Meputso ea tlhaho, Meriana ea ho se Phekolehe ha Meriana, le Lithethefatsi Tse se Nang Meriana (2011)

Neuropharmacology. 2011 December; 61(7): 1109-1122. E hatisitsoe Inthaneteng 2011 April 1. doi:  10.1016 / j.neuropharm.2011.03.010

PMCID: PMC3139704  NIHMSID: NIHMS287046
Moetso oa khatiso oa ho qetela oa mohatisi o fumaneha ho Neuropharmacology
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inahaneloang

Tho na le tekanyo e phahameng ea ho kena-kenana pakeng tsa libaka tsa bokooa tse amehang ho pheliseng meputso ea tlhaho le lithethefatsi tsa tlhekefetso Lithethefatsi tse seng "lithethefatsi" kapa "boitšoaro" li se li ngotsoe ka ho eketsehileng tleliniking, 'me ho kula ho akarelletsa mesebetsi e qobelloang e kang ho reka, ho ja, ho ikoetlisa, boitšoaro ba ho kopanela liphate le ho becha.

Joaloka ho lemalla lithethefatsi, lithethefatsi tseo e seng tsa lithethefatsi tse bonahatsoang matšoao, ho kenyeletsa ho labalabela, ho laola boitšoaro, ho mamella, ho tlohela, le ho khutlela morao. Liphetoho tsena ka boitšoaro li bontša hore polasetiki e ka 'na ea etsahala libakeng tsa bokooa tse amanang le lithethefatsi tsa lithethefatsi.

Tlhahlobisong ena, ke akaretsa lintlha tse bontšang hore ho pepesehela meputso e seng ea lithethefatsi ho ka fetola polasetiki ea neural libakeng tsa boko bo amehang ke lithethefatsi tsa tlhekefetso. Phuputso e fana ka maikutlo a hore ho na le ho tšoana ho hongata pakeng tsa lefu lena la pelo le bakoang ke meputso ea tlhaho le lithethefatsi le hore, ho itšetlehile ka moputso, ho pepesehela makhetlo a tlhaho ho ka 'na ha etsa hore motho a se ke a hlola a khothaletsoa kapa a hanyetsa boitšoaro bo hlephileng.

Keywords: ho batla, ho lemala, ho susumetsa, ho matlafatsa, boitšoaro bo lemalloang, botlasetiki

1. Selelekela

Hona joale ho na le lipapali tse ngata tsa thelevishene tse ngotseng batho ba qobellang ho kopanela boitšoarong boo ho ka boleloang hore bo tloaelehile, empa ba etse joalo ka mokhoa o mpe haholo bophelong ba bona le ba malapa a bona. PBatho ba nang le lintho tse ka nkoa e le "tse seng lithethefatsi" kapa "boitšoaro bo hlephileng" bo ntse bo e-ba boitsebiso bo eketsehileng tleliniking, 'me matšoao a kenyelletsa mesebetsi e qobelloang e kang ho reka, ho ja, ho ikoetlisa, boitšoaro ba thobalano, papali ea chelete le lipapali tsa video. (Holden, 2001; Grant et al a, 2006a). Le hoja lihlooho tsa lipapali tsa thelevishene li ka 'na tsa bonahala e le liketsahalo tse feteletseng le tse sa tloaelehang, mefuta ena ea mathata e tloaelehile haholo. Litekanyetso tsa ho ata ha batho United States li hakantsoe ho 1-2% bakeng sa papali ea papali ea chelete (Welte et al a, 2001), 5% bakeng sa boitšoaro bo bobe ba ho kopanela liphate (Schaffer le Zimmerman, 1990), 2.8% bakeng sa bothata ba ho ja lijo-thollo (Hudson et al a, 2007) le 5-6% bakeng sa theko e tlamang (Mnyama, 2007).

Le hoja DSM-IV e amohela mathata ana le mekhoa e meng ea "ho lemalla", hona joale ha e hlalosoe e le ho lemalla boitšoaro. Sena se ka ba ka lebaka la hore DSM-IV e qoba nako ea ho lemalla lithethefatsi esita leha e bua ka lithethefatsi tsa tlhekefetso, ho e-na le ho khetha "mantsoe a hlekefetsang" le "ho itšetleha". Nakong ea DSM-IV, ho lemalla boitšoaro ho itšetlehile ka likarolo tse kang "mathata a amanang le lithethefatsi", "mathata a ho ja" le "mathata a ho laola maikutlo a se nang likarolo tse ling" (Holden, 2001; Potenza, 2006). Haufinyane tjena, ho bile le mokhoa oa ho nahana ka lithethefatsi tsena tseo e seng tsa lithethefatsi tse lokelang ho tšoana haholo le tšebeliso e mpe ea lithethefatsi le botšepehi (Rogers le Smit, 2000; Wang et al a, 2004b; Volkow le Bohlale, 2005; Grant et al a., 2006a; Petry, 2006; Teegarden le Bale, 2007; Deadwyler, 2010; Grant et al a, 2010). Ha e le hantle, lithethefatsi tseo e seng tsa lithethefatsi li lumellana le tlhaloso ea khale ea ho lemala e akarelletsang ho kopanela boitšoarong ho sa tsotellehe liphello tse mpe tse mpe (Holden, 2001; Hyman et al a, 2006). Ketsahalo ena e 'nile ea ananeloa ke litsebi tsa kelello,' me tlhahiso ea tlhahlobo ea DSM-5 e kenyelletsa mofuta oa Tlhekefetso le Boits'oaro bo Amanang ((APA), 2010). Ka hare ho sehlopha sena, sehlopha sa Boits'oaro ba Boits'oaro se 'nile sa hlophisoa, se kenyeletsang papali ea papali ea chelete le ho lemalla ho lemalla marang-rang ((APA), 2010; O'Brien, 2010; Tao et al a, 2010).

Joaloka lithethefatsi tse ngata, lithethefatsi tseo e seng tsa lithethefatsi li bonahatsa mekhoa e tšoanang ea kelello le boitšoaro ho kenyeletsa ho labalabela, ho laola boitšoaro, ho mamella, ho tlosoa, le litekanyetso tse phahameng tsa ho khutlela morao (Letšoao, 1990; Lejoyeux et al a, 2000; Mokhatlo oa Sechaba oa Tlhekefetso ea Lithethefatsi (NIDA) et al a, 2002; Potenza, 2006). Litsela tse teng pakeng tsa lithethefatsi le meputso e seng ea lithethefatsi li ka boela tsa bonoa ka physiologically. Liphuputso tse sebelisoang ke batho ba nang le litsebi tsa mahlale li bontšitse hore papali ea chelete (Breiter et al a, 2001), ho reka (Knutson et al a, 2007), orgasm (Komisaruk et al a, 2004), bapala lipapali tsa video (Koepp et al a, 1998; Hoeft et al a, 2008) le ho bona lijo tse monate (Wang et al a, 2004a) etsa hore libaka tse ngata tsa boko bo tšoane (ke hore, mesocorticolimbic system le amygdala e atolositsoeng) e le lithethefatsi tsa tlhekefetso (Volkow et al a, 2004). Sehlooho sena se tla hlahloba bopaki ba mehlolo ea hore tlhaho ea tlhaho ea matla ea tlhaho e ka lebisa ho polasetiki boitšoarong le ho itšehla thajana hoo hangata ho hopotsang liphetoho tse bonoang ka mor'a ho pepesa lithethefatsi tsa tlhekefetso, haholo-holo kelello ea maikutlo. Bakeng sa tlhahlobo ea joale, polasetiki e tla hlalosoa ka mokhoa o pharaletseng e le ho feto-fetoha leha e le efe ka boitšoaro kapa mosebetsi oa mahlaseli, se tšoanangho sebelisoa lentsoe leo qalong le hlalositsoeng ke William James (James, 1890). Synaptic plasticity e tla bua ka phetoho e lekaneng le synapse, e tloaelehileng e lekantsoe ka mekhoa ea electrophysiological (mohlala, liphetoho tsa lenane la AMPA / NMDA). Plastiki e tla sebelisoa ka tsela e fetotsoeng ea synthetic (synaptic kapa intracellular) e lekanyelitsoeng ke likokoana-hloko ka phapang pakeng tsa mechine e fetisisang kapa e hlahisoang ke basal, kapa ea ho tsamaisa kapa ka phetoho ea nako e telele ea leha e le efe ea limolek'hule tsena. Plastiki ea boitšoaro e tla bua ka mekhoa e metle ea boitšoaro (mehlala e 'maloa e tšohloa Karolong ea 1.1).

Li-circulars tsa Neural tse kenyelletsang ho bokellana ha meputso ea tlhaho li nahanoa hore li "tlatlapuoa" ka lithethefatsi tsa tlhekefetso, 'me ho nahanoa hore polasetiki lipakeng tsena e ikarabella bakeng sa polasetiki ea boitšoaro (e leng ho eketseha ho batla lithethefatsi le takatso)Kelley le Berridge, 2002; Aston-Jones le Harris, 2004; Kalivas le O'Brien, 2008; Wanat et al a, 2009b). Bopaki ba ho tlatlapuoa hona ho bonahala mefuteng e 'maloa ea polasetiki libakeng tsa boko tse tsejoang ho ama tšusumetso, ts'ebetso ea batsamaisi, le moputso oa ts'ebetso (Kalivas le O'Brien, 2008; Thomas et al a, 2008; Frascella et al a, 2010; Koob le Volkow, 2010; Pierce le Vanderschuren, 2010; Russo et al a, 2010). Mehlala ea liphoofolo e re file tlhaloso ea liphetoho tse tebileng tseo tsamaiso ea lithethefatsi tsa tlhekefetso e ka fanang ka tsona. Liphetoho li fapana le ho fetoha ha mekhoa ea methapo ea meriana ho fetola cell morphology le liphetoho mesebetsing ea transcriptional (Robinson le Kolb, 2004; Kalivas et al a, 2009; Russo et al a., 2010). Lihlopha tse 'maloa li boetse li tlalehile lithethefatsi tsa tlhekefetso tse fetolang polasetiki ea synaptic libakeng tse ka sehloohong tsa boko bo kenyelletsoeng ho lemalla lithethefatsi (bakeng sa ho hlahloba, bona (Winder et al a, 2002; Kauer le Malenka, 2007; Luscher le Bellone, 2008; Thomas et al a., 2008). Boholo ba li-neuroadaptations tse hlalosoang bo bile libakeng tsa mesocorticolimbic tsamaiso le amygdala e atolositsoeng (E nyenyane et al a, 2006; Schramm-Sapyta et al a, 2006; Kauer le Malenka, 2007; Kalivas et al a., 2009; Koob le Volkow, 2010; Russo et al a., 2010; Mameli et al a, 2011).

Ho itšetlehile ka mesebetsi e tsebahalang ea libaka tsena ho tsamaisa maikutlo, ho sebetsana le meputso ea tlhaho, le boitšoaro bo susumelletsang, ho lumeloa haholo hore polasetiki ena e na le liphetoho tse mpe tsa boitšoaro bo amanang le ho lemala. Ho batho, tse ling tsa liphetoho tsena li kenyeletsa ho etsa liqeto tse sa khoneheng, ho fokotsa monate ho tsoa meputsong ea tlhaho (anhedonia), le ho lakatsa (Majewska, 1996; Bechara, 2005; O'Brien, 2005). Mekhoeng ea liphoofolo, mekhoa ena e fetotsoeng e ka ithutoa ka mehato ea boipheliso ho latela histori ea tsamaiso ea lithethefatsi, 'me libaka tse tšoanang tsa boko bo nahanngoa hore li ka rarolla mehato ena (Markou le Koob, 1991; Shaham et al a, 2003; Bevins le Besheer, 2005; Winstanley, 2007). Litekanyo tsena li fana ka motheo oa tlhahlobo ea lits'ebetso tsa pharmacotherapies tse ka thusang ho phekola lithethefatsi.

Bopaki ba morao tjena bo fana ka maikutlo a hore lithethefatsi tse seng tsa lithethefatsi li ka lebisa lits'etsing tse ling tse tšoanang le tse tlalehiloeng ka nako e telele ea tšebeliso ea lithethefatsi. Le hoja boholo ba mehlala ena ea polasetiki e tsoa lithutong tsa liphoofolo, litlaleho li boetse li kenyeletsa mehlala e tsoang lithutong tsa batho.

Tlhahlobisong ena, re tla hlahloba khopolo ea hore litlhohonolofatso tsa tlhaho li khone ho fokotsa polasetiki ea meriana le boitšoaro ka litsela tse ts'oanang le ho lemalla lithethefatsi. Tlhahlobo ea morao-rao ea ketsahalo ena e ka re fa tsebo ea boitšoaro bo bobe ba ho itšoara le ho ts'ehetsa "pharmacotherapies" e ka thusang bobeli ba lithethefatsi le lithethefatsi tse se nang lithethefatsi (Frascella et al a., 2010).

1.1. Likhopolo tsa polasetiki ea boitšoaro le lithethefatsi

Tšimong ea ho lemalla lithethefatsi, ho na le likhopolo tse 'maloa tse hlalosang kamoo polasetiki ea neural le boitšoaro e tlatsetsa kateng ho lemaletseng lithethefatsi. Khopolo e 'ngoe ke ea ho khothatsa-ho matlafatsa (Robinson le Berridge, 1993, 2001, 2008). Aho ea ka khopolo ena, batho ba nang le tšoaetso ea letho, ho pepeseha ha lithethefatsi ka makhetlo-khetlo ho lebisa tlhokomelong (ho mamellana ka ho feletseng) ea lintho tse susumetsang-tse susumelletsang lithethefatsi le lintlha tse amanang le lithethefatsi. Phetoho ena ke bonyane e arohanngoa ke ho lokolloa ha nucleus accumbens (NAc) dopamine (DA) e latelang ho pepesehela lits'oants'o tse amanang le lithethefatsi. Ho itšoara hantle, sena se amahanngoa le ho eketseha ha takatso le lithethefatsi tsa lithethefatsi ha motho a pepesehela lits'ebeletso tse amanang le ho noa (e leng pipe ea crack). Mehlaleng ea liphoofolo, ho susumelletseha ho susumetsa batho ho ka etsa hore ho be le mekhoa e metle ka ho lekanyetsa boitšoaro ba ho batla lithethefatsi ho arabela lipakeng tse kopanetsoeng le tsamaiso ea lithethefatsi (Robinson le Berridge, 2008). Ho hlokomeloa ha li-locomotor ho boetse ho etsahala ka makhetlo a 'maloa a lithethefatsi tsa tlhekefetso' me e ka 'na ea e-ba mohato o sa tobang oa ho khothaletsa ho khothaletsa batho,Robinson le Berridge, 2008). Ka ho hlakileng, mekhoa ea ho hlohlelletsa e ka boela ea fetolela pakeng tsa meputso ea lithethefatsi le e seng ea lithethefatsi (Fiorino le Phillips, 1999; Avena le Hoebel, 2003b; Robinson le Berridge, 2008). Ho batho, karolo ea dopamine e bontšang ka ts'ebetso ea ts'oaetso ea ts'oaetso e sa tsoa totobatsoa ke ho shebella dopamine dysregulation syndrome ho bakuli ba bang ba jang lithethefatsi tsa dopaminergic. Ts'oaetso ena e khetholloa ka keketseho e bakoang ke meriana (kapa ho qobella) ho ba le meputso e seng ea lithethefatsi e kang ho becha, ho reka kapa ho kopanela liphate (Evans et al a, 2006; Aiken, 2007; Lader, 2008).

Khopolo e 'ngoe e' nileng ea etsoa ho hlalosa hore na polasetiki e amanang le lithethefatsi e tlatsetsa joang ho lemaletseng joala ke khopolo ea ts'oaetso ea bahanyetsi (Solomone, 1980; Koob et al a, 1989; Koob le Le Moal, 2008). Ka bokhutšoanyane, khopolo ena ea tšusumetso e bolela hore ho na le mekhoa e 'meli e sebetsanoang nakong ea liphihlelo tse pheta-phetoang: ea pele e kenyelletsa mahlaseli kapa hedonic habituation, ts'ebetso ea bobeli ke ho khaotsa ho tsuba (Solomon le Corbit, 1974). Mohlala o fanoeng ke Solomone o amana le tšebeliso ea opiate, moo ho mamelloa ho hlahisitsoeng ke liphello tse bohloko tsa hedonic ka mor'a ho ts'oaetsanoa ha lithethefatsi khafetsa, 'me matšoao a mabe a ho tlohela ho tla hlaha e leng se tla susumetsa tšebeliso ea lithethefatsi (ho tsosolosa hampe) (Solomone, 1980). Phetolelo ena ea pele ea khopolo e ne e qapiloe qalong ho hlalosa boits'oaro bo fetotsoeng ka ho ipapisa le meputso e mabeli ea lithethefatsi le e se nang lithethefatsi (bakeng sa ho hlahloba, bona (Solomone, 1980)). Ho atolosoa ha khopolo ea ts'ebetso ea bahanyetsi ke mohlala oa allostatic oa bokooa bo susumelletsang boko (Koob le Le Moal, 2001, 2008). Bka mokhoa o fapaneng, mohlala ona o kenyelletsa likhopolo tse hanyetsang tsa moputso le meputso e khahlanong le moputso, athe ho qetela ho kenyeletsa ho hlōleha ho khutlela ntlong ea homeostatic, e lebisang ho amehang hampe le ho fokotsa moputso oa tlhaho, e leng se eketsang tšusumetso ea ho lokisa boemo bona (Koob le Le Moal, 2008). Bopaki ba seuroplasticity e laolang boemo bona bo fetotsoeng bo fokolang bo tsoa liphuthong tse 'maloa, ho kenyeletsa dBasal e tebileng ea NAC DA e latelang ho tsuba lithethefatsi ka likhoto (Weiss et al a, 1992), e fokotsehe li-receptor tse hlaselang tsa D2 ka striatum le ho ba le lino tse tahang le bo-heroin ba hlokang boits'oaro (Volkow et al a., 2004; Zijlstra et al a, 2008), le ho eketseha ho tsitsitseng habonolo (ICSS) moeli nakong ea ho tlosoa ha cocaine ho tlohela likhoto (Markou le Koob, 1991). Ntle le liphetoho ho bonts'oa ha DA, maqheka a boima a maholo a boetse a ngolisoa. Mohlala o motle ka ho fetisisa o eketsa pontšo ea CRF ho hypothalamus, nucleus e bohareng ea amygdala, le nucleus ea bethe ea stria terminalis ka mor'a ho tlosoa ha lithethefatsi tse ngata tsa tlhekefetso (Koob le Le Moal, 2008).

Tlhaloso ea boraro e hlalosang li-neuroplasticity e tlatsetsang ho lemala ke ho hiroa ha methapo ea methapo ea methapo ea meriana ho pholletsa le lithethefatsi tse ngata. (Everitt et al a, 2001; Everitt et al a, 2008; Graybiel, 2008; Ostlund le Balleine, 2008; Pierce le Vanderschuren, 2010). Ka mohlala, litlhapi tse seng tsa batho tsa ho itlhahisa ho bontšoa ha cocaine li fetola metabolism ea tsoekere le litekanyetso tsa dopamine D2 receptor le motlakase oa dopamine o amang tšenyo ea pele ea ventral, empa ka ho eketseha ha lihlahisoa ho eketsa ho ea holimo (Porrino et al a, 2004a; Porrino et al a, 2004b). Keketseho ena "e fana ka maikutlo a hore likarolo tsa boits'oaro bo kantle ho tšusumetso ea k'hok'heine li ba nyane le tse nyane ka nako e ntseng e eketseha ea ho pepesehela ts'ebeliso ea lithethefatsi e hlahisang taolo ea koae likarolong tsohle tsa bophelo ba sethethefatsi" (Porrino et al a., 2004a). Plastiki ena e ntseng e tsoela pele ho tloha ventral ho ea ho dorsal striatum e tšoana le lingoliloeng tsa khale mabapi le phetoho ho tloha ho sepheo-ho ea ho ithuta ka tloaelo (Balleine le Dickinson, 1998) 'me o na le correlate ea anatomical e tšehetsang bokhoni ba ho atolosa thuto e thehiloeng ke moputso ho kenya letsoho butle-butle lintlha tse ling tsa ho itšehla thajana ea striatum (Moahi et al a, 2000).

2. Moputso oa lijo

Mohlomong moputso o moholo ka ho fetisisa oa thuto ke oa lijo. Lijo ke moputso oa quintessential ho lithuto tse ngata tsa rodent 'me li sebelisitsoe e le ts'ebeliso ea mekhoa e kang mesebetsi ea boipheliso, litlhahlobo tsa litsela, thuto ea maze, lipapali tsa papali ea chelete le boemo ba sebaka (Skinner, 1930; Ettenberg le Camp, 1986; Kandel et al a, 2000; Kelley, 2004; Tzschentke, 2007; Zeeb et al a, 2009). Likokoanyana tse neng li koetliselitsoe ho ts'epa sepahla hore li fumane li-intravenous self-administration of lithethefatsi, lijo tse ntle haholo tse kang tsoekere le saccharin li ile tsa bontšoa ho fokotsa boinotši ba cocaine le heroine (Carroll et al a, 1989; Lenoir le Ahmed, 2008), Le li-reinforcers tsa tlhaho li 'nile tsa bontšoa hore li-cocaine tse tsamaisoang ka ntle li itšetlehile ka bongata bo ikhethang ba likhoto tse lekiloeng (Lenoir et al a, 2007; Cantin et al a, 2010). Sena se ka bolela hore lijo tse monate li na le phaello e phahameng ho feta cocaine, esita le liphoofolong tse nang le histori e pharaletseng ea ho noa lithethefatsi (Cantin et al a., 2010). Le hoja ts'ebetso ena e ka bonahala e le bofokoli mehleng ea kajeno ea mefuta e meng ea ho lemalla k'hok'heine, likhomo tse seng kae li khetha cocaine ho tsoekere kapa saccharin (Cantin et al a., 2010). Ho ka khoneha hore liphoofolo tsena li ka 'na tsa emela batho ba "tlokotsing," e leng sa bohlokoa haholo ho boemo ba motho. Pono ena e hlahlojoa haholoanyane Puisanong (Karolo ea 6.1).

Mosebetsi o tsoang li laboratori tse ngata o bontšitse mehlala ea polasetiki ka lipotoloho tse amanang le moputso ka mor'a ho fumana lijo tse monate. Ho ikamahanya le mekhoa e metle ka morao historing ea ho ja lijo tse monate ho tšoantšitsoe le tse hlokometsoeng ka mor'a lithethefatsi tsa tlhekefetso, e leng ho susumelletsa bo-rasaense ba 'maloa ho etsa tlhahiso ea hore ho senyeha ha lijo lijo ho ka tšoana le ho lemalla (Hoebel et al a, 1989; Le Magnen, 1990; Wang et al a., 2004b; Volkow le Bohlale, 2005; Davis le Carter, 2009; Nair et al a, 2009a; Corsica le Pelchat, 2010). Laboratori ea Bartley Hoebel e na le boitsebiso bo bongata bo bontšang bo-pula-maliboho ba boitšoaro ka mor'a histori ea ho fumana tsoekere, e leng se entseng hore eena le basebetsi-'moho le eena ba etse tlhahiso ea hore tšebeliso ea tsoekere e finyellang litekanyetso tsa ho lemala (Li-oats et al a, 2008). Pono ena e tšehetsoa ke taba ea hore mehlala e mengata ea polasetiki e bonoang ka mor'a ho hlahisa lithethefatsi khafetsa e boetse e hlokomeloa ka mor'a hore ho be le monyetla oa ho fumana tsoekere feela, empa le mafura. Mefuta e sa tšoaneng ea lijo tse monate e 'nile ea sebelisetsoa ho ithuta polasetiki, ho akarelletsa le tsoekere e phahameng, mafura a mangata le lijo tsa "Bophirimela" kapa "lijo tsa ho ja lijo" ho leka ho bapisa mefuta e fapaneng ea ho ja batho.

Pontšo e 'ngoe ea polasetiki e bakoang ke lijo ke hore "ho fokotsa sefahleho"Ea mosebetsi oa likhoebo pakeng tsa tsoekere le li-psychostimulants tsa tsoekere li ka etsoa ka tatellano ea phekolo (Avena le Hoebel, 2003b, a; Gosnell, 2005). Ho fokotsa tšoaetso ea mokokotlo ke ntho e tsotehang e hlahang ho latela tlhahiso ea pele ho mohlokomeli oa tikoloho kapa oa setsi sa meriana (e kang khatello ea kelello kapa psychostimulant, ka ho latellana) e hlahisang karabo e ntlafetseng (ka tloaelo ea khoebo) ho moemeli o fapaneng oa tikoloho kapa oa meriana (Antelman et al a, 1980; O'Donnell le Miczek, 1980; Kalivas et al a, 1986; Vezina et al a, 1989). Mekhoa ea ho fana ka ts'oaetso e amang li-psycho-stimulants e akarelletsa ma-neurons a DA, le ho khothaletsoa ho hoholo ho lumeloa hore ho tsoa mekhoeng e tloaelehileng ea liketso pakeng tsa mekhoa e mabeli (Antelman et al a., 1980; Herman et al a, 1984; Kalivas le Stewart, 1991; Eena le Nestler, 1995).

Ho khothaletsoa ho hoholo ho li-psycho-stimulants ho boetse ho bonoa liphoofolong tse fepa tsoekere e phahameng / lijo tse mafura nakong ea nako ea phomolo le ea morao-rao.s (Shalev et al a, 2010). Ho fumana hore na ho pepeseha ho ja lijo tse mafura ho ka fetola liphello tse "thabisang" (ho matlafatsa) ho sebelisa lithethefatsi hampe, Davis et al. liphoofolo tse lekiloeng li fepa lijo tse ngata tse mafura bakeng sa ho fetola kutloisiso ea amphetamine ho sebelisa sebaka sa boemo bo khethehileng (CPP) paradigm (Davis et al a, 2008). Ka mohlala ona, liphoofolo li lumelloa pele ho hlahloba lisebelisoa tse ngata tsa kamoreng (pele ho tlhahlobo) moo kamore e 'ngoe le e' ngoe e nang le litšoantšo tse sa bonahaleng tse bonts'ang, tse tactile, le tse fapaneng. Nakong ea likopano, liphoofolo li koaletsoe ka kamoreng e 'ngoe' me li kopane le moputso (mohlala, ente ea amphetamine kapa lijo ka kamoreng). Mesebetsi ena e pheta-pheta ebile e kenngoa ka nako ho na le likarolo tsa boemo bo kenyang kamoreng e 'ngoe ea lisebelisoa le boemo ba ho laola (mohlala, jenito ea saline kapa lijo). Karolo ea teko e etsoa tlas'a maemo a tšoanang le a pele ho tlhahlobo le CPP e bonts'oa ha liphoofolo li bontša khetho ea bohlokoa bakeng sa kamore e neng e kopanngoa le moputso oa lithethefatsi kapa oa lithethefatsi. Davis et al. ba fumane hore litoe tse ngata tse fepehileng li ile tsa hlōleha ho hlahisa boemo ba sebaka se ratang sebaka sa amphetamine, e leng ho fana ka maikutlo a ho lumellana ho hoholo pakeng tsa ho kenngoa ha lijo tse mafura le boemo bo matlafatsoang ke amphetamine (Davis et al a., 2008).

Ntle le lipulasetiki tsa boitšoaro, ho ja ka mokhoa o feteletseng oa mefuta e itseng ea lijo ho boetse ho amana le polasetiki ea 'mele. Ka ho khetheha, pontšo ea dopamine le opioid e bonahala eka e ka fetoha liphetoho ka morao ho fihlella ka hare ho tsoekere e phahameng kapa lijo tse mafura haholo. Nakong ea NAc, likarolo tsa lijo tsa nakoana le ho fumana tsoekere le chow li eketsa D1 le D3 tse amohelang lijo (ebang ke mRNA kapa protheine), ha ho ntse ho fokotseha methapo ea D2 ho NAc le dorsal striatum (Colantuoni et al a., 2001; Bello et al a, 2002; Spangler et al a, 2004). Phello ena e ile ea boela ea boleloa ka ho atolosoa ka mokhoa o atolositsoeng oa lijo tse mafura haholo likokoanyana, le ho fokotseha ka ho fetisisa ho D2 ho hlahang likhoto tse boima ka ho fetisisa (Johnson le Kenny, 2010). Tsena mekhoa e metsoako ea li-receptor tse hlahelletseng le tse hlaselang li tšoana le tse bonoang ke litoeba tse fuoang cocaine kapa morphine hangata (Lichelete et al a, 1993; Unterwald et al a, 1994a; Spangler et al a, 2003; Conrad et al a, 2010). Ho feta moo, ho fokotseha ha li-receptor tse hlaselang D2 ho boetse ho bonahala ho basebelisi ba batho ba psychostimulant le lino tse tahang (Volkow et al a, 1990; Volkow et al a, 1993; Volkow et al a, 1996; Zijlstra et al a., 2008), le ho batho ba baholo ba nang le bobebe, moo litaba tsa D2 li fumanoang li sa tsamaisane hantle le moelelo oa 'mele oa' mele (Wang et al a., 2004b). Pontšo ea li-opioid e ts'oaetsoang e boetse e ameha haholo ka lijo (Gosnell le Levine, 2009). Ho tsoekere e sa tloaelehang kapa lijo tse monate / mafura li eketsa ho kopanya li-opioid receptor ho NAc, cingulate cortex, hippocampus le locus coeruleus (Colantuoni et al a., 2001) le ho fokotsa enkephalin mRNA ka NAc (Kelley et al a, 2003; Spangler et al a., 2004). K'hemik'hale ea lipulasetiki ka mahlaseli a mahlo a DA le ho bonts'oa ha li-opioid li boetse li bontšitsoe hore li hlaha ho bana ba litoeba tsa basali ba fepa lijo tse ngata tsa mafura nakong ea bokhachane (Vucetic et al a, 2010). Bana bana ba phahame ka ho fetisa dopamine (DAT) sebakeng sa ventral tegmental (VTA), NAc le prefrontal cortex (PFC), le ho eketsa preproenkephalin le li-receptor tse nang le opioid ka NAc le PFC (Vucetic et al a., 2010). Ho thahasellisang ke hore liphetoho tsena li ne li amahanngoa le phetoho ea epigenetic (hypomethylation) ea likarolo tse khothalletsang liprotheine kaofela.

Liphello tsamaisong ea corticotropin-release (CRF) ka mafura a phahameng a mafura / a phahameng a tsoekere a boetse a hopotsa ba fanoang ke lithethefatsi tsa tlhekefetso. CRF ho amygdala e ile ea eketseha ka mor'a ho tlosoa ha lihora tsa 24 lijong tse mafura haholo, ha liphoofolo tse bolokiloeng lijong tsena li ne li sa fetola amygdala CRF (Teegarden le Bale, 2007). Ka mehlala ea li-preclinical, sena se fetotsoe ponts'o ea CRF se nahanoa hore se tla nyenyefatsa mekhoa e matla ea ho matlafatsa le ho eketsa "li-binge" ho noa ethanol (Koob, 2010). Ka lebaka leo, bahanyetsi ba CRF ba ntse ba etsoa tlhahiso ea phekolo ea joala le lithethefatsi tsa lithethefatsi (Sarnyai et al a, 2001; Koob et al a, 2009; Lowery le Thiele, 2010). Ho itšetlehile ka lintlha tsena, li-antagonists tsa CRF le tsona li ka lebelloa hore li thuse batho ba bang hore ba se ke ba tlohela ho ja lijo tse tsoekere tse phahameng haholo nakong ea phetoho ea phepo e nepahetseng.

Lintlha tsa phetolelo ke sehlopha se seng sa molek'hule se amehang ho rarollang liphello tse tšoarellang tsa lithethefatsi tsa tlhekefetso ka ho toba ka liphatsa tsa lefutso (McClung le Nestler, 2008). E le ho tšehetsa khopolo ea hore lijo li khone ho etsa hore polasetiki ea mongobo e fokotsehe, ho na le mabaka a mangata a ho ngolisa a fetotsoeng ke lijo. Nac phospho-CREB e fokotsoe lihora tsa 24 ka mor'a ho tlohela ho tsoa lijong tse phahameng tsa lik'habohaedreite le lihora tse peli tsa 24 le beke ea 1 ka mor'a ho tlohela ho ja lijo tse mafura, athe fosB ea delta ea delta e eketseha nakong ea ho fumana lijo tse mafura haholo (Teegarden le Bale, 2007) kapa sucrose (Wallace et al a, 2008). Nakong ea NAc, fokotseha phospho-CREB e boetse e bonoa nakong ea ho tlohela amphetamine le morphine (McDaid et al a, 2006a; McDaid et al a, 2006b), le FosB ea delta e boetse e eketseha ka mor'a ho tlosoa ha lithethefatsi tsena hammoho le cocaine, nicotine, ethanol le phencyclidine (McClung et al a, 2004; McDaid et al a., 2006a; McDaid et al a., 2006b). Ho ts'oana le ts'ebetsong ea bona e ts'oanelang ho eketsa boitšoaro ba ho batla lithethefatsi, lits'elello tsena li ka boela tsa ama boitšoaro bo latelang ba ho fepa, kaha tlhaloso e fetisisang ea delta FosB ka sepheo sa ventral e eketsa tšusumetso ea ho fumana lijo (Olausson et al a, 2006) le sucrose (Wallace et al a., 2008).

Synaptic plasticity e potolohileng e amanang le lithethefatsi e amantsoe le Ka vivo tsamaiso ea lithethefatsi tse ngata tsa tlhekefetso. Li-VTA, lihlopha tse 'maloa tsa ho lemalla lithethefatsi, empa e seng lithethefatsi tse sebelisang meriana ea boloetse ba meriana ho etsa hore polasetiki ea synaptic (Etsahale et al a, 2003; Stuber et al a, 2008a; Wanat et al a, 2009a). Ho fihlela joale, ho na le boitsebiso bo fokolang ka ho toba bo lekanyang liphello tsa lijo ka syntaptic plasticity tse nang le li-neurocircuitry tse amanang le lithethefatsi. Mokhoa o sebetsang o amanang le lijo (chow kapa sucrose pellets) o ile oa eketseha tumellano ea AMPA / NMDA sebakeng sa ventral ho fihlela matsatsi a supileng ka mor'a koetliso (Chen et al a, 2008a). Ha cocaine e ne e ikarabella, phello e ile ea nka likhoeli tse tharo, 'me phello ena ha ea ka ea bonoa ka ho tsamaisoa ha cocaine (Chen et al a., 2008a). Nako e nyenyane ea EPSP VTA e ile ea boela ea eketseha ho fihlela likhoeli tse tharo ka mor'a k'hok'heine ea boipheliso, 'me ho fihlela libeke tse tharo tse latelang sucrose (empa e se khetho) ho itlhophisa, ho fana ka maikutlo a hore pontšo ea glutamatergic e matlafatsoa pele ho nako le ka mor'a-synaptically (Chen et al a., 2008a).

Litlaleho tsena li bontša hore mehato e meng ea synaptic plasticity mokhoeng ona oa mesolimbic (mohlala, ratios ea AMPA / NMDA) e ka amahanngoa le thuto ea takatso ea lijo ka kakaretso. Sena se tšehetsoa ke 'nete ea hore thuto ea Pavlovian e amanang le lijo e le moputso oa VTA LTP nakong ea ho fumana (letsatsi la 3 la boemo bo botle) ​​(Stuber et al a, 2008b). Le hoja bopaki ba polasetiki bo ne bo hlokomeloa letsatsing la 3, e ne e le sieo matsatsi a mabeli hamorao, e fana ka maikutlo a hore boipuso bo ikemetseng bo lebisa ho lipulasetiki tse tšoarellang ka har'a lipotoloho tsena (Stuber et al a., 2008b). Hona ho bonahala eka ho bile joalo le bakeng sa polasetiki e amanang le k'hok'heine ea boipheliso, kaha liphahlasetiki tse entsoeng ka bongata ba cocaine tse se nang phetoho le VTA li boetse li phela nakoana (Borgland et al a, 2004; Chen et al a., 2008a). Leha ho le joalo, tlhahlobo ea lithuto tsena tse sebetsang ha e fane ka lebaka la hore ho atolosoa ha lijo tse monate ho ka lebisa ho nako e telele ea syntaptic plastiki. Nakong ea lipatlisiso tsa maemo a tloaelehileng a sebetsang, liphoofolo li lumelloa ho fumana moputso o fokolang oa lijo ho feta nakong ea ho feptjoa mahala kapa ho finyelloa. Lipatlisiso tsa nakong e tlang li tla lokela ho etsoa ho fumana hore na liphello tsa ho fumana monyetla oa ho fumana lijo tse natefisang haholo ka syntaptic plasticity.

3. Moputso oa thobalano

Ho kopanela liphate ke moputso oo, joaloka lijo, e leng oa bohlokoa bakeng sa ho phela ha mofuta o itseng. Joaloka lijo le lithethefatsi tse 'maloa tsa tlhekefetso, boitšoaro bo bobe ba ho kopanela liphate bo phahamisa mahlaseli a DA (Meisel et al a, 1993; Mermelstein le Becker, 1995). Hape ke boitšoaro bo lekantsoeng ka mekhoa ea ho matlafatsa boleng ba basebetsi (Lebōpo le Jordan, 1956; Caggiula le Hoebel, 1966; Everitt et al a, 1987; Crawford et al a, 1993) le mekhoa ea boemo ba maemo (Paredes le Vazquez, 1999; Martinez le Paredes, 2001; Tzschentke, 2007). Bafo ba batho kalafo ea boitšoaro bo qobelloang ba ho kopanela liphate (ho arolelanoa e le "Bothata ba ho kopanela liphate ho seng joalo ho hlalositsoe" DSM-IV) ba na le matšoao a mangata a amanang le ho lemalla lithethefatsi, ho kenyeletsa ho eketseha, ho tlohela, bothata ba ho emisa kapa ho fokotsa ts'ebetso, liphello (Orford, 1978; Khauta le Heffner, 1998; Garcia le Thibaut, 2010). Ha re nahana ka mekhoa ena e feto-fetohang boitšoarong, hoa utloahala ho nahana ka li-neuroadaptations tse hlahelang ka har'a mesocorticolimbic circuitry. Joalokaha ho bonoa ka ho pepeseha ha tsoekere khafetsa, ho kopana khafetsa ka likamano tsa botona le botšehali linthong tse tona tse tšositsoeng ka amphetamine ka tekanyo ea ho lokisa (Pitchers et al a, 2010a). Ho kopana liphate ka makhetlo a mangata ho boetse ho eketsa ts'ebeliso ea li-sucrose le ho khetha sebaka sa lebelo le tlase la amphetamine, e leng ho fana ka maikutlo a ho khothalelana ho pholletsa le phihlelo ea thobalano le moputso oa lithethefatsi (Wallace et al a., 2008; Pitchers et al a, 2010b). E boetse e tšoana le liphello tse matlafatsang tsa lithethefatsi tsa tlhekefetso (Segal le Mandell, 1974; Robinson le Becker, 1982; Robinson le Berridge, 2008), ho pheta-pheta likamano tsa thobalano ho matlafatsa karabo ea NAC DA nakong ea kamano ea thobalano hamorao (Kohlert le Meisel, 1999). Ho fokotsa moeli ho boetse ho na le likarolo tse peli, kaha histori ea tsamaiso ea amphetamine e thusa boitšoaro ba thobalano le ho eketsa keketseho e amanang le NAC DA (Fiorino le Phillips, 1999).

AHo hlalosoa bakeng sa moputso oa lijo, phihlelo ea thobalano e ka boela ea lebisa ho ts'ebetsong ea li-cascades tse amanang le polasetiki. FosB ea delta facto ea motlakase e eketsehile ho NAc, PFC, dorsal striatum le VTA ho latela boitšoaro bo hlephileng ba ho kopanela liphate (Wallace et al a., 2008; Pitchers et al a., 2010b). Keketseho ea tlhaho ea FosB ea delta kapa tšoaetso e matla ea kokoana-hloko ea FosB ea delta ka hare ho NAc e tsamaisa mokhoa oa ho kopanela liphate, 'me NAC e thibetsoe ke delta FosB e thibela boitšoaro bona (Li-Hedges et al a, 2009; Pitchers et al a., 2010b). Ho feta moo, ho ba le tšoaetso e matla ea kokoana-hloko ea FosB ea delta ho eketsa boemo ba sebaka seo ho khetholloang ho sona tikolohong e nang le phihlelo ea thobalano (Li-Hedges et al a., 2009).

The MAP kinase e bontšang tsela ke tsela e 'ngoe e amanang le polasetiki e sebetsanang le phihlelo ea ho kopanela liphate khafetsa (Bradley et al a, 2005). KeBasali ba nang le phihlelo ea ho kopanela liphate, ho kopanela liphate ho lebisitse ho PERK2 e phahameng ho NAc (Meisel le Mullins, 2006). Ho eketseha ha NAC pERK ho bakoa ke lithethefatsi tse 'maloa tsa tlhekefetso, empa eseng ka lithethefatsi tse sa sebeliseng lithethefatsi, ho fana ka maikutlo a hore NAC ERK ts'ebetso e ka amahanngoa le polasetiki e amanang le lithethefatsi (Valjent et al a, 2004). Ho feta moo, phuputso ea morao tjena e fumane hore pERK e ne e bakoa ke ho kopanela liphate ka li-neurons tse tšoanang tsa NAC, basolateral amygdala, le li-anteior cingulate cortex tseo pele li neng li nkoa ke methamphetamine (Frohmader et al a, 2010). Khetho ena e khethehileng e fana ka maikutlo a hore ts'ebetsong ena ea ho hlahisa sebaka sa NAC le libaka tse ling tsa mesocorticolimbic e ka lebisa ka ho toba ho polasetiki e khothalletsang boitšoaro ba nakong e tlang (Girault et al a, 2007).

Mekhoa ea methapo ea methapo ea mesocorticolimbic e boetse e fetotsoe ka mor'a boiphihlelo ba thobalano. Pitchers le basebetsi-'moho haufinyane ba tlalehile ho eketseha ha li-dendrites le li-spend dintritic ka hare ho NAc ka likhoto nakong ea "ho tlohela" ho tsoa thobalanong (Pitchers et al a., 2010a). To phaella ka litlhaloso tse ling tse bontšang hore boiphihlelo ba thobalano bo ka fetola morpholoji oa dendritic ka tsela e ts'oanang le ho pepesa lithethefatsi khafetsa (Fiorino le Kolb, 2003; Robinson le Kolb, 2004; Meisel le Mullins, 2006).

4. Meputso oa ho ikoetlisa

Ho fihlella ka lebili la ho ikoetlisa ho sebetsa joaloka motlakase lireng tsa laboratory (Belke le Heyman, 1994; Belke le Dunlop, 1998; Lett et al a, 2000). Joaloka lithethefatsi tsa tlhekefetso le litlhohonolofatso tse ling tsa tlhaho, ho ikoetlisa ka litoeba ho amahanngoa le ho eketseha ha DA ho bontša ka NAC le striatum (Ho lokolotsoe le Yamamoto, 1985; Hattori et al a, 1994). Ho ikoetlisa ho boetse ho phahamisa boko le mafura a mali a li-opioid tse mamellang batho le litoeba (Christie le Chesher, 1982; Janal et al a, 1984; Schwarz le Kindermann, 1992; Asahina et al a, 2003). Sepheo se seng sa li-opioids ke sesebelisoa sa opiate receptor, karoloana ea lithethefatsi tsa opiate tsa tlhekefetso tse kang heroin le morphine. Ts'ebetso ena e boetse e bonahala e atolosoa likarabong tsa boitšoaro ho lithethefatsi tsa tlhekefetso. Ho fapana le meputso ea tlhaho eo ho buuoang ka eona ho fihlela joale, liphuputso tse ngata li fumane hore ho ikoetlisa ho ikoetlisa ho thibela liphello tsa lithethefatsi tsa tlhekefetso. Ka mohlala, ho itaola ha morphine, ethanol le cocaine kaofela ho fokotseha ka mor'a ho ikoetlisa (Cosgrove et al a, 2002; Smith et al a, 2008; Ehringer et al a, 2009; Hosseini et al a, 2009). Ho ikoetlisetsa boiphihlelo ho thibela CPP ho MDMA le cocaine le ho fokotsa ho eketseha ha MDMA ho NAc DA (Chen et al a, 2008b; Thanos et al a, 2010). Ho ikoetlisa pele ho koetliso ea boipheliso e ne e boetse e khona ho fokotsa ho batla lithethefatsi le ho tsosolosa, le hoja thutong ena ho itlhokomela ha cocaine ha hoa ameha (Zlebnik et al a, 2010). Phuputsong e tšoanang, cocaine e batlang le ho tsosolosa ts'ebetsong e ile ea fokotsoa ka likhoto tse neng li sebelisoa nakong ea ho itlosa lithethefatsi (Lynch et al a, 2010). Kel liphoofolo tse nang le histori ea boiphihlelo ba likoloi, ho tlosoa ha likooa ho lebisa ho tlohelang lithethefatsi-joalo ka matšoao a kenyeletsang, ho eketseha ho tšoenyeha le ho hlekefetsoa, ​​le ho khoneha ho tlosoa ke naloxonel (Hoffmann et al a, 1987; Kanarek et al a, 2009).

Ho phaella litabeng tsa boitšoaro bo fetotsoeng ho lithethefatsi tsa tlhekefetso, ho na le mapolesa a nang le methapo ea mali e bontšitsoeng ke ho eketseha ha dynorphin ho striatum le NAc ka mor'a hore e sebetse, ntho e hlollang e boetse e bonoa ke batho ba lemaletseng cocaine le liphoofolong ka mor'a ho tsamaisoa ke cocaine kapa ethanol (Lindholm et al a, 2000; Werme et al a, 2000; Wee le Koob, 2010). Hape ho hopotsa likokoana-hloko tse amanang le polasetiki ea neural, mochine oa motlakase oa delta FosB o susumelitsoe ho NAc ea liphoofolo tse nang le phihlelo ea likoloi (Werme et al a, 2002). Liphetoho tsena li ka 'na tsa e-ba tlas'a boemo ba "ho tlosoa" ha ho etsoa ka morao ho tlosoa ho kena ha likoloi liphoofolong tse nang le phihlelo ea pele (Hoffmann et al a., 1987; Kanarek et al a., 2009). Ka lehlakoreng le leng, ho ikoetlisa nakong ea ho ipholla lithethefatsi ho boetse ho amana le ho fokotseha ha ts'ebetso e tsosolositsoeng ea ERK ho PFC (Lynch et al a., 2010). Ena ke sepheo sa bohlokoa haholo se nahanang ka karolo ea ERK likarolong tse ngata tsa addiction (Valjent et al a., 2004; Lu et al a, 2006; Girault et al a., 2007) le ho fumana hore ts'ebetso ea ERK ka har'a PFC e amahanngoa le ho kenyelletsoa ha takatso ea lithethefatsi (Koya et al a, 2009). Matšoao a li-striatal a dopamine D2 receptor a boetse a tlalehoa hore a tla eketseha ka mor'a ho ikoetlisa (MacRae et al a, 1987; Foley le nama, 2008), phello e fapaneng le eo e hlokometsoeng ka mor'a ho iponahatsa ka kelello ea psychostimulant ka litoeba, litlhapi le batho (Volkow et al a., 1990; Nara et al a, 2002; Conrad et al a., 2010). Ho ka khoneha hore liphetoho tsena li ka tlatsetsa tšusumetsong e "sireletsang" ea ho ikoetlisa mabapi le tšebeliso e mpe ea lithethefatsi / lithethefatsi. Tšehetso bakeng sa khopolo ena e tsoa liphuputsong tse boletsoeng pejana karolong ena e bontšang ho fokotseha ha lithethefatsi tsa boipheliso, ho batla le ho tsosolosa liphoofolo tse lumelloa ho ikoetlisa. Ho boetse ho na le tšehetso ea hore boikoetliso bo ka 'na ba "hlōlisana" le ho itšireletsa ka lithethefatsi, ha lebili le sebetsang le fokotsa phepelo ea amphetamine ha bobeli ba matlafatsang ba fumaneha ka nako e tšoanang (Kanarek et al a, 1995).

Ho ikoetlisa ho boetse ho na le liphello ka har'a hippocampus, moo e susumetsang polasetiki (e bonahatsoang ho LTP e phahameng le thuto e ntlafetseng ea sebaka) le ho eketsa lefu la neurogenis le polelo ea liphatsa tse ngata tse amanang le polasetiki (Kanarek et al a., 1995; van Praag et al a, 1999; Gomez-Pinilla et al a, 2002; Molteni et al a, 2002). Ho fokotseha ha hippocampal neurogenis ho 'nile ha amahanngoa le mekhoa ea ho tepella maikutlo joaloka lithuto tsa maqheka (Duman et al a, 1999; Sahay le Hen, 2007), 'me e lumellana le bokhoni ba ho eketsa lefu la hippocampal neurogenisis, ho ikoetlisa ho bontšitsoe hore ho na le phello e tebileng ea ho imeloa kelellong mokhoeng o tepeletseng oa likhoto (Bjornebekk et al a, 2006), le ho ntlafatsa matšoao a tepeletseng ho bakuli ba batho (Ernst et al a, 2006). Ho na le kamano e sa tsoa tlalehoa pakeng tsa ho hatelloa ha hippocampal neurogenis le ho eketseha ha li-cocaine ho noa le ho batla mekhoa e metleng (Noonan et al a, 2010) hammoho le bopaki bo fetileng ba hore ho pepeseha khatello ea kelello (phekolo e fokotsang hippocampal neurogenesis), ho eketsa ho noa lithethefatsi (Covington le Miczek, 2005), ke habohlokoa ho nahana ka liphello tsa boikoetliso mosebetsing oa hippocampal ho phaella ho tse sebetsang ka mesolimbic. Hobane boikoetliso bo lebisa ho polasetiki maemong a mabeli a tsamaeang le ho tepella maikutlo (e leng hippocampal) le liphutheho tse amanang le ho batla lithethefatsi (e leng maonolimbic system), ho thata ho fumana hore na ho na le liphello life tse tobileng tsa "lithethefatsi tse khahlanong le lithethefatsi" tsa boikoetliso.

Tumellanong le liphello tsa boikoetliso litabeng tsa lithethefatsi, ho boetse ho na le bopaki ba hore ho matha ho ka fokotsa khetho bakeng sa li-reinforcers tsa tlhaho. Tlas'a maemo a ho finyella lijo tse fokolang, likhoto tse nang le phihlelo ea ho khanna li tla khaotsa ho ja ho fihlela lefung (Routtenberg le Kuznesof, 1967; Routtenberg, 1968). Ketsahalo ena e fetisisang e hlokomeloa feela ha nako ea lijo e fihlella ka nako e tsoelang pele ho fihlella lebili, le hoja e ka fana ka maikutlo a hore ho ipeha kotsing ea boikoetliso ho ka fokotsa tšusumetso ka tsela e akaretsang bakeng sa lithethefatsi le ba sa sebeliseng lithethefatsi. Tlhahlobo ea ho qetela ea liphello tsa boikoetliso ke hore lebili le tsamaeang ka hare ho phoofolo ea liphoofolo le ka sebetsa joaloka mokhoa oa ho ntlafatsa tikoloho. Le ha ho le thata ho arohana ka ho feletseng le litlhoko tsa tikoloho ho tsoa boitsing ba 'mele (EE ho hlokometse liphoofolo ho ikoetlisa haholo), liphello tsa dissociable tsa EE le ho ikoetlisa li tlalehiloe (van Praag et al a., 1999; Olson et al a, 2006).

5. Tšusumetso e hlollang / e ts'oanelang maikutlo / Phaello ea tikoloho

Litšisinyeho tsa morao-rao, tšusumetso ea maikutlo, le ho ntlafatsa maemo a mangata li matlafatsa liphoofolo, ho akarelletsa le litoeba (Van de Weerd et al a, 1998; Besheer et al a, 1999; Li-Bevins le Bardo, 1999; Mellen le Sevenich MacPhee, 2001; Dommett et al a, 2005; Kaine et al a, 2006; Olsen le Winder, 2009). Mehaho e machaba, tšusumetso e utloahalang, le ho ntlafatsa tikoloho (EE) kaofela li bontšitsoe ho etsa hore tsamaiso ea DA ea mahlo (Chiodo et al a, 1980; Horvitz et al a, 1997; Rebec et al a, 1997a; Rebec et al a, 1997b; Wood le Rebec, 2004; Dommett et al a., 2005; Segovia et al a, 2010), ho fana ka maikutlo a hore ho na le lithethefatsi tse potolohang. Ho batho ba bangata, boikutlo le ho batla lintho tse ncha li 'nile tsa amahanngoa le ho ba le tšusumetso, ho noa, le ho tiea ha tšebeliso e mpe ea lithethefatsi (Cloninger, 1987; kelly et al a, 2006); bakeng sa ho hlahloba, bona (Zuckerman, 1986). Li-rodents, ho arabela lichabeng tse ncha li boetse li amana le litebello tsa lithethefatsi tse latelang (Piazza et al a, 1989; Kaine et al a, 2005; Meyer et al a, 2010), ho fana ka maikutlo a hore tsena tse peli tsa phenotypes covary. Ka lebaka la lintlha tsena le litsebi tsa tšoaetso ea mali, ho nahanoa hore e kopana le mesocorticolimbic circuitry e sebetsanang le karabo le lithethefatsi tsa tlhekefetso (Rebec et al a., 1997a; Rebec et al a., 1997b; Bardo le Dwoskin, 2004). Matšeliso a utloahalang (haholo-holo a bonahalang le a hlokang ho etsa lintho tse itseng) a 'nile a ithutoa bakeng sa thepa ea bona ea ho matlafatsa (Marx et al a, 1955; Stewart, 1960; Kaine et al a., 2006; Liu et al a, 2007; Olsen le Winder, 2010), 'me re sa tsoa bontša hore ho kenngoa ha dopaminergic le glutamatergic ho bonts'a mekhoa ea ho matlafatsa lintho tse sa tšoaneng (Olsen le Winder, 2009; Olsen et al a, 2010). Plastiki e latela khanya e sa tloaelehang kapa e sa utloahaleng ka mekhahlelo eo ho ke keng ha e-ba le eona e fokolang, le hoja ho na le bopaki bo pharaletseng bakeng sa polasetiki ea neural ka mor'a ts'ebetso e matla kapa ho lahleheloa ke lisebelisoa tsa maikutlo (Kaas, 1991; Rauschecker, 1999; Ntlheng et al a, 2005; Smith et al a, 2009). Leha ho le joalo, ho na le letlotlo la lintlha tse mabapi le polasetiki ea neural e amanang le bolulo tikolohong e ntlafalitsoeng (e akarelletsang likarolo tsa lihlooho tse ling tseo ho buisanoang ka tsona, tse akarelletsang mokhoa o tsitsitseng le ho ikoetlisa; bakeng sa litlhaloso tse ling tse tebileng, bona (Kolb le Whishaw, 1998; van Praag et al a, 2000a; Nithianantharajah le Hannan, 2006)). Khopolo e tsebahalang ea Hebb ea ho ithuta e susumelitsoe ke liphetho tseo a li fumaneng tse bonts'ang hore likhoto tse lutseng tikolohong e ntlafalitsoeng (ntlong ea hae) li sebetsa hantle mesebetsing ea ho ithuta ho feta balekane ba litšila ba lulang laboratoring (Hebb, 1947). Liphuputso tse latelang li fumane liphetoho tse khōlō boima ba boko, angiogenesis, neurogenesis, gliogenesis, le sebopeho sa dendritic ho arabela ho ntlafatso ea tikoloho (EE) (Bennett et al a, 1969; Greenough le Chang, 1989; Kolb le Whishaw, 1998; van Praag et al a, 2000b). Litaba tsa morao-rao tse tsoang liphuputsong tsa microarray li bontšitse hore EE matlo a etsa hore ho bontšoe liphatsa tsa lefutso tse amanang le polasetiki ea NMDA e itšetlehileng ka eona le ho se sireletsehe ha pelo (Rampon et al a, 2000). Sehlopha se ts'oanang se fumane hore ho ipapisa le tikoloho ea EE bakeng sa lihora tsa 3 feela (e leng ho ipapisa le maikutlo a mangata a libuka) ho ne ho e-na le liphello tse tšoanang, ho eketsa maikutlo a liphatsa tsa lefutso litseleng tse amanang le neuritogenesis le plasticity (Rampon et al a., 2000).

Joaloka ho ikoetlisa, moputso oa lipolotiki o susumelitsoeng ke EE o bonahala o fokotsa kutloisiso ea lithethefatsi tsa tlhekefetso 'me e ka fana ka "phantotype e sireletsang" khahlanong le ho nka lithethefatsi (Litepisi le Bardo, 2009; Thiel et al a, 2009; Solinas et al a, 2010; Thiel et al a, 2011). Ha li bapisoa le liphoofolo tse futsanehileng, EE e hlahisitse ho ema ka ho lekaneng moeeng oa karohano ea ho lokisa lisebelisoa ka morphine, hammoho le ho hlokomoloha mokhoa oa ho hlohlelletsa batho ba nang le morphine le amphetamine (Bardo et al a, 1995; Bardo et al a, 1997). Tloaelo e tšoanang e ile ea hlokomeloa ka mor'a phekolo ea psychostimulant, moo EE e ileng ea sitisa mofuthu oa ho sebelisa le ho khothaletsa tlhahiso ea bokoali le ho fokotseha k'hok'heine ho itlhophisa le ho batla boitšoaro (le hoja EE e eketsehile cocaine CPP) (Green et al a, 2003; Green et al a, 2010). Hoa thahasellisa hore ebe EE ha ea ka ea baka phapang pakeng tsa NAC kapa ts'oaetso ea DA e hlaselang kapa ka ho fumana li-opiate receptor libakeng tse 'maloa tsa mesocorticolimbic tsa lipatlisiso (Bardo et al a., 1997), le hoja Segovia le basebetsi-'moho le bona ba ile ba fumana keketseho ea Basal le K+-Stimed NAC DA e latelang EE (Segovia et al a., 2010). Ho PFC (empa e seng NAc kapa striatum), litsi tsa EE li fumanoe li fokolitse matla a ho tsamaisa dopamine (Zhu et al a, 2005). Keketseho e hlahisoang ke pontšo ea prefrontal DA e ka ba le tšusumetso e matla ea ho etsa mesebetsi, ho se ts'oanehe le ho itlhokomela ka lithethefatsi (Deutch, 1992; Olsen le Duvauchelle, 2001, 2006; Everitt et al a., 2008; Del Arco le Mora, 2009). Mosebetsi oa morao-rao o hlokometse mosebetsi oa CREB mme oa fokotsa BDNF ho NAc e latelang matsatsi a 30 EE ho bapisoa le likhoto tse futsanehileng (Green et al a., 2010), le hoja maemo a NAc BDNF a ne a le joalo pakeng tsa EE le likhohlo tse laolang selemo se seng sa bolulo (Segovia et al a., 2010). EE e boetse e ama mosebetsi oa transcriptional o bakoang ke lithethefatsi tsa tlhekefetso. Ho kenyelletsoa ha liphatsa tsa lefutso tsa pele zif268 ho NAc ka cocaine e fokotsehile, joalo ka ho bonts'oa ha k'hok'hoine ea delta FosB ka statum (le hoja EE ka boeona e fumanoe ho phahamisa FosB ea sekepe se hlaselang).Solinas et al a, 2009). Tšusumetso ena "ea tšireletso" ha e bonoe feela tšimong ea tahi. Tekanyo ea polasetiki e bakoang ke EE e kholo hoo e ntseng e tsoela pele ho ithutoa ka mekhoa ea ho sireletsa le ho ntlafatsa ho hlaphoheloa ha mafu a mangata a likokoana-hloko (van Praag et al a., 2000a; Spiers le Hannan, 2005; Nithianantharajah le Hannan, 2006; Laviola et al a, 2008; Lonetti et al a, 2010), le tlaleho ea morao-rao e bile e fumane keketseho e itšetlehileng ka hypothalamic ea phekolo ea kankere ha liphoofolo li ne li lula ho EE (Cao et al a, 2010). Joalokaha ho tšohliloe tabeng ea boikoetliso, liqeto tse mabapi le liphello tsa EE ka ho itlhokomela ka lithethefatsi li lokela ho etsoa ha li ntse li nahanisisa ka liphello tse ka 'nang tsa e-ba khahlanong le ho sithabela ha bolulo. Joaloka boikoetliso, EE e 'nile ea bonahala e eketsa hippocampal neurogenisis (van Praag et al a., 2000b) le ho fokotsa liphello tse tepeletseng maikutlo tsa khatello ea kelello ka litoeba (Laviola et al a., 2008).

6. Puisano

Ho batho ba bang, ho na le phetoho e tsoang ho "tloaelehileng" ho qobelloa ho kopanela liphapong tsa tlhaho (tse kang lijo kapa thobalano), boemo boo ba bang ba bo bitsitseng meriana ea boitšoaro kapa e seng lithethefatsi (Holden, 2001; Grant et al a., 2006a). Ha lipatlisiso tsa lithethefatsi tse se nang lithethefatsi li ntse li tsoela pele, tsebo e fumanoang ho tloha metseng ea ho lemalla lithethefatsi, tšusumetso le khatello e feteletseng ea lithethefatsi e tla tlatsetsa ho nts'etsopele ea mekhoa ea phekolo ea lithethefatsi tse se nang lithethefatsi. Ho na le bopaki bo bongata bo bontšang hore lithethefatsi tse sebelisoang ho phekola lithethefatsi li ka ba mokhoa o atlehang oa ho phekola lithethefatsi tseo e seng tsa lithethefatsi. Ka mohlala, naltrexone, nalmefine, N-acetyl-cysteine, le modafanil kaofela li tlalehiloe ho fokotsa takatso ea batho ba nang le boloetse ba papali ea chelete (Kim et al a, 2001; Grant et al a, 2006b; Leung le Cottler, 2009). Bahanyetsi ba liphiri ba boetse ba bonts'episitse litšepiso tse nyenyane tsa ho phekola boitšoaro bo bobe ba ho kopanela liphate (Grant le Kim, 2001), 'me ho ipholisa ho bontšitse katleho ho fokotsa likhao tsa boima le boima boemong ba bakuli ba nang le bothata ba ho ja lijo tse ngata (McElroy et al a, 2007). Katleho ea litlhare tsena bakeng sa lithethefatsi tse sa sebeliseng lithethefatsi li tsoela pele ho bontša hore ho na le li-substrate tse tloaelehileng tsa meriana le lipilisi tse sa sebeliseng lithethefatsi.

Mekhoa ea liphoofolo e susumetsang le e tsitsitseng e tla thusa ho fana ka temohisiso ka mekhoa ea meriana e bakoang ke lithethefatsi tse se nang lithethefatsi (Potenza, 2009; Winstanley et al a, 2010). Mefuta e meng ea lithethefatsi tse sa sebeliseng lithethefatsi li etsoa habonolo ka litoeba ho feta tse ling. Ka mohlala, paradigms e sebelisa ho fihlella lijo tse matlafatsang haholo e fane ka moralo o babatsehang bakeng sa ho ithuta phetoho ho e-ja lijo tse qobelloang kapa tse feteletseng. Mefuta e nang le mekhoa e metle ea ho fihlella ho mafura a phahameng, tsoekere e phahameng, kapa "lijo tsa motsoako oa lijo" e tlisa lijo tse eketsehileng le ho phahamisa boima, likarolo tse ka sehloohong tsa botenya ba motho (Rothwell le Stock, 1979, 1984; Lin et al a, 2000). Litlhare tsena li ka eketsa tšusumetso ea nakong e tlang bakeng sa lijo (Wojnicki et al a, 2006) le ho lebisa liphetohong tsa polasetiki ea neural ka mokhoa oa mesolimbic dopamine (Hoebel et al a, 2009). Mefuta ea boipheliso ea boipheliso e fumanehile hape hore lintlha tse amanang le lijo le khatello ea kelello li ka lebisa ho khutlisetseng ho batla lijo (Ward et al a., 2007; Grimm et al a, 2008; Nair et al a., 2009b), mohlolo o boetse o tlalehile bakeng sa dieters ea batho (Drewnowski, 1997; Berthoud, 2004). Ka hona, mefuta ena ea mefuta e matlafetse ho matlafatsa 'me e ka etsa hore ho be le li-neuroadaptations tse re thusang ho utloisisa maemo a motho a kang ho qobella lijo kapa ho khutlela mekhoeng e mengata ea ho ja ka mor'a phetoho e ntle ea lijo.

Ntlha e 'ngoe ea tsoelo-pele ea morao-rao e bile ho nts'etsopele ea mekhoa ea papali ea papali ea papali ea chelete le khetho e kotsi (van den Bos et al a, 2006; Rivalan et al a, 2009; St Onge le Floresco, 2009; Zeeb et al a., 2009; Jentsch et al a, 2010). Liphuputso li bontšitse hore likhoto li khona ho etsa mosebetsi oa ho becha oa Iowa (IGT) (Rivalan et al a., 2009; Zeeb et al a., 2009) le mosebetsi oa mochine oa slot (Winstanley et al a, 2011). Phuputso e 'ngoe e fumane hore litsuoa tse neng li sebetsa ka hohle ho IGT li ne li e-na le matla a ho utloisisa bohloko le moputso o phahameng oa ho nka (Rivalan et al a., 2009), e tšoanang le litšoaneleho tse 'nileng tsa amahanngoa le papali ea papali ea chelete le ho lemalla lithethefatsi ho bakuli ba batho (Cloninger, 1987; Zuckerman, 1991; Cunningham-Williams et al a, 2005; Potenza, 2008). Ho sebelisa li-rodent, liphuputso li boetse li lebisa tlhokomelo mekhoeng ea "neural" ea "ho khanna" le ho ntlafatsa papali ea chelete e ka fanang ka temohisiso ho nts'etsopele ea pharmacotherapi bakeng sa papali ea papali ea chelete (Winstanley, 2011; Winstanley et al a., 2011).

Liphuputso tsa mekhatlo ka ho sebelisa tšusumetso e matla joaloka ho matlafatsa li fumane hore ho na le mekhoa e mengata ea limolek'hule e itekanetseng ho itlhophisa ha batho ba nang le boikutlo bo matla ba lithethefatsi le lithethefatsi tsa tlhekefetso (Olsen le Winder, 2009; Olsen et al a., 2010). Le hoja lipatlisiso tsa tšebetsong ena li sa le monyenyane, liteko tsena le tse tlang nakong e tlang li ka fana ka temohisiso ea mekhoa e ka sebelisoang ea phekolo ea phekolo ea ho sebelisa k'homphieutha kapa ho bapala video.

Le ha tsoelo-pele ena le tse ling tsa mekhoa ea boits'oaro li qala ho re fa leseli la lits'ebetso tse tlisoang ke ho se lemalle lithethefatsi, ho na le liphephetso le meeli ha o leka ho etsisa boitšoaro bo joalo. Moeli o mong ke hore mefuteng e mengata, ha ho na litlamorao tse kholo tsa ho nka liqeto tse fosahetseng kapa ho nka karolo ka mokhoa o fetelletseng mekhoeng eo. Mohlala, mesebetsi ea papali ea papali ea litoeba e sebelisa meputso e menyenyane kapa ho lieha ho eketseha lipakeng tsa meputso ho arabela liqeto tse fosahetseng, empa phoofolo ha e kotsing ea ho lahleheloa ke ntlo ea eona kamora ho lahleheloa ke letoto. Thibelo e 'ngoe ke hore ho kenella ka mokhoa o fetelletseng mekhoeng e kang ho itšebeletsa lijo kapa lithethefatsi maemong a laboratori e kanna ea ba litholoana tsa liphoofolo tse se nang monyetla oa ho fumana meputso e meng eo e seng ea lithethefatsi (Ahmed, 2005). Boemo bona bo ikhethang bo 'nile ba etsoa tlhahiso ea ho beha batho ba kotsing ea ho beha likotsi molokong oa batho (Ahmed, 2005), le hoja e sa ntsane e emela mohaho oa lihlopha tsena tsa lithuto.

Ho tsoela pele ho ithuta ka ts'ebetso e feteletseng, e qobelloang, kapa e senyehileng ha ho ja, ho becha le mekhoa e meng e se nang lithethefatsi e tla ba ntho ea bohlokoa ho ntlafatsa kutloisiso ea rona ea lithethefatsi tseo e seng tsa lithethefatsi. Litholoana tsa lithuto tsa mekhoa e metle li sebelisa mekhoa ena li kopantsoe le lipatlisiso ho batho ba tla ts'ehetsa li-pharmotherapy tse "crossover" tse ka tsoelang molemo meriana ea lithethefatsi le e seng lithethefatsi (Grant et al a., 2006a; Potenza, 2009; Frascella et al a., 2010).

Lipotso tse ling tsa 6.1

Potso e le 'ngoe e setseng ke hore batho ba tšoanang ba neurons ba susumetsoa ke melemo ea lithethefatsi le ea tlhaho. Le hoja ho na le bopaki bo bongata ba hore ho na le libaka tse ngata tse teng sebakeng sa boko tse amanang le meputso ea tlhaho le lithethefatsi tsa tlhekefetso (Sekepe et al a, 2000; Karama et al a, 2002; Ho ba le bana et al a, 2008), ho na le boitsebiso bo fapaneng mabapi le ho kena-kenana le batho ba nang le li-neural tse amehang ke meputso ea tlhaho le lithethefatsi. Litekoto tse se nang molekane tse tsoang ho ratral le ratana le batho bao e seng li-ventral striatum li bontša hore batho ba fapaneng ba neural ba kopanngoa nakong ea ho itlhophisa ka litlhohonolofatso tsa tlhaho (lijo, metsi le sucrose) khahlanong le cocaine kapa ethanol, le hoja ho ne ho e-na le tekanyo e kholo pakeng tsa meputso e fapaneng ea tlhaho e sebelisoang lithutong tsena (Bowman et al a, 1996; Carelli et al a, 2000; Carelli, 2002; Robinson le Carelli, 2008). Hape ho na le bopaki ba hore lithethefatsi tsa lihlopha tse fapaneng li kopanya li-neural tse khethollang ka har'a tsamaiso ea mesocorticolimbic. Litekete tse se nang molekane tse tsoang ho PFC le NAc ea likhoto ho fana ka cocaine kapa heroine li senotse hore batho ba sa tšoaneng ba neurons ba ne ba kopane ka nako e le 'ngoe nakong ea tebello ea nako le ho kenngoa ka morao (Chang et al a, 1998). Phapang pakeng tsa moputso oa tlhaho le lithethefatsi e ka 'na ea se ke ea e-ba ntho e feletseng, leha ho le joalo, kaha ho na le bopaki bo khahlanong le bona. Ho latela methamphetamine le phihlelo ea ho kopanela liphate nako e telele, ho bile le ketsahalo e ikhethileng ea li-neurons tse nkiloeng ke meputso ena e mabeli NAC, ka hare ho cingulate cortex le basolateral amygdala (Frohmader et al a., 2010). Ka hona, ho hiroa ha batho ba nang le meriana ka lithethefatsi tse ling tsa tlhekefetso ho ka 'na ha fapana le ea meputso ea tlhaho, empa eseng e meng. Liphuputso tsa nakong e tlang li tla sebelisoa ka libaktheri tse felletseng tsa meputso ea tlhaho le lithethefatsi ho tla rarolla bothata bona.

Potso e 'ngoe e hlahang ke hore na ho ithuta ka mekhoa ea tlhaho ea moputso ho ka re thusa joang ho utloisisa lithethefatsi le lithethefatsi tse se nang lithethefatsi. Bopaki ba morao-rao bo bontša hore ho pepesehela meputso e meng e sa sebeliseng lithethefatsi ho ka fana ka "tšireletso" ho tsoa mererong ea lithethefatsi. Ka mohlala, tsoekere le saccharin li ka fokotsa boinotši ba cocaine le heroine (Carroll et al a., 1989; Lenoir le Ahmed, 2008), 'me li-reinforcers tsa tlhaho li' nile tsa bontšoa hore li na le k'hok'heine ea ho tsoa ka ntle ho khethollo ka bongata bo boholo ba likhoto (Lenoir et al a., 2007; Cantin et al a., 2010). Ka tlhahlobo ea liphoofolo ka lipatlisiso, Cantin et al a. ba tlaleha hore ke ~ 9% feela ea litoe tse khethang cocaine ho feta saccharin. Ntho e thahasellisang ke hore karolo ena e nyenyane ea liphoofolo e emela baahi ba nang le "ts'oaetso". Liphuputso tse sebelisang cocaine ho itokisetsa boipiletso li lekile ho khetholla likhoto tse "lemalang" ho sebelisa mekhoa e ntlafalitsoeng ho bontša mekhoa ea DSM-IV bakeng sa ho itšetleha ka lithethefatsi (Deroche-Gamonet et al a., 2004; Belin et al a, 2009; Kasanetz et al a, 2010). Liphuputso tsena li fumane hore hoo e ka bang ~ 17-20% ea liphoofolo ho itlhahisa ka cocaine e finyella lintlha tsohle tse tharo, ha litekanyetso tsa litekanyetso tsa ho itšetleha ka k'hok'heine ho batho ba neng ba pepesehetse lithethefatsi ho tloha ~ 5-15% (Anthony et al a, 1994; O'Brien le Anthony, 2005). Kahoo, liphoofolong tse ngata tsoekere le saccharin li bonahala li matlafatsa ho feta cocaine. Potso e khahlisang haholo ke hore na liphoofolo tse fokolang tse fumanang se matlafatsang lithethefatsi li khethoa li emela sechaba se "tlokotsing" se loketseng thuto ea bokhoba. Kahoo, ho bapisa khetho ea liphoofolo ka bonngoe bakeng sa lithethefatsi le meputso ea tlhaho ho ka hlahisa temohisiso maemong a tlokotsing a amanang le ho lemalla lithethefatsi.

Potso ea ho qetela ke hore ho phehella litlhohonolofatso tsa tlhaho ho ka thusa ho thibela kapa ho alama lithethefatsi. Tlhokomelo ea tikoloho e 'nile ea etsoa e le mokhoa oa thibelo le oa phekolo ea ho lemalla lithethefatsi ho itšetlehile ka lithuto tsa meriana e mengata ea lithethefatsi tsa tlhekefetso (Bardo et al a, 2001; Deehan et al a, 2007; Solinas et al a, 2008; Solinas et al a., 2010). Lithuto tsa batšoaruoa ba batho li fana ka maikutlo a hore ho ntlafatsa tikoloho ka tšebeliso ea "metseng ea meriana" ha e le hantle ke mokhoa o atlehang oa phekolo bakeng sa ho fokotsa tlōlo ea molao le tšebeliso e mpe ea lithethefatsi nakong e tlang (Inciardi et al a, 2001; Butzin et al a, 2005). Liphetho tsena li tšepisa 'me li fana ka maikutlo a hore maruo a tikoloho a ka ntlafatsa li-neuroadaptations tse amanang le tšebeliso ea lithethefatsi e sa foleng. Ho ts'oana le ntlafatso ea tikoloho, liphuputso li fumane hore boikoetliso bo fokotsa boits'oaro bo botle le ho khutlela lithethefatsi tsa tlhekefetso (Cosgrove et al a., 2002; Zlebnik et al a., 2010). Hape ho na le bopaki bo bong ba hore liphuputso tsena tsa motheo li fetoleloa ho batho, kaha boikoetliso bo fokotsa matšoao a ho tlohela le ho khutlela ho batho ba tsubang (Daniel et al a, 2006; Prochaska et al a, 2008), le lenaneo le le leng la pholiso ea lithethefatsi le bile le katleho ho barupeluoa ba koetlisang le ho hlōlisana le marathon e le karolo ea lenaneo (Butler, 2005).

7. Litlhaloso tse qetellang

Ho na le lipapiso tse ngata pakeng tsa lithethefatsi tse se nang lithethefatsi le lithethefatsi tsa lithethefatsi, tse kenyeletsang ho lakatsa, ho laola boitšoaro, ho mamella, ho tlohela, le ho khutlela morao haholo (Letšoao, 1990; Lejoyeux et al., 2000; Mokhatlo oa Sechaba oa Tlhekefetso ea Lithethefatsi (NIDA) le al., 2002; Potenza, 2006). Joalokaha ke se ke hlahlobile, ho na le glut ea bopaki ba hore litlhohonolofatso tsa tlhaho li khonne ho fokotsa polasetiki ka potoloho e amanang le lithethefatsi. Sena ha sea lokela ho makatsa, joalo ka 1) lithethefatsi tsa tlhekefetso li etsa liketso ka hare ho boko bo tšoanang, le hoja li le joalo ho feta meputso ea tlhaho (Kelley le Berridge, 2002), le 2) ba ithutile litloaelano pakeng tsa lintho tse kang lijo kapa menyetla ea thobalano le maemo a fokolisang boteng a molemo ho tsoa ponong ea bophelo mme ke mosebetsi oa tlhaho oa boko (Alcock, 2005). Ho batho ba bang, polasetiki ena e ka kenya letsoho moetlong oa ho qobella batho ho itšoara ka boitšoaro bo tšoanelang ho lemalla lithethefatsi. Lintlha tse ngata li fana ka maikutlo a hore ho ja, ho reka, ho bapala papali ea chelete, ho bapala lipapali tsa video, le ho qeta nako Inthaneteng ke boitšoaro bo ka fetohang boitšoaro bo qobelloang bo tsoelang pele ho sa tsotellehe liphello tse bohloko (E monyenyane, 1998; Tejeiro Salguero le Moran, 2002; Davis le Carter, 2009; Garcia le Thibaut, 2010; Lejoyeux le Weinstein, 2010). Joalokaha ho lemalla lithethefatsi, ho na le nako ea phetoho ho tloha ho itekanetseng ho ea ho sebelisoang ka mokhoa o qobelloang (Grant et al a., 2006a), le hoja ho le thata ho hula moeli pakeng tsa "ho tloaeleha" le ho phehella ha moputso oa moputso. Mokhoa o mong oa ho etsa phapang ena ke ho hlahloba bakuli ba sebelisang mekhoa ea DSM bakeng sa ho itšetleha ka lithethefatsi. Ho sebelisa mokhoa ona, litlaleho li entsoe hore litekanyetso tsena tsa DSM li ka finyelloa ha li sebelisoa ho bakuli ba qobellang ho kopanela liphate (Goodman, 1992), papali ea chelete (Potenza, 2006), tšebeliso ea marang-rang (Griffiths, 1998), le ho ja (Ifland et al a, 2009). Ho nkoa ka hore DSM-5 e lebeletsoe hore e kenye lihlopha tsa tekano le tse matla ka hare ho "tahi le mathata a amanang" (Mokhatlo oa Mahlale oa Amerika, 2010), e ka 'na ea e-ba makhoba a bafuputsi le baoki ba hlokang ho nahana ka ho lemalla ho lemalla bothata. Metseng e meng, mofuta ona oa nomenclature o thusitse ho lemosa hore mathata a kang autism le tahi ea bothata ba botalane a na le mefuta e mengata ea boima. Tabeng ea ho lemala (lithethefatsi kapa e seng lithethefatsi), ho tsebahatsa matšoao esita le ka tlaase ho monyako oa "tekanyo" ho ka thusa ho khetholla batho ba kotsing le ho lumella mehato e atlehang haholoanyane. Liphuputso tsa nakong e tlang li tla tsoelapele ho senola hore na ho hahamalla meputso ea tlhaho ho ka ba ho qobella batho ba bang joang le hore na ho molemo hakae ho sebetsana le lithethefatsi tse seng tsa lithethefatsi.

​          

Lethathamo 1          

Kakaretso ea Pulasetiki e Etsoang ka Mor'a Lintho Tse Phelang.

Liteboho

Thuso ea lichelete e fanoe ke thuso ea NIH DA026994. Nka rata ho leboha Kelly Conrad, Ph.D. le Tiffany Wills, Ph.D. bakeng sa litlhaloso tse hahang liphetolelong tse fetileng tsa buka ena e ngotsoeng ka letsoho.

Mongolo o botlaaseng ba leqephe

Boitlhotlhollo ba Mohoeletsi: Ena ke faele ea PDF ea mongolo o ngotsoeng ka letsoho o sa amoheloang o amoheletsoeng bakeng sa ho hatisoa. Joaloka tšebeletso ho bareki ba rona re fana ka phetolelo ena ea pele ea mongolo o ngotsoeng ka letsoho. Mongolo o ngotsoeng ka letsoho o tla ba le ho kopitsa, ho kenya lihlopha le ho hlahloba bopaki bo hlahang pele o hatisoa ka mokhoa oa oona oa ho qetela. Ka kopo hlokomela hore nakong ea mekhoa ea tlhahiso ea lihlahisoa e ka fumanoa e ka amang litaba, le litsebiso tsohle tsa molao tse sebetsang koranteng e amanang le eona.

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