Tšoaea liphoso. 2016 Aug; 93: 62-70. doi: 10.1016 / j.mehy.2016.05.015.
Patrono E1, Gasbarri A2, Tom C3, Nishijo H4.
Pale ea Sehlooho
- Selelekela
- Khopolo-taba ea "ho tsoela pele ka nakoana" e amanang le tšusumetso e mpe, ts'oaetso ea hedonic le thuto e mpe.
- Neuro-bio-physiological semelo sa ho lemalla lithethefatsi "likhopolo tsa nakoana"
- Motheo oa neural oa boitšoaro bo susumetsoang ke lithethefatsi
- Motheo oa neural oa tloaelo ea ho ithuta lithethefatsi
- Ho nepahala ha poleloana e reng "ho lemalla lijo"
- Motheo oa neural oa ho lemalla lijo
- Electrophysiological motheo oa boitšoaro bo tataisoang ke lijo
- Boitšoaro bo bocha ba ho lemalla
- Nahanisisa
- Bangoli le bafani
- Likhohlano tsa thahasello
- References
inahaneloang
Keywords:
Ho lemalla lithethefatsi / lijo, Tšusumetso, Ho ithuta tloaelo, Phallo ea Hedonic, Phetoho, Mokhoa oa moputso
Selelekela
Bokhoba, ho tsoa ho Latin "addictus" ("lekhoba la mokoloto" kapa "subjugate"), ke lefu le sa foleng la ho qobelloa le ho khutlela morao le amang batho kelellong ho feta nameng. Ke boemo bo sa foleng bo kenyelletsang libaka tse 'maloa tsa boko le lipotoloho, tse kenyelletsang mesebetsi e mengata e kang moputso, tšusumetso le mohopolo. Lekhoba la tahi butle-butle le lebisa boholo ba matla a lona ho batleng, ho fumaneng, le ho fumaneng le ho sebelisa lintho tsa tlhekefetso. Sena se etsahala leha o kula, o hloleha bophelong mme o senya likamano.
Haufinyane, bokhoba ba tahi bo hlalositsoe ho DSM-V e le "mokhoa oa ts'ebeliso ea ntho" o khetholloang ke tahlehelo ea taolo ea boits'oaro bo amanang le ts'ebeliso ea lithethefatsi, ho latela boits'oaro boo leha ho ka ba le litlamorao tse mpe. tšusumetso e matla ea ho nka lintho [1]. Ho felloa ke taolo, ho lelekisa, le tšebetso e matla e susumetsang ho nka lintho li ka hlahlojoa le ho nahanoa ho tloha boemong ba kelello ho isa boemong ba limolek'hule.
Likhopolo tse tharo tse fapaneng li tataisa lipatlisiso tsa liteko tsa bokhoba ba lithethefatsi [[2], [3], [4]]. E 'ngoe le e' ngoe ea likhopolo tsena e nahana ka likarolo tse ikhethileng, joalo ka tšusumetso e sa tloaelehang [2], hedonic dysregulation [3], le tloaelo e sa tloaelehang ea ho ithuta [4] e le sebapali se ka sehloohong ho hlalosa ts'ebetso eohle ea boits'oaro bo lemalloang. Morero oa mantlha oa thuto ena ke ho hlahisa likhopolo tse ncha tsa phetoho ho tloha ts'ebelisong e laoloang ho ea ts'ebetsong ea lithethefatsi tse lemalloang ka kakaretso ea likhopolo tse tharo tse fapaneng, ho shejoa likarolo tsohle tse le 'ngoe tsa khopolo e le' ngoe hammoho ho "tsoelopele" ea nakoana sebelisa hampe tšebeliso ea lithethefatsi tse lemalloang.
Mona re shebisisa likhopolo tse tharo tse kholo tsa kelello tse lekang ho hlalosa temana ho tloha ts'ebelisong e sa tloaelehang ho ea ho ts'ebeliso e mpe ea lisebelisoa tsa litlhare: khopolo ea khothatso, khopolo-taba ea hedonic dysregulation, le khopolo ea ho ithuta e thehiloeng ho tloaelo
Khopolo ea "khothatso ea ho hlohlelletsa"
Thutong ea kelello, ka kakaretso tšusumetso e nkuoa e le boemo ba kahare bo tataisang le ho ntlafatsa boitšoaro ba motho, ho ea fihla pakaneng. Mekhoa ea kelello e tataisang boits'oaro ba bokhoba e ka ithutoa ka mohopolo o susumetsang, ho utloisisa hore na ke litsamaiso life tsa boko tse amehang. Boitšoaro bo qobelloang ba ho batla / ho nka lithethefatsi le ho khutlela mokhoeng (ho pepesehela tšusumetso e amanang le ntho eo kapa ka lebaka la khatello ea maikutlo) li bakoa ke phetoho tsamaisong ea tšusumetso le mohatong oa takatso (o batlang). Berridge le Robinson ba hlalositse ketsahalo ena ka "khopolo ea khothatso ea ts'usumetso" [2]. Ba fana ka maikutlo a hore ts'ebeliso e sa foleng ea sethethefatsi e lebisa ho ntlafatseng phetoho ea methapo ka har'a sistimi ea moputso, ho matlafatsa sistimi ho lithethefatsi le litlamorao tse amanang le eona. Ntlafatso ea li-pair-drug tse susumetsang lithethefatsi li eketsa boleng ba khothatso, ho hlahisa "phetoho" ho basebelisi ba lithethefatsi ba batla lithethefatsi, leha li sa fumane joaloka ho tsoa ho bona [5] (Feie. 1). Feie. 1 e bontša joang rata 'me ho batla e ka latela litsela tse fapaneng tsa kelello / boko ka phapang ea papiso ea mohopolo. Leha khopolo ena e hlalosa likarolo tse ngata tsa bokhoba ba motho, joalo ka ho batla setlhare ka mokhoa o fetelletseng, takatso e matla, le ho oela hape, e ka se hlalose feela karolo ea mantlha ea bokhoba ba lithethefatsi: ho hloleha ha makhoba ho laola kapa ho emisa ts'ebeliso ea sethethefatsi, ho sa tsotelehe litlamorao tse mpe le boits'oaro bo kotsi ba ts'ebeliso ea eona e telele. Ho lemalla lithethefatsi ke kelello e rarahaneng ea kelello e khetholloang, bonyane ka karolo e 'ngoe, ke monyaka o susumetsoang ke lithethefatsi, mehopolo e amanang le lithethefatsi, le litšoaneleho tsa maikutlo tse amanang le lithethefatsi tse hokahantsoeng le "takatso" ea "li ratang" [[6], [7]]. Ho se leka-lekane ha "ho batla" ka bobeli (mohlala, khothatso-khothatso) le "ho rata" ho ka ba le seabo ho kenyeng boits'oaro ba ho lemalla [8]. Leha ho le joalo, leha mohopolo ona o sa hane menyaka e tlisoang ke lithethefatsi, ho khaotsa, kapa litloaelo joalo ka mabaka a boits'oaro ba ho batla / ho nka lithethefatsi, e nahana hore lintlha tse ling, joalo ka ho matlafatsoa ho batla, e ka hlalosa hamolemo ho qobelloa le ho khutlela bokhobeng.
Feie. 1
Mofuta oa khothatso ea boikhohomoso ba tšusumetso ea khothatso. Ho "rata" le "ho batla" ho tsamaellana le litsamaiso tse arohaneng tsa kelello le methapo. Li-stimuli tse maemong a itseng (CS) le li-stimuli tse se nang maemo (US) li hlahisa papiso ea mohopolo. Lits'oants'o tsa DA ho NAc le neostriatum li hlahisa lintho tse batlang li le teng (litšusumetso-salience tsa tšusumetso). Ka lehlakoreng le leng, DA ha e itlhahise ka kotlolloho ho NAc le neostriatum ka mokhoa o tšoanang le ho rata (hedonia) le ho ithuta-ho kopanya meputso. Ho hlokahala litlatsetso tse ling tsa tlhaiso-leseling bakeng sa boitlhahlobo ba motho ba boithabiso le tšusumetso, molemong oa ho ba le tsebo ea maikutlo a ipapisang le "ho rata" le "ho batla".
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Khopolo ea "hedonic dysregulation"
Karolo ea "ho hlohlelletsa" bokhobeng e hlalositsoe e le mohato o boreleli ho ea "maemong a ts'usumetso". Tšebeliso ea pele e khothalletsoa ke thepa e thabisang ea sethethefatsi, joalo ka euphoric e phahameng, ha ts'ebeliso e lemalloang e nahanoa hore e ka hola ka "matlafatso a mabe"10]. Matlafatso a fosahetseng ke ts'ebetso eo ka eona ho ntšang tšusumetso e matla, joalo ka maikutlo a mabe a ho tlohela, ho eketsang palo ea batho ba kenang lithethefatsi [3]. Bakeng sa ho qoba dysphoria le ho se utloise bohloko, basebelisi ba lithethefatsi ba noa meriana ea meriana [11]. Leha ho le joalo, basebelisi ba lithethefatsi ba tsoela pele ho tloha ts'ebelisong e sa tloaelehang ho ea ho lithethefatsi, 'me lintlha tse khothalletsang "phetoho" ts'ebelisong ea lithethefatsi li nahanoa hore li tlohele ho se ts'oarehe matsatsing a pele, ho ea ho qobelloang linakong tsa ho qetela. Takatso (takatso e matla le e matla) e na le karolo ea bohlokoa bokhobeng, 'me e nkuoa e le karolo ea likarolo tse tharo: "ho ba le mohopolo / tebello", "ho itlopa joala / tahi", le "ho tlohela / phello e mpe" [10]. Mekhahlelo ena e meraro ea sebelisana, e tebile ka matla, e nyenyefatsa hedonic homeostasis ea sistimi ea moputso, mme qetellong e tlise mosebelisi tahi [[3], [10]] (Feie. 2). Feie. 2 e hlalosa potoloho e holimo-limo ea ho lemalla lithethefatsi eo ho eona "ho tsepamisa mohopolo / tebello" e hlahang e le tšusumetso e matla ea ho sebelisa lithethefatsi leha bophelo ba hae bo le boikarabello bo bongata le likamano tsa batho. Sethala sa "ho itlopa joala / botahoa" se totobatsa tlhokeho ea bongata ba lithethefatsi hore motho a be le litlamorao tse tšoanang. "Ho tlohela / phello e mpe" ho bolela litlamorao tsa kelello le 'mele tse bakoang ke ho ba sieo ha ts'ebeliso e mpe ea lithethefatsi, e hlokang tlhokomelo ea bongaka (mohlala, ts'ebeliso ea meriana ea methadone).
Feie. 2
Ho potoloha ka selikalikoe se holimo ho ea holimo ho ea tlase. Setšoantšo se hlalosa potoloho e holimo-tlase ea bokhoba ba tahi. Takatso e amehile haholo ts'ebetsong moo ts'ebeliso ea lithethefatsi ka linako tse ling e ka lebisang tlhekefetsong, mme kamora moo ea khutlela morao. Sena se hlalosoa ka lintlha tse tharo: "ho itšunya-tšunya / ho lebella", "ho itlopa joala / tahi", le phello ea "ho tlohela / ho se rate". Mekhahlelo ena e meraro e ea sebelisana, e ba matla le ho feta, e nyenyefatsa hedonic homeostasis ea sistimi ea moputso, mme e lebise ho boemo ba mafu bo tsejoang e le bokhoba.
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Khopolo-taba ea hedonic dysregulation e hlakisa tšebetso ho tloha ts'ebelisong le ts'ebeliso e mpe ea lithethefatsi joalo ka "selikalikoe se sehlōhō se holimo", ho shebiloe karolo ea bohlokoa ea mofuta o mong oa ho se lekalekane maemong a basebedisi ba lithethefatsi [3]. Leha ho le joalo, khopolo ena e ke ke ea hlalosa feela karolo ea likarolo tse ling tsa mantlha tsa bokhoba ba lithethefatsi joalo ka ho hlohlelletsa ka mokhoa o sa tloaelehang ntho le boits'oaro ba sesebelisoa ho fumana ntho eo. Potoloho ea moputso oa mesolimbic ho ne ho lumeloa hore e kentse tšusumetso ea hedonic e amanang le boiphihlelo ba lithethefatsi. Haufinyane, ho nkuoa hore potoloho ena e sebetsa ka mokhoa o rarahaneng ho feta, e akaretsa tlhokomelo, tebello ea moputso, le khothatso [12].
Khopolo ea "ho ithuta ka tloaelo"
Everitt o nka bokhoba ba lithethefatsi e le karolo ea hoqetela ea mehato e mengata ea phetoho ho tloha ts'ebetsong ea pele le e laoloang ea lithethefatsi.[13], [18], [19]] (Feie. 3). Feie. 3 e hlalosa mehato e latelang ka ho lemalla lithethefatsi. Ha ntho e nkuoa ka boithatelo molemong oa tšusumetso ea eona, boits'oaro ba boits'oaro bo fetoha "tloaelo", ka tahlehelo ea taolo butle-butle. Kahoo, mochini o matlafatsang oa karabelo o bapala karolo ea bohlokoa ho boloka boits'oaro ba seletsa. Kamora nako, matla a ts'usumetso (ntho) ho sebetsa joalo ka matlafatso (conditioned reinforcer) a fana ka mofuta oa taolo holima boits'oaro ba ho batla / ho nka. Ka hona, bokhoba ba lithethefatsi bo ka qala e le "boitšoaro bo tataisoang ke sepheo"; hamorao, ka tlhokomelo ea "boits'oaro ba lisebelisoa", e ka fetoha "boits'oaro bo tloahelehileng", e hlohlelletsa mofuta oa thuto o ipapisitseng le tloaelo (thuto e ipapisang le tloaelo) [[13], [16], [18]].
Feie. 3
Ho latela mehato ea tšebeliso le tšebeliso e mpe ea lintho. Ho ea ka Everitt le basebetsi-'moho le eena, bokhoba ba lithethefatsi ke letoto la mehato e lateloang ke ts'ebeliso ea pele, ea boithatelo le ea maikutlo e sebelisang lintho tse lemalloang ho fihlela tahlehelo ea taolo ts'ebelisong ea tsona lintho ka phetoho ea karolo ea matlafatso . Haholo-holo, ha ntho e nkuoa ka boithatelo molemong oa tšusumetso, boits'oaro ba boits'oaro bo fetoha "tloaelo", ka tahlehelo ea butle-butle ea taolo. Kahoo, mochini o matlafatsang oa karabelo o bapala karolo ea bohlokoa ho boloka boits'oaro ba seletsa. Kamora nako, matla a ts'usumetso (ntho) ho sebetsa joalo ka matlafatso (conditioned reinforcer) a fana ka mofuta oa taolo holima boits'oaro ba ho batla / ho nka.
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Khopolo-taba ea "ho tsoela pele ka nakoana" e amanang le tšusumetso e mpe, ts'oaetso ea hedonic le thuto e mpe.
Boithuto bona bo ikemiselitse ho lekola likhopolo tse tharo tse kholo tsa bokhoba ba lithethefatsi ho latela pono e ncha ea bonngoe, ka likhopolo-taba tsa khopolo ea "tsoelopele ea nakoana" e ikhethang moo "tšusumetso e mpe", "ts'oaetso ea hedonic", le "thuto e sa tloaelehang" robala hammoho e le ho hlalosa phetoho ho tloha ts'ebelisong e 'ngoe ea tšebeliso e mpe ea lithethefatsi (Feie. 4). Feie. 4 e bonts'a tatellano ea nako eo likarolo tse tharo tse kholo li hlalosoang e le "ts'ebetso e le 'ngoe" ea nakoana ho tloha kopanong ea pele le lithethefatsi ho lemalla ka bohona. Bongata ba lingoliloeng bo hlahlobile hantle karolo ea e 'ngoe le e' ngoe ea likhopolo tse tharo tsa ho lemalla lithethefatsi. Ntle le moo, ho hlalositsoe hore phetoho e tsoelang pele e etsahala ho tloha moetlong o susumetsoang ke boits'oaro / boits'oaro bo susumetsoang ke ts'oaetso ea hedonic e qalileng ho susumetsoa nakong ea ho ithuta tloaelo mme e ntse e tsoela pele ka tšusumetso e mpe ea ho sebelisa lithethefatsi. Moralo oa phetisetso ea lisebelisoa tsa Pavlovian (PIT) o ela hloko maemo a mabeli: (1) lits'ebetso tsa Pavlovia tse hlalosang kutloisiso ea sephetho lipakeng tsa se susumetsang (S) le li matlafatso (R); le (2) boits'oaro ba lisebelisoa tse utloisisang sephetho lipakeng tsa likarabo tse mafolofolo (R), le sephetho (O) [[20], [21]]. Neuro-bio-physiologically, sena se tsamaellana le phetoho e tsoelang pele ho tloha ho ventral ho ea ho taolo e nyane ea taolo ea boits'oaro ba ho batla / ho nka lithethefatsi [12]. Kahoo, ho a khonahala ho nahana ka "tsoelo-pele ea nakoana" e ikhethang eo ho eona (1) "thuto-moetlo" e tsoelang pele e etsahalang nakong ea ts'ebeliso e mpe ea lithethefatsi, moo "hedonic dysregulation" e ts'oaroang hape (2) e lebisang ho "leseli le tsoelang pele" ho susumetsa boitseko ”bo susumetsang boitšoaro bo sebelisang lithethefatsi. Leha ho le joalo, ho ea ka tsebo ea rona, ha ho na bopaki ba pono e kopaneng ea likhopolo-taba tse tharo ka likhopolo-taba tsa "nakoana". Liphuputso tse 'maloa tsa batho le tsa liphoofolo li bonts'itse hore nako ea moputso e na le karolo e matla ho sebetsaneng le moputso [[22], [23]]. Ntle le moo, lifensetere tsa nako le "litefiso tsa moputso" li bohlokoa haholo bakeng sa maemo, mme li-neuron tsa DA li kentse letsoho ho sebetseng ha tlhaiso-leseling ea nakoana ka meputso. Boemong ba bongaka, hona ho tla thusa ho utloisisa hore na o kenella joang nakong ea ts'ebeliso ea nakoana ea tšebeliso e mpe ea tšebeliso e mpe ea lithethefatsi, le ho hlahisa maano a macha a kalafo molemong oa ho qoba bofetoheli ba boits'oaro ba ho batla / ho nka lithethefatsi . Kamora nako, ts'usumetso, ts'oaetso ea hedonic, le thuto e ipapisitseng le tloaelo li ka nkuoa e le likarolo tse le 'ngoe tsa boits'oaro bo ikhethang le bo rarahaneng ba ho batla / ho nka lithethefatsi.
Feie. 4
Lethathamo la nako la boikaketsi la likhakanyo tsa "nakoana". Setšoantšo se hlalosang tatellano ea nako eo ka eona likarolo tse tharo tsa mantlha li hlalosoang e le "ts'ebetso e le 'ngoe" ea nakoana ho tloha kopanong ea pele le lithethefatsi ho lemalla. Nakong ena, liphetoho tsa boits'oaro bo sebetsa ho dysregulation ea hedonic le ho emela boleng ba sethethefatsi se bakang tloaelo ea ho ithuta, le ho lahleheloa haholo ke taolo ea tšebeliso ea lithethefatsi.
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Neuro-bio-physiological semelo sa ho lemalla lithethefatsi "likhopolo tsa nakoana"
Ntle le litekanyetso tsa boits'oaro tse hlalositsoeng kaholimo, lithuto tse 'maloa li hlahisitse khokahano lipakeng tsa lipotoloho tsa neural tse sebelisitsoeng moahong oa ho batla / oa ho sebelisa lithethefatsi. Ho bohlokoa ho hlokomela hore ts'ebeliso e mpe ea lithethefatsi e kenya ts'ebetsong libaka tse ngata tsa "cortico-subcortical" tsa boko le lipotoloho tsa neurotransmission tse amehang ho "matlafatso ea lithethefatsi". Bakeng sa ho netefatsa likhopolo-taba tsa hore likarolo tse tharo tse ntlafalitsoeng khopolong e ngoe le e ngoe li ka lula ho "tsoelo-pele ea nakoana" e hlalosang bohle hammoho ho tloha ts'ebelisong ea tšebeliso e mpe ea lithethefatsi, motheo oa boitšoaro bo susumetsoang ke lithethefatsi le tloaelo ea lithethefatsi- boitšoaro bo ithutoang bo tla ntlafatsoa
Motheo oa neural oa boitšoaro bo susumetsoang ke lithethefatsi
Ka lehlakoreng le leng, "mokokotlo" oa NAc o bonahala e le sebaka sa bohlokoa se hokahanyang boits'oaro bo ithutoang bo arabelang tšusumetso e bolelang liketsahalo tse amanang le ts'usumetso [[30], [37], [38], [39]]. Ho feta moo, polelo ea boits'oaro bo feto-fetohang e kanna ea hlophisoa ke ho lokolloa ha DA mokokotlong oa NAc nakong ea likarabo ho susumetsa ketsahalo e putsang [[40], [41]]. Ka kakaretso, DA e kanna ea ba le mesebetsi e 'meli mme e kanna ea ba bohlokoa ho "phetoho" ho tloha ts'ebelisong ea lithethefatsi ka linako tse ling ho ea ts'ebetsong. Alamo ea pele ke 'mele ho hlaha ha lintho tse ncha tse matla, mme kamora ho susumetsa ho ithuta methapo ea pelo. Ea bobeli ke ho lemosa sebopuoa ka pono e atamelang ea ketsahalo e tloahelehileng, mme se khothalelitsoe motheong oa mekhatlo e ithutoang e neng e entsoe pejana ka ho bolela liketsahalo tsa tikoloho [42]. Kamora nako, ho hlalositsoe letoto la li-cortico-striato-pallido-cortical loops tse tšoanang moo ventral striatum (VS), ho kenyeletsoa le mantlha ea NAc e amanang le thuto ea maikutlo; le dorsal striatum (DS), ho kenyeletsoa NA shell ea NAc e amana le ts'ebetso ea kelello le makoloi [[43], [44]].
Motheo oa neural oa tloaelo ea ho ithuta lithethefatsi
Sena se hlahisa potso ea hore na li-transmissions tse khethollang methapo ea methapo mokokotlong oa BLA le NAc ke likarolo tsa sisteme ea boko ka har'a "limbic cortical-ventral striato-pallidal" circry [57]. Karolo e 'ngoe ke hobane mokhoa oa seo ho thoeng ke "disconnection", DS le VS li sebelisana ka ho latellana, maemong a fapaneng a ts'ebetso, joalo ka PIT mabapi le boits'oaro bo tataisoang ke sepheo [21]. Nako e telele, VS e khothalelitsoe hore e boloke mohokahanyo oa maikutlo, tšusumetso le ketso ka lebaka la likhokahano tsa eona tse kholo lipakeng tsa meaho e joalo ka BLA le orbitofrontal cortex (oFC) [[21], [57], [58]] . Motsoako oa NAc o bohlokoa maemong a Pavlovia, hape le nakong ea litšebelisano mekhoeng ea ho ithuta ea "Pavlovian-instrumental" e amanang le boits'oaro ba boithatelo [[21], [38], [45]]. Ka lehlakoreng le leng, ho hlalositsoe hore DS e na le karolo mesebetsing ea kelello le ea makoloi, e fana ka motheo oa methapo ea kutlo bakeng sa tsona ka bobeli tataisoa sepheo 'me tloaelo ea ho laola ea "thuto ea liletsa" [[59], [60], [61], [62]]. Mehato e latellanang ea ho ithuta ea li-Pavlovia e ka ba bohlokoa haholo phetohong ho tloha ts'ebelisong e 'ngoe ea lithethefatsi ho ea ts'ebetsong, e ka kenyelletsang boits'oaro bo qobelloang ba ho batla / ho sebelisa lithethefatsi [13].
Haufinyane tjena, litlhahlobo tse 'maloa tsa liteko le ts'ebetso li ts'ehetsa mohopolo oa lipotoloho tse tloaelehileng tsa methapo e etsang karolo e ikhethileng bokong ba basal, e bitsoang "amygdala e atolositsoeng". Potoloho ena e ka abeloa ho sebetsa ka litlamorao, maikutlong le litloaelong tsa ho lemalla lithethefatsi [[63], [64], [65], [66]]. Amygdala e atolositsoeng e na le likarolo tse 'maloa tsa basal forebrain tse kang mokokotlo oa bethe oa stria terminalis (BNST), bohareng ba medial amygdala (CeA), le khetla ea NAc [[63], [64]]. Meaho ena e na le ho ts'oana ha morpholoji, immunohistochemistry, le khokahano [[65], [66]], mme li fumana likhokahano tse amanang ho tsoa mehahong ea maoto le matsoho e kang hippocampus (HP), le BLA. Amygdala e atolositsoeng e na le likarolo tsa bohlokoa tse kenyelletsang sistimi ea methapo ea kutlo e amanang le "litlamorao tse ntle tsa ts'ebeliso" ea lithethefatsi tsa tlhekefetso, le likarolo tse ling tse kholo tse amanang le khatello ea kelello 'me li amahanngoa le "litlamorao tse mpe tsa ho matlafatsa" tsa bokhoba ba lithethefatsi [[63], [67 ]]. Kahoo, lithuto tse ling li ka batlisisa karolo ea amygdala e atolositsoeng phetohong ho tloha ts'ebelisong ea ts'ebeliso e mpe ea lithethefatsi.
Boitšoaro bo bocha ba ho lemalla
Lilemong tse mashome a fetileng, mokhoa oa ho ja o fetohile haholo. Har'a liphetoho tsa nalane tse hlahileng lekholong la ho qetela la lilemo, Linaha tsa Bophirimela li thusa ho beha liphetoho tsa setso sa lijo, tse senotseng tloaelo ea ho ja khafetsa haholo-holo lijo tseo pele li neng li nkuoa li sa fumanehe ebile li le bohlokoa. Tloaelo e atileng ea ho ja ho feta kamoo ho hlokahalang, hangata e tsamaeang le ho se leka-lekane ho hoholo lipakeng tsa likarolo tse fapaneng tsa lijo, e lebisitse ketsahalong e phahameng ea mathata a ho ja (ED). Haufinyane tjena, likhopolo-taba tsa hore litsamaiso tse tšoanang tsa boko le lipotoloho tsa methapo ea kutlo li kentse letsoho liphellong tse putsang tse amanang le lijo le lithethefatsi. Ho ka nahanoa hore ho fetoha ka mekhoa e tšoanang ea methapo ea lijo le lithethefatsi [[68], [69], [70]], ho phahamisa likhopolo tsa hore mathata a ho ja joala a ka nkuoa e le boits'oaro bo lemalloang. Mona, re ntlafalitse lithuto tse bonts'ang monyetla oa ho ithuta likarolo tsa mantlha tsa mathata a ho ja, joalo ka ho ja ka mokhoa o qobelloang, le lipapatso tse sebelisitsoeng ho etsa lipatlisiso tsa ho lemalla lithethefatsi pele ho bongaka.
Ho nepahala ha poleloana e reng "ho lemalla lijo"
Ho ja ka ho qobelloa, ho tšoana haholo le ho qobelloa ho sebelisa lithethefatsi [78], 'me ho ja ka mokhoa o tlamang ho ka nkuoa e le "temallo" ka bohona. Liphuputso ho batho le liphoofolo tsa laboratori li bonts'itse hore, kathoko ho matla a lekanang, boitšoaro ba ho ja bo laoloa ke lintlha tse sa amaneng le taolo ea metabolic le tlhaiso-leseling e tsoang liphuputsong tsa bongaka e fana ka maikutlo a hore batho ba bang ba jang haholo ba ka ba le boits'oaro bo ts'oanang le ba lithethefatsi ha ba ja lijo tse monate. , [26]]. Ho 'nile ha etsoa tlhahiso ea hore ho ja haholo ha lijo tse nang le tatso ho ka hlahisa neuroadaptations ea nako e telele meputsong le marang-rang a khatello ea kelello ea [[83], [10]], e ts'oanang le e hlahisoang ke ts'ebeliso e mpe ea lithethefatsi ea nako e telele [84]. Ha li kopantsoe hammoho, bopaki bona bo fana ka maikutlo a hore ho ja ka qobello, hammoho le ho batla lithethefatsi ka mokhoa o qobelloang ho ka hlalosoa ho sebelisoa likhopolo tse tharo tse kholo tse khannang lipatlisiso tsa liteko tsa ts'ebeliso ea lithethefatsi, ka hona ho lekola monyetla oa mofuta oa "phetoho" ho tsoa ts'ebelisong e itekanetseng ea lijo tse khahlisang tlhekefetsong ea bona.
Bopaki ba morao-rao bo tsoang ho litoeba le litšoene bo bontša monyetla oa ho hlahisa mefuta ea liphoofolo ea mathata a ho ja [[71], [72], [77], [85], [86], [87]]. Ho bonts'itsoe hore likhoto tse nang le monyetla oa ho nka tharollo ea saccharin e se nang khalori kapa ho itšebelletsa li-infusions tse kenang methapong, ka mokhoa o ke keng oa latoloa ba ile ba khetha tharollo ea pele ho fapana le ea bobeli [77]. Sena se fana ka maikutlo a hore na limatlafatsi tse kholo tse lijong tse monate li ka kenya tšebetsong joang meputso ea boko ntle le mojaro oa tsona oa khalori [78]. Ho feta moo, lijo tse khahlisang li ka kenya ts'ebetsong sistimi ea methapo ea kutlo e amanang le moputso, tšusumetso le ho etsa liqeto [69]. Lijo tse hlabosehang haholo li baka mehopolo e tšoarellang nako e telele mefuteng e sa rateheng ea batho ea mofuta oa chokolete [86], 'me ho ba sieo ha moputso oa tšohanyetso ho baka boits'oaro bo ts'oanang le matšoenyeho (ke hore, tlhahlobo), ntle le liphetoho maemong a khatello ea kelello ea cortisol [ 87]. Ho its'etleha liphuputsong tsena, boits'oaro bo amanang le ho ithuta ha lintlha tse amanang le lijo ho bonahala bo le bohlokoa ketsahalong le / kapa ho khutleng hape ha mathata a ho ja. Kamora nako, kaha likarolo tsa mantlha tsa bokhoba ba lithethefatsi, joalo ka boits'oaro bo qobelloang ba ho batla le ho oela hape li kanna tsa hlahisoa hape ho sebelisoa mefuta e mengata ea liphoofolo, ho ka nkuoa e le monyetla oa ho ithuta ho lemalla lijo u sebelisa mefuta ea liphoofolo eo pejana e hlalositseng likarolo tsa mantlha tsa bokhoba ba lithethefatsi.
Motheo oa neural oa ho lemalla lijo
Ts'ebetso ea sehokela se nang le DA lipotolohong tsa moputso oa bokong ke eona e hlakileng le e ke keng ea qojoa e hlalosoang boitšoarong ba ho batla lijo le lithethefatsi [[25], [26], [69]]. Haholo-holo, ho lokolloa ha DA ho bonahala ho amana le moputso o ikhethang ho tsoa ts'ebelisong ea lithethefatsi le lijo ho batho [[25], [69]]. Tsoseletso e phetoang ea mesolimbic ea DA e susumetsoang ke ho pepesetsoa lithethefatsi tse lemalloang e hlahisa liphetoho tsa polasetiki ea boko tse lebisang ho batleng lithethefatsi hampe. Ka mokhoa o ts'oanang, ho pheta-phetoa lijo tse hlabosang khafetsa ho ka baka ts'ebeliso ea lijo tse qobelloang ho sebelisoa lits'ebetso tse ts'oanang tsa phetisetso ea methapo. Ho feta moo, lithuto tsa neuroimaging li senotse liphetoho polelong ea ho amohela li-DA lithutong tse ngata tse tšoanang le tse fumanoang lihloohong tse lemalloang ke lithethefatsi [[69], [78], [89], [90]].
Mathata a ho ja a khetholloa ke boitšoaro bo qobelloang ba ho ja, leha ho na le maemo a kotsi. Ho 'nile ha nahanoa hore tšebelisano e rarahaneng ea liphatsa tsa lefutso le tikoloho e kanna ea ba ntlha ea bohlokoa ea boits'oaro ba ho ja bo qobelloang [[91], [92]]. Liphuputso tse 'maloa li kentse li-receptor tsa DA tsa mofuta oa 2 (D2Rs) tšekamelong ea boits'oaro bo ts'oanang, joalo ka ha e etsahala litlamong tsa lithethefatsi [[18], [93]]. Ho feta moo, e bonts'itse tšebelisano ea tikoloho ea liphatsa tsa lefutso ka mokhoa oa ho qobella ba batlang / ho nka boitšoaro ba ts'ebeliso ea litoeba ba sebelisa C57 le litoeba tsa DBA maemong a hatelloang [[88], [94]]. Thutong ena, re hlahisitse boitšoaro bo qobelloang ba ho ja re sebelisa papiso ea khatello ea maemo a boits'oaro ba ho batla chokolete [71] molemong oa ho bapisa litoeba tse hatelletsoeng tsa C57 le DBA. Ho feta moo, ho 'nile ha nahanoa hore phumaneho e tlase ea li-D2R tse bokellaneng e nkuoa e le sesosa sa kotsi ea liphatsa tsa lefutso ketsahalong ea boitšoaro bo qobelloang ke lijo le hore tikoloho e ka baka boits'oaro ba ho ja bo fetelletseng bo fetolang polelo ea li-D2R ho striatum. Ho fihlela sepheo sena, re lekantse polelo ea D1Rs le D2Rs ho striatum le D1Rs, D2Rs le NE-ergic α1 receptors (α1Rs) maemong a mpFC, ka ho latellana, ke blot bophirima [88]. Re bonts'itse hore ho pepesehela boemo bo itseng ba tikoloho (thibelo ea lijo) bo susumetsang boitšoaro bo qobelloang ba ho ja, ho latela semelo sa lefutso, se amanang le phokotso e fumanehang ea NAc D2Rs. Ka lehlakoreng le leng, striatum D2Rs up-regulation le mpFC α1Rs down-regulation li susumetsoa nakong ea boits'oaro ba ho ja. Liphuputso tsena li tiisa karolo ea bohlokoa ea tšebelisano ea tikoloho le liphatsa tsa lefutso mokhoeng oa ho ja o qobelloang, hape e ts'ehetsa mohopolo oa hore phumaneho e tlase ea NAc D2Rs ke "kotsi" ea lefutso e bakang boitšoaro bo qobelloang ba ho ja. Kamora nako, striatum D2R le mpFC α1R counteract melao ho nahanoa hore e ka ba "likarabo tsa neuroadaptive" tse tsamaellanang le phetoho ho tloha ho susumetsoa ho ea ho boitšoaro bo qobelloang ba ho ja, mme ka lebaka leo ke ho lemalla lijo, joalo ka ha e se e le mohopolo oa bokhoba ba lithethefatsi [[88], [94 ]].
Electrophysiological motheo oa boitšoaro bo tataisoang ke lijo
Ho khahlisang ke hore ho fumanoe boteng ba mefuta e 'meli ea methapo ea kutlo ho NAc [[102], [103]]: li-spne interneurons tse potlakileng (FSIs) le li-spiny neurons tse mahareng (MSNs). Ho tlalehiloe hore li-FSI li thibela li-MSN ka matla, tse fanang ka taolo ea "nako ea bona ea spike" [[102], [104]], mme e arabelang ka mokhoa o fapaneng le oa li-MSN ho putsa [[102], [105]]. Liphuputso tsena li fana ka maikutlo a hore li-FSI le li-MSN li na le likarolo tse fapaneng mekhoeng eo ea boitšoaro e amanang le tšusumetso le ho ithuta tloaelo. Kamora nako, NAc e bapala karolo ea bohlokoa ho boits'oaro le boits'oaro. Ka tloaelo, ho fumanoe hore methapo e mengata ea methapo ea kutlo ho NAc le VS e arabela ka mokhoa o fapaneng ka mokhoa o mong le o mong oa likarolo tse khahlisang le tse felisang [[97], [98], [99], [101]]. Kaha li-neuron tse ngata tsa NAc li thibetsoe ho feta ho hlasimoloha nakong ea boits'oaro, mekhoa ea thibelo ea NAc e ka ntlafatsa boits'oaro ba ho batla lijo. Sena ha se bakoe ke ho se sebetse hoa NAc ka kakaretso, empa ka lebaka la ho khutsisa li-neuron tse joalo tse thibelang boits'oaro ba ho batla lijo. Leha ho le joalo, li-neurone tse ngata tse thibelitsoeng tse khannang boits'oaro ba batho ba ho ja li thabile haholo nakong eo basebetsi ba arabang litaba tse amanang le lijo tikolohong. Ho ka buisanoa ka taba ea hore na ho ka khoneha ka motlakase ho khetholla karolo e sa arohaneng ea likarolo tsa mesolimbic tsa sistimi ea moputso ho etsa lipatlisiso tsa phetoho e ka bang teng ho tloha mokhoeng o tloaelehileng oa ho ja.
Nahanisisa
Potso ea pele ke hore na likhopolo tse tharo tsa khopolo-taba, "khothaletso ea matla a ho hlonepha", "hedonic dysregulation theory" le "theology-based learning theory" li khona ho hlalosa ka bomong likarolo tsa psychopathological tsa bokhoba ba lithethefatsi. Ntle le moo, ho na le monyetla oa hore likhopolo tsena tse tharo li ka nkuoa e le likarolo tsa mohopolo o ikhethileng o akaretsang o ka hlalosang hantle likarolo tsa psychopathological tsa bokhoba ba lithethefatsi. Khopolo-taba ea hore "tšusumetso e mpe", "hedonic dysregulation", le "thuto e sa sebetseng" e ka ba likarolo tse le 'ngoe tse ka kenyelletsoang hammoho le "nakoana e tsoelang pele" moahong o rarahaneng oa ho batla / ho sebelisa lithethefatsi o lokelang ho tsotelloa.
Karolo e tlohang ts'ebelisong e mpe ea lithethefatsi ho ea tlhekefetsong e amana le phetoho e tsoang ho matlafatso e ntle ho isa ho e mpe, ka liphetoho ho motheo oa tšusumetso [106]. Moputso oa lithethefatsi o na le likarolo tse peli: e 'ngoe ea takatso ea lijo (e shebileng lijo) le e' ngoe e phethelang (tlhahlobo ea hedonic), eo hape e bitsoang "ho batla" le "ho rata", ka ho latellana. Ho hlalositsoe hore "ho batla" le "ho rata" ho ka sebetsa ka boikemelo, ho hlalosa karohano ea kelello le kelello pakeng tsa bona [[2], [5]]. Ho feta moo, ho 'nile ha hlalosoa hore takatso (e matla e hlokang) le liphetoho tse tsoelang pele tsa methapo ea pelo lia ameha ho tloha ts'ebetsong ho ea ts'ebetsong [11]. Ho feta moo, ho 'nile ha boleloa hore ke thuto e mpe e thehiloeng mokhoeng o ka qholotsang boitšoaro bo batlang lithethefatsi [4]. Leha ho le joalo, likhopolo-taba tsena tse tharo li khona ho hlalosa likarolo tse le 'ngoe tsa bothata bohle ba bokhoba ba lithethefatsi, joalo ka boits'oaro ba ho batla ka mokhoa o tlamang le ho khutlela morao. Ntle le moo, ho a khonahala ho nahana ka "tsoelo-pele ea nakoana" eo ho eona (1) ho ithuta ka mokhoa o tsoelang pele o tsoelang pele ho etsahalang nakong ea ts'ebeliso e mpe ea lithethefatsi, nakong eo ts'ebetso ea hedonic e ts'oaroang hape (2) e lebisang ho "hlohlelletsoang" ho hlohlelletsa butle-butle. boits'oaro ba ho sebelisa lithethefatsi. Kamora nako, ts'usumetso, ts'oaetso ea hedonic, le thuto e ipapisitseng le tloaelo li ka nkuoa e le likarolo tse le 'ngoe tsa boits'oaro bo ikhethang le bo rarahaneng ba ho batla / ho nka lithethefatsi; Bopaki ba neuroanatomical le neurobiological bo tšohloang mona bo lumellana le likhopolo-taba tsena. Leha ho le joalo, leha lithuto tse 'maloa li fupulitse hore na litsobotsi tsena tse tharo li ameha joang lithethefatsing, ha ho tsejoe hanyane ka ho ba teng ha tsona ka "nako e tsoelang pele" ea nakoana. Liphuputso tse 'maloa tsa batho le tsa liphoofolo li bonts'itse hore nako ea moputso e na le karolo e matla ho sebetsaneng le moputso [[22], [23]]. Ntle le moo, lifensetere tsa nako le "litefiso tsa moputso" li bohlokoa haholo bakeng sa maemo, mme li-neuron tsa DA li kentse letsoho ho sebetseng ha tlhaiso-leseling ea nakoana ka meputso. Li-neuron tsa DA-ergic tsamaisong ea meso-cortico-limbic li bonts'a nako ea ho putsa esale pele ka kutloisiso e susumetsoang ke likarabo tse amanang le moputso le ke monyetla oa monyetla oa moputso [22]. Sena se matlafatsa likhopolo tsa "tsoelo-pele" ea nako e le ngoe ho tloha ts'ebelisong ea nako le nako ho isa ts'ebelisong e mpe ea lintho, e buelletsoeng ke potoloho ea meso-cortico-limbic DA-ergic. Boemong ba bongaka, hona ho tla thusa ho utloisisa hore na o kenella joang "neng" nako ea "temporal Continu" ho tloha ts'ebelisong e ngoe ea tšebeliso e mpe ea lithethefatsi, le ho hlahisa maano a macha a kalafo molemong oa ho qoba bofetoheli ba ho batla lithethefatsi / ho nka boitšoaro. Ho feta moo, ho 'nile ha boleloa hore seo ho thoeng ke "potoloho ea amygdala" se ka abeloa ho sebetsa ka litlamorao, maikutlong le litloaelong tsa ho lemalla lithethefatsi [[63], [64], [65], [66]] . Meaho ea boko e nang le amygdala e atolositsoeng e ts'oana le morpholoji, immunohistochemistry le khokahano.
Boitsebiso bo ntseng bo hola bo nahana ka monyetla oa ho ba le boitšoaro / 'mele o kenang lipakeng tsa bokhoba ba lithethefatsi le lijo. Mosebetsi oa morao-rao oa sehlopha sa rona o supile hore phetiso ea mpFC Norepinephrine (NE) le eona e bapala karolo ea bohlokoa ho qobelloeng ho batla / ho nka boits'oaro, e fana ka maikutlo a hore mpFC NE e na le seabo ho susumelletsang ho batla / ho nka lijo, tse laoloang ke phetiso ea mesolimbic DA-ergic [71]. Ho feta moo, ho bonts'itsoe hore mpFC NE e ntlafatsa ts'oaetso ea methapo ea pelo ea GABA-ergic ka li-receptor tsa α1 [110], e fana ka maikutlo a karolo ea bohlokoa ea NE ho ts'ebetso ea ho khutlela mokhoeng oa ho batla lithethefatsi [[111], [112], [113] , [114], [115]]. Kahoo, lipatlisiso tse ling mabapi le karolo ea NE ho tsekisanong le li-interneuronal amygdaloid ts'ebetso li khothalelitsoe ka matla, ho utloisisa hamolemo tsela e ka bang ea meso-cortico-limbic ho fetoheng ha lithethefatsi le lithethefatsi [[116], [117], [ 118]].
Potso ea bobeli ke hore na likarolo tse tharo tse hlahisitsoeng kaholimo (tšusumetso e mpe, ts'oaetso ea hedonic le thuto e sa tloaelehang), le boits'oaro ba batho ba lemaletseng lithethefatsi le tsona li ka hlalosa boits'oaro ba psychopathological bo khethollang mathata a ho ja. Leha ho na le lithuto tse 'maloa mabapi le ho kopana hoa boitšoaro / methapo ea pelo lipakeng tsa bokhoba ba lithethefatsi le lijo, ha ho tsejoe hanyane ka karolo e ka bang teng ea "tšusumetso e mpe", "ho nyenyefatsa ha hedonic" le "thuto e sa sebetseng" ka boits'oaro ba psychopathological bo khethollang phetoho e ka bang teng ho lemalla lijo, ho tloha ho tloaelehileng ho ea ho boitšoaro bo tlamang Likhopolo tsena tse tharo li ka tlatsetsa kutloisisong e ntlafetseng ea likarolo tsa kelello tsa mathata a ho ja, joalo ka ts'ebeliso e tlamang le ho khutlela mokhoeng oo, o ts'oanang le litšobotsi tsa bokhoba ba lithethefatsi. Kahoo, mesebetsi ea nako e tlang e ka ikemisetsa ho utloisisa hamolemo lintlha tsa bohlokoa tse khethollang likarolo tsa psycho-physio-pathological tsa lithethefatsi le lithethefatsi, joalo ka ts'ebeliso e tlamang le ho khutlela morao.
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