Matšoao a lipeo le likhahla: Ts'ebetso ea bona ho kotsing ea lithethefatsi ho batho (2013)

Marco Leyton^a,** 'me Paul Vezina^b,*

Boitsebiso ba Mongoli ► Tlhahisoleseding ea Copyright le License ►

Ho ts'oaroa ka mekhoa e lemalloang ho amana le ho eketseha le ho fokotseha hoa ts'ebetso ea striatal. Lintlha tsena ka bobeli li tlalehiloe bathong hammoho le mehlaleng ea liphoofolo. Leha ho le joalo, mekhoa e bakang litlamorao tsena tse hanyetsanang le tsela eo li amanang ka teng ho ntlafatso ea boitšoaro le polelo ea bokhoba ba tahi li lula li sa hlake. Thutong ea ha joale ea lithuto tsa batho, re hlalosa lintlha tse 'maloa tse ka' nang tsa susumetsa hore na litšisinyeho tsa maikutlo tsa batho ba bang li ka bonoa mme ra fana ka mohlala oa mofuta o kopanyang tšusumetso ea likarabo tsena tse hanyetsanang poleloaneng ea boitšoaro bo amanang le bokhoba. Ntho ea bohlokoa mohlaleng ona ke karolo e bapaloang ke ho ba teng ha khahlano le ho ba sieo hoa mekhoa e amanang le bokhoba ba tahi le bokhoni ba bona ba ho laola ho araba lithethefatsi tse sebelisitsoeng hampe le meputso e meng. Ts'ebetso ea striatal le linaha tse khothalletsang tšusumetso li eketseha boteng ba tsona 'me li fokotsehile ka ho ba sieo ha tsona. Ho hloka kutloano lipakeng tsa linaha tsena ho ka baka boikokobetso bo tsoelang pele ba lithahasello ha lithethefatsi li ntse li ntlafala le ho supa lits'ebetsong tse loketseng ho tobisa kalafo.

3.1. Litlamorao tsa khoele

Ho batho ba sebelisang lithethefatsi hampe, ho pepesehela litlhare tse susumetsang tse amanang le lithethefatsi ho hlahisa likarabo tse fapaneng tsa boitšoaro, boits'oaro le mmele.Carter le Tiffany, 1999; Childress et al., 1988; O'Brien et al., 1990). Hore likarabo tsena li tšoana le lithethefatsi li lumellana le bokhoni ba tsona ba ho susumetsa linaha tse susumetsang tse amanang le moriana ona (Stewart et al., 1984; Robinson le Berridge, 2003)¹.

Mebuso e hloahloa e kenyelletsa ho tsepamisa likelello tsa bona meputsong le ho nyoloheng ha bona e le kannete. Lits'ebetso tse mahlonoko tse amanang le ts'ebetso ea striatum ha li hloke ho lemoha (Fischman, 1989; Tiffany, 1990; Konyana et al., 1991; Winkielman et al., 2005; Childress et al., 2008; Makala le al., 2009; Perkins, 2009; Berridge, 2012; Metsi et al., 2012); ho lakatsa ho tseba ho ka ba haufi haholo le tšebetso ea meaho ea cortical (Goldstein et al., 2009; de Lange et al., 2011). Leha ho le joalo, ho ipeha lebaka ka boiketsetso ke tlhahlobo e sebelisoang hangata le ea tlhaho le tlhahlobo ea tlhaho ea lintho tse fumanehang ka li-diary tsa nako tsa motlakase li tiisa hore ho pepesetsoa litheko tsa lithethefatsi, le ho tsosa takatso ea tsona litabeng tsa litakatso, hangata ho etsahala ka metsotso le lihora pele ho lits'oaetso tse ncha tsa ts'ebeliso ea lithethefatsi tse matlafatsang. (Epstein et al., 2009). Ka mokhoa o ts'oanang lithutong tsa laboratori, takatso ea ho lakatsa le ho batla moputso ho tlalehiloe hore e eketsa ho pepeseha ho pepesoa litloaelo tse amanang le amphetamine (Culbertson et al., 2010; Tolivar et al., 2010), cocaine (Childress et al., 1988, 1993), joala (George et al., 2001; Bragulat et al., 2008), koae (Droungas et al., 1995; Carter le Tiffany, 2001; Wray et al., 2011), heroin (Fatseas et al., 2011; Zhao et al., 2012a), le meputso ea tlhaho joalo ka lijo (Jansen, 1998; Kelley le Berridge, 2002; Mahler le de Wit, 2010) le thobalano (Conaglen le Evans, 2006; Kim le Zauberman, ka khatiso).

Likhetsi li na le litlamorao tse ngata ha lithuto li tseba hore haufinyane ho tla ba le monyetla oa ho sebelisa lithethefatsi (Carter le Tiffany, 2001; Dar et al., 2005; Juliano le Brandon, 1998). Tsena, ehlile, ke maemo a tloaelehileng ao likhoto li hlahang tlholehong ea tlhaho. Papiso e tsotehang ea ketsahalo ena e sa tsoa tlalehoa ho bapalami ba lifofane. Batho ba tsubang ka nako e khutšoane (3-5.5 h) kapa lifofaneng tse telele (8-13 h) ba hlahisitse litakatso tsa koae ho elella qetellong ea leeto. Litakatso qetellong ea sefofane se sekhutšoane li ne li le matla joalo ka litakatso qetellong ea sefofane se selelele mme li phahame haholo ho feta tse bonoang nakong e khuts'oanyane nakong ea sefofane se selelele (Dar et al., 2010).

Litloaelo tse amanang le lithethefatsi li ka boetse tsa hlahisa litlamorao tsa boitšoaro. Tsena li kenyelletsa likhetho tsa sebaka se hlophisitsoeng (Bana le de Wit, 2009, mochine oa khatiso) le khethollo ea maikutlo (Cox et al., 2006; Hogarth et al., 2008; Makala le al., 2009; Little et al., 2012,, e tiisa maemoFoltin le Haney, 2000), ts'ebetso e potlakileng ea ts'ebeliso ea lithethefatsi (Herman, 1974), hammoho le ts'ebeliso e matla ea lithethefatsi (Panlilio et al., 2005; Hogarth et al., 2007) le ho itaolaHerman, 1974; Droungas et al., 1995; Mucha et al., 1998; Hogarth et al., 2010).

3.2. Litlamorao tsa lithethefatsi

Joalokaha ho tšohliloe ka holimo, lingoliloeng tse ngata tsa liphoofolo li bontša hore taolo e pheta-phetoang ea lithethefatsi tse hlekefelitsoeng e ka fetola litlamorao. Ho batho, phetoho e ntle ka ho fetesisa e bonoang ka mor'a ho pepesetsoa lithethefatsi khafetsa e bile mamello ea nakoana ho litlamorao tse tlisoang ke lintho tse khothatsang (Brauer et al., 1996) le litlamorao tse nyahamisang tsa opiate le benzodiazepines (Hug, 1972)². Ha ho bapisoa, monyetla oa hore maikutlo a lithethefatsi a ka ba teng bathong o nkuoe e le phehisano le ho feta. Bopaki ba pele bo tsoa liphatlalatsong tse entsoeng Amerika le Japane kamora Ntoa ea Bobeli ea Lefatše nakong ea likoluoa ​​tse matla tsa tlhekefetso ea lithethefatsi tse kang amphetamine. Nalane e khutliselitsoeng nako ena e bontšitse hore ho pepesetsoa litekanyetso tse phahameng tsa amphetamines (hangata 100 mg kapa ho feta) ho ka lebisa matšoao a psychotic, ho kenyelletsa ho bona lipono le ho thetsa (Connell, 1958; Ellinwood, 1967; Griffith et al., 1972; Sato, 1992; Sato et al., 1992). Litlamorao tsena li ka hlahisoa hape maemong a laboratori (Angrist le Gershon, 1970; Bell, 1973). Nako ea nako e lebisang ketsahalong ea psychotic ea pele e fumanoe e fapana pakeng tsa batho, phello e ka amanang le lethal dose, khafetsa ea tšebeliso, ts'ebeliso e mpe ea lintho tse ling le ho ba teng ha mekhoa ea tlokotsi e neng e le teng pele. Ka mokhoa o makatsang, linako tsa ts'ebeliso e mpe ea lithethefatsi li ile tsa lateloa ho batho ba bang ka tšitiso ea nako e telele ea ho hlaha hape ha matšoao a psychotic kamora ho pepesetsoa tekanyetso e tlase haholo ea lithethefatsi (Sato, 1992; Sato et al., 1992).

Le hoja e khahla, litlaleho tse kaholimo ha li fane ka bopaki bo tobileng ba tlhahlobo ea hore ho pepesetsoa lithethefatsi khafetsa ho ka hlahisa maikutlo a kang a liketsahalo ho batho. Bopaki bona bo tlalehiloe haufinyane tjena. Lithutong tse tšeletseng tsa tse supileng tse laoloang tsa laboratori moo barupeluoa ba fumaneng bonyane 20 mg (po) ea d-amphetamine ka thulaganyo e ngoe le e 'ngoe, ho khothaletsa litlamorao tsa matla a lithethefatsi ho ile ha bonoa (Lethathamo 1). Phuputsong ea morao tjena, bopaki ba hore phello ena e ka tla tlasa taolo ea tikoloho le bona bo ile ba bonahala. Bafo ba fumaneng litekanyetso tse peli tsa d-amphetamine ka phapusing e le 'ngoe o tlalehile karabelo e khahlisang ho lethal dose ea bobeli athe ba ileng ba amohela tekanyetso ea bobeli ka phapusing e fapaneng ba bontšitse, haeba ho na le letho, bopaki ba mamello (Bana le de Wit, ka khatiso).

  

Lethathamo 1

Nts'etsopele e thehiloeng ho tekanyetso ea maikutlo e arabelang khafetsa d-amphetamine lithutong tsa batho tse phetseng hantle.

Hoa hlokomeleha hore linako tsa nako ea sensitization- le liketsahalo tsa mamello-li tšoana³. Le ha maikutlo a teng ke ntho e tšoarellang halelele, mohlomong e bile e sa feleng (Robinson le Becker, 1986; Boileau et al., 2006), mamello e lieha ho feta (Vogel et al., 1948; Hug, 1972; Brauer et al., 1996). Ho joalo, sesosa se ka sehloohong sa ts'ebeliso e feteletseng ea lithethefatsi le lefu le bakoang ke bokhoni ba ts'ebeliso ea lithethefatsi e bolela hore e bile le nako e telele haholo kamora hore mamello e felile.Merrall et al., 2010).

3.3. Litlamorao tsa li-cue le li-cue + lithethefatsi litebong tse fapaneng tsa thuto

Likarolong tse ka tlase, re hlahloba litlamorao tsa lithahasello tsa lithethefatsi le litheko le litlhare. Litlamorao tsena li hlahlojoa ka kotloloho lithutong tse phetseng hantle ntle le ho lemalla, lithutong tse kotsing ea ho lemalla, le lithutong tse nang le mathata a tšebeliso ea lithethefatsi. Ho khetholla lipakeng tsa batho bana ho bohlokoa kaha lithethefatsi le lithethefatsi tsa lithethefatsi li hlahisa litlamorao tse fapaneng ho batho ba fapaneng. Kaha litlamorao tsa ho pepesetsoa lithethefatsi tse matla le tse pheta-phetang li ka sebelisana le litšobotsi tse itseng tseo motho a li hlahisang, li ka fana ka leseli linthong tse laolang nts'etsopele le polelo ea boitšoaro bo susumetsang bo lebisitsoeng ho fumana lithethefatsi tsa tlhekefetso le ho ipusa. Ho joalo, joalo ka ha ho hlokometsoe khafetsa, ke ba bang feela ba sebelisang lithethefatsi ba nang le bothata ba tšebeliso ea lithethefatsi (Tsuang et al., 1998; Zinkernagel et al., 2001; Anthony, 2002; Agrawal et al., 2012; Kendler et al., 2012). Lintlha tse fumanoeng li susumetsa tsoelo-pele ea bokhoba ba tahi li kenyelletsa litšobotsi tsa hae (Ayduk et al., 2000; Conrod et al., 2000; Tarter et al., 2003), nalane ea bophelo ba pele (Hyman et al., 2006; Enoke et al., 2010), tloaelo e fetohang ea setso le setsoNutt, 2012), phapang ea motho ka mong ea li-enzyme tse khethehileng tsa lithethefatsi (Ferguson le Tyndale, 2011), le mabaka a mang a eketsanghang ka mekhoa e sa hlakileng. Moelelo oa litlhahiso tsena bakeng sa ho ithuta mekhoa e amanang le tšebeliso ea lithethefatsi le bokhoba ke tlhoko ea ho khetholla le ho tšoaea litlamorao tse ka hlahang ka mokhoa o ikhethileng ka har'a setulo sa batho ba bang (bona le Saunders le Robinson, makasine ona).

4.1. Litlamorao tsa khoele

Ho pepesehela liketsahalo tse amanang le moputso nako le nako ho hlohlelletsa batho ba phetseng hantle (Knutson le Cooper, 2005). Sena se ithutoe ka lintlha tse qaqileng haholo mabapi le moputso oa chelete. Lithutong tsena ho hlahisoa mefuta e mengata ea khothatso. Tsena li kenyelletsa (i) lintlha tse tsebahalang tseo lithuto li seng li ntse li tseba hore li amana le ho ba teng kapa ho se be teng ha meputso, (ii) lintlha tse neng li sa nke lehlakore tseo lithuto li ithutang ka tsona nakong ea thuto, (iii) lintlha tse bonts'ang hore moputso o tla hlahisoa kamora ho emela ho fetisa. kapa kamora ho emisoa ha karabo ea ts'ebetso, le (iv) moputso ka boeona. E 'ngoe le e' ngoe ea likarolo tsena e ka ama boholo ba karabelo ea striatal le hore na e bonoa haholo kahare ho ventral kapa dorsal striatum (O'Doherty et al., 2004; Knutson le Cooper, 2005). Tlhahlobo ea tlhahlobo ea hona joale e mabapi le kamoo boholo ba likarabo tsena tsa tharollo bo anngoeng ke phapang ea motho ka mong le sehlopha.

Ntle le moputso oa chelete, ho tlalehiloe litaba tsa batho ba phetseng hantle ho bontša tšebetso e latelang kamora ho pepesehela litloaelo tse amanang le lijo (Tse nyenyane le al., 2001; Beaver et al., 2006; Hommer et al., Ka khatiso; Demos et al., 2012; Tang et al., 2012), thobalano (Hamann et al., 2004; Cloutier et al., 2008; Demos et al., 2012), le joala (Seo et al., 2011)⁴. Ho na le bopaki ba hore likarabo tsena tsa fMRI tse lekantsoeng le phallo ea mali (CF) e kanna ea ba li tsamaisana le keketseho ea tokollo ea DA (lebokose 1). Mohlala, ho lokolloa ha striatal DA e lekantsoeng lithutong tse phetseng hantle ka positron emission tomography (PET) e ka ikamahanya le ts'ebetso e lekantsoeng ea fMRI (Schott et al., 2008). Habohlokoa le ho feta, bopaki ba tokollo ea DA bo bonoe lithutong tsa batho tse phetseng hantle tse bapalang lipapali tsa video (Koepp et al., 1998) le ho hlahella pepeneneng ho litheko tse pejana tse nang le moputso oa chelete (Zald et al., 2004; Schott et al., 2008; Martin-Soelch et al., 2011; cf, Hakyemez et al., 2008), lijo (Volkow et al., 2002; Tse nyenyane le al., 2003), joala (Yoder et al., 2009) le amphetamine (Boileau et al., 2007).

Boholo ba karabelo e hlahisitsoeng ke DA ea cue e kanna ea fapana ka bonnete bo lebelletsoeng ba hore moputso o tla fumanoa. Mohlala, matsatsing a seng a batho, keketseho e kholo ka ho fetisisa ea ho ts'oaroa ha lisele ea DA e bonoang e bonahala tlasa maemo a ho hloka botsitso haholo (Fiorillo et al., 2003). Bopaki ba morao-rao bo hlahisa monyetla oa hore phello ena ea ho hloka botsitso e ka hlaha ho batho le eona: bakuli ba nang le lefu la Parkinson ba bonts'a karabelo e kholo ea DA-placebo-haeba ba tsebisoa hore monyetla oa ho fumana meriana ea L-DOPA ke 75% ha o bapisoa le 100% (Lidstone et al., 2010)⁵.

4.2. Litholoana tsa litlolo + lithethefatsi

Joalokaha ho bonoa liphoofolong tsa laboratori, ho na le bopaki ba tšebelisano-lipakeng lipakeng tsa lithethefatsi le litheko tse amanang le moputso ka ho fetola e 'ngoe le e' ngoe. Lithutong tse phetseng hantle tsa batho, sena se bonoe ka ho hlaka lithutong tse peli moo litlamorao tsa dopaminergic tsa methylphenidate li ileng tsa matlafatsoa ke ho ba teng hoa litabatabelo tsa mantlha tsa takatso ea lijo (Volkow et al., 2002, 2004). Phuputsong ea pele, e entsoeng lithutong tse sa hlokeng lijo tse nang le phepo e ntle (16-20 h abstinent), motswako oa lethalinyana le tlase la methylphenidate (20 mg, po) le litheko tsa lijo (pono, oloticory, tatso) li hlahisitse kholo e kholo ea striatal DA le tlala e kholo e tlalehiloeng ho feta ea e mong (Volkow et al., 2002). Phapang e le 'ngoe ho DA e lokolla e amanang le tlala ea boits'oaro le takatso ea lijo. Phuputsong ea bobeli, methylphenidate (20 mg, po) e ile ea natefisa litekanyetso tse ntle tsa DA ha feela e entsoe ka mosebetsi o ikhethang oa lipalo moo lithuto li ka fumanang moputso oa chelete. Ha tokollo ea DA e le kholo, lithuto tse khahlisang le ho feta li tlaleha mosebetsi oo e le (Volkow et al., 2004).

Phuputso ea boraro e fane ka tlhahlobo ea pele e hlakileng ea hore na ho laoloa hangata hoa lithethefatsi ho ka lebisa tlhokomelong ea DA bathong (Feie. 1). Lithuto tse phetseng hantle li ile tsa pepesetsoa litekanyetso tse tharo tsa d-amphetamine (0.3 mg / kg, po) lenaneong le leng la matsatsi a mang. Kamora ho phomola ha libeke tse peli, ho ile ha fanoa ka tekanyetso ea bone. Karabelo ea DA ho tekanyetso ena ea bone e ne e le kholo haholo ho feta tekano eo e fanoeng ke lethal dose la pele. Tekanyetso ea bohlano, e fanoe selemo se felletseng hamorao, e hlahisitse phello e kholo le ho feta (Boileau et al., 2006). Haholo-holo, litekanyetso tsohle tsa d-amphetamine e ne e tsamaisoa tikolohong e ts'oanang (lisebelisoa tsa PET), e fana ka sephetho se fumanoeng se lumellana le maikutlo a ikhethang a tikoloho. Le ha thuto ena e sa bonts'a hore na maikutlo a DA a ka be a hlahisitsoe le haeba amphetamine e ka be e entsoe libakeng tse ling, lithuto tse peli tsa morao-rao tse entsoeng ho basebelisi ba lithethefatsi tse sa tšepahaleng li lumellana le tlhahiso ea hore ho ba teng ha khahlano le ho ba teng ha tšusumetso ea lithethefatsi ho ka susumetsa kannete boholo ba likarabo tsa DA tse susumetsoang ke lithethefatsi. Phuputsong ea pele, liphapang tsa motho ka mong tse eketsang koketseha ea koae ka lebaka la DA li hlalositsoe ke nalane ea bophelo ba tšebeliso e mpe ea lithethefatsi seterateng: kholo ea ts'ebeliso ea lithethefatsi e fetileng, e kholo le karabelo ea DA (Cox et al., 2009). Thutong ena, barupeluoa ba ile ba lokisa moriana, ba o laola, 'me ba iphelisa ka mokhoa oo ba tloaetseng ka oona. Ka mantsoe a mang, likhoele tse amanang le koae li ne li le teng ka ho hlakileng 'me li sebelisana le tsona. Ha re bapisa, phuputsong ea bobeli e ts'oanang, basebelisi ba lithethefatsi ba phetseng hantle, ba sa tšepahaleng ba ile ba fuoa tekanyetso e ipatileng ea d-amphetamine. Maemong ana, liphapang tsa ho lokolloa ha DA li ne li amana hantle le tšebeliso ea lithethefatsi: ha kholo ea tšebeliso ea lithethefatsi e le kholo, karabelo ea DA e nyane (Casey et al., 2012). Kaha litlamorao tse ts'oanang li bontšitsoe hantle lithutong tse entsoeng ho liphoofolo tsa maele (Anagnostaras le Robinson, 1996; Anagnostaras et al., 2002; Stewart le Vezina, 1988, 1991; Vezina le Leyton, 2009), moleko o lekang leha e le oa ho nahana ka liphetho tsena ke hore ho ba teng ha ho bapisoa le ho se sebetse hoa litlatsetso tse amanang le lithethefatsi ho fetotse karabelo ho ts'usumetso e sa laoloang ea lithethefatsi. Kahoo, boteng ba mekhoa e amanang le moputso o ikhethang o kanna oa etsa hore karabelo ea dopaminergic e ntlafalitsoeng e qholotsoe ke phetoho ea meriana; ho ba sieo hoa mekhoa e joalo ho ka thibela tlhahiso ea likarabo tsa DA tse ntlafalitsoeng.

  

Feie. 1

Amphetamine-eletso ea maikutlo a DA bathong. Baithuti ba phetseng hantle ba fumane litekanyetso tse hlano tsa d-amphetamine (0.3 mg / kg, po) ha a ntse a robetse ka har'a skena sa PET. Litekanyetso tse tharo tsa pele li ne li fanoa ka letsatsi le leng le le leng la bobeli. Mojaro oa bone o ile oa fuoa ho latela a ...

4.3. Phapang e amanang le lilemo: se boleloang ke ntlafatso

Lingolo tse hlahang li lebisa tlhokomelo ho liphapang tsa ho ts'oaroa ha striatal ho arabela lithetleng tse amanang le meputso lilemong tsa bocha (13-15 ea lilemo li) ka lebaka la batho ba baholo (bacha ba 20s). Mohlala, bacha ba tlalehiloe hore ba bonts'a ts'ebetso e kholo ho feta batho ba baholo ha ba hlahisoa ka khothalletso e bontšang monyetla oa ho arabela chelete (Geier et al., 2010) le karabelo ea ho amohela moputso (Ernst et al., 2005; Galvan et al., 2006). Ho feta moo, har'a bacha, ha ba ba le karabelo e matla lithutong tsena, ba ba le maikutlo a matla le ho feta ka ho batla litšobotsi tsa botho le ho itlaleha nyakallo (Bjork et al., 2008a)⁶. Likarabo tsena tse amanang le lilemo li hlahisitsoe ho tla ikarabella bakeng sa liphapang tsa nts'etsopele ea boitšoaro bo nkang kotsi le ho batla moputso (Spear, 2011; Ernst le Fudge, 2009; Somerville et al., 2010). Ho joalo, ho na le bopaki ba hore litla-morao tsena li na le bonnete. Mohlala, hara baithuti ba phetseng hantle (n = 58), ha kholo ea boko e bokella karabelo litabeng tsa lijo, boima ba lithuto bo eketsehileng bo fumanoeng kamora ho latela likhoeli tse tšeletseng hamorao; ha karabelo e kholo ho lithahasello tsa thobalano e le kholo haholo ho feta thobalano (Demos et al., 2012).

5.1. Litlamorao tsa khoele

Lingolo tse nyane li hlalosa likarabo ho moputso le ho fana ka meputso e amanang le lithuto tse kotsing ea ho ba le mathata a tšebeliso ea lithethefatsi (bona Lisebelisoa tsa 2 'me Le3) .3). Mohlala, ha ho bapisoa le taolo e tlase e kotsi ea bophelo bo botle, likarabo tse kholo tsa boikoetliso li 'nile tsa bonoa lithutong tse kotsing ea lelapa bakeng sa joala ha li etsa Taki ea Papali ea Iowa (Acheson et al., 2009) le ho pepesetsoa monko oa joala (Kareken et al., 2004; Oberlin et al., 2012). Ha ho bapisoa, lithutong moo ho hlahisitsoeng mekhoa ea chelete e sa tloaelehang kapa e sa nke lehlakore, batho ba kotsing e kholo ba bontša likarabo tse nyane ho feta taolo e ntle (Andrews et al., 2011; Schneider et al., 2012; Yau et al., 2012).

  

Lethathamo 2

fMRI BOLD ts'ebetso e matla e bonoang lithutong tsa batho boteng le ho se be teng hoa meputso e amanang le moputso. Batho bao e ne e le batho ba nang le bothata ba ho kenella, kapa ba nang le bothata ba ho lemalla hona joale.

  

Lethathamo 3

PET [¹¹C] karabelo ea papali ea maiketsetso e shebelloang lithutong tsa batho boteng le ho se be teng hoa meputso e amanang le moputso. Batho bao e ne e le batho ba nang le bothata ba ho kenella, kapa ba nang le bothata ba ho lemalla hona joale.

5.2. Litholoana tsa litlolo + lithethefatsi

Ho na le bopaki ba hore litlamorao tsa lithethefatsi le litloaelo tse amanang le lithethefatsi li ka kenella lithutong tse kotsing ea ho lemalla. Libakeng tsa joala tse sa tsitseng tse senang koae, ka mohlala, ho enta joala ho fumanoe ho eketsa karabelo e matla litekong tsa koae (King et al., 2010). Ka lehlakoreng le leng, ho na le bopaki ba hore likotsi li ka eketsa litlamorao tsa lithethefatsi. Lithutong tse kotsing e phahameng ea bokhoba ba litheko, likarabo tsa DA tse tiileng li ile tsa natefeloa ha li bapisoa le litaba tse kotsing e tlase ha ntho eo e kenelletsoa ka mokhoa o tloaelehileng (Setiawan et al., 2010) empa ea fokotseha ha sethethefatsi se fanoa ha ho se na litheko tse amanang le lithethefatsi (Casey et al., 2012). Karabelo e se nang liphoso e bonts'itse mokhoa oa lelapa le phello ea tšebeliso e mpe ea lithethefatsi nakong e fetileng: kholo ea nalane ea bophelo ba tšebeliso ea lithethefatsi, e nyane le karabelo ea DA (Casey et al., 2012). Litlamorao tsa tšebeliso ea malapa le tšebeliso ea lithethefatsi tse fetileng li ne li ikemetse. Sena se bontšitsoe ka litsela tse peli. Taba ea pele, sehlopha se laoloang se ne se kenyellelitsoe ho sebelisa lithethefatsi tse matlafatsang tse sebelisang litekanyetso tse amanang le tšebeliso ea lithethefatsi ho lithuto tse kotsing e kholo empa li se na nalane ea malapa ea mathata a tšebeliso ea lithethefatsi. Lithuto tse kotsing e kholo tse nang le nalane ea malapa ea ts'oaetso ea ts'ebeliso ea lithethefatsi li bonts'itse tokollo e tlase ea DA ho feta ena "kotsi e tlase" ea lithethefatsi e sebelisang sehlopha kapa lithuto tse matlafatsang tsa lithethefatsi. Taba ea bobeli, ho kenyelletsa nalane ea tšebeliso ea lithethefatsi e le phapang e nyarosang ea tlhahlobo ea lipalo ha ea ka ea nyenyefatsa tlatsetso ea nalane ea lelapa. Ka mantsoe a mang, nalane ea tšebeliso ea malapa le lithethefatsi e hlahisitse phello e ts'oanang empa e sebetsa e le bafani ba ikemetseng.

6.1. Litlamorao tsa khoele

Litlhahlobo tse peli tsa morao-rao tse entsoeng morao tjena ka boithaopo li ile tsa fihlela qeto ea hore striatum e lula e ntlafalitsoe ka ho pepesetsoa litheko tse amanang le lithethefatsi lithutong tse kopana le mekhoa ea tlhahlobo ea tšebeliso ea lithethefatsi.s (Chase et al., 2011; Tang et al., 2012). Tlikarabo tsa hese li tsitsitse (Schacht et al., 2011) hape e phahame, ha e bapisoa le batho ba sa sebeliseng lithethefatsi hampe. Mohlala, ha ho bapisoa le ba noang bobebe sechabeng, ho tlalehiloe lino tse tahang hore li bonts'a ts'ebetso e kholo ea ts'ebetso ea joala. (Vollstädt-Klein et al., 2010; Ihssen et al., 2011): Ha ho e-ba le karabelo e kholo, e tla ba le ho feta le ho feta ha lehloeo (Vollstädt-Klein et al., 2011) mme le matšoao a ho noella a noang haholo le ho feta ke a tebileng le ho feta (Vollstädt-Klein et al., 2010). Ka mokhoa o ts'oanang, lithutong tse ngata tsa batho ba noang joala haholo ba 326, ke moo kholo ea ts'ebetso ea joala e khothalletsang ts'ebetso ho feta, le ho feta ha mathata a tšebeliso ea lino tse tahang. (Claus et al., 2011)⁷.

Ho na le bopaki ba hore ts'ebetso e kholo ea ts'ebetso ea ts'ebetso e kanna ea tsamaea le keketseho ea tokollo ea DA. Liphetoho tsa boleng bo tlamang ba PET ba matšoao a hlakileng a tokollo ea DA e bonngoe kamora ho pepesetsoa litloaelo tse amanang le cocaine (Volkow et al., 2006; Wong et al., 2006; Fotros et al., 2012) le heroin (Zijlstra et al., 2008). Ha kholo e lokollotsoeng ea DA e thehiloeng tsebong, e ba le takatso e matla le ho feta (Volkow et al., 2006; Wong et al., 2006; Zijlstra et al., 2008; Fotros et al., 2012).

Joalo ka ha ho bonoa bathong ba bang, ho boetse ho na le bopaki ho ba nang le mathata a tšebeliso ea lithethefatsi hore ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso e fosahetse ho e-na le ho khothaletsoa ha mekhoa e amanang le bokhoba ba ho lemalla e se teng. Ha ho bapisoa le ho laola lihlooho, ts'ebetso ea meketjana e senotsoeng e etsahala ka lebaka la litšoantšo tsa lijo tse lemalloang ke joala (Ihssen et al., 2011) le ho batho ba sa tsubeng kapa ba sa nke lehlakore (Peters et al., 2011) le lino tse tahang (Hlakola et al., 2007; Beck et al., 2009; cf Bjork et al., 2008b).

6.2. Litholoana tsa litlolo + lithethefatsi

Lithutong tse nang le mathata a tšebeliso ea lithethefatsi, likarabo tse susumetsang tse susumetsang tse tlisoang ke lithethefatsi tsa DA li tlalehiloe li fokotsehile haholo ha li bapisoa le tse bonoang taolong e phetseng hantle (Volkow et al., 1997, 2007; Martinez et al., 2005, 2007, 2011, 2012; Wang et al., 2012; Thompson et al., Ka khatiso; cf Urban et al., 2012;; bona Lisebelisoa tsa 2 'me Le3) .3). Phokotso ena e kanna ea mpefatsa setšoantšo sa bongaka. Ha karabelo ea DA e le tlase, ketso e matla ea ho itaola ea lithethefatsi e shebelloang ka linako tse fapaneng moo lithethefatsi le mekhoa e amanang le tsona li neng li fumaneha (Martinez et al., 2007) le ho hobe le ho feta sephetho sa bongaka se latelang (Martinez et al., 2011; Wang et al., 2012).

Haholoholo, leha ho le joalo, lithutong tsohle tse ka holimo, ho lokolloa ha DA ho ile ha lekanngoa ha ho se na litokelo tsa lithethefatsi. Sena se hlahisa monyetla oa hore, leha e se e le morao haholo ho lemalla, likarabo tse fokotsoang tsa DA li bonts'itse, bonyane karolo e 'ngoe, ekaba ho ba sieo ha ts'usumetso ea lithethefatsi tse hlokahalang ho thusa ho fana ka karabelo e ntlafalitsoeng ea dopaminergic kapa boteng ba tšusumetso ea lithethefatsi e sa lefelloeng e ka sitisang. karabelo ena (Vezina le Leyton, 2009). Re tseba phuputso e le 'ngoe feela e lekileng tlhahlobo ena ka mokhoa o hlakileng. Thutong ena, lithuto tse itšetlehileng ka koae li ile tsa fanoa ka amphetamine lithupelong tsa liteko le kapa ntle le lithethefatsi tsa lithethefatsi tse teng (livideo tsa batšoantšisi tse tsamaisang tšebeliso ea lithethefatsi). Ha ho bapisoa le seboka sa liteko se entsoeng ntle le litlhare tsa lithethefatsi, boteng ba litheko tsa lithethefatsi bo hlile bo fokotsitse karabelo ea DA ho feta (Volkow et al., 2008), phello e fapaneng le e lebisang ho se boletsoeng esale pele ke bangoli. Ho bona sena, leha ho le joalo ho eketsa bopaki ba hore mekhoa ea tikoloho e ka fetola litlamorao tsa phephetso ea lithethefatsi. Ho feta moo, joalo ka ha bangoli ba hlokometse, kaha litafole li sa ka tsa bolela esale pele hore lithethefatsi li tla fumaneha, ho kanna ha ba le phoso ea ho profeta e amanang le ho theoha ha tokollo ea DA (Schultz et al., 1997; Yoder et al., 2009). Tlhaloso ena, leha ho le joalo, e ntse e nahanisisa ho fihlela lithuto tse ngata li lekola tlhahiso eo ho tlalehiloe. Lisosa tse ling tse ka lebisang ho fokotseheng ha tlhahiso ea DA e theotsoeng lithethefatsing ho batho ba itšetlehileng ka lithethefatsi li kenyelletsa litlamorao tsa neurotoxic tsa ts'ebeliso e matla ea lithethefatsi (Little et al., 2003, 2009) le mekhoa ea likotsi e ka bang teng pele (Casey et al., 2012). Meeli ea mekhoa le eona e ka sebetsa. Joalokaha ho hlokometsoe ke Narendran le Martinez (2008), karabelo ea dopaminergic e fokotsitsoeng e ka boela ea bontša ho fokotseha ha D2 kapa D3 DA receptor, ho fokotseha ha karolelano ea D3 ho li-receptor tsa D2 DA, kapa keketseho ea litekanyetso tsa motheo tsa DA. Liteko tsa pele tsa ho sebetsana le a mang a menyetla ena, leha ho le joalo, li fana ka maikutlo a hore batho ba lemaletseng lithethefatsi tsa lithethefatsi, ba lekoa tlas'a maemo a tšoanang le lithutong tse kaholimo, ba na le maemo a tlase ho feta a DA (Martinez et al., 2009) hape e phahame ho fapana le maemo a tlase a D3 DA receptor bonyane libakeng tsa D3 DA receptor rich brain tse kang midbrain le globus pallidus (Boileau et al., 2012).

Tlhahlobo ena e ile ea khoneha ka lithuso tse tsoang ho Canadian Institutes for Health Research (MOP-36429 le MOP-64426, ML) le National Institutes of Health (DA09397, PV). Re nehelana ka maikutlo ana ho Ann Kelley. Matla a hae a se nang meeli, lerato la hae la bophelo, le tsebo e tebileng le cheseho bakeng sa mosebetsi oa hae li ile tsa mo etsa mohlala ho rona bohle.

¹Stimuli e amanang le opiates le ethanol li hlahisa motsoako o rarahaneng oa litlamorao tse kang tsa lithethefatsi le tse tlisoang ke lithethefatsi (Wikler, 1973; Eikelboom le Stewart, 1982; Stewart et al., 1984; O'Brien et al., 1998; Stewart, 2004). Bakeng sa lipuisano tsa hore na mebuso e haelloang e ka eketsa matla a susumetsang joang le boikemelo ba mekhoa e metle ea boithabiso, bona Toate (1986), Hutcheson et al. (2001), 'me Berridge (2012). Karolo ea libaka tsa dysphoric ts'ebetsong ea ts'ebetso ea ts'ebeliso ea matla a matlafatso e boetse e hlahisitsoe ho maikutlo a ts'ebetso ea bahanyetsi mabapi le tšebeliso ea lithethefatsi (Koob le Le Moal, 1997). Mebuso ena hangata e bonoa hang kamora ho pepesetsoa lithethefatsi ka nako e telele le ha li sa khahlisoa empa ho khothalelitsoe ho khothala ha tsona ka maemo a netefalitsoeng ho kenya letsoho ho khutlisetseng hape (Siegel, 1979).

²Mamello ea pharmacological e bolela ho fokotseha ha potency ea lithethefatsi kapa katleho (ke hore, phello e matla) ka ho pepesetsoa khafetsa. Ka lehlakoreng le leng, sensitization, e boetse e bitsoang reverse-tolerance, e bua ka keketseho ea potency ea lithethefatsi kapa ho sebetsa hantle (ka linako tse ling e hlahisoa e le karabelo ea bohlokoa ho tekanyetso e sa sebetseng). Maemo ana ka bobeli a hlalosa ho lemoha ho susumetsang; ka bo bona ha ba hokahanye mochine.

³Ntle le lithuto tse fapaneng tsa nako ea ho mamellana le ho susumetsa maikutlo, ho ka ba le phokotso ea nakoana hoba e 'ngoe le e' ngoe ea liphetoho tsena e ka hlaha ka nako e ts'oanang lits'ebetsong tse fapaneng, joalo ka, ka mohlala, tse laolang ho phefumoloha khahlano le tse susumetsang tse matlafatsang.

⁴Ts'ebetso ea likhoebo e ka etsahala le ka mor'a tahlehelo ea chelete (Kühn et al., 2011). Thutong ena, bankakarolo e ne e le libapali tsa video tse lilemo li 154 tse lilemo li 14. Ba bapalang khafetsa (> 9 h / beke) ba bonts'itse karabelo e kholo ea tahlehelo ea chelete joalo ka ha e lekantsoe ke imaging e sebetsang ea matla a khoheli (fMRI) ha e bapisoa le libapali tse sa sebetseng khafetsa. Ha e le hantle, tšusumetso e bontšang tahlehelo e bohlokoa haholo ho bapalami. Har'a bapalami ba litsebi, ts'ebetso e kholo ea ts'ebetso e boetse e bolela esale pele ho tsamaea ka potlako, phello e kanna ea bonts'a bokhoni bo ntlafalitsoeng ba ho sebelisa mekhoa ea ho atamela (Wan et al., 2011).

⁵Maemo ana a ho fana ka moputso o sa tsitsang a etsisa karolo ea mantlha ea papali ea chelete. Ho feta moo, ka litoeba, ho fana ka moputso o sa tsitsang ho ka eketsa matla a tšusumetso ea cue (Robinson le Berridge, 2012) mme e lebise ho boits'oaro ba boits'oaro phephetsong ea amphetamine (Singer le al., 2012).

⁶Ho boetse ho na le maemo ha likarabo tse tlase tsa bophelo bo botle li bonoa, leha litholoana tse tlalehiloeng ho fihlela joale li rarahane mme lintlha tse khethollang li lula li sa hlaka. Mohlala, likarabo tse tlase tsa bonyatsi li hlokometsoe ho bacha le batho ba baholo ba neng ba hlahloba katse pele ba ka e arabela (Geier et al., 2010). Ka mokhoa o ts'oanang, ha bacha ba bonts'a likarabo tse kholo ho feta ho batho ba baholo meputso.Ernst et al., 2005; Galvan et al., 2006), phaello ea karabelo e matla pakeng tsa meputso e meholo e bapisoang le e nyane ($ 5 bapisoa le lisente tsa 20) ho tlalehiloe e le tse fokolang (Bjork et al., 2004). Tlhaloso e ngoe ke hore bacha ba bonts'a likarabo tse kholo ho litheko le ho putsa likarolo tse tsamaeang ka matsoho empa likarabo tse nyane ho mekhoa e meholo e hlokang ho hlahlojoa.

⁷Boithuto ba morao-rao bo bontša kamoo ho eketseha le ho fokotseha ha mesebetsi ea boikoetliso ho ka fapana kateng le boits'oaro ba ho batla lithethefatsi le ho lemalla. Mokuli ea lemaletseng joala haholo o ile a amohela linako tse ling tsa ho hlohlona ka matla a khoheli (TMS) ea "dorsal anterior cingulate cortex". Ts'ebetso ea boko ba tikoloho le litakatso tsa ho ipolelisa li lekantsoe ka nako e ts'oanang. Joalokaha ho ne ho lebelletsoe, takatso ea takatso ea joala e amanang le joala e ne e amahanngoa le ts'ebetso e eketsehileng ea li-nucleus accumbens. Ka mokhoa o makatsang, TMS e fokolitse takatso le ts'usumetso e matla ea li-nucleus tse hlahisitsoeng, litlamorao tse bolokiloeng likhoeli tse tharo (De Ridder et al., 2011).

⁸Mathata a amanang le ho ja a arolelana likarolo tse fapaneng le mathata a ts'ebeliso ea lithethefatsi le ho becha ha methapo ea kutlo. Ho batla meputso e litšila, ho sitisoa ke tšusumetso e mpe, le litlatsetso tse ling tse fapaneng hangata ke tšebeliso e mpe ea boitšoaro. Ho nona ho boetse ho khothalelitsoe ho ba mokhoa oa bokhoba ba boits'oaro, leha mohopolo ona o phehisana khang haholo. Bakeng sa puisano ea litaba tsena, bona Ziauddeen et al. (2012).

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