ho feta moo, ba ile ba bontša hore prefrontal NE ka ketso ea eona ho NAC DA ke ea bohlokoa bakeng sa ho fana ka botsitso bo susumelletsang maemo maemong a itseng, joalokaha ho tla bontšoa serapeng se latelang.

Prefrontal NE- accumbal DA e ts'oanang le ts'ehetso e ts'oanang le khatello e amanang le khatello

Meriana e meng ea lithethefatsi, ho phaella ho amphetamine, eketsa ho lokolloa ha DA ho NAc ka prefrontal NE, joalokaha ho bontšoa ke liteko tse thehiloeng ho intracerebral microdialysis meleng le ho khetholla NE ho felisoa mpFC. Ho khethoa ha NE ho tlosoa ke neurotoxin 6-hydroxydopamine le pele ho phekoloa le motho ea khethiloeng ke DA transporter ea thibelang GBR-12909 e hlahisitsoeng ka 90% NE ea ho felisoa, e se nang liphello tse kholo ho DA. E le ho qoba liphetoho tse kholo molaong oa li-receptor, tlhahlobo ea methapo ea pelo le ea boitšoaro e ile ea etsoa ka bekeng e le 'ngoe ho tloha ho buuoa. Morphine (Ventura et al., 2005), Cocaine (Ventura et al., 2007), ethanol (Ventura le al., 2006, ha ho lokiselitsoe) ho bontšitsoe ho hlahisa keketseho e itšetlehileng ka menyetla ea NE ka mpFC le keketseho e tšoanang ea DA ho NAc. Khetho ea khethollo ea NE e ile ea felisa ho eketseha ha phallo ea bo-prefrontal NE le DA ho NAc, e leng se tiisang karolo ea bohlokoa ea NE ka mpFC ka ts'ebetsong ea ts'ebetso ea DA e bakoang ke lihlopha tse fapaneng tsa lithethefatsi tsa tlhekefetso. Ke habohlokoa hore re hlokomele hore lithethefatsi tsohle tse hlahlojoang li ile tsa eketseha ha DA e tsoa ka mpFC, e sa kang ea angoa ke khathatso ea NE. Leha ho le joalo, motho a ka 'na a nahana hore, ka lebaka la karolo e tsejoang e thibelang ho khetholla DA ea DA pele ho DA e lokolloa ho NAc e hlokometseng liphoofolong tse fumanang lithethefatsi (mohlala, amphetamine) kapa khatello ea kelello, ho hlōleha ha keketseho ea DA ho NAC ea NE mpFC e feletsoe ke lihlooho tse fumanang lithethefatsi e ne e bakoa ke ketso e tloaelehileng ea ho thibela prefrontal DA ha ho se na N. Pono e joalo, e tla tiisa karolo ea bohlokoa ea "ho khothaletsa" karolo ea prefrontal NE ho DA e ikemetseng, ho bolela hore leha ho le joalo, karolo ea tlatsetso ea DA ho mpFC e neng e tla ba le tšusumetso e ka lebisang ho "flatting" accomal DA ha cortical e se e felile. Monyetla ona o ne o laoloa ke liteko tse tlatsetsang tse bontšang hore ho felisoa ha NE le DA ho mpFC ha ho fetole phetoho ea DA e sa khoneng ho lokolloa litulong tse amohelang AMPH ha li bapisoa le liphoofolo tse khethiloeng ke NE. Bopaki ba bopaki bo fana ka maikutlo a hore DA ea prefrontal cortex e kopanngoa le NE ho tloha li-terminals tsa noradrenergic (Devoto et al., 2001, 2002). Ho feta moo, ho 'nile ha tlalehoa hore DA ea sebakeng sena sa boko hangata a hloekisoa ke NE transporter (Tanda et al., 1997;; Moron et al., 2002). Lintlha tse fapaneng tsa lintlha tse fumanoang likarolong le litoeba, li bontšitse ho se na liphello tsa ho felisoa ha NE ho DA ea basekelisi, ho fana ka maikutlo a hore ho fokotseha ha DA ho tsoa lifelong tsa li-terminals tse senyehileng ho fanoa ke ho fumaneha ha DA ka bongata ka lebaka la ho fokotseha ha eona ho tloha li-terminals tsena (Ventura et al., 2005;; Pascucci le al., 2007). Leha ho le joalo, litoeba tsa NE tse senyehileng li ile tsa bontša ho eketseha ha phetoho ea DA e entsoeng ka morphine e tšoanang le e bontšitsoeng ke Sham liphoofolo, ka tsela eo e fana ka maikutlo a hore likhetho tsa prefrontal noradrenergic le dopaminergic li senyehile. Ho lumellana le maikutlo ana, khetho ea prefrontal NE ho senyeha ha likhoto ha hoa ka ha ama khatello ea merusu ea DA ea khatello ea maikutlo le ho khetholla ha DA ha hoa ka ha ama khatello ea khatello ea kelello. Li kopantsoe, lintlha tsena li bonts'a hore, ka bobeli bo matlafatsang (mochine oa morphine) le maemo a khathatsang (boemo bo sithabetsang), NE le DA e lokolloa mpFC e ikemetse.

Bopaki bona bo fana ka maikutlo a hore NE ke ntho e tloaelehileng e laolang likarabo tse fapaneng ho susumetsa ts'ebetsong ea DA ho NAc, ho sa tsotellehe hore na ho na le litlhare tsa mofuta ofe kapa ofe tse amanang le litsebo tsa meriana. Lisebelisoa tsa marang-rang tse ka khonehang li 'nile tsa boleloa pele' me li tla nkoa hape. Mona ke habohlokoa hore u bontše hore sehlopha se fapaneng sa lintho tse thabisang hammoho le liphihlelo tse tsotehang tse kang khatello ea kelello e ka 'na ea etsa hore ho be le setsoalle se tloaelehileng sa correction-subcortical network.

Karolo ea mesoccumbens DA tsamaiso e susumelitsoe hantle. Leha ho le joalo, ebang le tsamaiso, e amang prefrontal NE le accomal DA, e na le karolo, e hloka ts'ehetso ea liteko. Ho ithuta ho khothalletsa batho ho ithuta le ho susumelletsa batho hore ba be le tšusumetso, maemo a tloaelehileng a sebelisoa hangata ka likhoto le litoeba, empa mefuta ea ho qetela e atile ho tloha mekhoeng e sebelisoang haholo bakeng sa ho ithuta lithethefatsi ka likhoto, ho hlahisa mathata a mangata ho litoeba. Leha ho le joalo, mokhoa ona o lumella ho fana ka ts'oaetso e susumetsang ho susumelletsa batho hore ba be le mekhoa e metle (e khotsofatsang) kapa e fanang ka tšusumetso e matla (US). Ka lekhetlo la pele phapanyetsano pakeng tsa ts'oaetso le tikoloho (CS) e lebisa ho khethollo ea sebaka (CPP), ha ho ntse ho etsoa tlhahiso ea bobeli (CPA). Mokhoa oa ho fana ka boikutlo ba ho susumetsa maikutlo o hakanngoa ke khetho (kapa ts'oaetso) e bontšitsoeng ha taba e lokela ho khetha pakeng tsa tikoloho e neng e kopane le US le tikoloho e sa jeleng paate (Tzschentke, 1998;; Mueller le Stewart, 2000). Mokhoa ona o boetse oa thusa ho hlahloba ho khutlela morao ho khethollo ea pele (kapa ts'oaetso) kamora ho fela, 'me ke mokhoa o khethollang mokhoa oa ho lemalla (Lu et al., 2003;; Shaham et al., 2003). Ka sebele, phuputso e boletsoeng esale pele e bontšitse hore khetho ea prefrontal cortical NE e senyeha ntle le ho fokotsa ho tsoa ha DA e entsoeng ke amphetamine e eketsehileng ho NAc, e holofetseng CPP e bakoang ke ho susumetsa. Liphello tsena ha lia ka tsa bakoa ke ho fokotsa likoloi, kapa ho ba le mathata a ho ithuta, kaha liphoofolo tse tlotsitsoeng li ne li sa fapane le li-sham tsa boitšoaro, 'me, ka ho khetheha, li ne li khona ho ithuta ka ho kopanela liphate joalokaha ho bontšoa ka tlhahlobo ea ho qoba (Ventura et al., 2003).

Ho phaella moo, liphetho tsena li bontša hore li-prefrontal cortical tse hloekileng ha lia hlokahala hore CPP e bakoe ke morphine, cocaine, kapa ethanol hammoho le ho khutlisetsa (ho khutlela) ho tima CPP morphine le ho kenya tlhahlobo ea ethanol tlhahlobo ea khetho. Kahoo, ba bonts'a hore prefrontal NE ke ea bohlokoa bakeng sa ho lokolloa ha DA ho NAC e bakoang ke lithethefatsi tse lemalloang le ho fanoa ka sebete se susumelletsang lithethefatsi tse amanang le lithethefatsi.

Leha ho le joalo, liphello tse amanang le liphihlelo tse fapaneng li bontša hore tsamaiso ea noradrenergic ea ts'ebetso ea ts'ebetsong ea DA e bonahala hape bakeng sa khatello ea kelello, e bontšang hore ho na le marang-rang a tloaelehileng a sebetsanang le ho etsa lintho tse thabisang (tse khotsofatsang) le tse fanang ka tšusumetso. Ho lekanya khopolo ena re rerile liteko tse peli. Ka lekhetlo la pele re hlokometse hore tlhahiso ea phekolo ea phekolo ea lithiamente e kang lithium chloride e tsamaisoang ka litsela tse hlahisitsoeng ke litoeba e ile ea etsa hore ho be le keketseho e hlakileng ea NE ho mpFC le DA ho accumcums e ileng ea felisoa ke khetho ea prefrontal NE ea ho felisoa. Ho feta moo, lithium e kentse CPA e ileng ea felisoa ke prefrontal NE ho senyeha, ka hona ho netefatsa hore prefrontal NE ke ea bohlokoa bakeng sa ho fana ka boikutlo ba ho susumetsa maikutlo ho amanang le boiphihlelo bo bolelang (Ventura et al., 2007).

Mohato o latelang o ile oa bontšoa ke liphetho tsa pele tse ileng tsa fumanoa ha re etsa qeto ea ho hlahloba karolo ea khetho ea CA ea prefrontal-e lekaneng ea ho fana ka boikutlo bo susumetsang ba tlhaho bo sa pheleng. Dintlha tse fetileng libukeng tse lumelletsoeng ho nahana hore tšusumetso e joalo ea khatello kapa e thibelang ho hlahisa tšebetsong e kenyelletsoeng ea phetiso ea prefrontal noradrenergic, ka hona ho feta moo ke matla a matla a hore li-prefrontal li lokolloe E tla ba (Feenstra et al., 2000;; Ventura et al., 2008 bakeng sa tlhahlobo). Haeba ho ne ho le joalo, joale prefrontal ha e lokolloa e ka nkoa e le letšoao la bothata ba boikhathollo. Ho ts'ehetsa ts'ehetso ea ts'ebetso ea prefrontal ea NE-accumbal system ke ea bohlokoa bakeng sa ho fana ka ts'ebetso e ts'oanelang molemong oa ts'ebeliso ea boipheliso eo re e sebelisitseng e le boiphihlelo bo sa amaneng le phekolo ea mantlha e leng khatello ea matla (lisebelisoa tse ka hare) tse ka fanoang e le hore li fane ka liphello tse tšoanang ho tse monate ( e khotsofatsang) lihlahisoa tse kang lijo tse monate pele li hlalosoa. Ha ho etsoa liteko tsa pele tsa boemo ba boemo bo botle, tseo ho tsona ho neng ho bapisoa likhatello tse peli tseo re li bonang, li ile tsa hlokomela hore li fapane le liphello tse hlollang, tse khantšang lihlahisoa tse ntseng li le holimo ho feta mabone a sa hlahelang. Phello ena e bapisoa le liphello tsa maemo a mabeli a ts'ebetsong a prefrontal cortical. Maemo a mabeli a khantšang a ile a eketseha pele a sa lokolloa, empa leseli la ho hlahisa lihlahisoa le hlahisitse keketseho e hlakileng ho feta lebone le sa tsitsang. Ho feta moo, karabo ea noradrenergic mpFC e ne e bapisoa le keketseho e entsoeng ke DA ho NAc (Ventura et al., Ha ho lokisetsoa).

Joale, re ile ra hlahloba hore na re khotsofatsa hakae e seng tšebetso ea metsoako, e sebelisoang joaloka US sebakeng sa boemo bo hlophisitsoeng, e hlokehang hore e sebetsane hantle le sebaka sa DA se ikemetseng se sebetsang bakeng sa ho fana ka matla a ho susumetsa. Re hlokometse hore litoeba li khetha chokolete e tšoeu (WCh) sekotong sa 'Milk (MCh) ka tekong ea khetho ea mahala, khetho e ileng ea tiisoa pharadigm ea CPP moo litoeba li khethang tikoloho e kopantsoeng le WCh ha e bapisoa le eona e kopanetsoeng ka khekotso ea MC . Ka kakaretso, microdialysis e sa sebetsaneng le maikutlo e bontšitse hore ho pepa ha WCh ho hlahisa e phahameng ho feta ho lokolloa mpFC ho feta MCh (Ventura et al., 2008, ha ho lokiselitsoe) ho tsamaisana le ts'ebetso ea DA e tsoetseng pele ho NAc. Liphello tsena li bonts'a hore prefrontal NE le DA ea ikemetseng ba arabela ka mekhoa e fapaneng ea bohlokoa, ebang ke e monate kapa e tsotehang, ka mokhoa o hlophisitsoeng.

Khothatso ea khothatso ea khothatso e bontšitse karolo ea bohlokoa ea boemo bo susumetsang ba litho (ba lapile, ba nyoriloeng, ba khathetse, ba falimehile joalo-joalo) ha ba tobana le tšusumetso kapa phihlelo. Ho imeloa kelellong ho 'nile ha lebisoa tlhokomelo e kholo lithutong tse amanang le mohopolo, haholo-holo tse amanang le lithethefatsi, tsa ho feto-fetoha ha metsoako e ka hlahisang mekhoa ea boko e amehang ho arabelang ho khaotsa lithethefatsi, ho ts'oanela ho ithuta le ho khutlela morao. Re ne re ipotsa hore na ho pepeseha pele ho liphihlelo tse sithabetsang ho ka ama pono ea "ho lemoha" ea ts'ebetso le ho arabela ha system ea prefrontal-accumbal CA, mme haeba liphetoho tse joalo li ka ama tšebetso ea botsitso bo susumelletsang maemo a rona a teko. Re ne re sebelisa regimen ea thibelo ea lijo e le khatello ea maikutlo e sa foleng e neng e boetse e bontšoa hore e fetole boitšoaro ba boitšoaro ho amphetamine, mme e ama tšebetso ea boikutlo bo susumelletsang maikutlo ho litoeba (Cabib et al., 2000;; Guarnieri et al., 2011). Thibelo ea lijo (FR) e lebisitse holimo ho NE ho lokolloa mpFC le ho lokolloa ha DA ho NAc ho bapisoa le litoeba tsa taolo. Keketseho ena e ne e tšoana le e bontšitsoeng ke litoeba tse sa fuoeng mahala (Non-FR) tse pepesitsoeng ho WCh, kahoo li bontša hore boemo ba sebōpeho, kamoo ho lebeletsoeng kateng, bo susumelitseng karabelo ho tšusumetso e matlafatsang. Phello ena e ka 'na ea hlalosoa ka ho hlaka hore ho hloka lijo ho tla etsa hore e be monate haholoanyane. Leha ho le joalo, boitsebiso ba rona bo bonts'a hore tsamaiso ea FR ke boemo ba tikoloho bo amang tsela eo motho a nahanang ka eona, ho sa tsotellehe mekhoa e amanang le lijo. Ka sebele, re hlokometse hore FR e entse liphello tse bakoang ke khatello ea maikutlo e sa fokolang (leseli le ka hare) le tšoanang le liphello tse hlahisoang ke litoeba tsa FR ntle le khatello e matla haholo (leseli le hlahang ka hare). Sena se bolela hore FR e khona ho eketsa botumo ba bobeli bo thabisang (ho putsang; lijo) le ho pheta-pheta (mabone a khathatsang) ho susumetsa, ho sa tsotellehe mekhoa e amanang le tlala. Hlokomela hore lintlheng tse ling Sham le NE tse nang le litoeba tse senyehileng tse amanang le lijo (ho itšehla thajana) li ile tsa bontša liphello tse tšoanang ho tsa liphoofolo tsa F, kahoo li bontša hore liphello tsa prefrontal NE ho felisoa ha MCP-e bakoang ke CPP e ke ke ea e-ba teng e hlalosoa ka karabo ea homeostatic ho thibelo ea lijo (Ventura et al., 2008). Thibelo ea lijo e ka boela ea nkoa e le e lebisang mofuteng oa motlakase oa motlakase (Niv et al., 2006;; Phillips le al., 2007) e neng e tla "matlafatsa" tšusumetso. Mokhoa ona o bonahala o itšetlehile ka bohlokwa ba ho hloka. Liphello tsa rona, leha ho le joalo, li bontša hore motlakase o sebelisoang ke mekhoa ea thibelo ea lijo pele ho pepeseha tšusumetsong e itseng e ama feela tšusumetso e matla ea phepo ea phepo empa e boetse e baka tšusumetso e matla. Ha e le hantle, liphello tse senyang tsa leseli le ka hare li matla haholo-lijong tse thibetsoeng ho feta litoeba tse fuoang mahala. Ka hona, liphetoho tsa motlakase ka kakaretso li lokela ho kenyeletsa mekhoa e tloaelehileng ea mekhoa ea tsamaiso e laolang liphihlelo tse matla le tse tsosang takatso.

Ho fumanoa hammoho, liphetho tsena li bontša hore karabo ea khetho ea CA ea prefrontal ke letšoao la maikutlo a susumetsang maikutlo / a susumelletsoang ke litšusumetso tse fapaneng tse fapaneng ho itšetlehile ka litšoaneleho tsa boikhathollo kapa boemo ba lihloliloeng. Karabo ea likarabo tsa prefrontal NE e ne e lumellana le liphetho tsa pele mme e re eletsa ho netefatsa karolo ea khetho ea CA ea prefrontal-ho fana ka matla a ho susumetsa a amanang le mekhoa e fapaneng e fapaneng. Re sebelisa li-paradigms tsa liteko tsa lithuto tse ling lihloohong tse tšoanang, re ile ra hlahloba liphello tsa khethollo ea khethollo ea NE le ho senyeha ha karabo ea CA le ho fanoa ka boikutlo bo susumelletsang maikutlo bo lekantsoeng le boemo ba sebaka. Ho makatsang ke hore re hlokometse hore NE ea ho felisoa ha eona e felisitse keketseho ea prefrontal cortical ha e lokolloa ebile e lokolloa ke DA, e ts'oanang le liteko tse fetileng. Leha ho le joalo, e thibelitse ho khethoa ha sebaka (CPP) liphoofolong tse pepesehileng ho WCh le liphoofolong tse sa thibeloeng lijo (FR) tse pepenelitsoeng ka tsokolate ea lebese (MCh; maemo ka bobeli a botumo bo phahameng) empa eseng ka liphoofolo tse seng tsa F (tse fuoeng mahala) tse pepesitsoeng ho MCh (botšepehi bo tlaase). Ho feta moo, e thibelitse sebaka sa aversion (CPA) liphoofolong tse pepesetsoeng ke leseli la lipalesa (IPL) le liphoofolong tsa FR tse pepenene le leseli le nang le phapang (IL; Figure11).

 

Setšoantšo sa 1

Liphello tsa prefrontal cortical norepinephrine e fokolloa ke khetho ea sebaka (CPP) e entsoeng ka chokolete (chokolete ea lebese e laolang, MCh; chokolete ea lebese lijo li thibetsoe MCh + FR; chokolete e tšoeu e laola, WCh) ...

Liphello tsena li bontša hore pFC NE ho senyeha ho ama phapang ea boikutlo bo susumetsang feela ha botšepehi ba UCS bo phahame ka ho lekaneng ho etsa hore ts'ebetso ea CA e bolokehe, e leng se bontšang hore tsamaiso ea CA ea prefrontal-e kenyeletsang ho sebetsana le ts'ebetso ea ho susumetsa maikutlo ka mokhoa o khethollang ha botumo bo matla bo susumetsang e sebetsanoe. Botšepehi bo bolela bokhoni ba ho tsosoa habonolo (Horvitz, 2000). Tlhahiso e sa hlokahaleng e etsa hore ho be le mekhoa ea ho ba le moelelo oa boitsebiso bo fumanehang molemong oa ho hlahisa maikutlo kapa ho fetola boitšoaro (Zink et al., 2006). Ha ho e-na le tšusumetso e matla haholoanyane, ho ka etsahala hore ebe e tla lebisa tlhokomelong kapa ho fetola boitšoaro. Litlaleho tsa morao-rao ho batho li bontšitse hore striatum e na le karolo e kholo ho etsa hore ho be le mekhoa e metle ea lisebelisuoa ho etsa lintho tse sa lokelang (Zink et al., 2003, 2006). Leha ho le joalo, prefrontal cortex, ka lebaka la mesebetsi ea eona ea "tsamaiso", e na le karolo e ka sehloohong ea ho kenya letsoho le ho susumelletsa batho ho etsa lintho tse seng kae.

Ho feta moo, litlaleho li bontša hore ventral striatum (kapa NAc) le prefrontal cortex e etsa karolo e tloaelehileng ea ho sebetsa ka mokhoa o hlophisitsoeng le o thibelang matla (Berridge le Robinson, 1998;; Darracq et al., 1998;; Becerra et al., 2001;; Jensen et al., 2003;; Kensinger le Schacter, 2006;; Borsook et al., 2007), 'Me lithuto tsa neuroimaging ho batho li fana ka maikutlo a hore libaka tse fapaneng tsa preortal cortex (O'Doherty et al., 2001;; Tse nyenyane le al., 2001;; Killgore et al., 2003;; Wang et al., 2004) le ea striatum (Jensen et al., 2003;; Zink le al., 2006;; Borsook et al., 2007) li sebelisoa ke tlhaho ea tlhaho e ntle kapa e fosahetseng. Hape, re kile ra bontša hore phetisetso ea NE prefrontal e sa hlokahaleng e hlokahalang bakeng sa tšusumetso e matla ea boipheliso (ka liphoofolo tse thibelang lijo) le moputso oa meriana o amanang le ts'oaetso hammoho le phekolo ea phekolo ea meriana e amanang le ts'oaetso ka ho feto-fetoha ha DA ho NAC (Ventura et al. ,, 2007). Ka lebaka leo, ho ka etsahala hore liphello tsa prefrontal NE ho felisoa ka CPP le CPA liphoofolong tse nang le tšusumetso e matla haholo li itšetlehile ka karabo e senyehileng ea tsamaiso ea CA ea prefrontal, eo ts'ebetsong ea eona e sa amohelehang le e sa tsitsang haholo ke setsi sa ho susumetsa botšepehi. Leha ho le joalo, libaka tse ling tsa boko le li-neurotransmitters li ka 'na tsa kopanngoa. Ka lebaka leo, kaha amygdala e ameha ka boemo ba lipapali tsa maikutlo le ho phetha karolo e khethehileng ea ho hlophisa mohopolo oa ho hopola liphihlelo (Balleine, 2005;; Balleine le Killcross, 2006;; McGaugh, 2006), 'me ba fane ka likamano tse rarahaneng tse sebetsang le tse sebetsang pakeng tsa sebaka sena sa boko le prefrontal cortex (Cardinal et al., 2002;; Holland le Gallagher, 2004;; Roozendaal et al., 2004) karolo ea prefrontal cortex-amygdala tsamaiso ea liphello tsa boitsebiso bo bongata bo tlalehiloeng mona bo tlameha ho nkoa (Belova et al., 2007).

Nahanisisa

Kabelo ea ts'ebeliso e susumetsang e amana le botšepehi ba UCS (Dallman et al., 2003;; Pecina et al., 2006). Ka hona, ha UCS e ntse e le matla haholoanyane, ho ka ba bonolo ho kopanela le eona ka lebaka la tšusumetso e matla ea boipheliso. Pele ho phihlelo ke ntho e kholo ea tšusumetso ea tšusumetso ea ntho leha e le efe e susumelitsoeng (Borsook et al., 2007) le ho tsosoa maikutlong ho bakoang ke ho susumetsa maikutlo ho eketsa tlhokomelo e fanoeng ho susumetsa ho susumetsa ka bobeli kemiso ea pele ea ho lemoha le ho kopanya (Anderson et al., 2006;; McGaugh, 2006). Re fane ka bopaki ba hore phetiso ea prefrontal-accumbal CA e hlokahalang bakeng sa ho ba le tšusumetso e ts'oanelang molemong oa boipheliso bo amanang le moputso le bokoenehi feela tlas'a maemo ao a ka khonang ho eketsa ho eketseha ha likhahla tsa CA ho arabela mekhoa e matla ea tlhaho e sa amoheleheng, ntle le valence.

Ka hona, khetho ea khethollo ea litsela NE e felisa boemo ba sebaka seo ho susumelitsoeng ke lintho tse matla haholo (e leng, WCh le IPL) liphoofolong tse laolang le ka boiketlo bo bobebe (e leng, MCh le IL) lihlopheng tse hatelletsoeng, empa li ne li se na liphello tse kholo ho laola liphoofolo tse pepeneneng ho ba le boikaketsi bo bonolo. Liphello tsena li bonts'a hore phetisetso ea CA ea prefrontal-accumbal transmission e hlokahalang bakeng sa ho fumana thepa ea boemo bo hlophisitsoeng e le ho khotsofatsoa ka mekhoa e metle ea tlhaho kapa liketsahalo tse tsosang takatso sebakeng sa boemo ba boemo ba maemo. Mabaka a mangata a fapaneng a na le karolo e kholo ea ho laola mekhoa e susumetsang, ho kenyeletsa le mefuta-futa e ka hare ea sebopeho (e leng, boemo bo susumetsang maikutlo, maikutlo a khatello ea kelello) le matlotlo (e leng, matla kapa matla), ka bobeli li ama mekhoa e susumelletsang batho ba nang le boikemisetso (Berridge le Robinson ,, 1998;; Richard le Berridge, 2011). Ho sa tsoa ts'oanngoa hore mekhoa ea bokooa e nang le tšusumetso e matla le e tsosang takatso e sebetsa "ka mokhoa o kopanetsoeng bakeng sa mekhoa e amanang le matla a maholo (botumo) empa e se valence" (Belova et al., 2007), ka hona ho fana ka maikutlo a hore tloaelo e tloaelehileng ea neural e ka 'na ea ameha ho sebetsanang le boikemisetso ba boikhathollo, ho sa tsotellehe hore na valence ke eng. Ho feta moo, ho tsosa thabo e khahlehang kapa e tsosang takatso e etsang hore likarabo tse hlakileng tsa valence li fane ka tlhahiso ea hore ho ntlafatsoe tlhokomelo le mohopolo ka tsela e tloaelehileng, e sa amoheleheng ea valence (Belova et al., 2007) le prefrontal cortex e kentse letsoho mosebetsing oa ho sebetsana le mekhoa e metle e khotsofatsang le e tsitsitseng (Rolls, 2000; O'Doherty et al., 2001;; Killgore et al., 2003;; Ventura et al., 2007).

Phetiso ea Dopaminergic ka hare ho NAc e nkoa e le ho finyella tšusumetso ea hedonic ea moputso kapa likarolo tse ling tsa thuto ea moputso (Everitt le Robbins, 2005 bakeng sa tlhahlobo). Liphello tsa rona, tumellanong le pono e fapaneng (Berridge le Robinson, 1998), bonts'a hore phetoho ea DA ka NAC e phetha karolo ea bobeli ka boits'oaro le ka boikutlo bo susumelletsoeng ke boipheliso; ntho ea bohlokoa ka ho fetisisa, leha ho le joalo, li bontša hore ts'ebetso ena e susumetsang e tsamaisoa ke prefrontal cortical NE.

Norepinephrine e mpFC e ka 'na ea etsa hore mesoaso a hlahise DA ho lokolloa ka sekhahla sa li-prefrontal cortical ho VTA DA liseleng (Sesack le Pickel, 1992;; Shi et al., 2000) le / kapa ka likarolo tsa corticoaccumbal glutamatergic (Darracq et al., 2001). Ho feta moo, karolo ea mpFC e lebisitsoeng ho LC ka ho sebelisa tšusumetso e ntle e ka etsoa hobane kopano ena e bontšitsoe ho kenya VTA DA neurons (Grenhoff et al., 1993;; Jodo et al., 1998;; Liprando et al., 2004), e leng se ka etsang hore DA e lokolloe ka NAC. Leha ho le joalo, kaha amygdala e ameha ka boemo ba Pavlovian ba maikutlo a maikutlo mme e bapala karolo e itseng ho hopolisa mohopolo bakeng sa liphihlelo tse tsosang takatso (Balleine le Killcross, 2006;; McGaugh, 2006), 'me ba fane ka likamano tse rarahaneng tse sebetsang le tse sebetsang pakeng tsa sebaka sena sa boko le prefrontal cortex (Cardinal et al., 2002;; Roozendaal et al., 2004), karolo ea tsamaiso ea prefrontal cortex-amygdala tsamaiso ea liphello tsa boitsebiso bo bongata bo tlalehiloeng mona bo tlameha ho nkoa (Belova et al., 2007;; Mahler le Berridge, 2011).

Hlokomela hore phetisetso ea NAc le dopaminergic e nkoa e le karolo ea bohlokoa mesebetsing e susumetsang ntle le karolo eo DA e bapalang ka eona likarolong tse ling tsa ts'usumetso le thuto ea lihlopha (Salamone et al., 2005). Ha e le hantle, ho latela maikutlo ao ho belaellang hore ho bokella DA ho etsa mosebetsi o le mong feela, bopaki bo bongata bo tšehetsa khopolo ea hore DA e ameha ho etsa boiteko kapa ho etsa liqeto tse amanang le boiteko (Salamone et al., 2007;; Bardgett et al., 2009), seo ha se lumellane le ho ameha ha tsamaiso ena ka thuto ea lihlopha, tsusumetso e susumetsang, kapa phetoho ea pavlovian-instrumental. Ho bonahala lithuto tsa liphoofolo le tsa batho li lumellana le seo, hammoho le lithuto tsa liphoofolo tse tsepamisitsoeng ka boiteko bo amanang le boiteko ba DNA e ikemetseng, liphuputso tsa lingaka li lumellana le khopolo ea hore mekhoa ea DA e ameha ho ts'ebetsong ea boitšoaro, e bontšang ho tšoana ho ts'oanang pakeng tsa mekhoa ea boko e amehang mekhoa e amanang le boithaopo liphoofolong le ba amehang matla a matla a matla bathong (Salamone et al., 2007). Ho ea ka pono ena NAC e sebetsanoang le eona e lokela ho nkoa, hammoho le prefrontal cortex le amygdala, e le karolo ea boko bo potolohileng mesebetsi e amanang le boiteko. Mohahong ona, tsamaiso ea prefrontal / accumbal CA eo re e nahaneng e ka 'na ea bonahala e le karolo ea marang-rang a rarahaneng a amanang le likarolo tsa boko ba likarolo le tse ling tse amanang le boiteko bo amanang le boiteko ba ho laola liphello tsa tšusumetso,' me mohlomong li amahanya matla a matla a boiteko bo matla. Ka pono ea rona phello ea tšusumetso ea bohlokoa ke ea bohlokoa litabeng tsa ts'ebetso tse lebisang ho fana ka ts'oaetso e susumetsang, ka lebaka la botsitso bo hlokometsoeng. Seo se bolela hore tšusumetso ea lihlahisoa tse ts'oanang le maikutlo a susumetsang maikutlo a susumetsang mekhoa ea mokhatlo e lebisang molemong oa tšusumetso, e leng se bontšang karolo ea bohlokoa ea ho ba le maikutlo a meholo ha motho a pepesa UCS. Sebaka sa prefrontal / accumbal system re rera ho laola mekhoa e susumelletsang ho susumetsa maikutlo ho ea ka matla a ho hloka botsitso ho lokela ho nkoa e kenyelelitsoe mananeong a rarahaneng a laolang maikutlo a nahannoeng (Phillips et al., 2003b). Khatello ea maikutlo, ho ea ka likhopolo tsa ho hlahloba (Arnold, 1960;; Lazaro, 1991) ho 'nile ha boleloa hore ho na le mekhoa e meraro: ho khetholla maikutlo a maikutlo a ts'ebeliso, ho hlahisa boemo bo botle ka lebaka la tšusumetso, le tsamaiso ea naha e amang maikutlo. Joalokaha ho bontšoa lingoliloeng tsa batho le liphoofolo (Phillips et al., 2003b bakeng sa ho hlahloba), mekhoa ena e itšetlehile ka mekhoa e fapaneng ea bokooa maikutlo a amang libaka tsa bokooa ho akarelletsa mesencephalic, cortical le subcortical tse kang amygdala, insula, ventral striatum, ventral, le dorsal anterior cingulate gyrus, tsamaiso ea septo-hippocampus, prefrontal cortex, tsohle tse khetholloang ke likamano tse sebetsang hantle (Salzman le Fusi, 2010). Lenaneo la septo-hippocampus le 'nile la nkoa e le setšoantšo se ikemetseng, se nang le karolo e kholo ea ho lekanyetsa tekanyo ea likhohlano lipakeng tsa mekhoa e fapaneng ea boitšoaro e laoloang (Gray le McNaughton, 2000). Amygdala o na le karolo e tummeng mofuteng le ts'ebetsong ea ho kopanya mohopolo ho itšetlehile ka ho tsosoa maikutlong. Morao tjena karolo ea sebaka sena ha ho etsoa liqeto e 'nile ea etsoa. Ha e le hantle, amygdala e ka hlahisa likarabo tse hlakileng tse khonang ho etsa hore e be le tšusumetso e matla ho khethoa, 'me ho nahanoa hore litekanyetso tsa maikutlo tsa boemo ba Pavlovian li sebelisoa ka liletsa (mekhoa ea ho itšetleha ka mekhoa e metle) le ho ithuta ka libaka tse ling tsa boko bo kang le striatum le prefrontal cortex (Seymour le Dolan, 2008).

Ke habohlokoa ho hlokomela hore "litekanyetso" li ameha ke ketso ea li-hormone tsa khatello ea maikutlo, tse kang glucocorticoids, ka amygdala, 'me liphello tsena li laola khokahano ea mohopolo e bontšang hore ho na le kamano pakeng tsa matla a maikutlo le matla a ho hopola (Roozendaal, 2000;; Setlow et al., 2000;; McGaugh, 2005). Ho feta moo, li-glucocorticoids li 'nile tsa bontšoa hore ke likokoana-hloko tsa mohloli oa moputso (Piazza le Le Moal, 1997) le bopaki bo bongata ba bopaki bo bontša hore li phetha karolo ea ho feto-fetoha ha mehopolo ea maikutlo e tsitsang takatso le e sithabetsang e bontšang hore ho tloaeleha ha thuto e nang le matla a ho khotsofatsa le ho senya ho ka 'na ha e-ba le mokhoa o tloaelehileng (Zorawski le Killcross, 2002).

Re fane ka bopaki ba hore tsamaiso ea prefrontal-accumbal CA e ameha ho sebetsanang le ts'ebetso ea ho susumetsa maikutlo ka mokhoa o khethollang ha ho ba le matla a ho susumetsa ka matla, ka tsela eo ho bonts'a hore ho na le mekhoa e fapaneng ea neural tsamaiso e kenyelletsoeng ho fana ka matla a ho susumetsa a amanang le mekhoa e bonolo. Liphello tsa rona li lumellana le tse neng li bontšitse hore ho fetisetsoa ha DA hase kamehla ho amehang moeeng (Nader et al., 1997, bakeng sa tlhahlobo). Ho fapana le khopolo-taba ea DA e itšetlehileng ka mokhoa o le mong oa mokhoa oa moputso, mohlala o sa amoheloeng / o amoheletsoeng o 'nile oa behoa bofelong ba lilemo tse robong tse bolelang hore mekhoa e' meli e fapaneng ea meputso ea li-neurobiological e ka arohanngoa habeli, e 'ngoe le e' ngoe e etsa hore monehelo oa bohlokoa boitšoarong bo susumelletsoeng ho itšetlehile ka boemo ba ho hlekefetsoa. Hlokomela hore mohlala ona o tšehetsoa ke liteko tseo liphoofolo tse nang le lithethefatsi li nkoang li lekana le lijo (tse ling, tse sa amoheloeng), ho fapana le liphoofolo tse itšetlehileng ka lithethefatsi ka ho tlohela kapa liphoofolo tse thibeloang ke lijo tse nkiloeng e le tsa bohlokoa (Nader et al., 1997;; Laviolette et al., 2004). Mohlala ona o na le liphello tse peli tsa bohlokoa. Ntlha ea pele, kamano pakeng tsa litsamaiso tse peli e bonahala eka e kopane. Boemo ba ho hlekefetsa bo sitisa mokhoa o sa amoheloeng [o amanang le lejoe la peduncolo-pontine (TPP)]. Ka hona, ts'ebetso e fapaneng ea mekhoa e 'meli e boleloa ka ho khetheha hore na liphoofolo li na le boemo ba ho tlosoa kapa che (Nader et al., 1997). Taba ea bobeli ke hore boemo ba ho hlekefetsoa bo kenyelletsa tsamaiso ea bobeli ea tšusumetso e ntle ea methapo ea pelo, e leng karolo ea eona ke DA.

Potso e totobetseng e hlahisoang ke mohlala ona ke hore na boitšoaro bohle bo susumelletsoeng bo ka nkoa bo na le karolo e sa amoheloang le karolo e hanetsoeng. Ha e ntse e botsoa ke bahlaseli (Nader et al., 1997(Tlhahlobo): "Na litšusumetso tse ling li sebetsa feela ka e 'ngoe ea litsamaiso tse peli tse?" Le ha puisano ena e se ka sepheo sa mosebetsi oa rona oa hona joale, re ke ke ra thusa ho hlokomela ho tšoana pakeng tsa seo re se fumaneng tsamaisong ea prefrontal-accumbal CA le sistimi e sa hlokeng / e hlokang, ka hore sistimi ea rona e bohlokoa molemong oa boits'oaro bo susumetsang. ha masapo a hlasimollang a phahame 'me a tšoauoa ka tšusumetso e matla maikutlong (ekaba e ntle kapa e mpe). Maemong ana, sistimi e ngoe e amehang ts'ebetsong e tlase ea "salience" e thibetsoe kapa "off-line", 'me sistimi ena e fumanehang marang-rang ha ts'ebetso e tlase e sebetsoa (le eo re neng re sa e lebella), e ts'oana le sistimi e sa hlokeng thuso, e tšoauoa ka tšusumetso e tlase ea maikutlo. Liphetho tsa rona li boetse li fana ka maikutlo a matla a hore, joalo ka tlhahiso ea mofuta o sa amoheloeng / o sa amoheloeng, sistimi e sebetsanang le botsitso bo phahameng (prefrontal-accumbal CA system) le eo ho nahanoang hore o kentse letsoho ho tlase ha e kopane. Mabapi le li-neural dynamics tse amehang ho kenyelelong e khethiloeng le e ikhethileng ea litsamaiso tsena, re ka supa hore keketseho e hlophisitsoeng ea ho tsoa ha NE ho mpFC ho ipapisitse le bohale bo tlase kapa bo phahameng ba tšusumetso, e kanna ea kenyelletsa li-subtypes tse fapaneng tsa AR, tse tla , ho latela boemo bo fanoeng ba NE, e tla etsa lipotoloho tse fapaneng, 'me, maemong a botsitso bo phahameng, ho kenyeletsoa le DA ho NAc. Ona ke sepheo sa liteko tse tsoelang pele tse ka hlakisang potso ena ea bohlokoa.

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References