Ho lemalloa ke lijo tse nang le li-palatable: Ho bapisa Neurobiology ea Bulimia Nervosa ho ea ho Lithethefatsi Tsa Lithethefatsi (2014)

Natalie A. Hadad, MA le Lori A. Knackstedt, Ph.D.

Boitsebiso ba Mongoli ► Tlhahisoleseding ea Copyright le License ►

Modeling BN e sa hlatsoeng

Moetso oa "thibelo ea lijo" kapa oa ho hloka "o sebelisa likhoto ho pheta mofuta oa BN o sa hlatsoeng litšila ka ho beha nako ea lithibelo tsa lijo kapa ho beoa le monyetla oa ho fihlella mahala ho lijo tsa 'mino o monate kapa tse monate. Hagan le Moss 1991; 1997). Kamora mekhahlelo e meraro ea ho haelloa ke lijo ho 75% ea boima ba 'mele bo lateloang ke ho fokotsa boima ba' mele, likhoto li bonts'a ho ja-ja joalo ka hora ea pele ea ho fepa ha ratHagan le Moss 1991). Ka mokhoa o ts'oanang, likhoto li beiloe tlas'a 12-libeke tsa matsatsi a thibelo ea lijo tsa matsatsi a 4 tse lateloang ke 2- ho ea matsatsing a matsatsi a 4 ea phihlello ea mahala ea lijo tsa chow kapa tse fumanehang li na le hyperphagia nakong ea ho fihlella mahalaHagan le Moss 1997). Haholo-holo, likhoto tsena li bonts'a mekhoa e meleele ea ho fepa ka nako e telele mme li tsoela pele ho bontša boits'oaro bo jang nako le nako ka mor'a ho khutlela kemisong e tloaelehileng ea ho fepa le boima ba 'mele, haholo ha ho fanoa ka lijo tse monate.Hagan le Moss 1997).

Ka "mofuta oa ts'oaetso ea tsoekere", likhoto li fuoa monyetla oa ho fumana tharollo ea tsoekere: 12-16 lihora tse ngata tsa phokotso ea lijo tse lateloang ke lihora tsa 8-12 tsa phihlello ea 10% sucrose kapa 25% glucose plus chow le metsi letsatsi le letsatsi. Avena et al. 2008a, b; Avena et al. 2006a; Colantuoni et al. 2002). Ha ho bapisoa le ho laola likhoto, likhoto li fuoa mokhoa o sa lekanyetsoang oa ts'ebetso ea sucrose le ho bonts'a boits'oaro bo tšoanang le, bo hlalosoang ke palo ea sucrose e jeoang ka hora ea pele ea nako e 'ngoe le e' ngoe ea phihlello (Avena et al. 2008a; Avena et al. 2006a; Colantuoni et al. 2002). Haholo-holo, likhoto tse fuoang monyetla oa ho fumana tharollo ea sucrose ka boithaopo li ja chow ho tloaelehileng ho feta likhoto tse fuoang nako le nakoAvena et al. 2008a; Avena et al. 2006a). Hypophagia ena e ts'oana le mekhoa ea ho ja ea BN-batho ba tloaetseng ho fokotsa ho ja lijo tse tlang pele le ho latela ho loana.Mokhatlo oa Maiketsetso oa Ma-Amerika 2013). Likhoto tse fanoeng phihlello ea tsoekere nako le nako (empa eseng kamehla chow) li boetse li bonts'a matšoao a ho tlohela (mohlala, ho bua ha meno, ho sisinyeha ha hlooho kamora ho qeta lihora tse 24-36). Moetso ona o lumella tlhahlobo ea likarolo tsa methapo nakong ea ha ho itlopa lijo le lithibelo tse latelang, tse bontšang hantle lintlha tsa bohlokoa tsa BN e sa hloekiseng.

Ho fapana le mefuta e hlalositsoeng kaholimo, mofuta oa "phihlello e lekantsoeng" ha o pepese likhoto lithibelong tsa lijo kapa khaello. Ho fapana le moo, likhoto li fuoa phihlello ea 'mino ea kop le maemo a tloaelehileng, hammoho le phihlello ea nako le nako lijong tse matlafalitsoeng tse nang le mafura, tsoekere, kapa motsoako oa mafura / tsoekere bakeng sa lihora tsa 1-2 (mohlala, Corwin le Wojnicki 2006; Wong et al. 2009). Likhoto tse fumaneng monyetla oa ho kenella nakoana ho 100% ea ho fokotsa limela ka mafura le ka boithaopo li fokotsa ts'ebeliso e tloaelehileng ea chowCorwin le Wojnicki 2006). Phokotso ena ea tšebeliso e tloaelehileng ea ts'oaetso e tšoana le likhoto tse fuoang phihlello nakong ea tharollo ea 10% sucrose (mohlala, Avena et al. 2008a) le hypophagia e bonoang ho BN-batho ka bomong (Mokhatlo oa Maiketsetso oa Ma-Amerika 2013). Kahoo, mofuta oa "phihlello" o lekantsoeng o hlahisa mokhoa oa ho ja oa batho ba sa itlhatsoeng ba BN ka ho hapa lithibelo tse ikemetseng hammoho le ho itlopa lijo.

Ha ba kopantsoe hammoho, mofuta oa "thibelo ea lijo / ho hloka", mofuta oa "tšebeliso ea tsoekere", le "mokhoa o fokolang" oa ho jella ho ja. Ho feta moo, ba tšoauoa ka thibelo e lekang- kapa ea boithati. Joalokaha ho hlalositsoe ka holimo, ho itlopa le lithibelo ke likarolo tse peli tsa bohlokoa tsa BN e sa hloekiseng. Kahoo, ka ho feto-fetola linako tsa ho itlopa lijo tse thata le lithibelo tsa ho ja le / kapa lijo tse monate, mefuta ena e sebetsa e le mefuta ea liphoofolo e khotsofatsang ea BN e sa hloekiseng.

Modeling oa ho hloekisa BN

Ho etsa mofuta oa phoofolo oa mofuta oa ho hlatsoa oa BN ho bile thata hobane likhoto li haelloa ke sebopeho sa mesifa. Ka hona, molemong oa ho hapa boits'oaro bo bobe ba ho itlhatsoa le bohloeki mohlaleng o le mong oa liphoofolo, bafuputsi ba kopantse mokhoa oa ho fepa ka sham le ho ja ho itlopa lijo (mohlala, Avena et al. 2006b). Ka mokhoa oa ho fepa ka "sham" fistula, e kenngoa ka mpeng kapa ka mpeng, e baka ho se ikamahanye pakeng tsa lijo le mpa ea mpa ea mpa le mala. Hobane gastric fistula e baka mokelikeli o kentsoeng ka mpeng hore e tlohe mpeng ea rat, ho kenella ka caloric ho lekane (Casper et al. 2008). Ka cycling sham-fed rats ka nako ea thibelo ea lihora tsa 12 e lateloang ke lihora tsa 12 tsa ho fumana mahala lijo, likhoto li itlopa lijo tse monate le ho itlhatsoa ka fistula ea gastric (Avena et al. 2006b). Ts'ebetso ena e sa tsoa netefatsoa har'a batho ba BN-bona (bona Klein le Smith 2013). Ka ho khetheha, basali ba BN ba fetotsoeng-sham-fepa ka ho inama le ho tšela mathe ka litharollo tsa metsi ba kenella ho hyperphagia athe litekanyetso tse tloaelehileng le basali ba nang le Anorexia Nervosa ha ba joalo. Kahoo, leha mefuta ea liphoofolo e sa khone ho hlakisa mathata a batho a ho ja (Avena le Bocarsly 2012), mokhoa oa ho fepa oa sham o kopaneng le ho ja ho tlangoa ka mokhoa o nepahetseng o tšoaea BN.

Litekanyetso tsa ho kenyelletsoa tlhahlobisong ea joale

Mefuta ea liphoofolo e hlalositsoeng kaholimo e hlahisa litšobotsi tsa mantlha tsa BN. Ho etsisa BN e sa hloekiseng, "thibelo ea lijo / tlholeho," "tšebeliso ea tsoekere", le "phihlello e fokolang" ea batho ba nyalanang ka lithibelo tsa liteko kapa tsa boithati. Habohlokoa, tsena ke litšobotsi tse peli tsa bohlokoa tsa BN e sa hloekisang (Mokhatlo oa Maiketsetso oa Ma-Amerika 2000). Ho hapa likarolo tse peli tsa sehlooho tsa ho hlatsoa BN (Mokhatlo oa Maiketsetso oa Ma-Amerika 2000), mofuta oa sham-feed / bingeing o pheta ho itlopa lijo hammoho le ho hlatsoa. Ho na le mefuta e meng ea BN, e kang mofuta oa khatello ea khatello eo baratani ba thibeleng lijo ka khatello ea maikutlo (mohlala, Hagan et al. 2002; Inoue et al. 1998). Leha ho le joalo, mefuta ena ha e e-so sebelisoe ho lekola liphetoho tse amanang le methapo ea kutlo tse boletsoeng bukeng ena e ngotsoeng ka letsoho, ka hona, li ke ke tsa tšohloa.

Tlhahlobo ea hona joale e kenyelletsa mefuta ea liphoofolo e hlalositsoeng ka holimo. Kaha thibelo le ho itlopa lijo ke likarolo tsa mantlha tsa BN (Mokhatlo oa Maiketsetso oa Ma-Amerika 2013), e kenyellelitsoeng mona ke lintho tse fumanoeng lithutong tse kenyeletsang ebang ho itima lijo kapa ho itlopa lijo liphoofolo tse etsang mosebetsi oa matsoho. Re bapisa sephetho sa liphuputso tse joalo ho ba fumanoeng ba sebelisa mefuta e fapa-fapaneng ea bokhoba ba lithethefatsi eo e mong le e mong a nkang likarolo tsa bohlokoa tsa bokhoba ba batho: maemo a khethiloeng a sebaka, ts'ebetso ea lithethefatsi, tšebeliso ea joala ka molomo le ho khutlisetsoa ka morao ho tšebeliso ea lithethefatsi ka mor'a ho felisoa ha lithethefatsi. karabelo e batlang lithethefatsi. Taba ea bohlokoa ke hore, ho fapana le litlhahlobo tsa morao-rao tse bapisang khatello ea methapo ea kutlo le ts'ebeliso ea ho itlopa lijo liphoofolong tse lebisang ho batenya (mohlala, DiLeone et al. 2012; Volkow et al. 2013), liphumano tse tsoang liphuputsong tse sebelisang meetso ea liphoofolo tse batenya ha li kenyelelitsoe mona hobane batho ba BN ha ba na boima ba mofuta o mong le o mong (Mokhatlo oa Maiketsetso oa Ma-Amerika 2013).

Nuklea e bokella dopamine

Ho hlohlelletsoa ha li-neuron tsa DA ho VTA ho etsa hore DA e lokolloe ho NAc mme e laole boitšoaro bo susumetsang le phihlello ea bokhoba ba lithethefatsi. Ethanol, nikotini, opiate, amphetamine, le koae li eketsa maemo a DA ho NAc, empa lithethefatsi tse sa sebelisoang hampe ke batho ha li fetole maemo a DA sebakeng sena. (Di Chiara le Imperato 1988). Ntle le moo, ha ts'ebetso ea DA e tsoelapele ka ts'ebetso e latelang khafetsa ea lithethefatsi, phello ea lijo tokisong ea DA e phela ka nako e telele ntle le haeba ho fumaneha hoa lijo ke pale kapa ho se lumellane (Ljungberg et al. 1992; Mirenowicz le Schultz 1994). Mona re bua ka datha e nkiloeng mefuteng ea liphoofolo ea ho hlatsoa le e sa hloekiseng BN e bonts'ang karabelo ea NAc DA lijong tse fumanehang habonolo e fapana le ea chow e tloaelehileng.

Thutong ea bona ea likhoto tse bonoang ke sham-fed-sucrose-binging, Avena le basebetsi-'moho (2006b) e hlahlobe tokollo ea NAc DA ho araba sucrose. Likhoto lihlopheng tse fepeloang ke shamric tse neng li bulehile ka nako ea hora tsa pele tsa ho fumana lijo li bonts'itse mokhoa oa ho itlopa lijo 'me li jele setsi ka mokhoa o nepahetseng nakong ea hora ea pele ea ho fumana matsatsi ohle a liteko (matsatsi a 1, 2, le 21) likhoto tse feptjoang tsa 'nete tseo gistric fistulas ea hae e ileng ea lula e koetsoe. Ka vivo micodialysis e senotse hore NAc extracellular DA e eketsehile haholo bakeng sa litoeba ka bobeli ba sham le ba fepileng e le kannete ka karabelo ea ho latsoa sucrose ka matsatsi ohle a liteko. Habohlokoa, le ha sucrose e entsoe nakong ea ho itlopa ka lekhetlo la pele e ile ea huleloa hang-hang ho tsoa lipoteng tsa likhoto tse fuoeng ke sham, karabelo ea DA ho NAc e ntse e tsoela pele ho bonoa ka letsatsi la 21. Liphetho tse tšoanang li fumanoe ho sebelisoa mefuta e fapaneng ea "tšebeliso ea tsoekere". Ho hlahisa likhoto sebakeng sa thibelo ea lijo tsa lihora tsa 12 tse lateloang ke nako ea phihlello ea mahala ea sephetho sa tsoekere ho itlopa joala letsatsi le letsatsi le ho tsoela pele ho lokolloa ha DA ka khetla ea NAc matsatsing a 1, 2, le 21 ea phihlello ea tsoekere (Rada et al. 2005). Ka lehlakoreng le leng, litoeba tse laolang litheolelo tse nang le phihlello ea libob tsa chow kapa tsoekere kapa lipapatso tsa libitum tsa chowot tse nang le phihlello ea ho khetha li-1-hora feela ka matsatsi a mabeli ha li itlame ka tsoekere, ebile ha li bontše ho lokolloa ha DA ka khetla ea NAc. Phuputsong e 'ngoe, likhoto li ne li sa fuoe lijo bakeng sa lihora tsa 16 li lateloa ke phihlello ea chow bakeng sa lihora tsa 8 ka tharollo ea sucrose ea 10% e fumanehang bakeng sa lihora tse peli tsa pele bakeng sa matsatsi a 21, ho fella ka ho lutla ha tsoekere le keketseho e kholo ho extracellular NAc DA ka letsatsi 21 (Avena et al. 2008b). Ka letsatsi 28, kamora matsatsi a 7 a fokotsoe ho 85% ea boima ba 'mele ba bona ba pele, likhoto tse noang sucrose li bonts'itse keketseho ea NAc DA e neng e phahame haholo ho feta tokollo ea NAc DA e bakiloeng ke ho nwa sucrose ka boima ba mmele bo tloaelehileng ka letsatsi la 21 (Avena et al. 2008b). Phuputsong e 'ngoe, likhalase tsa libaesekele matsatsing a 28 a protocol ea "ts'ebeliso ea tsoekere" e lateloang ke lihora tsa 36 tsa ho itima lijo li fokotsehe ka mokhoa o tlase oa NAc khetla ea DA ka likhoto tse fuoeng nako e telele (ad libitum).Avena et al. 2008a).

Ho nngoe hammoho, ha lithibelo kapa phepelo ea sham hammoho le li-sucrose-bingeing e hlahisa litholoana tsa NAc DA tsa kantle tse sa luleng nako e telele (mohlala, Avena et al. 2008b; Avena et al. 2006b; Colantuoni et al. 2001; Rada et al. 2005), Maemo a DA a fokotseha khetla ea NAc nakong ea ho itima lijo (mohlala, Avena et al. 2008a). Ha phihlello ea lihora tsa 2 ho sucrose e fumanoa hape kamora linako tsa ho itima lijo, maemo a DAC a kantle ho naha a feta se bonoang ho liphoofolo tse laoloang ho fihlella sucrose, e leng sesupo sa karabelo e ts'oaroang ea DA (mohlala ,. Avena et al. 2008b). Ka mokhoa o ts'oanang, likhoto tse pepesitsoeng cocaine, morphine, nikotine, tetrahydrocannabinol, le pontšo ea li-heroin li eketsehile ka ntle ho NAc DA (mohlala ,. Di Chiara le Imperato 1988; Gaddnas et al. 2002; Pothos et al. 1991; Tanda et al. 1997), athe ho tlosoa hoa lintho tsena ho fokotseha NAc DA (Acquas le Di Chiara 1992; Barak, Carnicella, Yowell, & Ron, 2011; Gaddnas et al. 2002; Mateo, Ho hloka, Morgan, Roberts, & Jones, 2005; Natividad et al. 2010; Pothos et al. 1991; Rada, Jensen, & Hoebel, 2001; Weiss et al. 1992; Zhang et al. 2012). Ka mokhoa o ts'oanang, sekhahla sa ho thunya ha li-neuron tsa VTA DA se fokotseha ho morphine (Diana et al. 1999) le cannabinoid (Diana et al. 1998) ho tlosa. E ts'oanang le ts'ebetso ea DA ha e arabela ho ikama ka mor'a nako ea thibelo (Avena et al. 2008b), Ho tsepamisa mohopolo ho NAc DA ho eketseha ha likhoto li boetse li pepesetsoa nicotine kamora nako ea matsatsi a 1 kapa 10 ea ho tlohela ho 4 kapa libeke tsa 12 tsa ho itšireletsa ka molomo tsa nicotine (Zhang et al. 2012). Sekhahla sa ho thunya ha li-neuron tsa VTA DA se eketseha haholo ho arabeleng morphine (Diana et al. 1999) le cannabinoid (Diana et al. 1998) Tsamaiso ka mor'a ho tlohela. Leha ho le joalo, ente ea phephetso ea koae ka mor'a matsatsi a 1 kapa 7 ea ho khaotsa ho ipusa ka mokhoa o atolositsoeng e sitoa ho eketsa NAc DA, e bonts'ang nts'etsopele ea mamello mme e seng sensitization (Mateo et al., 2005). Ka mor'a ho iphumanela taolo ea nakoana ea nicotine ka boeona, phephetso ea nicotine kamora lihora tsa 24 tsa ho tlohela e hlahisa maemo a phahameng a NAc DA a tlase haholo ho feta a hlokometsoeng ho litheko tsa lithethefatsi-naïve, hape e bonts'a nts'etsopele ea mamello (Rahman, Zhang, Engleman, & Corrigall, 2004). Ha a ntse a atoloswa phihlello ea methamphetamineLe Cozannet, Markou, & Kuczenski, 2013) hlahisa litholoana tse tšoanang le Rahman et al. (2004), methamphetamine phepelo ea methapo ea methapo ea methapo ea methapo ea methapo le litekanyetso tse khutšoane tsa ts'ebetso ea methamphetamine ho etsa hore tlhahiso ea DA e lokolloe mabapi le taolo ea naïve (Lominac, Sacramento, Szumlinski, & Kippin, 2012).

Ka kakaretso, ha ts'ebetso ea lijo tse nchafatsoang kamora nako ea ho nyahlatsa e hlahisa tokollo ea DA e khahlisang, phello e ts'oanang e bonoa kamora ho khaola nicotine e tsoang ho motho ka mong, tsamaiso ea methamphetamine ea nakoana le taolo e seng phehisano ea li-cannabinoids, morphine, le methamphetamine. Ts'ebetso ea DAT e fokotseha kamora nako ea ho itima lijo (Patterson et al., 1998), e ka tlatsetsang ho DA e phahameng e bonoang sebakeng sena sa boko nakong ea ho fepa hape. Tšusumetso e tšoanang e bonoa nakong ea ho khaotsa ho sebelisa methamphetamine e laetsoeng ke liteko (Sejeremane, Hanson, & Fleckenstein, 2012).

Nyutlelie e bokella polelo ea dopamine receptor

Lits'oaetso tse utulluoang khafetsa-phetisetso ea ho fokotsa ts'ebeliso le phihlello ea bobeli tsoekere le chow bakeng sa matsatsi a 31 li eketsa tsoelo-pele ea tsoekere butle, empa eseng ho ja haholo (Colantuoni et al. 2001). Lihora tse leshome le metso e 'meli ho isa ho 15 kamora ho loma, li-receptor tsa D1 tse kokotang khetla ea NAc le mantlha li phahame haholo litlamong tse thibelitsoeng ke lijo, tsoekere le tsoekere.. Within 1.5 ho isa ho lihora tsa 2.5 kamora ho hlaba, litoeba tse thibetsoeng lijo mme li fuoe monyetla o lekaneng oa ho li-sucrose le chow bakeng sa matsatsi a 7 li bonts'a haholo D2 e tlamang ho NAc e amanang le likhoto tse fuoeng phihlello e le 'ngoe feela (Bello et al. 2002). E amanang le ho laola liphoofolo tse fuoang chow feela, likhoto tse nang le monyetla oa ho kenella sucrose bakeng sa matsatsi a 21 li itšepa 'me lipontšo li fokotsehile D2 mRNA mme li eketsehile D3 mRNA ka hora ea NAc 1 kamora hore e fihle ho sucrose le chow (Spangler et al. 2004).

Keketseho e ts'oanang ea li-receptor tsa NAc D1 tse kopanyang le / kapa mRNA li fumanoe kamora ho pheta-phetoa ho sa pheheng khang ea cocaine (Unterwald et al. 2001), nicotine (Bahk et al. 2002), le amphetamine (Mocha et al. 2011). Empa, Le Foll et al. (2003) e fumane feela D3 e tlamang le mRNA empa ha ho na phetoho ho D1 ka mor'a nicotine e seng e nang le khang. Ka mokhoa o ts'oanang Metaxas et al. (2010) ha a fumana phetoho ponahalong ea D1 ka mor'a ho itaola. Boitlhokomelo ba joala bo tsoelang pele le ba nako e tlangSari et al. 2006), le phihlello e pharaletseng ea ho itaola ka koae (Ben-Shahar et al. 2007) eketsa D1 mRNA hammoho le polelo ea eona ea sebopeho (Conrad et al. 2010).

Keketseho ea polelo ea D1 e kanna ea lebisa karabelo e khahlisang ho DA. Ho lokolloa ha DA le ts'usumetso e latelang ea li-receptor tsa D1 ho NAc tse etsahalang ka lebaka la ts'ebetso ea lithethefatsi tse lemallo li hlahisa cascade e kenyelletsang keketseho ea polelo ea lintlha tse ngotsoeng joalo ka ΔFosB (bakeng sa tlhahlobo ea bona Nestler et al. 2001). Ho thibela ts'ebetso ea ho hatisoa ha ΔFosB ho fokotsa litlamorao tse tlisoang ke lithethefatsi (Zachariou et al. 2006) Ho bua haholo ho ntlafatsa moputso oa lithethefatsi (Colby et al. 2003; Kelz et al. 1999; Zachariou et al. 2006). Thibelo ea lijo e boetse e eketsa maemo a ΔFosB ho NAc ea likhoto (Stamp et al. 2008; Vialou et al. 2011), e eketsang tšusumetso ea ho fumana meputso ea lijo tse fumanehang habonolo, joalo ka bopaki ba ho fumana hore vaerase e nang le tšibollo ea bongaka ea ΔFosB e eketsa tšebeliso ea lijo tse matlafatsoang (Vialou et al. 2011). TEe, ho ka etsahala hore BN e eketsehe maemo a ΔFosB ho NAc ka tsela e ts'oanang le lithethefatsi tse lematsang, ka ho etsa joalo e eketsa boleng bo khotsofatsang ba ho itlopa lijo.

Ho itlopa joala ho boetse ho fella ka hore D2 e fokotsehe e kopane ho NAc (mohlala, Bello et al. 2002; Colantuoni et al. 2001; Spangler et al. 2004). Haholo, Taq1A, polymorphism e tloaelehileng e fumanoang har'a BN le batho ba lemaletseng lithethefatsi (Berggren et al. 2006; Connor et al. 2008; Nisoli et al. 2007), e amana le khatello ea methapo ea methapo ea D2 e fokotsitsoeng (Neville et al. 2004). Le ha koae e fokotsa polelo ea D2 ho NAc (Conrad et al. 2010), nicotine e sebelisoang hangata ho litekoBahk et al. 2002), amphetamine e sebetsitsoeng ka litekoMukda et al. 2009), le joala bo ikemetseng (Sari et al. 2006) eketsa polelo ea D2 har'a likhoto. Ka lebaka la ts'ebetso le batho ba lemaletseng lithethefatsi tsa batho ba bonts'ang liphokotso ho D2 binding (Volkow et al. 2001; Volkow et al. 1993), hoa thabisa hore ketsahalo e ts'oanang ha e bonoe ho latela nicotine, amphetamine kapa ho pepesetsoa joala liphoofolong. Leha ho le joalo, phokotso ea tlamo ea D2 e bonoang bathong e kanna ea bonts'a tlhahiso ea lithethefatsi, ka hona maemo a tlase a D2 a ne a ke ke a bonoa ka mor'a ho pepesetsoa liphoofolo. Phokotso ea polelo ea D2 e kanna ea hlahisa keketseho ea DA e ka tsamaisang ho itlopa lijo kapa ho batla lithethefatsi.

Ka bokhutšoanyane, ho choachoha ka sekhahla mefuteng ea liphoofolo ea sephetho sa BN ho phahamisa moeli oa NAc DA, ho eketsa li-receptor tsa D1 le D3 mRNA, le ho fokotsa D2 receptor binding le mRNA ho NAc. Ha D1 le D3 e fetoha e tšoanang le e hlahisoang ke lithethefatsi tse tlatsetsang (ntle le nicotine bakeng sa liphetoho tsa D1), Phokotso ea D2 ha e bonoe lithutong tse ngata tsa liphoofolo tsa bokhoba ba lithethefatsi. Ho ka etsahala hore ha litheko tsa D2 tse teng ho batho li sebeletsa ho khanna tšebeliso ea lithethefatsi, liphokotso tsena li etella pele ts'ebeliso ea lithethefatsi mme ha li bakoe ke eona.

Dopamine sebakeng se potolohileng ka hare

Mele ea lisele tsa Dopaminergic morerong oa VTA ho ea ho PFC, hippocampus, amygdala le NAc. Ho lokolloa ha Somatodendritic ho DA le hona hoa etsahala ho VTA ha ho thunngoa lisele (Ha a et et al. 2004) hape e na le tšusumetso e kholo mosebetsing oa dopaminergic VTA neurons. Mofuta ona oa tokollo ea DA o kenya tšebetsong li-inhibitory tsa D2 autoreceptors (Cragg le Greenfield 1997), ka tsela ena e thibelang ho tsubeloa ha sele ho DA ho VTA (Bernardini et al. 1991; Wang 1981; White le Wang 1984) le tokollo ea DA maemong a PFC le NAcKalivas le Duffy 1991; Zhang et al. 1994). Ka hona, tokollo ea somatodendritic ea DA ho VTA e bapala karolo ea bohlokoahali tokisetsong ea phetisetso ea DA hammoho le lipalo tsa mesocorticolimbic.

Ho vivo micodialysis e sebelisitsoe ho hlahloba lits'oants'o tsa VTA DA nakong ea ho fepa hape. Likhoto li ile tsa fokotsoa lijo le metsi bakeng sa lihora tsa 36 pele ho nako ea ho fepa hape nakong eo ho buuoang ka micodialysis (Yoshida et al. 1992). Keketseho e kholo ea lits'ebetso tsa VTA DA e ile ea bonoa nakong ea ho fepa le ho noha ho amanang le motheo. Maemo a VTA DA a ile a ntlafatsoa bakeng sa metsotso ea 20-40 kamora ho fela ha linako tsa ho fepa le ho noa. Ka mokhoa o ts'oanang, ente ea IP ea ethanol e etsa hore VTA DA e be le nako e telele kamora metsotso ea 20, ebe e phahamisa metsotso ea 40 kamora ho ente ebe e theohela ho basement (Kohl et al. 1998). Ka mokhoa o ts'oanang, intravenous (Bradberry le Roth 1989) le IP (Reith et al. 1997; Zhang et al. 2001) tsamaiso ea koae le liente tsa IP tsa methamphetamine e hlobaetsangZhang et al. 2001) eketsa DA ea kantle ho naha ho VTA. Ha liphetho tsa Yoshida et al. (1992) Boithuto bo bonts'a karolo ea bohlokoa ea VTA DA ho fepa boits'oaro, likhoto thutong li ne li potoloha feela ka nako e le 'ngoe ea lithibelo tsa lijo le ho iphelisa, le litloaelo tsa ho ja ka tsela e sa tloaelehang li sa hlahlojoe. Ntle le moo, ho ne ho se na sehlopha sa taolo thutong, ka hona ha ho tsejoe hore na litlamorao tse tšoanang li ne li ka bonoa har'a litoeba li sa pepesoa ke paradigm ea ho nyahlatsa. Kahoo, ho hlokahala tlhahlobo e tšoanang ho sebelisa mohlala oa phoofolo ea BN.

Phetisetso hammoho le projeke ea mesolimbic e boetse e fetoloa ka maemo a DAT mRNA. DAT mRNA e hlophisitsoe ho VTA mme e laola ho khutlisoa ha DA kahare ho VTA. E boetse e fallisetsoa ho NAc ho ea hlophisa ho khutlisoa ha synaptic ho DA. Ho fihla joale, ke phuputso e le 'ngoe feela e lekotseng liphetoho tsa DAT ho VTA e sebelisang mofuta oa phoofolo ea BN (Bello et al. 2003). Phuputsong, likhoto li ne li khibetsoe ke lijo kapa li fuoe phihlello ea lipapatso tsa ho itlama kapa li-chow tse tloaelehileng, ebe li lateloa ke lijo tsa pele tsa sucrose kapa chow tse tloaelehileng. Likhoto tse thibeloang ke lijo tse fuoeng mokhoa oa ho fumana li-sucrose li jelloa haholo ho feta sehlopha se seng sa likhoto. Leha ho le joalo, ho fapana le lipatlisiso tsa nakong e fetileng (mohlala, Avena et al. 2008a; Avena et al. 2006a; Colantuoni et al. 2002; Corwin le Wojnicki 2006; Hagan le Moss 1997), liphapang tsa sehlopha tsa ho ja ka mokhoa oa sucrose ha lia ka tsa fumanoa (Bello et al. 2003). Liphetho tsa likhohlano li kanna tsa bakoa ke hore Bello le basebetsi-mmoho ba ile ba palama likhoto ka har'a protocol hanngoe feela mme ba hlahisa likhoto tse nang le monyetla oa metsotsoana ea 20 ho sucrose. Leha ho le joalo, ho se tšoane ha lihlopha ho jang lijo tsa sucrose ho hlaha ha likhoto li potoloha ka lebaka la ho hloka le ho fihlella makhetlo a 'maloa' me li fuoa monyetla oa ho sucrose bakeng sa lihora tsa 1 ho isa ho 12 (mohlala, Avena et al. 2008a; Avena et al. 2006a; Colantuoni et al. 2002; Corwin le Wojnicki 2006; Hagan le Moss 1997). Leha ho le joalo, likhoto li ile tsa fumanoa li eketsa ho ja ha tsona ka makhetlo a mararo nakong ea matsatsi a 7 (Bello et al. 2003), e bonts'a boits'oaro bo joalo ka boits'oaro. E amanang le taolo le likhoto tse fanoeng mahala kapa tse lokiselitsoeng ho fihlela chow, likhoto tse fuoeng thibelo e lekantsoeng ea sucrose e hlophisitsoeng e bonts'a maemo a mangata a ho tlama a DAT le a mRNA ho VTA le DAT e tlamang ho NAc (Bello et al. 2003). Joalokaha ho tšohliloe kaholimo, NAc DA e nyoloha holim'a tlhahiso ea lijo tse fumanehang habonolo, 'me ho eketseha ha polelo ea DAT ho NAc ho ka etsahala e le ho leka ho lefella keketseho ena. Sena se fana ka maikutlo a hore BN e sa hlatsoeng letho hammoho le ho itlotsa lijo e baka litlamorao ho VTA DA e fapaneng le e hlahisoang ke ho ts'oaroa ha lijo tse sa phekoleheng. Ho pepesetsoa khafetsa ho amphetamine (Lu le Wolf 1997; Shilling et al. 1997) le nikotine (Li et al. 2004) e eketsa VTA DAT mRNA. Ka lehlakoreng le leng, koae e se nang phehisano e fokotseha (Cerruti et al. 1994), le ha phihlello ea boikhopolo ba koae ka bobeli le ha e na matla ha e na phello ea (Ben-Shahar et al. 2006), Polelo ea DAT mRNA ho VTA.

Patlisiso e sebelisang mehlala ea liphoofolo lithibelo tsa lijo e fana ka maikutlo a hore dopaminergic VTA efferents e ka laola tšobotsi ena ea bohlokoa ea BN e sa hloekiseng. E amanang le taolo ea likhoto tse nang le phihlello ea lijo mahala, likhoto tse tlisoang ke thibelo ea lijo tse sa foleng li eketsa tlhahiso ea VTA ea li-enzyme tse peli tse kenyellelitsoeng ho DA syntheine: tyrosine hydroxylase (TH) le monko o monate oa L-amino acid decarboxylase (AAAD) (Lindblom et al. 2006). Kahoo, nako ea ho itima lijo e ka lokisa li-neuron tsa VTA DA ho lokolla bongata bo boholo ba DA ho NAc ha ho hlahisoa lijo tse monate. Lithibelo tsa lijo tse sa feleng li fella ka keketseho e kholo ho polelo ea DAT ho VTA (Lindblom et al. 2006). Leha ho le joalo, ho bohlokoa ho hlokomela hore thibelo ea lijo ke tšobotsi e le 'ngoe ea BN e sa hloekisang. Kahoo, lipatlisiso tsa nako e tlang li lokela ho lekola hore na ho itlopa lijo tse ngata ho tsamaisana le thibelo ea lijo kapa ho hloekisoa ha litšusumetso tsa VTA TH, AAAD le DAT. Ts'ebetso ea koae e sa foleng le morphine li eketsa haholo ts'ebetso ea "VTA TH"Beitner-Johnson le Nestler 1991), empa tsamaiso ea methamphetamine ha e fetole haholo maemo a TH mRNA ho VTA (Shishido et al. 1997).

Ka kakaretso, mehlala ea liphoofolo e etsisang BN e sa hloekiseng BN le likarolo tse ling tsa bohlokoa tsa BN, joalo ka thibelo ea lijo, e sebelisitsoe ho fumana palo e eketsehang ea DAT mRNA, polelo e phahameng ea li-enzyme tse amanang le synthesis ea DA (TH and AAAD), le ho eketsa likhathatso tsa DA ho VTA. Liphetho tsena li bapisoa le neuroadaptations e fumanoang kamora ho phetoa hangata ha amphetamine, morphine, le nicotine, empa li hanyetsana le tse hlahisoang ke koae e sa hanyetsanang le ho itšireletsa hammoho le tsamaiso ea methamphetamine. Ha ho nkuoa hammoho, lipatlisiso tsa pele tse hlahlojoang karolong ena li bonts'a hore liphetoho tsa VTA dopaminergic tse teng mehlaleng ea liphoofolo tsa BN li ts'oana le tse hlahang ka mora ho pepesetsoa lithethefatsi tse ling tse lemalloang.

Litlamorao tsa bahanyetsi ba dopamine mabapi le ho itlopa joala le ho batla lithethefatsi

Hobane ho lokolloa ha DA ho hlaha ho NAc nakong ea ho loma, liphuputso tse ngata li lekotse bokhoni ba tsamaiso ea methapo ba D1 le D2 receptor antagonists ho fetolela mokhoa ona. U sebelisa protocol e fihlellang e nang le motsoako oa mafura / sucrose, Wong le basebetsi-'moho (2009) e fumane hore D2 antagonist raclopride e fokotsa phokotso e thehiloeng ho litekanyetso tšebelisong ea lijoako tsa lijo tse fumanehang habonolo tse nang le mohopolo o itseng oa sucrose. Thutong ea bona, likhoto li ne li lumelloa ho fihlella motsoako oa ho khutsufatsa ha 100% ka 3.2, 10, kapa 32% sucrose (w / w) bakeng sa hora e le ngoe, ka phihlello ea letsatsi le letsatsi kapa ea nakoana (MWF). Ke likhoto feela tse fumaneng monyetla oa ho ja lijo tse matlafatsoang tse nang le 3.2 kapa 10% sucrose tse fihlelletseng mokhoa oa ho itlopa. Ho liphoofolo tsena, tekanyetso ea 0.1 mg / kg (IP) ea raclopride e eketsehile ho itlopa lijo ha lethalinyana la 0.3 mg / kg (IP) e fokotsehile tšebeliso ea lijo tse matlafatsoang ho likhoto tse jang 3.2% sucrose. Raclopride ha ea ka ea ba le phello ea ho ja har'a litoeba tse fuoang letsatsi le letsatsi- kapa phihlello ea nako e telele (32%) motsoako oa "sucrose concentration fat" / sucrose motsoako o mong le o mong, leha e le hona ho ama tšebeliso ho likhoto tse fuoang phihlello ea letsatsi le letsatsi. Phuputsong e ts'oanang ke sehlopha se le seng, litekanyetso tse ts'oanang tsa raclopride li ile tsa lekoa bakeng sa bokhoni ba tsona ba ho fokotsa ts'ebeliso ea ho itlopa joala ebang Lijo tse nang le mafura (ho khutsufatsa) kapa lijo tse nang le sucrose (3.2, 10, le 32%) ka mor'a hore liphoofolo li fuoe lijo tsena ka mehla kapa ka linako tsohleCorwin le Wojnicki 2009). E tšoanang le liphetho tsa Wong et al. (2009) boithuto, tekanyetso ea 0.1 mg / kg ea raclopride e eketsehile haholo ts'ebetso ea ho khutsufatsa har'a likhoto tse pepesitsoeng protocol ea ho fihlella e fokolang mme e fuoe phihlello ea nako ea 1 ea hora ho mafura a 100%, empa litlamorao tsena ha lia ka tsa bonoa har'a likhoto tse fuoang phihlello ea mafura letsatsi le letsatsi (Corwin le Wojnicki 2009). Tekanyetso e phahameng ka ho fetisisa ea raclopride (0.3 mg / kg) e fokotse tšebeliso ea sucrose bakeng sa bohle maemo a ho checha ho lekana. Phuputsong e 'ngoe, likhoto tse tšoaroang ka 0.3 mg / kg (IP) raclopride mme li fuoe phihlello ea nako ea 4-hora ho 56% solid emulsion e matla kapa ho fihlella ha 4 ka hora ea 18%, 32%, kapa 56% mafura a emulsions a fokotsehile haholo mokgoa wa bona (Rao et al. 2008). Raclopride ha e fetole tšebeliso ea kamehla ea chowCorwin le Wojnicki 2009; Rao et al. 2008; Wong et al. 2009), e bonts'a hore mofuta oa li-raclopride o susumetsa tšebeliso ea lijo tse matlafatsoang 'me o etsa joalo ho liphoofolo tse jang lijo tsena.

E amanang le bokhoba ba lithethefatsi, 0.1 mg / kg raclopride e bonts'a ho ts'oaroa hoa koae hoa cocoa (Crombag et al. 2002) le 0.25 mg / kg raclopride e kenang e khutlisetsoa ka hare ho heroin-indued (Shaham le Stewart 1996). Tsamaiso ea tekanyetso ea tekanyetso (0.1 mg / kg) e phahameng le e phahameng (0.3 mg / kg) ea matsatsi a mahlano a latellanang e thibela cannabinoid (WIN) - ho thibela joala hape (Alen et al. 2008). Ho kenella ka hare ho moriana oa amygdala ho hlahisang litheko tse tsoang ho cue-primed tsa ho batla koae tse lekanang le litlamorao tsa ho ja lijo tse matla: lethal dose le tlase le thusa ho khutlisetsoa ha tekanyetso e phahameng e e fihlisa.Berglind et al. 2006). Ha ho kopantsoe hammoho, litekanyetso tse phahameng tsa morafo oa raclopride oa theoha, ha litekanyetso tse tlase li eketseha, tšebeliso ea mafura le ea sucrose ho likhoto tse lutlang, empa eseng likotong tse sa tlatleng tse fuoang monyetla oa ho fumana lijo tse monate. E amanang le ho khutlisetsoa ha motho ea batlang lithethefatsi, litlamorao tsa morafo oa ho itlopa lijo li tšoana hantle le tse hlahisoang ke li-infra-amygdala infusions empa eseng li-ente tsa tsamaiso.

D1 antagonist SCH 23390 e fokotsa ho itlopa lijo tse fumanehang habonolo. Ho phekola likhoto ka 0.1 kapa 0.3 mg / kg (IP) SCH 23390 e fokotsa tšebeliso ea li-3.2%, 10%, le 32% litlolo tsa sucrose tsa metsi ho likhoto tse fuoang phihlello e fokolang (hora e le ngoe / letsatsi) ea ho ipolaea letsatsi le leng le le leng kapa ka linako tsohle. phatlalatsoang bakeng sa likhoto tse fuoang phihlello ea nakoana (Corwin le Wojnicki 2009). Ho feta moo, tekanyetso ea 0.3 mg / kg SCH 23390 e fokotseha haholo ho khutsufatsa tšebeliso ea likhoto tse fuoang letsatsi le letsatsi le phihlello ea phihlello ea hora ea 1 le hora ha 0.3 mg / kg tekanyetso e sena matla. Haholo, SCH 23390 ha e susumetse tšebeliso ea kamehla ea chowle (Corwin le Wojnicki 2009; Rao et al. 2008; Wong et al. 2009). Ka mokhoa o ts'oanang, ho phekola likhoto ka SCH 23390 ho etsa hore mofani a arabele ka matla ho amanang le tšusumetso e amanang le koae, empa karabelo ho litheko tse tloaelehileng tse amanang le chow ha li na tšusumetso ho litekanyetso tse ngata (Weissenborn et al. 1996). SCH 22390 e bonts'a ntlafatso ea boits'oaro ba koae-molemong oaCrombag et al. 2002))Shaham le Stewart 1996), ho khutlela morao ethanol (Liu & Weiss, 2002) le ho khutlisetsoa ka hare ho lijo tse haelloang ke lijo tsa heroin (Tobin et al. 2009) ka likhoto. SCH 22390 e fokotsa ho itaola ka nicotine (Sorge & Clarke, 2009; Litepisi, Neugebauer, & Bardo, 2010) le tsamaiso ea koaeSorge & Clarke, 2009). Le ha SCH 22390 e fumana haholo ho batla koae ka mor'a nako ea ho khaotsa ho ba batona le ba batšehali e fuoang phihlello e khutšoane ea ho itlhokomela ka koae, sena se fokotseha liphoofolong tse fuoeng phihlello e atileng (Ramoa, Doyle, Lycas, Chernau, & Lynch, 2013), tumellanong le phokotso ea tokollo ea DA e etsahalang kamora ho fihlella ho atolositsoeng (ho tšohliloeng ka holimo). Ka bokhutšoanyane, D1 antagonist SCH 22390 e thibela tšebeliso ea lijo tse matlafatsoang hape e fumana ho khutlisetsoa hoa ho batla lithethefatsi.

Hobane tokollo e ntlafalitsoeng ea DA e bonoa ho NAc nakong ea ho itlopa lijo, e ho leka ho fana ka maikutlo a hore litlamorao tsa tsamaiso ea D1 le D2 tsa ho loants'oa ha litle li tsamaisoa ke NAc. Ho etsa tlhahlobo ea bokhoni ba ho kenella ka mokhoa o ikhethileng oa li-agonists le antagonists ho NAc ho fokotsa ho itlopa lijo hoa hlokahala. D2 antagonist raclopride e fana ka phello e ntle ho tšebeliso e ngata ea lijo tse monate; hona ho ka hlaha ka lebaka la sebopeho se fapaneng sa lipalo tse peli tsa li-receptor tsa D2 (pele ho le post-synaptic). Litekanyetso tse tlase tsa agonists li hlohlelletsa li-autoreceptors tsa pre-synaptic D2, ka tsela eo li fokotsa ho lokolloa ha DA (Henry et al. 1998). Ho ka khothatsoa hore litekanyetso tse tlase tsa morusu oa antagonist le tsona li ka ba le phello e ikhethileng ho li-autoreceptors, ka ho etsa joalo li eketsa motlakase oa DA (mohlala, Bona et al. 1991) le ho khanna tšebeliso ea lijo tse matlafatsoang. Tekanyetso e phahameng e ne e tla thibela li-receptor tsa post-synaptic, ka tsela eo, li fokotse tšebeliso ea lijo tse matlafatsang. Liphetho tsena li bonts'a hore DA e lokolla ebile e tlama ho post-synaptic D1, mme mohlomong D2, li-receptors li hlohlelletsa ho ja. Ho eketsa tokollo ea DA ka ho qhekella ha D2 autoreceptors le hona ho eketsa ho itlopa nako. Liphetho tsena li fumanoe tse tšoanang tsa ho tlama ha D1 le ho fokotsa tlamo ea D2 ho NAc ka likhoto tse nang le nalane ea ho itlopa lijo tse monate. Ha re kopantsoe hammoho, ho ka etsahala hore polelo e fokotsehileng ea NAc D2 e lebisa ho tokollo e ntlafalitsoeng ea DA nakong ea likotlo tse thata ha e ntse e ntlafatsoa polelo ea D1 primes post-synaptic neurons ho arabela ka mokhoa o matla ho DA e lokolotsoeng nakong ea ho itlopa.

Glutamatergic neurotransication ho BN

Liphetoho polelong ea li-receptor le glutamate le li-subunits li hlahlobiloe haholo kamora ho iphekola ha lithethefatsi tse lemalloang ke litoeba. Glutamate e na le mefuta e mengata ea li-receptor e fumanehang ka pele le ka morao ho liketsahalo. Mona re bua ka datha e amehang mabapi le li-receptor tse tharo tsa post-synaptic tse tsejoang ho hokahanya neuroplasticity: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-d-aspartate (NMDA), le metabotropic glutamate receptor 5 (mGluR5).

Kamora ho tlohela ts'ebetso ea ho itaola ka mokhoa o pharaletseng, ho na le keketseho ea polelo ea kameho ea NAc ea GluA1 subunit ea tetrameric AMPA receptor, empa ha ho na phetoho ho polelo ea GluA2 subunit (Conrad et al. 2008). Ho feto-fetoha ha maemo ho etsa hore polelo e eketsehe ea li-receptor tsa calcium-permeable, GluA2-e haellang ea AMPA (CP-AMPA), eo ka nako eo e eketsang thabo ea li-neurons tsa post-synaptic, ka tsela eo li matlafatsa likhokahano tsa synaptic (Conrad et al. 2008). Ho eketseha ha li-CP-AMPA ho hlokometsoe kamora matsatsi a 30, 45, le 70 matsatsi a ho tlohela, empa eseng kamora letsatsi le le leng feela la ho tlohela (Conrad et al., 2008; Ferrario et al., 2011; Wolf & Tseng, 2012) kapa kamora ho fihlella ha nakoana feela ho tsamaiso ea koaePurgianto et al. 2013). Likhoto tse thibetsoeng ke lijo li bonts'a keketseho e kholo ponts'ong ea post-synaptic density ea GluA1 ho NAc e amanang le taolo ha polelo ea GluA2 e sa fetohe (Peng et al. 2011). Kahoo, hoa khoneha hore linako tsa thibelo ea lijo tse bang teng nakong ea BN li baka ho kenyelletsoa ha li-CP-AMPA tseo ka nako eo li fetolang karabelo ea li-neuron tsa post-synaptic ho NAc ho glutamate e tlang. Ho ipusa ka lithethefatsi tse lemalloang ho boetse ho fella ka keketseho ea glutamate e lokollotsoeng ho NAc, e tlohelang ho oela hape kamora nako e se nang lithethefatsi; keketseho ena e bontšitsoe hore e etsahala maemong a ho tsubella ho joala (Gass et al. 2011), cocaine (McFarland et al. 2003), le heroin (LaLumiere le Kalivas 2008). Ho lokolloa ha glutamate ho kopaneng le li-neurons tsa post-synaptic tse ntle haholo tse nang le li-CP-AMPA ho hlahisa potoloho e khothalletsoang ho tsamaisa boits'oaro ba ho batla lithethefatsi (ka merero ea NAc ho ea libakeng tse hlahisoang ke boko). Ho fihla joale, ha ho na lithuto tse sebelisang mefuta ea liphoofolo tsa BN kapa ho itlopa lijo tse amanang le ho ja li hlahlobe maemo a glutamate ho NAc kapa libakeng tse ling tsa boko kamora ho ts'ebeliso ea lijo tse matlafatsoang kamora nako ea thibelo (thibelo ea lijo). Leha ho le joalo, haeba keketseho e joalo e ne e ka ba teng, e ne e tla ts'ehetsa maikutlo a hore tahlehelo ea taolo ea tšebeliso ea lijo tse matlafatsang le lithethefatsi tse lemalloang ka mor'a nako ea ho khaotsa e itšetleha ka ts'ebetso e tšoanang ea methapo.

E ts'ehetsa maikutlo a hore ho lokolloa ha glutamate ho ameha BN, memeline ea NMDA receptor antagonist e fokotse tšebeliso ea li-lard-like like lats tse sa hlokeng letho mme e hlahisa keketseho e ts'oanang ea ts'ebeliso ea laboratori e tloaelehilengPopik et al. 2011). Phuputso e ts'oanang e bonts'itse hore MTEP (3- (2-Methyl-4-thiazolyl-ethynyl) pyridine), module ea sa sebetseng hantle oa mGluR5, e hlahisitse mokhoa oa ho fokotsa tšebeliso ea lard. U sebelisa mofuta oa mofuta oa bono oa bothata ba ho ja tse jang tse ling moo litšoane li neng li khona ho fihlela tsoekere nako le nako ha li sebelisa mofuta o tloaelehileng oa pop, Bisaga le basebetsi mmoho (2008) o fumane hore li-memantine le MTEP li fokotsa tšebeliso ea tsoekere joalo ka. Kameho e ts'oanang ea memantine khafetsa ho ja lijo tse matla e ile ea bonoa tekong ea bongaka (Brennan et al. 2008).

Le ha lithuto tsa glutamate Microbalalysis li ntse li lokela ho etsoa ho sebelisoa mehlala ea liphoofolo tsa BN, taba ea hore glutamate receptor antagonists memantine le MTEP li fokotseha ho ja lijo tse tšehetsang maikutlo a hore ho itlopa lijo ho kenyelletsa phetisetso ea glutamatergic, leha e ka ba sebakeng sa boko ka ntle ho NAc. Litonong, MTEP e bontšitsoe ka ts'epahalo hore e fokotse ho batla koae (Bäckström le Hyytiä 2006; Knackstedt et al. 2013; Kumaresan et al. 2009; Martin-Fardon et al. 2009), joala (Sidhpura et al. 2010), methamphetamine (Osborne le Olive 2008), le li-opioids (Brown et al. 2012). Liteko tse ngata tse nyane tsa tlhahlobo ea bophelo li fumane hore memantine e fokotsa litlamorao tsa nicotine (Jackson et al. 2009) le heroin (Comer le Sullivan 2007) hape e fokotsa matšoao a bang teng ha motho a e-tsoa joala (Krupitsky et al. 2007) le li-opioids (Bisaga et al. 2001). Leha ho le joalo, phuputso e kholo, e laoloang ke placebo e bontšitse hore memantine ha e fokotse ho nwa ho bakuli ba lebelletseng joala.Evans et al. 2007). Hoa thahasellisa hore thutong ea sefofane sa 29 e nang le mamello ea mamello ea XNUMX, memantine e fokotse nako e sebelisitsoeng ho becha le ho eketsa maemo a kelello (Grant et al. 2010), ho bonts'a hore memantine e kanna ea sebetsa ho bakuli ba lemaletseng lits'ebetso joalo ka ho becha le ho itlopa joala empa eseng lithethefatsi tse lemalloang. Ka kakaretso, leha ho na le monyetla oa lipatlisiso tse sebelisang mehlala ea liphoofolo tsa BN ho hlahloba liphetoho lipakeng tsa phetisetso ea glutamate, lipatlisiso tsa pele tse hlahlojoang karolong ena li fana ka maikutlo a hore liphetoho tse tšoanang tsamaisong ea glutamate neurotransmitter e ka ba tlasa BN le ho batla lithethefatsi.

Ho lahleheloa ke taolo

Ho lemalla lithethefatsi ho kenyelletsa phetoho ea ho tloha ho fokola, ts'ebetso ea botsamaisi ho ea ho boits'oaro bo bobe le tahlehelo ea taolo ho ts'ebeliso ea lithethefatsi e hlahisoang ke ho sitisoa ke mosebetsi oa PFCKalivas le O'Brien 2008; Koob le Le Moal 2001). Joalokaha ho boletsoe pejana, e 'ngoe ea litšobotsi tsa bohlokoa tsa BN ke maikutlo a tahlehelo ea taolo ea ho ja, ka ho se khone ho emisa ho ja kapa ho laola hore na motho o ja eng kapa hore na o ja eng (Mokhatlo oa Maiketsetso oa Ma-Amerika 2013). Lipatlisiso tse sebetsang tsa matla a tšebetso ea maqhubu a (fMRI) li fumane hore, ho latela taolo e phetseng hantle, batho ba BN-ba bonts'a mesebetsi e tlase haholo ea PFC nakong ea mesebetsi ea taolo ea taolo e kholo joalo ka taolo ea ho potlaka (Marsh et al. 2011; Marsh et al. 2009). Maemo a tlase a ts'ebetso litseleng tse ka pele-pele, ho kenyelletsa le infColatal PFC, li amana le karabelo e sa potlakileng (Marsh et al. 2009), e bonts'a ts'ebetso e kholo ea ts'ebetso har'a batho ba BN. E amanang le taolo, BN-batho ba bonts'a ts'ebetso e phahameng ho PFC ha e hlahisoa ka litšoantšo tsa lijo (Uher et al. 2004), e qotsoe ka mantsoe a fosahetseng mabapi le setšoantšo sa mmele (Miyake et al. 2010), kapa ho bontšoa 'mele e boima haholo (Spangler le Allen 2012).

Ha ba kopantsoe hammoho, batho ba BN ba bonts'a tšibollo ea maikutlo ha e hlahisoa ka mekhoa e sa amaneng le lijo le ts'ebetso e fetelletseng ha e fanoa ka lintlha tse amanang le ho se sebetse hantle. Mokhoa ona oa tšebetso o boetse o bonoa har'a ba lemaletseng lithethefatsi. Haholo-holo, ts'ebetso ea kelello ho PFC ha e araba mesebetsi e meng e amanang le lithethefatsi e amanang le lithethefatsi e bonahala hara basebelisi ba sa foleng ba cocaine (Goldstein et al. 2007), methamphetamine (Kim et al. 2011; Nestor et al. 2011; Salo et al. 2009), le joala (Crego et al. 2010; Maurage et al. 2012). Ho hlahisa batho ba lemaletseng litšoantšo tse tsosang takatso e amanang le lithethefatsi ho eketsa tšebetso ea PFC har'a ba lemaletseng joala.George et al. 2001; Grusser et al. 2004; Tapert et al. 2004), cocaine (Wilcox et al. 2011), le batho ba ikhethileng ba nicotie (Lee et al. 2005). Kahoo, batho ba BN-ba bonahatsa mekhoa e hanyetsang ea ts'ebetso ea PFC e ts'oanang le batho ba lemaletseng lithethefatsi.

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