Khatello ea Kelello e sa Feleng, Tšebeliso ea Lithethefatsi le Tlokotsi ea ho Lemalla (2008)

TLHOKOMELISO: Matšoenyeho a ka eketsa tlokotsi ea ho lemalla. Matšoenyeho a ka eketsa tlokotsi ea ho lemalla, ho kenyeletsa le lithethefatsi tse litšila tse tsosang takatso ea boitšoaro bo bobe
Khatello ea kelello e sa feleng, ts'ebeliso ea lithethefatsi, le tlokotsi ea ho lemalla

Rajita Sinha Ann NY Acad Sci. Sengoloa se ngotsoeng; e fumaneha ho PMC 2009 August 26. E phatlalalitsoe ka foromo e hlophisitsoeng ea hoqetela e le: Ann NY Acad Sci. 2008 Mphalane; 1141: 105-130. Doi: 10.1196 / annals.1441.030. Lefapha la Psychiatry, Sekolo sa Bongaka sa Yale University, New Haven, Connecticut, USA Aterese ea mangolo: Rajita Sinha, Ph.D., Moprofesa, Lefapha la Psychiatry, Motsamaisi, Setsi sa khatello ea maikutlo sa Yale Yunivesithi, Yale University School of Medicine, 2 Church Stress Boroa, Suite 209, New Haven, CT 06515. Lentsoe: + 203 − 974 − 9608; fekse: + 203 − 974 − 7076. Email: [imeile e sirelelitsoe]

inahaneloang
Khatello ea kelello ke ntho e tsebahalang e ka bakang tlhabollo ea bokhoba ba tahi le ho lemallang bothateng ba ho lemalla. Letoto la liphuputso tse thehiloeng ho baahi le la mafu a tšoaeang li bonts'a khatello ea maikutlo le maemo a fapaneng a motho ka mong a rerang tšebeliso ea lithethefatsi le tlhekefetso. Patlisiso e entsoeng esale pele e boetse e bonts'a hore ho pepeseha khatello ea maikutlo ho ntlafatsa ts'ebetso ea lithethefatsi le ho khutlisa ho batla lithethefatsi ho liphoofolo tse nang le boiphihlelo. Litlamorao tse bohloko tsa khatello ea pele ea bophelo, ho hlekefetsoa ha bana le mathata a fetotsoeng ho corticotropin ho tlosoa hoa mabaka le hypothalamic-pituitary-adrenal axis (CRF / HPA), extrahypothalamic CRF, aronomal arousal, le system e bohareng ea noradrenergic le tsona li hlahisoa. . Litlamorao tsa liphetoho tsena ho li-corticostriatal-limbic susumetsang, ho ithuta le ho feto-fetoha ha lits'ebetso tse kenyelletsang mesolimbic dopamine, glutamate, le gamma-amino-butyric acid (GABA) litseleng li tšohloa e le sepheo sa pathophysiology e amanang le kotsi e amanang le khatello ea maikutlo. Litlamorao tsa tšebeliso ea lithethefatsi khafetsa le tse sa fetoheng kamehla lithutong tsena tse nang le khatello ea maikutlo le ts'usumetso e boetse e hlahlojoa, ka tlhokomelo e ikhethileng ea phello ea liphetoho tsena taolong ea khatello ea maikutlo, taolo ea tšusumetso, le nts'etsopele ea ho batla lithethefatsi tse tlamang le ho khutlisetsa ts'oaetso. Kamora nako, ho hlahisoa liphokoletso tsa ho etsa hore re utloisise botsoalle lipakeng tsa khatello ea maikutlo le bokhoba ba ts'ebeliso ea ts'ebetso, ka tšepo ea hore ho araba lipotso tsena tse se nang likarabo ho tla susumetsa haholo mekhoa e mecha ea thibelo le kalafo ho sebetsana le tlokotsi ea ho lemalla.

Selelekela
Ho sithabela maikutlo ho 'nile ha tsebahala ho eketsa ho ba kotsing ea ho lemalla. Lilemo tse leshome tse fetileng li lebisitse keketseho e kholo ho utloisiseng mekhoa e ka sehloohong ea mokhatlo ona. Lits'oants'o tsa boitšoaro le tsa neurobiological li ntse li bonoa, 'me ho fumanoe bopaki bo bong ba liphetoho tsa limolek'hule le tsa cellular tse amanang le khatello ea maikutlo le ho lemalla. Lithuto tsa batho li ruile molemo ka ho hlaha ha lisebelisoa tse bobebe tsa ho nahana ka boko le tlhahlobo ea sefapano ea mekhoa e khothalletsoang ea laboratori ea khatello ea maikutlo le ho lakatsa le ho kopanela le bona libakeng tse ikhethileng tsa boko tse amanang le meputso le kotsi ea ho lemalla. Pampiri ena e bua haholo ka kamano e lipakeng tsa khatello ea maikutlo le bokhoba ba batho empa e boetse e tsoa libukeng tse pharalletseng tsa liphoofolo ho ts'ehetsa maikutlo a khothalletsoang. Tlhaloso ea khatello ea maikutlo le underpinnings ea eona ea neural e hlahisoa ka mokhoa o ikhethileng oa litlamorao tsa ts'usumetso le boits'oaro. Boemong ba bopaki bo matla ba lefu la seoa bo hokahanyang mahlomola a bongoana le batho ba baholo le kotsi ea ho lemalla, ho hlahisoa lipatlisiso tsa mantlha le tsa botho tse supang mekhoa e tlatselletsang ea motheo oa mokhatlo ona. Karolo e mahlonoko e bonoa bakeng sa li-circuits tsa pele tse kenyelletsoang ho ithuteng ho tenyetsehang le tšebetso ea botsamaisi, ho kenyelletsa taolo ea khatello le litakatso / litabatabelo, kopanong pakeng tsa khatello ea maikutlo le kotsi ea ho lemalla. Leha ho le joalo, lipotso tse 'maloa li lula li sa arajoa ho utloisisa kotsi ea ho lemalla ho amanang le khatello ea maikutlo,' me e ea hlahlojoa e le ho tsebisa lipatlisiso tsa nako e tlang. Kamora nako, litlamorao tsa tšebeliso e mpe ea lithethefatsi ho khatello ea maikutlo le litsela tsa moputso haholo-holo mabapi le kotsi ea ho khutla li hlahlojoa. Lits'oants'o tsa nako e tlang mabapi le ho sebetsana le kotsi ea ho boelana le khatello ea maikutlo tse amanang le khatello ea maikutlo maemong a kliniki le tsona li tšohloa.

Khatello ea maikutlo, khatello ea maikutlo le ho ba le boitšoaro
Poleloana “khatello ea maikutlo” e bua ka lits'ebetso tse kenyelletsang pono, boits'oaro, le karabelo liketsahalong tse kotsi, tse sokelang kapa tse qholotsang.1-3 Boemo ba khatello ea maikutlo bo ka baka maikutlo kapa bohloeki 'me ba kenya likarabo tsa khatello ea maikutlo le lits'ebetso tse lumellanang ho khutlisetsa homeostasis.2,4– Mehlala ea 6 Mehlala ea khatello ea maikutlo e kenyelletsa likhohlano tsa batho, ho senyeha ha kamano, lefu la setho se haufi sa lelapa, le ho lahleheloa ke ngoana. Matšoenyeho a tloaelehileng a 'mele ke tlala kapa ho haelloa ke lijo, ho hloka boroko kapa ho hloka boroko, khatello e matla ea maikutlo kapa hypothermia, le litsi tsa tlhekefetso ea lithethefatsi. Ntle le moo, tšebeliso ea kamehla ea lithethefatsi tse ngata tsa kelello tse hlaselang hape e sebetsa e le khatello ea maikutlo litabeng tsa meriana. Mofuta ona oa conceptualization o lumella ho nahanoa ka thoko ho (1) liketsahalo tsa kahare le kantle kapa tse susumetsang tse hlokang kapa ho jara phello ea setho; (2) lits'ebetso tsa neural tse lekolang litlhoko le ho lekola ho fumaneha ha lisebelisoa tse feto-fetohang ho sebetsana ka katleho le litlhoko (boitsebelo); (3) ketsahalo e ikokobelitseng, boits'oaro, le boikoetliso bo bonts'ang khatello ea setho sa mmele; (4) neuroadaptations tsamaisong ea methapo ea maikutlo le e susumetsang e amanang le khatello ea maikutlo e sa foleng; le (5) boikoetliso, boikutlong, le boikoetliso ba mmele ho arabela ho khatello ea maikutlo.
Leha khatello ea maikutlo hangata e amahanngoa le ho ama hampe le ho sithabela, e ka kenyelletsa "khatello e ntle ea maikutlo" e thehiloeng ho tšusumetso ea kantle le e ka hare e thata empa e le nako e telele 'me e fana ka likarabo tse lemohang le tsa boits'oaro tse hlahisang mohopolo oa ho sebetsa hantle le se finyeletsoeng, 'me se ka bonoa e le se monate ebile se thabisa.1,3,6,7 Maemo a joalo a itšetleha ka ts'usumetso e lekaneng le ts'ebetso ea botsamaisi ho fihlela sephetho se lebisitsoeng ho sepheo le homeostasis.3,6,8 Leha ho le joalo, ho phehella, ho pheta-pheta, kapa ho phephetsa khatello ea maikutlo ka nako e telele, mohlala, linaha tse amanang le ho eketseha ho matla kapa ho phehella ha khatello ea maikutlo — ho hoholo le ho se laolehe le maemo a sithabetsang, ho theola mohopolo kapa ho tenyetseha, le ho eketseha ha karabelo ea khatello ea maikutlo le kotsi ea ho hloloheloa ho ea pele lapeng.1,6,9-11 Ka hona, boholo ba botebo , controllability, ho tsebahala pele, ho sebetsa hantle le ho tenyetseha ha maemo ho bohlokoa ka tlasa tlase fumana karolo ea khatello ea maikutlo kotsing e eketsehang ea boits'oaro bo bobe joalo ka ho lemalla.

Pono le bohlahlobi ba khatello ea maikutlo bo its'etleha ho likarolo tse ikhethileng tsa khopolo ea kantle kapa ea kahare, sebopeho sa botho, ho fumaneha hoa lisebelisoa tsa kahare (ho kenyeletsa boemo ba mmele), maikutlo a pele ho nako (ho kenyelletsa litumelo le litebello) Tlhahlobo ea maikutlo e susumetsa joalo ka khatello le sephetho sa boikoetliso, boits'oaro, maikutlo le maikutlo a arohaneng. Libaka tsa boko tse kang amygdala, hippocampus, insula, orbitof mbeleal, medial prepoleal, le cortates cortices li ameha molemong oa pono le bohloeki ba maikutlo a sithabetsang le a sithabetsang, le mohopolo oa bongo (locus ceruleus le libaka tse amanang le boroko), hypothalamus, thalamus, libaka tse nang le maemo a phahameng le a mang li nka karolo karabong ea 'mele le ea maikutlo. Ka bobeli libaka tsena li kenya letsoho phihlelong ea mahlomola. Likarabo tsa 'mele li bonahala ka litsela tse peli tse kholo tsa khatello ea maikutlo, e leng corticotropin releasing factor (CRF) e lokollotsoeng ho tloha patricricular nucleus (PVN) ea hypothalamus, e tsosang li-hormone tsa adrenocorticotrophin ho tsoa pituitary ea ka ntle, eo ka mora moo e tsosang sephiri sa cortisol / corticosterone ho tsoa. gland ea adrenal, le tsamaiso ea methapo e ikemetseng, e hokahantsoeng ka lits'ebetso tsa kutlo tsa kutlo tsa kutlo (SAM ).4,12

Ntle le moo, CRF e na le tšusumetso e pharalletseng libakeng tsa extrahypothalamic ho pholletsa le libaka tsa corticostriatal-limbic dikarolo mme e bapala karolo ea bohlokoa ho fetoheng karabelo ea khatello ea maikutlo le boitšoaro.13 Ho feta moo, li-catecholamine tse bohareng, haholo-holo noradrenaline le dopamine, li kenya letsoho ho fetoleng mekhoa ea sepheo sa boko (ho kenyeletsa le sebaka sa ho kenella ka mokokotlong kapa VTA, li-nucleus accumbens [NAc], le libaka tsa pele tsa [mPFC]) tse bohlokoa ho laoleng khatello ea maikutlo, ho fana ka taolo ea boits'oaro le boits'oaro, le ho buisana ka likarabo tsa boits'oaro le tsa kelello tse bohlokoa bakeng sa ho ikamahanya le maemo le homeostasis.8,14,15 The hypothalamic and extrahypothalamic CRF pathways le bohareng ba catechoamines e ts'oara mekhoa ea ts'usumetso ea kelello ho ama ka mokhoa o tebileng mekhoa e lumellanang le ea homeostatic. Mohlala, likarolo tse fapaneng tsa medial preambilial cortex li kentse letsoho mesebetsing e phahameng ea kelello kapa taolo e phahameng, joalo ka ho laola le ho thibela litšusumetso, ho laola khatello ea maikutlo, ho tsepamisa maikutlo le ho tjeka, ho lekola boits'oaro, ho hokahanya boits'oaro le litlamorao ka nako, ho nahana ka mekhoa e meng pele ho nka khato, Likarabo tse nkang liqeto.16,17 Boithuto ba kelello le boits'oaro bo bontšitse ka mokhoa o hlakileng hore ka maemo a ntseng a eketseha a khatello ea maikutlo le a mmele kapa a amang hampe, ho na le ho fokotseha ha taolo ea boits'oaro le ho eketseha ha boiketsiso, le ka maemo a ntseng a eketseha a khatello, le ho hloka taolo ha maikutlo , kholo ea kotsi ea boits'oaro bo bobe.18-27 Bopaki ba tšebetso ea methapo e bonts'a hore ka maemo a ntseng a eketseha a khatello ea maikutlo, ho na le ho fokotseha ha ts'ebetso ea pele le ts'ebetso e eketsehang ea methapo ea methapo e emisang boitšoaro bo tlase le taolo ea kelello.28,29 Ka hona, ts'ebetso ea kelello e susumetsang. Litsela ke liphofu tsa mantlha tsa methapo ea boko Ho sebelisa lik'hemik'hale le ho fana ka mokhoa o bohlokoa o ka sebelisang khatello ea maikutlo ho sithabetsang ha motho a le mothating oa ho lemalla.

Khatello ea Kelello le Kholiso ea Lits'oants'o Tse Tebileng
Ho na le sengoloa sa bohlokoa khokahanong ea bohlokoa lipakeng tsa khatello ea maikutlo e matla le e sa foleng le tšusumetso ea ho sebelisa lithethefatsi tse lemalloang (bona30 bakeng sa tlhahlobo). Boholo ba likhopolo tse kholo tsa bokhoba ba tahi bo boetse bo supa karolo ea bohlokoa ea khatello ea maikutlo mekhoeng ea ho lemalla. Tsena li tsoa mehlaleng ea kelello ea bokhoba ba tahi bo shebang tšebeliso ea lithethefatsi le tlhekefetso joalo ka leano la ho sebetsana le khatello ea maikutlo, ho fokotsa tsitsipano, ho itaola, le ho fokotsa khatello e amanang le ho tlohela chelete, 31-37 ho mefuta e amanang le khatello ea maikutlo le khatello ea maikutlo. Likhopolo tsa allostasis ho hlalosa kamoo neuroadaptations moputsong, ho ithuteng, le tseleng ea khatello ea maikutlo li ka ntlafatsang takatso, tahlehelo ea taolo le khatello, likarolo tsa bohlokoa phetohong ho tloha ts'ebeliso e sa tloaelehang ea lintho ho ea ho se khone ho emisa ts'ebeliso e sa feleng leha ho e-na le litlamorao tse mpe. Karolo ea bokhoba ba taolo.38-40 Karolong ena, re sekaseka lintlha tse khahlisang tsa bopaki bo supang karolo ea bohlokoa eo khatello ea maikutlo e e phethang ho eketseheng ha tlhekefetso ea ho lemalla.

Mathata a sa foleng le ho ba kotsing e eketsehileng ea ts'ebeliso ea lithethefatsi
Ho na le bopaki bo bongata bo tsoang liphuputsong tse etselitsoeng baahi le tsa bongaka tse tšehetsang kamano e ntle lipakeng tsa mahlomola a kelello, tšusumetso e mpe, le khatello ea maikutlo le ts'oaetso ea ho lemalla. Bopaki sebakeng sena bo ka aroloa ka mefuta e meraro e pharaletseng. Ea pele e kenyelletsa lithuto tse lebelletsoeng ho bonts'a hore bacha ba tobanang le liketsahalo tse mpe tsa morao tjena tse mpe tse bonts'ang maemo a bonts'a likotsi tsa ts'ebeliso ea lithethefatsi le tlhekefetso.41-55 Liketsahalo tse mpe tsa bophelo tse kang ho lahleheloa ke motsoali, tlhalo ea batsoali le likhohlano, tšehetso e tlase ea batsoali, tlhekefetso ea 'mele le tlhekefetso, maikutlo tlhekefetso le ho se tsotelle, ho itšehla thajana le kamano e khelohileng, le sebopeho sa lelapa la motsoali a le mong kaofela li amahantsoe le kotsi e eketsehang ea tlhekefetso ea lithethefatsi.

Mofuta oa bobeli oa bopaki ke kamano e lipakeng tsa ho sithabela maikutlong le ho tšoaroa hampe, ho ama hampe, khatello e sa feleng le kotsi ea tlhekefetso ea lithethefatsi. Ho na le bopaki bo eketsehileng ba hore ho na le kopano e eketsehileng lipakeng tsa tlhekefetso ea thobalano le ho hlekefetsoa ha ngoana le ho hlekefetsoa le ts'ebeliso e mpe ea lithethefatsi le tlhekefetso.56-60 Ho boetse ho na le bopaki ba hore liketsahalo tsa morao-rao tse mpe tsa bophelo le tlhekefetso ea 'mele le ea thobalano e mong le e mong e fana ka monyetla oa ho ipeha kotsing ea ho lemalla. Ntle le tlhekefetso ea thobalano le 'mele, litlamorao tse mpe le mahlomola a sa foleng a rerela tlokotsing ea ho lemalla. Liphumano li bonts'a hore litla-morao tse mpe, ho kenyelletsa le maikutlo a mabe a tlisoang ke ho hlekefetsoa ha lithethefatsi.58-61 Liphuputso tse 'maloa li boetse li bontšitse kamano e kholo pakeng tsa ho ata ha khatello ea maikutlo le mathata a ho tšoenyeha, ho kenyeletsa mathata a morao-rao a sithabetsang maikutlo (PTSD), mathata a boits'oaro ba boitšoaro. le kotsi e eketsehang ea mathata a ts'ebeliso ea lithethefatsi.67-68 Ha khatello ea kelello e amahanngoa haholo le ho ata ha khatello ea maikutlo le khatello ea maikutlo le khatello ea maikutlo e sa foleng, 78 mekhatlo ena e phahamisa taba ea hore na mathata a kelello a hlalosoang e le khatello ea maikutlo a sa foleng a ka baka lebaka la mokhatlo oa bohlokoa pakeng tsa khatello ea maikutlo le tšebeliso ea lithethefatsi.

Mofuta oa boraro oa bopaki bo tsoang lipatlisisong tsa palo ea sechaba, lipatlisiso tsa morao-rao li hlahlobile ho pepesetsoa ha bophelo ba khatello ho ba khatello ea maikutlo le phello ea mathata a eketsehang a ho ba kotsing ea ho lemalla ka mor'a ho bala lintlha tse 'maloa tsa taolo tse joalo ka morabe / morabe, bong, boemo ba sechaba le boemo ba tlhekefetso ea lithethefatsi, ho ata ha mathata a mafu a kelello, nalane ea lelapa ea tšebeliso ea lithethefatsi, le mathata a boits'oaro le boitšoaro.81,82 Mathata kapa khatello ea maikutlo e ile ea hlahlojoa ho sebelisoa mokhoa oa ho hlahloba le ho bala palo ea liketsahalo tse fapaneng tse bileng teng ka nako e fanoeng nakong ea nako ea bophelo. Litlamorao tsa distal (liketsahalo tse etsahetseng ho feta selemo sa 1 pejana) le liphihlelo tsa khatello ea maikutlo (liketsahalo nakong ea selemo sa 1 sa morao-rao), le litlamorao tsa tsona litekanyetsong tsa likopano tsa tšebeliso ea lithethefatsi le tsona li ile tsa hlahlojoa. Liphumano li bonts'a hore palo e eketsehang ea liketsahalo tse sithabetsang e ne e le ponelopele e kholo ea ts'ebeliso ea joala le lithethefatsi ka mokhoa o itšetlehileng ka tekanyetso, esita le ka mor'a ho bala ka mabaka a taolo. Liketsahalo tse ka thoko le tse kholo li bohlokoa haholo mme ka boikemelo li amme ts'oaetso ea ho lemalla. Ntle le moo, litlamorao tse tlisoang ke tekanyetso ea khatello ea maikutlo e ka bang kotsing ea ho lemalla li ile tsa ba teng ho ba batona le ba Caucasian, African-American, le morabe oa naha ea Spain. Mefuta ea liketsahalo tse bohloko tse amanang haholo le ho lemalla ho lemalla e le tlhalo ea motsoali kapa likhohlano, ho lahloa kherehloa, ho qobelloa ho phela kantle le batsoali, ho lahleheloa ke ngoana ka lefu kapa ho tlosoa, ho se tšepahale ha tse ling tsa bohlokoa, ho lahleheloa ke ntlo bakeng la koluoa ​​ea tlhaho, lefu la ea haufi , ho hlekefetsoa maikutlong kapa ho se tsotelle, tlhekefetso ea thobalano, peto, tlhekefetso ea 'mele ke motsoali, mohlokomeli, setho sa lelapa, molekane, kapa e mong oa bohlokoa, lehlatsipa la ho thunya ka sethunya kapa liketso tse ling tse mabifi, le ho shebella tlhekefetso e mabifi. Tsena li bonts'a liketsahalo tse sithabetsang haholo le tse sithabetsang maikutlo, tseo ka tloaelo li sa laoleheng ebile li sa reroang. Lethathamo la 1 le akaretsa mefuta ea liketsahalo tsa bophelo, khatello ea maikutlo e sa foleng, tšoaro e mpe, le maemo a motho ka mong a amanang le kotsi ea ho lemalla.

TABLE 1
Mefuta ea Liketsahalo Tse fapaneng tsa Bophelo, Ho sithabela Maikutlong, Khatello ea Kelello le Maemo a Motho a Phethahetseng a Kotsi ea ho Lemaletse Kotsi

Khatello ea Khatello ea Khatello ea Khatello ea Kelello E Eketsa Qalo le Phallo ea Ts'ebetso ea Lithethefatsi
Ho na le bopaki bo tsoang liphuputsong tsa liphoofolo ho ts'ehetsa maikutlo a hore ho pepesetsoa khatello ea maikutlo ho matlafatsang khatello ea maikutlo ho eketsa ts'ebetso le ho eketseha ha tšebeliso ea lithethefatsi le tlhekefetso (bona30,83 bakeng sa litlhahlobo). Mohlala, mehlaleng ea liphoofolo, khatello ea ho hloloa ha sechaba, ho itšehla thajana, ho tsitsipana le ho tsitsipana maotong, khatello ea maikutlo le khatello ea maikutlo li tsebahala ka ho ntlafatsa ho nkela opiates, joala le tsamaiso ea maikutlo ea psychostimulant, ka likatse tse amanang le mofuta oa khatello ea maikutlo, liphatsa tsa lefutso. nalane ea liphoofolo, le mefuta e fapaneng ka mofuta oa lithethefatsi (bona84-87 bakeng sa litlhahlobo). Hape, leha ho na le liphumano tse mpe, bopaki bo bong bo supa hore khatello ea bophelo ba pele, ho sebelisa lits'ebetso tse joalo ka ho arohana ka thoko kapa karohano ea bo mme, le khatello ea maikutlo e telele le e phetoang e emelang liphihlelo tsa khatello ea maikutlo, e ntlafatsa boits'oaro ba nicotine, psychostimulants, le joala le / kapa litlamorao tsa boits'oaro bo bobe ba tsona.88-93 Haholo-holo, thobalano e bapala karolo ea bohlokoa ho ts'oenyellong e amanang le khatello ea maikutlo litlamorao tse matlafatsang tsa lithethefatsi le ho matlafatsong ea khatello ea maikutlo ea boitaolo ba lithethefatsi.93-97 Ho batho, ho na le bopaki bo bongata bo tsoang ho ba tlang pele le lithuto tsa nako e telele ho ts'ehetsa litlamorao tsa khatello ea tšebeliso ea lithethefatsi le ho nyoloha hoa bacha le bacha ba banyenyane.24,98-109 Ho feta moo, ho na le phapang ea thobalano litlamorao tsa ho sithabela maikutlong le ts'ebeliso e mpe ea menyetla ea thuto e tlisoang ke ho lemalla.74,110-114 litlamorao tsa ho pepesetsoa khatello ea maikutlo ts'ebelisong ea lithethefatsi li lekanyelitsoe ho lithethefatsi tsa molao tse joalo ka joala le nikotine, ka mabaka a boitšoaro. Leha ho le joalo, ho na le bopaki ba hore khatello ea maikutlo e eketsa ho tsuba le ho tsuba nicotine (bona83 bakeng sa tlhahlobo), empa litlamorao tsa nalane ea ho nooa, nalane ea mahlomola, khatello ea maikutlo sechabeng, le litebello li tsejoa li bapala karolo lithutong tsena tsa liteko.

Mekgwa e ka bang teng Tlas'a khatello ea Khatello ea Kelello Khahlanong le Khatello ea Khalefo
Ha bopaki bo sebelisang mekhoa e fapaneng bo bokelletse ho ts'ehetsa phello e kholo ea khatello ea maikutlo bakeng sa ts'enyo ea ho lemalla, karolo ena e hlahloba lipatlisiso mabapi le lihokela tsa neurobiological lipakeng tsa khatello ea maikutlo le litsela tsa moputso tse hlahisoang ke lithethefatsi tse hlekefetsang. Hoa tsebahala hore thepa e matlafatsang ea lithethefatsi tsa tlhekefetso e kenyelletsa ts'ebetso ea tsona ea mesolimbic dopaminergic (DA) pathways, e kenyeletsang dopamine neurons e simolohileng sebakeng sa ventral sekheo le ho fetela ho ventral striatum le preortal cortex (PFC) .115– 117 Tsela ena e kenyelletsa ho abela ho ba maqhubu a ho susumetsa, ts'ebetsong ea moputso, le ho ithuta le ho ikamahanya le maemo.14,118 Lithuto tsa monahano oa bongo oa motho li ts'ehetsa karolo ea lits'ebetso tsena moputsong oa lithethefatsi, joalo ka li-psychostimulants, joala, opioids, le nikotini kaofela li kenya ts'ebetsong matla Mesebetsi ea mesolimbic DA, haholo-holo, ventral le dorsal striatum, 'me ketsahalo e joalo e amanang le litekanyetso tsa lithethefatsi tsa boemo bo holimo kapa bo mafolofolo le ho lakatsa.119-126

Leha ho le joalo, ho pepeseha ha khatello ea maikutlo le maemo a ntseng a eketseha a glucocorticoids (GC) e boetse e ntlafatsa tlhahiso ea dopamine ho NAc.127-132 Suppression of GC ka adrenalectomy e fokotsa maemo a dopamine tlasa maemo a basal le likarabelo tsa khatello ea maikutlo le psychostimulants.131,133 Leha ho le joalo, GC e sa feleng. DA synthesis le phetoho ea eona ho NAc, 134 e fana ka maikutlo a hore liphetoho tse mabapi le li-axis tsa hypothalamic-pituitary-adrenal (HPA) le "glucocorticoids" li ka ama phetiso ea DA haholo. Ho boetse ho na le bopaki ba hore, joalo ka lithethefatsi tsa tlhekefetso, khatello ea maikutlo le khokahano e kopaneng ea CRF le li-glucocorticoids li ntlafatsa tšebetso ea glutamate ho VTA, eo ka lehlakoreng le leng e matlafatsang tšebetso ea lithuto tsa dopaminergic neurons.135-138 lithuto tsa kelello tsa motho li bontšitse ka ho eketsehileng hore keketseho e amanang le khatello ea maikutlo. ka cortisol e amahanngoa le ho bokelloa ha dopamine ka har'a ventral striatum, 125,139 'me bopaki bo bong bo senola hore keketseho e hlahisoang ke amphetamine cortisol e amana le dopamine e tlamang kahare ea cyral striatum le litekanyetso tsa amphetamine-indedu euphoria.140 Ho fanoe ka khatello eo le bobeli. lithethefatsi tsa tlhekefetso li kenya ts'ebetsong mesolimbic pathways, ha ho makatse hore ebe e 'ngoe le e' ngoe e baka liphetoho tsa synaptic ho VTA dopamine neurons le liphetoho tsa morphological ho medial prefrontal cortex.87,136,141,142

Ntle le karolo ea moputso, 'mele o ntseng o hola oa lithuto tsa batho ba nahanang le tlhaiso-leseling e bonts'a hore boemo ba morao-rao bo kenyellelitsoe maemong a phopholetsang, ka boiphihlelo ba boipiletso, bo susumetsang bohloko, le ka ho lebella sepheo se khathollang.143-146 Bopaki bo joalo e supa karolo ea mesolimbic dopamine litseleng tse fetang moputso, hape e le e 'ngoe e kenyelletsang maikutlo le tlhoko ea karabelo ea boits'oaro nakong ea liketsahalo (tsa boithati kapa tsa takatso) ea liketsahalo.147-150 Ho feta moo, libaka tse ling tse hokahaneng le litsela tsa DA tsa mesolimbic le tse amehang ho. moputso, ho ithuta, le boits'oaro bo tataisang le bo tsamaisanang le sepheo ke litereke tsa amygdala, hippocampus, insula, le libaka tse amanang tsa corticolimbic.118,151 Libaka tsena, hammoho le litsela tsa mesolimbic DA, li bapala karolo ea bohlokoa ho ferekaneng, maikutlo le ts'ebetsong ea khatello, taolo ea ho susumetsa le ho etsa liqeto, le lithahasellong tsa lithethefatsi tsa tlhekefetso.29,152

Mekhoa ea Khatello ea Khatello ea Kelello e Akarelletsa ho Fumana Tsamaiso ea Lithethefatsi
Patlisiso e boetse e lekotse hore na keketseho e amanang le khatello ea maikutlo ea ho itaola ha lithethefatsi e kenelletsoa ke corticosterone (cortisol ho batho). Liphumano li bonts'a hore tokollo ea corticosterone e sebelisang HPA e bohlokoa bakeng sa ho fumana ts'ebetso ea lithethefatsi.131,153-155 Corticosterone tsamaiso e boetse e thusa litlamorao tsa psychomotor tsa cocaine le morphine.156 Ntle le moo, GC receptor antagonists injosed in the VTA decrease locomotor shughuli, 157 e fana ka tlhahiso ea hore ts'ebetso ea li-receptor tsa GC ho VTA e ka kopanya litlamorao tsa ts'ebetso e itšetlehileng ka dopamine. Lits'oants'o le ho tloswa ha mofuta oa GR li bonts'a ho fokotseha hoa tekanyo ea ts'ebetso ea ho itšebeletsa koae.158 Lintlha tsena li fana ka tlhahiso ea hore ho lokolloa ha corticosterone e amanang le HPA ho ka fokotsa karolo e itseng ea keketseho ea dopamine e bonoang kamora taolo ea lithethefatsi.

Le ha e le ka nako ea bokhopo e hokahanya khokahano lipakeng tsa cortisol, dopamine, le boits'oaro ba lithethefatsi ha e-so tlaleheloe, ho na le bopaki ba hore khatello ea maikutlo e amanang le ho ikamahanya le maemo a bophelo e amana le maemo a tlase a li-receptor tsa D2 le boits'oaro bo phahameng ba koae.159 Ho batho ba nang le maikutlo a nepahetseng emission tomography (PET) lithuto tse sebelisang [11C] raclopride e bonts'a hore ho pepeseha ha maikutlo a hlobaetsang ho eketsa ho lokolloa ha dopamine ka har'a ventral striatum (VS). Mohlala, thutong e nyane ea mohlala, Pruessner le basebetsi-'moho (2004) 139 ba fumane hore batho ba phetseng hantle ba nang le tlhokomelo e tlase ea bokhachane ba bontšitse ho lokolloa ha dopamine kahare ho nako ea khatello ea kelello joalo ka ha ho bapisoa le ba nang le nalane ea nalane. tlhokomelo e phahameng ea bo-mme. Ho feta moo, karabelo ea cortisol nakong ea mosebetsi oa khatello ea maikutlo e ile ea lumellana haholo (r = .78) ho lokolloa ha VS dopamine. Oswald le basebetsi mmoho (2005) 125 le bona ba bonts'itse hore likarabo tse tebileng tsa "phepo" ea amphetamine tse amanang le phetoho e kholo le keketseho e tšoanang ea dopamine ho VS e ne e le karolo e 'ngoe le e' ngoe e amanang le karabo ea cortisol ea amphetamine. Haufinyane tjena, sehlopha se tšoanang se boetse se bonts'itse kamano ea bohlokoa pakeng tsa maemo a cortisol le tokollo ea dopamine ho VS e sebelisa mosebetsi oa khatello ea kelello.140 Le ha lintlha tsena li tšehetsa khokahano lipakeng tsa khatello ea maikutlo le cortisol le phetisetso ea dopamine, lipatlisiso tsa batho tse hokahanyang liphetoho tse bakiloeng ke khatello ea maikutlo ts'ebetsong ea VS kapa dopamine e tlamang le ho ipeha kotsing ea ho lemalla ho hlokahala ho theha setsoalle lipakeng tsa khatello ea maikutlo, mesolimbic dopamine le kotsi ea ho lemalla.

Bophelo ba Pele le khatello ea maikutlo e sa foleng, Dopamine Systems, le Tsamaiso ea Lithethefatsi
Ho na le bopaki bo ntseng bo eketseha bo tsoang lipatlisisong tsa mahlale tsa mantlha tsa hore khatello ea bophelo ba bongoana le khatello ea maikutlo e sa feleng e ama mekhoa ea mesolimbic dopamine mme e bapala karolo ea boits'ebetso ba lithethefatsi. Ho pepesetsoa khafetsa le ka nako e telele ho karohano ea bo-mme kapa basali literekeng tse sa fetoheng hantle ho fetola nts'etsopele ea litsela tsa CRF tse bohareng.11 Liphoofolo tsena e le batho ba baholo li bonts'a HPA e fetelletseng le karabelo ea boitšoaro ho khatello ea maikutlo.160,161 Liphetoho tse joalo tsa 'mele le boits'oaro li amana le polelo e fetotsoeng ea CRF mRNA ho PVN, e eketsehang ea CRF joalo ka ho itšireletsa mafung sebakeng sa locus ceruleus (LC), le litekanyetso tse eketsehang tsa CRF ho LC le raphe nuclei.11 Liphoofolo tse kholo le tsona li bonts'a maikutlo a fokotsehileng a maikutlo a fosahetseng ho glucocorticoids, 162 'me liphetoho tsena li tsamaisana le GC e fokotsehileng polelo ea li-receptor ka hippocampus le frontort cortex.11,163 E fokotsoe li-receptor tsa GABA libakeng tsa 'mele tsa cell cell ho LC le ho theoha ha maemo a "benzodiazepine" (CBZ) a receptor ho LC le amygdala le tsona li tlalehiloe haholo.164 Habohlokoa le ho feta, likhoto tsa MS li bonts'a haholo e phahamisitse likarabo tsa DA ho khatello ea maikutlo e matla hammoho le maikutlo a susumetsang a khatello ea maikutlo ation le sensitization e matla ea boits'ebetso ho psychostimulant management.11,143,165 Sena se utluoang maikutlo a khatello le lithethefatsi tsa tlhekefetso se amana le tokollo e ntlafalitsoeng ea DA ho NAc, mantlha ea NAc-core, le libaka tsa transporter tsa DA tse tsamaeang le ho fokotsa libaka tsa li-receptor tsa D3. maemo a ka mokokotlong oa NAc.166-168 Ntle le moo, ho haella ha norepinephrine ho sa feleng ho etsa hore ho be le liphetoho tse tšoanang le maikutlo a ka amanang le liphetoho tseleng ea DA-signaling pathways.169,170

Matšoenyeho a bophelo ba bongoaneng le khatello ea nako e telele le e pheta-phetoang e boetse e ama hampe ntlafatso ea cortex ea pele, sebaka se itšetlehileng haholo ka boiphihlelo ba tikoloho bakeng sa ho fetoha ha maemo.171 PFC, haholo-holo PFC e nepahetseng, e bapala karolo ea bohlokoa ho ts'ebetsong maqhubu a HPA le likarabo tsa boikemisetso ba khatello ea maikutlo le taolong ea likarabo tsena.171 Mohlala, likotlo tsa PFC tse tsoang phepong li baka karabelo e ntlafalitsoeng ea HPA le ho ikemela ha khatello ea maikutlo. Tekanyo e phahameng ea li-receptor tsa glucocorticoid e boetse e fumanoa ho PFC, 'me kalafo e sa foleng ea GC e baka phetoho e makatsang ea ho hlophisoa hantle ha li-neuron tsa PFC tse ts'oanang le tse bonoang ho hippocampus.172,173 Ho feta moo, pelehi ea morao-rao ea morao-rao ea MS le karohano ea sechaba e fella ka mathata a sa tloaelehang a synaptic ho PFC le mathata a fetotsoeng a lits'oants'o tsa DA le serotonin (5-HT) literekeng tsohle tsa kalafo tsa PFC.174 Mathata a ho hlola boemo ba sechaba le 'ona a fetola maikutlo ho tsoa ho PFC mme a kenya letsoho ho taolong ea lithethefatsi.84 Lithuto tsa batho mabapi le litlamorao tsa neurobiological tsa tokomane ea tlhekefetso ea bana le neuroendocrine hammoho le liphetoho ka boholo le bophahamo ba libaka tsa pele, tsa thalamic, le cerebellar tse amanang le ts'oaetso e mpe le ho qalisoa ha litumeliso.175,176 Ka bobeli, tlhaiso-leseling e hlahisitsoeng karolong ena e totobatsa bohlokoa ba litlamorao tsa khatello ea maikutlo ho libaka tsa mesolimbic le tse tlang pele ho tse amehang boitekong bo amanang le khatello ea maikutlo. taolo.

Khatello ea Kelello, Boitšoaro, le Tlokotsi ea ho Lemalla
Matšoenyeho a tebileng a maikutlo a amahanngoa le tahlehelo ea taolo holim'a litšusumetso le ho sitoa ho thibela boits'oaro bo sa lokang le ho lieha ho khotsofatsa.20,177,178 Lintlha tsa Neurobiological li bontša hore khatello ea maikutlo e sitisa ho fetoloa ha catecholamine ea lipotoloho tse tlang pele, tseo ka lehlakoreng le leng li sitisang mesebetsi e metle ea ts'ebetso e joalo ka mohopolo oa ho sebetsa le boitšoaro. 17,28,179 Ho boetse ho na le bopaki bo ntseng bo eketseha ba hore bacha ba kotsing ea tlhekefetso ea lithethefatsi ba nang le maemo a 'maloa a khatello a tlalehiloeng ho Lethathamo la 1 ba bonts'a taolo e theohileng ea maikutlo le boits'oaro,' me ho fokotsa boitšoaro ho tsamaisana le kotsi ea tlhekefetso ea lithethefatsi le lits'ila tse ling. boits'oaro.104,152,180,181 Bacha ba kotsing ea ts'ebeliso e mpe ea lithethefatsi ba tsejoa ba fokotsehile ts'ebetsong ea ts'ebetso, taolo e tlase ea maikutlo le maikutlo, ho etsa liqeto tse fosahetseng, le litekanyetso tse kholo tsa boits'oaro bo khelohileng le ho ts'oenyeha.24,152,182-184 Litsela tsa corticostriatal-limbic dopamine li hokahane le ho qobelloa. , ho nka liqeto le kotsi ea ho lemalla, 185,186 mme joalo ka ha ho tšohliloe likarolo tse fetileng, libaka tse ikhethileng tsa tsela ena, joalo ka VTA, NAc, PFC, le amygdala, li kotsing ea ho tšoaetsoa khatello ea maikutlo le polasetiki e amanang le khatello ea maikutlo le bophelo ba bongoana. Phuputsong ea morao-rao ea PET ea morao-rao, Oswald (2007) 187 e ile ea hlahloba litlamorao tsa khatello ea maikutlo e sa feleng le ho se ts'oarehe ka tlhahiso ea amphetamine-induction striatal dopamine. Liphumano tsena li bonts'a hore ho ba le tšusumetso ea boleng bo phahameng ho ne ho amahanngoa le ho lokolloa ha dopamine ea VS e nepahetseng. Leha ho le joalo, litlamorao tsena li fetotsoe ke tšebelisano e kholo le khatello ea liketsahalo tsa bophelo bo sa feleng. Ka khatello e tlase ho isa tekanyong e ngata, ho lokolloa ha dopamine ho ne ho le kholo ka tlase ho feta lithutong tse phahameng tse susumetsang, empa ka khatello e phahameng, lihlopha tsena ka bobeli li bontšitse ho lokolloa ho tlase ha DA. Liphumano tsena li bonts'a litlamorao tsa khatello ea maikutlo le khatello ea maikutlo phepelong ea mesolimbic dopamine mme li totobatsa ntlha ea hore lintlha tsena ka bobeli li hloka ho nahanoa ka hloko ho utloisisa ka botlalo karolo ea khatello le ho potlakela ho ba kotsing ea ho lemalla.

Schematic Model ea Mathata a khatello ea kelello
Setšoantšo sa 1 se hlahisa mofuta oa merero ea khatello ea maikutlo ho ho lemalla. E totobatsa maikutlo a tšebeliso ea khatello ea maikutlo le tšebeliso e mpe ea lithethefatsi ho likarabo tse ikhethang tsa boitšoaro le methapo 'me e bontša litsela tse tloaelehileng tsa khatello ea maikutlo le lithethefatsi tsa tlhekefetso. Kholomo A e thathamisa mefuta e meraro ea maemo a tlokotsing: (1) lintlha tsa nts'etsopele / nts'etsopele ea motho ea ka pele, maikutlo a fosahetseng, boits'oaro / boits'oaro, ho se ts'oenyehe, kapa ho ipeha kotsing, le ho fetola maikutlo a pele ho litlamorao tse ntle tsa lithethefatsi; (2) mabaka a amanang le ho ba le khatello ea maikutlo joalo ka liketsahalo tse bohloko tsa bophelo ba pele, ho sithabela maikutlo le ho hlekefetsoa ha bana, liphihlelo tsa nako e telele le tse sa foleng tsa khatello ea maikutlo; le (3) ts'usumetso ea liphatsa tsa lefutso le nalane ea malapa ea psychopathology le bokhoba ba tahi, tse sa buuoang ka tsona mona empa li na le litlamorao tse kholo tsa kotsi ea ho lemalla le linthong tsa maikutlo le khatello ea maikutlo.188-194 E 'ngoe ea lintlha tsena e ka susumetsa e mong le e mong ho ama liphetoho litseleng tsa methapo ea kutlo tse amehang taolong ea khatello ea maikutlo le taolo ea boits'oaro le boitšoaro (kholomo ea B). Liphetoho tse ikhethileng tsa synaptic lits'ebetsong tsena maemong a limolek'hule le tsa cellular118,195 li fana ka motheo oa mochini oo khatello ea maikutlo le lintlha tsa setho le liphatsa tsa lefutso mo khokahanong A li sebetsang ho eketsa kotsi ea boits'oaro bo bobe bo emeloang moleng oa C. Mohlala o fana ka maikutlo a hore maikutlo a khatello a teng lintlha tsena tse tloksiang li baka khatello ea maikutlo le likarabo tsa boitšoaro tse eketsang kotsi ea ho lemalla. Mokhoa o ikhethileng oo khatello ea methapo ea kutlo e arabang o eketsa kotsi ena o kenyelletsa ho senyeha ha methapo ea khatello ea kelello, haholo lits'ebetso tsa CRF le NE, le ts'ebelisano ea tsona le mesocorticolimbicstriatal dopamine pathways le modulation ea eona ka glutamate le GABA.114,196,197 Ho feta moo, bopaki ba morao-rao bo fana ka maikutlo a hore khatello ea maikutlo limolek'hule tse laolang, ho kenyelletsa li-neuropeptide tse kang neuropeptide (NPY) endocannabinoids, le li-steroids tsa neuroactive li bapala karolo ea tlokotsi ea ho lemalla.198-203

Setšoantšo sa 1 (MISSING)
Mohlala oa merero ea khatello ea maikutlo bokhobeng, e emelang maikutlo a sefapano a khatello ea maikutlo le lithethefatsi mabapi le likarabo tsa boits'oaro le tsa neurochemical, tse kopantsoeng ke khatello ea maikutlo le mekhoa ea moputso. Kholomo A e thathamisa mefuta e meraro ea maemo a tlokotsing: (1) lintlha tsa nts'etsopele / nts'etsopele ea motho ea ka pele, tlhaselo e mpe ea maikutlo, boits'oaro / boits'oaro, ho se ts'oenyehe kapa ho nka kotsi, le ho fetola maikutlo a pele ho litlamorao tse ntle tsa lithethefatsi; (2) mabaka a amanang le ho ba le khatello ea maikutlo joalo ka liketsahalo tse bohloko tsa bophelo ba pele, ho sithabela maikutlo le ho hlekefetsoa ha bana, liphihlelo tsa nako e telele le tse sa foleng tsa khatello ea maikutlo; le (3) litšusumetso tsa lefutso le nalane ea lelapa ea psychopathology. E 'ngoe le e' ngoe ea lintlha tsena e susumetsa e mong le e mong ho ama liphetoho lipakeng tsa methapo ea methapo e amehang taolong ea khatello ea maikutlo le taolo ea boits'oaro le boitšoaro (Column B). Liphetoho tse joalo bonyane li leka ho hokahanya mekhoa eo khatello le maemo a motho le a liphatsa tsa lefutso a kopaneng a ka eketsang kotsi ea boits'oaro bo bobe bo hlahisoang moleng oa C ha motho a tobane le khatello ea maikutlo le maemo a phephetso.

Ts'ebeliso ea Lithethefatsi le Tlhekefetso le Liphetoho maemong a khatello le Moputso
Ts'ebeliso e mpe ea lithethefatsi e mpe le e sa foleng ea likarabo tsa khatello ea maikutlo
Ts'ebetso e matla ea lithethefatsi tse tloaetseng ho hlekefetsoa joalo ka joala, nicotine, cocaine, amphetamines le matekoane a sebetsang ka tšebetsong meputso ea boko (mesocorticolimbic dopaminergic system) le tsona li kenya tšebetsong lits'ebetso tsa khatello ea kelello (li-axis tsa CRF-HPA le li-system tsa tsamaiso ea methapo ea kutlo. plasma adrenocorticotropic hormone (ACTH) le corticosterone, liphetoho lebelong la pelo le khatello ea mali, le likarabo tsa letlalo tsa boitšoaro.204-217 Ka lehlakoreng le leng, ho pepesetsoa ka matla ho opiates ho fokotsa maemo a cortisol ho batho.218,219 Tšebeliso ea kamehla le e sa foleng ea lithethefatsi tsena e boetse e. e amanang le ho ikamahanya le maemo litsamaisong tsena tse ikhethang ka lithethefatsi. Mohlala, ho fetoha ha sekhahla sa pelo le phapang ea sekhahla sa pelo (HRV) ho tlalehoa ka tšebeliso e ngata le e sa foleng ea joala bo sa lebelloang.220-222 Ho eketseha hoa ts'ebetso ea axis ea HPA maemong a psychostimulants, le mamello ho litlamorao tse tlisoang ke lithethefatsi joalo ka ea morphine, nikotine, le joala le tsona li tlalehiloe.223-226 Tsena tsa litla-morao tsa lithethefatsi tsa tlhekefetso ho likarolo tse kholo tsa karabelo ea khatello ea maikutlo tsa mmele li ts'ehetsa sehlopha sa bona e le khatello ea meriana.

Boemo ba ho khaotsa ho hoholo bo amahanngoa le ho eketseha ha maemo a CRF ho CSF, plasma ACTH, cortisol, norepinephrine (NE), le maemo a epinephrine (EPI ).38,211,216,227-231 likarabo tsa pele tsa nako li amana le likarabo tse phahameng tsa basal cortisol le ACund le cortisol e sa tlosoang. karabelo mathateng a meriana le kelellong ho batho ba lemaletseng tahi le ba tsubang ba sa foleng, ha karabelo ea hyper ea lihormone tsa HPA ha e araba metyrapone e tlalehiloe ho batho ba lemaletseng joala le koae.232-236 Ho feta moo, ho itlopa joala le ho itlopa joala ho sa foleng ho boetse ho tsamaisana le kutloelo-bohloko. Likarabo tsa karohano, karabelo ea 234,237-239 le likarabo tse fetotsoeng tsa noradrenergic phetohong ea koae le tsona li se li bontšitsoe.240 Liphetoho tsohle tse kaholimo li bonts'a litlamorao tsa tšebeliso ea lithethefatsi le tlhekefetso ho likarabo tsa khatello ea mmele.

Le ha tsamaiso e matla ea lithethefatsi e eketsa dopamine ea mesolimbic, 241 ts'ebeliso e tloaelehileng le e sa foleng ea lithethefatsi tse tlisoang ke tlhekefetso le khatello ea maikutlo e matla e theoha ho laoloa ha mesolimbic dopamine pathways e fokotsehileng ho basal le ho susumetsoa ke dopamine e tlalehiloeng lithutong tse 'maloa tsa preclinical.242-251 Tšebeliso e mpe ea koae e boetse e bontšitsoe ho fetola ka matla tsela e bohareng ea methapo ea methapo tseleng le methapong ea methapo, likarolo tse ling tsa bokong ba pele, le li-cortex tsa pele tsa bongo.252,253 Boko ba motho ba kelello ba kelello bo hlophisa lintlha tsena tsa tlhaiso-leseling, ka li-receptor tsa D2 tse fokolisitsoeng le phetisetso ea dopamine kahare le kahare. libaka sebakeng sa lino tse tahang le batho ba hlekefetsang koae nakong ea ho khaotsa ho matla le ho khaotsa ho feteletseng (ho fihlela 3 − likhoeli tsa 4) .254-256 Ntle le moo, ho lokolloa ha dopamine ka har'a ventral striatum le anterior caudate ho ne ho amana le ho rata ho inkela k'hok'heine ka lebaka la ho amohela chelete ho batho ba hlekefetsang batho ba koae ka koae.257 Liphetoho tsena ke tšoanang le litlamorao tsa khatello ea maikutlo e telele le e phetoang khafetsa ho mesolimbic dopamine le norepinephrine tlhokeho e tlalehiloeng karolong e fetileng134,187,258 mme o phahamisa potso ea hore na litlamorao tse mpe tsa lithethefatsi ho extrahypothalamic CRF, noradrenergic, kapa glucocorticoid bonyane li ka fetolela liphetoho tsena tse amanang le dopamine ho corticostriatal. limbic dopamine litseleng.

Ka lehlakoreng le leng, ho pepesehela lithethefatsi ka matla, khafetsa le ho sa foleng ho fella ka "ho hlasimolla" kapa ho ntlafatsa boitšoaro le methapo ea kutlo ea lithethefatsi le khatello ea maikutlo. Liphetoho tsa Synaptic ho VTA, NAc, le medical PFC tse fetotsoeng ke litlamorao tsa glutamate ho dopamine neurons le CRF le litla-morao tsa noradrenergic ho DA le litsela tseo eseng tsa DA li kenya letsoho molemong oa boits'oaro ba khatello ea maikutlo le lithethefatsi tsa tlhekefetso.210,259-262 Ntle le moo, maemo a eketsehile a boko bo tsoang ho neurotrophic factor (BDNF) libakeng tsa mesolimbic dopamine bo amahanngoa le keketseho ea ho ts'oara lithethefatsi nakong ea ho tlohela ts'ebeliso e mpe ea lithethefatsi.263,264 Ho feta moo, maikutlo a boitšoaro a shebiloeng ka lithethefatsi tsa tlhekefetso le khatello ea maikutlo li amana le liphetoho tsa synaptic libakeng tsa mesolimbic dopamine, Haholo-holo VTA, NAc, le amygdala, le liphetoho tse joalo li kenya letsoho ho batleng lithethefatsi.118,265 Ka hona, ho na le liphetoho tse kholo tsa 'mele, neurochemical, le boits'oaro maikutlong le dopaminergic pathways tse amanang le tšebeliso e mpe ea lithethefatsi, tse ka amang ho lakatsa le ho qobelloa. ho batla, ho hlokomela tšebeliso ea lithethefatsi, le ho khutlisetsa kotsi. Ha ho hlake hantle hore na liphetoho tsena li phehella halelele hakae kapa hore na ho hlaphoheloa kapa ho tloaela mekhoa ea mekhoa le likarabo ho likarabo tse amanang le tsona.

Likarabo tse fetotsoeng tsa khatello ea maikutlo le ho lakatsa ho sebelisa tlhekefetso e mpe ea lithethefatsi
Matšoao a tleliniking a ho teneha, ho tšoenyeha, khatello ea maikutlo, mathata a ho robala, ho otsela, ho ba mabifi le takatso ea lithethefatsi li atile nakong ea ho tlohela joala haholo, koae, opiate, nikotini le matekoane.30,266-269 e etsa hore ho be le mathata kamora kalafo, e amanang le phetoho lipakeng tsa khatello ea maikutlo le dopamine.37,197,250,270 Ho ts'oana ha matšoao ana ho amana le sephetho sa kalafo, ho its'epahalla le ho tebela takatso e matla ea qeto ea litlamorao tse mpe tsa kalafo.271-274 Litakatso tsa lithethefatsi kapa "ho batla" lithethefatsi. e fapane ka mokhoa o fapaneng le matšoenyeho a mang le matšoao a amang a fosahetseng hobane a tsoa ho “takatso” kapa takatso ea ho hlohlelletsa lintho tse itseng. Leha ho le joalo, ka tšebeliso e mpe ea lithethefatsi, poleloana e tsamaisana le tlhoko ea 'mele, tlala, le boikemisetso bo matla ba ho batla ntho eo u e batlang, ka hona moemeli oa likarolo tse qobelloang haholo tsa ho lakatsa le lithethefatsi tse fumanoang ke bakuli ba lemaletseng.274-277 Haholo-holo , ho lakatsa le ho batla ka matla ho bonts'oa ka mokhoa o matla maemong a ho pepesetsoa khatello ea maikutlo, mekhoa e amanang le lithethefatsi, le lithethefatsi ka boeona mme e ka fetoha sesosa sa ts'ebetso ea ts'ebetso hape.30,274,278-281 Mehlala e mengata ea morao-rao ea ho lemalla e hlahisitse mohopolo oa hore sena se phahamisitse takatso kapa e batlang. ea lithethefatsi ke pontšo ea boitšoaro ea liphetoho tsa limolek'hule le tsa cellular khatellong le litseleng tsa dopamine tse tšohliloeng karolong e fetileng. Ehlile tšehetso e meng bakeng sa mohopolo ona e tsoa lithutong tsa laboratori le tsa monahano tse akaretsoang ka tlase.

Ka laboratoring ea ka, re hlahlobe litlamorao tsa khatello ea maikutlo le lithahasello tse amanang le lithethefatsi mabapi le litakatso tsa lithethefatsi ho joala, batho ba itšebelitseng k'hok'heine, le ba nang le kalafo ea kalafo ea naltrexone. Likarabo tsa lithethefatsi le khatello ea maikutlo li ile tsa hlahlojoa liketsong tsa kalafo tse amanang le kalafo, lits'itiso, lithethefatsi tse ileng tsa pepesoa maemo a sithabetsang a ho se ts'oenyehe ka lithethefatsi le maemo a ho se kopanele, ba sebelisa lits'ebetso tse tataisitsoeng tsa litšoantšo joalo ka mokhoa oa ho kenyelletsa.282 Lipatlisiso tsa rona tsa pele li bonts'a hore ka temallo. batho ka bomong, litšoantšo tsa khatello ea maikutlo li ile tsa tsosa maikutlo a mangata a ts'abo, masoabi le khalefo ha li bapisoa le khatello ea ho bua phatlalatsa, e ileng ea phahamisa tšabo empa ho se bohale kapa ho hlonama. Ntle le moo, litšoantšo tsa khatello ea maikutlo tsa motho li hlahisitse keketseho e kholo litakatsong tsa koae, ha ho bua phatlalatsa ho sa kang ha ba joalo.283-285 Ho eketseha ho hoholo ha sekhahla sa pelo, salivary cortisol, takatso ea lithethefatsi, le ho tšoenyeha ho hoholo ho boetse ho bonoa ka ho pepeseha ha maikutlo le khatello ea lithethefatsi tse sa hatelleheng. ha ho bapisoa le litloaelo tsa ho phomola tse sa jeleng paate ho batho ba itšetlehileng ka koae.285 Haufinyane tjena, re bonts'itse hore khatello ea maikutlo le ts'usumetso e amanang le lithethefatsi ka mokhoa o ts'oanang li eketsa ho lakatsa, ho tšoenyeha, maikutlo a fosahetseng, le karabelo ea 'mele ho lino tse tahang le ho kalafo e sebelisitsoeng ka naltrexone, opiate Ka lehlakoreng le leng, lino tse tahang le batho ba tsubang haufinyane ba bonts'a likarabo tse fetotsoeng tsa HPA le karabelo e hatelletsoeng ea HPA joalo ka ha e lekantsoe ke cortisol ho khatello ea maikutlo ha e bapisoa le balekane ba bona ba sa laoloang.286,287-288

Tekong e phethahetseng haholoanyane ea karabo ea khatello ea likokoana-hloko ho batho ba lemaletseng koae ka ho fetesisa, re tlalehetse hore ho pepeseha khatello ea maikutlo le likotsi tsa lithethefatsi ha ho bapisoa le mekhoa ea ho phomola e sa nke lehlakore e hlahisitseng axis ea HPA (ka keketseho ea maemo a ACTH, cortisol, le prolactin. ) hammoho le lits'ebetso tsa kutloano tsa meromoadrenomedullary, joalo ka ha li lekantsoe ke li-plasma norepinephrine le maemo a epinephrine.282 Ho feta moo, re fumane bopaki bo fokolang ba ho hlaphoheloa kapa ho khutlela ho basement maemong a ACTH, NE, le EPI esita le ho feta 1 h kamora ponts'o ea litšoantšo tsa 5-min . Liphumano tsena li atolositsoe hore li bapise ka kotloloho batho ba itšebelitseng koae le sehlopha sa batho ba nooang ba phetseng hantle, ba sebelisang maikutlo a amanang le khatello ea maikutlo le lithethefatsi tse amanang le joala ha ba bapisoa le litšoantšo tse sa nkeng lehlakore. Liphumano li bonts'itse hore bakuli ba cocaine ba bonts'itse kutloisiso e ntlafalitsoeng ea khatello ea maikutlo le maikutlo a bophelo bo botle le litekanyetso tse phahameng tsa takatso ea lithethefatsi ho khatello ea maikutlo le ho pepesetsoa lithethefatsi ha li bapisoa le taolo.291 Ka mokhoa o ts'oanang, re bapisitse le lino tse tahang tsa beke ea 4 le libeke tse sa amaneng le sechaba. Makhoba a ho hlaphoheloa joala nakong ea libeke tsa 4 a bonts'a litekanyo tse kholo tsa sekhahla sa pelo le bascary cortisol ha li bapisoa le ba noang joala. Kamor'a khatello ea maikutlo le bokhoba ba tahi ea joala, ba bonts'itse khatello e kholo ea khatello, takatso ea joala, le likarabo tsa khatello ea mali, empa pelo e hatelletsoeng le karabelo ea cortisol ha e bapisoa le taolo.239 Ho khahlisang, bakuli ba koae ka bobeli le lino tse tahang ba bonts'a ho tšoenyeha ho hoholo le maikutlo a mabe nakong ea ho pepeseha hoa lithethefatsi, ha ba noang batho ba sechaba ba tlaleha hore ho na le litla-morao tse mpe tse mpe le ho tšoenyeha ka ho pepesetsoa joala. Lintlha tsena li fana ka bopaki bo tobileng ba litakatso tse phahameng tsa lithethefatsi le likarabo tse fetotsoeng tsa hedonic ho khatello le maikutlo a lithethefatsi ho batho ba lemaletseng ha ba bapisoa le ba noang sechaba (bona sa feiga. 2). Li boetse li bonts'a hore liphetoho tse teng maemong a khatello ea 'mele li amana le maemo a phahameng a khatello ea maikutlo le litakatso tsa maikutlo le likhathatso. Sebopeho sa liphetoho tsena se tšoaetsoa ke khatello e matla ea maikutlo, takatso e matla, likarabo tse fetotsoeng, le likarabo tsa bophelo bo botle ho batho ba lemaletseng joala ha ba bapisoa le batho ba noang joala sechabeng.

Setšoantšo sa 2 (MISSING)
Liphoso tse bolelang le tse tloaelehileng bakeng sa litakatso tsa tlhoro le litekanyo tsa matšoenyeho nakong ea khatello ea maikutlo, lithethefatsi le maemo a litšoantšo tse sa jeleng paate. (A) Takatso ea tlhoro e phahame haholo ho bakuli ba sa itšepeng ba tahi le k'hok'heine ha ba bapisoa le ba noang sechabeng (P <0.0001). (B) Litekanyetso tsa tlhoro ea matšoenyeho li phahame haholo ho bakuli ba sa itlheng joala le koae ha ba bapisoa le ba noang sechabeng (P <0.001). (Lipalo-palo tse qaqileng tse fanoeng ho Fox et al. 291 le Sinha et al. 239)

Boithuto bo bongata bo boetse bo hlahlobe libaka tsa boko tse amanang le ho lakatsa batho ba lemalloang. Ho pepesehela lithahasello tsa lithethefatsi tse tsejoang ho eketsa ho lakatsa takatso ho eketsa ts'ebetso ho amygdala le libaka tsa pele tsa cortex, 292–294 ka phapang ea bong ho ts'ebetso ea amygdala le karabelo ea pele ea cortex ho batho ba itšetlehileng ka koae.295,296 Litakatso tsa takatso ea kelello tsa nicotine, methamphetamine, kapa opiates e boetse e kenya tšebetsong libaka tsa cortex ea pele, amygdala, hippocampus, insula, le VTA (bona Ref. 297). Ha khatello ea maikutlo le eona e phahamisa takatso ea lithethefatsi, re ile ra hlahloba ts'ebetso ea ts'ebetso ea ts'ebetso nakong ea khatello ea maikutlo le litšoantšo tse sa jeleng paate thutong e sebetsang ea matla a matla a matla a matla a kelello (fMRI). Le ha taolo e phetseng hantle le batho ba itšetlehileng ka koae ba bontšitse maemo a tšoanang a khatello le khatello ea maikutlo nakong ea khatello ea maikutlo, karabelo ea boko ho khatello ea maikutlo libakeng tsa paralimbic tse joalo ka libaka tsa anterior cingulate cortex, hippocampus, le libaka tsa parahippocampal li ne li le matla taolong ea bophelo bo botle nakong ea khatello ea maikutlo, ha k'hok'heine e le koae bakuli ba bontšitse ho ba sieo ho matla ha ts'ebetso e joalo.298 Ka lehlakoreng le leng, bakuli ba cocaine ba ne ba ekelitse mesebetsi sebakeng sa caudate le dorsal striatum nakong ea khatello ea maikutlo e neng e amana haholo le khatello ea maikutlo ea cocaine e lakatsang khatello ea maikutlo.

Boithuto ba morao-rao ba PET bo boetse bo bonts'itse khokahano ea bohlokoa pakeng tsa dorsal striatum le cueine e kentsoeng lithethefatsi.299,300 Liphumano tsena li lumellana le lithuto tsa monahano le bakuli ba noang joala tse bonts'ang kopano e lipakeng tsa libaka tse amanang le joala le takatso ea joala ho arabela tlhahiso ea libaka tse amanang le joala. stimuli.301,302 U sebelisa litšoantšo tsa PET le bakuli ba tahi le koae, lipatlisiso li bonts'itse kamano e kholo lipakeng tsa dopamine D2 receptor e tlamang VS le litakatso tsa lithethefatsi hammoho le tšusumetso ea boits'oaro.124,303,304 Ka lehlakoreng le leng, lithuto tsa neuropsychological le imaging tse hlahlobang pele. Ts'ebetso ea botsamaisi, ho kenyelletsa taolo ea tšusumetso, ho nka liqeto, le ho tjeka, ho bonts'itse bofokoli ba tšebetso le karabelo tse tebileng ho batho ba lemaletseng ha ba bapisoa le baithaopi ba laolang.305–312 Ka bobeli, liphumano tsena li bonts'a khatello ea maikutlo le takatso e matla ea litakatso le litheko tse matla. batla linaha ka keketso batho ba tlotsitsoeng ka molao ba kopantsoe le ts'ebetso e kholo ho striatum, empa ho fokotseha ha mesebetsi libakeng tse ikhethileng tsa cortrate le pele ho libaka le libaka tse amanang le tsona ho laola maikutlo le maikutlo.

Khatello ea Khatello ea Khatello ea Kelello ea Khatello ea Lithethefatsi le Ho Boela
Leha mekhoa e mengata ea boits'oaro e sebetsang ea kalafo le ea kalafo kalafong ea ho lemalla e le teng, hoa tsebahala hore litekanyetso tsa ho khutla bothateng li lula li le holimo.30,313,314 Ho pepesehela khatello ea maikutlo, tšusumetso e amanang le lithethefatsi, le lithethefatsi ka botsona li khutlisetsa boits'oaro ba ho batla lithethefatsi ho liphoofolo le ho eketsa ho oela hape. Tlhatlhobo ho batho ba lemaletseng.274,315-317 Lintlha tse joalo li hatisa tlhokahalo ea tlhokomelo e khethehileng ho ts'oaetso e sa feleng e le sepheo sa nts'etsopele ea kalafo ea lithethefatsi.

Lilemong tse leshome tse fetileng, palo e kholo ea lithuto tsa preclinical li bontšitse hore litsela tsa bongoana tsa CRF, noradrenergic, le glutamatergic li kenya letsoho ho khutlisetsong hoa ts'ebeliso ea lithethefatsi.86,316-320 Neuroadaptations e amanang le ts'ebeliso e mpe ea lithethefatsi e kenyelletsa ts'ebetso e kholo ea CRF le mekhoa ea glutamatergic, likarabo tse fetotsoeng tsa puso. le lits'ebetso tsa "dopamine" le "GABA" tse sa sebetseng, 'me liphetoho tsena li ka tsamaisana le litakatso tse phahameng le ho khutlela bothateng bo amanang le mofuta o sa feleng oa ho lemalla .118,196,197,274,313,321 Ntle le moo, ho sebelisa mehlala ea liphoofolo tsa ho itaola le ho khutlela morao, lithuto tsa preclinical li lemohile bahanyetsi ba CRF, alpha- Li-agonists tsa 2-adrenergic, le morao tjena, basebeletsi ba glutamatergic ba bohlokoa ho fokotseng ho ts'oenyeha ha maikutlo ho liphoofolo tse lemalloang ke basebetsi (bona316,317,322-324). Lintlha tsena li lumellana le liphumano tsa batho tse hlahlojoang karolong e fetileng e bonts'a liphetoho tse teng maemong a khatello le a dopaminergic li tsamaellanang le khatello e matla le litakatso le likarabo tse sa nepahalang tsa 'mele le taolo e bohlokoa ho taolo ea khatello ea maikutlo, takatso le taolo ea tšusumetso.

Patlisiso ea batho e se e qalile ho tseba matšoao a khatello le maikutlo a ho labalabela ho khutla hape. Ho utloisisa ka botlalo hore na khatello ea maikutlo le ts'ebetso ea litakatso tsa lithethefatsi e reretsoe ho khutla hape, re ile ra latela ts'ebeliso ea bakuli ba neng ba sa ts'oenyehe ka koae- le batho ba ts'ebelitseng joala lithutong tsa rona tse hlalositsoeng likarolong tse fetileng kamora ho tlohela ts'ebetso ea kalafo ea matsatsi a 90 ho hlahloba sephetho sa ho khutla hape. . Bakeng sa sehlopha sa cocaine, re fumane hore ho lakatsa khatello ea koae e hatelloang kelellong ka laboratoring ho boletse esale pele nako ea ho ts'oara koae. Le ha likarabo tsa khatello ea maikutlo tsa ACTH le cortisol li ne li sa amanngoe le nako ea ho khutlela morao, likarabo tsena li ne li hakantsoe ka boholo ba koae e ileng ea nooa nakong ea ho latela.325 Le ha litakatso tsa lithethefatsi tse amanang le lithethefatsi e ne e se boikemisetso ba ho khutla thutong ena, ho ne ho na le tlhoko e phahameng khokahano lipakeng tsa khatello ea maikutlo le lithethefatsi tse bakiloeng ke lithethefatsi le khatello ea maikutlo le litheko tsa motsoako oa lithethefatsi. Lintlha tsena li fana ka maikutlo a hore bonyane maemong a ts'ebeliso ea koae, khatello ea maikutlo le khatello ea maikutlo ea lithethefatsi li hlahisa boemo bo tšoanang bo qobelloang ba ho batla lithethefatsi bo amanang le ho oela hape kotsing. Maikutlong a joala, ho feto-fetoha ha maikutlo ho sa thabiseng, ho lakatsa joala ho tlisoang ke khatello ea maikutlo, le khatello ea maikutlo le mokhoa oa cortisol o kenyellelitsoeng ho amahanngoa le sephetho sa ho khutla ha joala.236,326-329 Bangoli ba hlokang toka ba Nicotine ba ileng ba pepesetsoa letoto la khatello ea maikutlo ba bonts'a ACTH, cortisol, le khatello ea mali e arabela karohanong ea khatello ea maikutlo empa ho eketseha ha litekanyetso tsa ho tsuba le ho lakatsa likotsi, mme likarabo tsena e ne e le ponelopele ea litlamorao tsa ho tsubella ha nicotine.289 Ka hona, bakeng sa sampole ea joala le ho tsuba, joalo ka sehlopheng sa cocaine, ho bonahala boemo ba litakatso tsa lithethefatsi bo tšoaetsoang ka ho eketseha. khatello ea maikutlo le tšusumetso e qobelloang ea lithethefatsi (ho lakatsa) le likarabo tse mpe tsa taolo ea khatello ea maikutlo (maikutlo a fetotsoeng a glucocorticoid kapa karohano e eketsehang ea Noradrenergic) e baka ts'abo e ntlafalitsoeng ea ho oela hape ts'ebelisong.

Liphumano tse fumanoeng lithutong tsa mahlale tsa mantlha le tsa laboratori ea batho le liphetho tsa tlhahlobo ea bongaka li hlahisa lipheo tse 'maloa tsa kalafo ea meriana ho sebetsana le khatello ea maikutlo ea ho phehella khatello ea maikutlo ea ho batla lithethefatsi le ho boela o ts'oha. Lintlha tsa mahlale tsa motheo li fana ka maikutlo a bahanyetsi ba CRF, alpha-2 adrenergic agonists, le li-glutamatergic agents li ka tšepisa ho sebetsana le ho oela hape ho amanang le khatello ea maikutlo. Ho hlokahala lithuto tsa laboratori tsa batho tse tla hlahloba litšepiso tsena ho hlahloba litšepiso tsa bona mabapi le matšoao a mahareng a boits'oaro bo amanang le khatello ea maikutlo bo amanang le khatello ea maikutlo bocha. Lithuto tse joalo li ka lebisa khatello ea maikutlo le litakatso tse bakoang ke lithethefatsi, litakatso tse amanang le HPA, litekanyetso tsa pelo, le phallo ea pelo, le likarabo libakeng tse ikhethang tsa boko.297 Mohlala, liphuputsong tsa mahlale le sephetho sa kliniki. re bonts'a hore lofexidine, alpha-2 adrenergic agonist, e fokotse haholo litekanyetso tse bakang khatello ea maikutlo le likhatello tse bakiloeng ke khatello ea maikutlo, ha e ntse e ntlafatsa sepheo sa ho khutlisa opiate ho naltrexone e tšoeroeng ke opiate, e itšetlehileng ka batho ka bomong.330 Ka mokhoa o tšoanang, maano a boitšoaro a fokotsehang ho tšoenyeha le khatello ea maikutlo tse amanang le khatello ea lithethefatsi le ho fokotsa likarabo tsa khatello ea maikutlo bakeng sa ho araba ka mokhoa o lumellanang maemong a phephetso e kholo ho ka u thusa ho fokotsa litlamorao tsa khatello ea maikutlo ho batlang lithethefatsi le ho khutla hape. Mohlala, ho fokotsa khatello ea khatello ea kelello (MBSR) ho sebetsa hantle molemong oa ho fokotsa khatello ea maikutlo hape ho feto-fetoha le maemo hoa maano ana ho ka ba molemo ho sebetsana le kotsi ea ho boela o le ts'ebelisong ea lithethefatsi.274

Kakaretso le Tsamaiso ea Bokamoso
Tlhahlobo ena e shebisisa bopaki bo bokellanang bo tsoang lipatlisisong tsa preclinical, tsa kliniki le tsa sechaba tse fanang ka maemo a sithabetsang haholo le khatello e sa feleng ea khatello ea maikutlo, ke hore, menyetla ea ho ts'oaroa hape le tlokotsi ea ho oela hape. Mefuta ea likhatello tse eketsang kotsi ea ho lemalla e bonoa ho Tafole 1. Lintho tse sithabetsang maikutlo hangata e ba tsa maikutlo haholo, liketsahalo tse sithabetsang tse sa laoleheng le tse sa lebelloang ho bana le batho ba baholo. Litema li tloha ho tahlehelo, pefo le mabifi ho ts'ehetso e mpe, likhohlano tsa batho, ho itšehla thajana le ho sithabela maikutlong. Ho boetse ho na le bopaki ba kamano e itšetlehileng ka tekanyetso lipakeng tsa tsietsi e bokelletsoeng le kotsi ea ho lemalla - ha palo ea khatello ea maikutlo e pepesetsoa motho, ha e le kotsing e kholo ea ho lemalla. Matšoenyeho a amanang le mosebetsi ha a na tšehetso e fokolang, empa maemo a motho ka mong a tšoanang le tšekamelo ea maikutlo a fosahetseng le boitšoaro bo bobe (mohlomong bo ts'oanang le ts'ebetso e mpe ea batsamaisi) le tsona li fana ka tšusumetso e ikhethang bothateng ba ho lemalla. Ho pepesetsoa khatello ea maikutlo joalo ka nako ea bokhachane le ho bokella khatello ea maikutlo (ho se lekane) ho fella ka liphetoho tsa neuroendocrine, 'mele, boits'oaro, le liphetoho tse etsahalang tse tšoarellang nako e telele ebile li ama hampe nts'etsopele ea methapo ea boko e kenyang ho ithuta, ho susumetsa le boits'oaro bo amanang le khatello ea maikutlo. . Patlisiso e sebetsanang ka kotloloho le liphetoho tse amanang le khatello ea maikutlo le kamano ea tsona le sepheo sa boits'oaro e hlokahala haholo. Bopaki ba ho hlakisa tlatsetso ea khatello ho liphetoho mesebetsing ea mesolimbic dopamine le kamano ea eona le ts'ebeliso ea lithethefatsi le eona ea hlokahala. Setšoantšo sa 1 se hlahisa mofuta oa mekhatlo e tšehelitsoeng lipatlisisong, hammoho le likheo tse setseng.

Tlhahlobo ea bopaki bo bonts'a litlamorao tsa ts'ebeliso ea lithethefatsi le tlhekefetso ho likarabo tsa khatello ea maikutlo le phetisetso ea dopamine e hlahisoa, hammoho le likarabo tse fetotsoeng tsa maikutlo le tse susumetsang tse amanang le ho lakatsa le ho khutlela ts'ebelisong ea lithethefatsi. Le ha tšebeliso e mpe ea lithethefatsi e baka phetoho lipakeng tsa khatello ea maikutlo le lits'oaetso tsa dopaminergic tse kenyelletsang ts'usumetso, boitaolo, le mekhoa e lumellanang e hlokahalang bakeng sa ho pholoha, bopaki ba hore liphetoho tse joalo li ntlafatsa ho batlana le lithethefatsi kapa litakatso le litloaelo tsa ts'ebeliso ea lithethefatsi lia fokola. Mohlala, lithuto tsa hore na ho pepesehela li-laesense le lithethefatsi tse seng molaong ho fetola kamano lipakeng tsa khatello ea maikutlo le taolo ea lithethefatsi ha ho na seoelo. Ha ho ntse ho na le neuroadaptations e ikhethang moputsong le libakeng tse amanang le tsona, ho bohlokoa hape ho hlahloba hore na ke liphetoho life tse kenyellelitsoeng ho eketseng tšebeliso ea lithethefatsi le ho ts'ehetsoa lits'ebetso tse joalo tsa tahlehelo tse kang tahlehelo e tsoelang pele ea taolo, ho phehella ho lakatsa, le ho eketseha ha taolo ea lithethefatsi. Kaha khatello ea maikutlo le eona e eketsa kotsi ea ho ferekana le khatello ea maikutlo le ho tšoenyeha hoo ho bohlokoa haholo ho hlahloba hore na ho na le lintlha tse amanang le khatello ea maikutlo tse bakang kotsi ea ho ba le khatello ea maikutlo le khatello ea maikutlo le kotsi ea ho lemalla. Ka mantsoe a mang, ke lintho life tse thusang ho itšireletsa mafung tse sirelletsang bakeng sa lefu le le leng empa e le mafutsana bakeng sa tse ling. Ho hlahloba lipuisano tsa tikoloho ho ka thusa haholo ho araba lipotso tse joalo.

Ho boetse ho fanoa ka tekolo ea lithuto tsa morao-rao tse mabapi le ho khutlisetsoa maikutlong ka lebaka la khatello ea lithethefatsi, ho lakatsa lithethefatsi, le ho oela hape bothateng. Litlamorao tsa tleleniki li kenyelletsa nts'etsopele ea mekhoa e mecha ea tlhahlobo le matšoao a tla ba molemo ho khetholla ba leng kotsing e kholo ea ho khutla hape ka lebaka la khatello ea maikutlo le litlhatlhobo tsa lingaka tsa bongaka tsa meriana tse lebisang khokahano lipakeng tsa khatello ea maikutlo le ho khutlela bothateng. Joalo ka ha ho bonts'itsoe ho Setšoantšo sa 2, batho ba lemaletseng ts'ebeliso ea lits'oaetso ba bonts'a maikutlo a ntlafalitsoeng a ho lakatsa le ho tšoenyeha ho hoholo maemong a amanang le khatello ea lithethefatsi, empa hore na likarabelo tse joalo tse fetotsoeng li emela phetoho ka lebaka la ts'ebeliso e mpe ea lithethefatsi kapa maemo a khatello ea kelello a hloka ho hlahlojoa le ho feta. Patlisiso mabapi le mekhoa eo khatello ea maikutlo le ts'ebeliso ea lithethefatsi li sa fetoheng tse sebelisang likarabo tsa boitšoaro tse hlokahalang li hlokahalang. Mekhoa e sebetsang ea phekolo e sebetsang e shebana le ho ntlafatsa karabelo. Leha ho le joalo, ho pepeseha khatello ea maikutlo le khatello ea maikutlo e sa foleng ho fokotsa khatello ea maikutlo le mekhoa ea ho sebetsana le maemo, ka hona, kalafo e shebaneng le ho ntlafatsa ho sebetsana le mathata e ka ba e sa lokelang ba nang le maemo a kotsi a amanang le khatello ea maikutlo. Nts'etsopele ea lipallo tse ncha tse lebisang boits'oaro, haholo maemong a khatello ea maikutlo. Patlisiso e hlophisitsoeng lipotsong tsena e tla lebisa kutlwisiso e kholo ea hore na khatello ea maikutlo e amana joang le ho khutla hape. Ntle le moo, lipatlisiso tse joalo li kanna tsa ba bohlokoa ho nts'etsopele lipheo tse ncha tsa kalafo ho fokotsa ho khutla, ka bobeli sebakeng sa nts'etsopele ea meriana le ho nts'etsopele mekhoa ea kalafo e shebileng litlamorao tsa khatello ea maikutlo ts'ebelisong ea lithethefatsi le ho khutlela mekhoeng ea lithethefatsi.

lumela hore baa fokola
Litokisetso tsa tlhahlobo ena li tšehelitsoe ke lithuso tse tsoang ho National Institutes of Health, P50-DA165556, R01-AA13892, R01-DA18219, le U01-RR24925.
Mongolo o botlaaseng ba leqephe
Likhohlano tsa Thahasello
Sengoli ha se phatlalatse hore ho na le likhohlano tsa phaello.

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