Boemo ba ho ipeha boemong bo bongata bo feteletseng (2013)

. Mongolo o ngotsoeng ka letsoho; e fumanehang ho PMC 2016 Apr 11.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

PMCID: PMC4827347

NIHMSID: NIHMS763035

inahaneloang

Boko ba rona bo thata ho arabela le ho batla meputso hanghang. Kahoo, ha ho makatse hore ebe batho ba bangata ba ja ho feta tekano, moo ba bang ba ka qetellang ba le botenya, athe ba bang ba sebelisa lithethefatsi, tseo ho tse ling li ka qetellang li lemaletse. Leha lijo le boima ba 'mele li le tlas'a taolo ea lapeng, ha lijo tse fumanehang habonolo li fumaneha, matla a ho hanela tšusumetso ea ho ja li itšetleha ka boitšoaro. Ha ho na molaoli oa homeostatic ho hlahloba tšebeliso ea lithethefatsi (ho kenyeletsa le joala); ka hona, taolo ea ts'ebeliso ea lithethefatsi e tsamaisoa haholo ke boitšoaro kapa litlamorao tse sa batleheng (ke hore, sedation bakeng sa joala). Tšitiso mahlakore ka bobeli a ts'ebetso ea methapo ea kutlo e tlisoang ke ho utloa moputso le e laoloang ke tšilafalo e ka lebisang ho kenelletseng ho ja lijo ho batho ba bang le tšebeliso e matla ea lithethefatsi ho ba bang. Ho na le bopaki bo ntseng bo eketseha ba hore tšitiso ea matla homeostasis e ka ama potoloho ea meputso le hore ho fetella lijo tse nang le moputso ho ka lebisa ho liphetoho mokhoeng oa moputso o lebisang ho kenyelletsong ha lijo ho amanang le phenotype e bonoang ke ho lemalla. Patlisiso ea bokhoba ba tai e hlahisitse bopaki bo bocha bo bonts'ang liphapang tsa bohlokoa bo lipakeng tsa methapo ea kutlo ea tlhaho le lefu la bokhoba le bonyane mefuta e meng ea botena. Tlhokomeliso ena e hlahisitse ngangisano e phetseng hantle ea ho leka le ho netefatsa hore na mathata ana a rarahaneng le a fapa-fapaneng a feta le hore na kutlwisiso e tebileng ea crosstalk pakeng tsa homeostatic le meputso ea meputso e tla tlisa menyetla e ikhethang ea thibelo le kalafo ea botena le botšehali. bokhoba ba lithethefatsi.

Keywords: Dopamine, bokhoba ba lithethefatsi, botenya, cortex ea pele, moputso, boitšoaro

Ka bobeli bokhoba le botena li bonts'a ho se leka-lekane likarabong tsa boko ho khothaletsa moputso tikolohong. Bakeng sa botenya, ho se leka-lekane hona ho ka ts'oaroa ke lits'oants'o tsa endocrinological tse fetolang mokhoa o matla le ho fetola kutlo ea melemo ea meputso ea lijo. Leha ho le joalo, botena bo boetse bo ka bakoa ke ho fihlella habonolo ha lijo tse matlafatsoang, tšebeliso e feteletseng ea eona e ka amang ho tšoaea lapeng le ho sitisa kutloisiso ea moputso oa lijo. Ho sebelisa lithethefatsi khafetsa, ka lehlakoreng le leng, ho ka senya seriti sa moputso, sepheo sa sona se ka sehloohong sa pharmacologic. Ka hona, Sisteme ea dopamine (DA), ho pholletsa le machoaccumbens / mesolimbic (moputso le maikutlo), mesostriatal (litloaelo, mekhoa, le motsamao), le mesocortical (mosebetsi o moholo) litseleng, ke karolo e tloaelehileng ho "neurobiology" ea mathata a mabeli (Setšoantšo sa 1).

Setšoantšo sa 1 

Khahlano e makatsang ea lithethefatsi tseo liketso tsa tsona li qholotsoang ke litlamorao tsa tlholeho e ka kotloloho mokholeng oa moputso oa boko dopamine tseleng (sebaka sa karolelano ea methapo [VTA], li-nucleus accumbens, le ventral pallidum) ...

Re khothaletsa hore mafu ana a mabeli a arolelane lits'ebetso tsa methapo eo, ha e sitisoa, e ka fella ka tšebeliso e qobelloang, ha e ntse e kenyelletsa mekhoa e ikhethileng ea neurobiological. Re hlahisa bopaki ba likarolo tse arolelanoang tsa neurobiological mme ha re re botenya ke lebaka la bokhoba ba lijo empa ho e-na le hoo, moputso oa lijo o bapala karolo ea bohlokoa ho ho ja ho tlola tekano le botenya, re bo bitsa karolo ea karolo ea botenya.

Likarolo tsa liphatsa tsa lefutso

Lintlha tsa kahisano le setso li tlatsetsa seoa sa botenya. Leha ho le joalo, lintlha ka bomong li boetse li thusa ho tseba hore na ke mang ea tla nona haholo maemong ana. Le ha liphuputso tsa lefutso li senotse lintlha tse ntlafalitsoeng tse atileng har'a batho ba batenya haholo, botenya bo boholo bo nahanoa hore bo tlas'a taolo ea polygenic. Ho joalo, boithuto ba morao-rao bo akaretsang bo entsoeng ho 249,796 batho ba mofuta oa Europe ba supile 32 loci e amanang le index ea 'mele (BMI). Leha ho le joalo, tsena 32 loci li hlalositse 1.5% feela ea phapang ea BMI (,), boemo boo ho seng bonolo ho bo ntlafatsa ka disampole tse kholo ka lebaka la tšebelisano e rarahaneng pakeng tsa lintho tsa tlhaho le tikoloho. Sena ke 'nete haholo neng le neng ha lijo tse nang le khalori e phahameng li fumaneha hohle eseng feela mohloli oa phepo, empa hape le moputso o matla oo ka boona o khothalletsang ho ja.

Mohlomong, ho pharalatsa sekhahla sa seo re se utloisisang ka kotsi ea liphatsa tsa lefutso bakeng sa botenya bo fetang mefuta e hokahaneng le matla homeostasis () ho kenyelletsa liphatsa tsa lefutso tse fetolang karabelo ea rona tikolohong ho ka eketsa liperesente tsa phapang ea BMI e hlalositsoeng ke mefuta. Mohlala, liphatsa tsa lefutso tse susumetsang botho li ka baka botenya haeba li senya mamello e hlokahalang bakeng sa ho ikoetlisa. Ka mokhoa o ts'oanang, liphatsa tsa lefutso tse fetolang taolo e phahameng, ho kenyelletsa le boits'oaro, li ka thusa ho loants'a kotsi ea ho nona libakeng tse nang le lijo tse ngata. Sena se ka hlalosa kamano ea botona le liphatsa tsa lefutso tse amehang ka mokokotlo oa DA, joalo ka DRD2 Taq I A1 allele, e 'nileng ea amahanngoa le bokhoba ba tahi (). Ka mokhoa o ts'oanang, ho na le liphatsa tsa lefutso lipakeng tsa moputso le litsela tsa homeostatic, joalo ka cannabinoid receptor 1 (CNR1) mofuta, mefuta e fapaneng eo ho eona ho amanang le BMI le kotsi ea botenya ka lithuto tse ngata (), hammoho le bokhoba ba tahi (). Hape, re hopoleng hape maemong ana hore li-opioid tsa mehleng ea khale li kenyelletsa likarabo tsa hedonic ka lijo le lithethefatsi le hore polymorphism ea A118G e sebetsang ho mofuta oa μ-opioid receptor gene (OPRM1) e amahantsoe le ho ba kotsing ea mathata a ho ja -) le bokhoba ba tahi ().

Liphetoho tsa limolek'hule: Tsepamisa maikutlo ho Dopamine

Qeto ea ho ja (kapa che) ha e anngoe feela ke boemo bo kahare ba caloric equation empa hape e hlahisoa ke lintho tse senang botsitso, tse kang khaello ea lijo le lithahasello tsa tikoloho tse etsang hore re arabeloe. Lilemo tse leshome tse fetileng li sibollotse litšebelisano tse ngata tsa limolek'hule le tšebetsong lipakeng tsa homeostatic le meputso ea taolo ea lijo. Ka ho khetheha, lihormone tse 'maloa le li-neuropeptide tse kenyellelitsoeng ho matla homeostasis li susumetsa tsela ea moputso ea DA (). Ka kakaretso, lipontšo tsa homereatic orexigenic li eketsa ts'ebetso ea lisele tse tsoang hare tsa sebaka sa Vral ha li pepesetsoa takatso ea lijo, athe li-anorexigenic li thibela DA ho thunya le ho fokotsa ho lokolloa ha DA (). Ho feta moo, li-neurons tsa VTA le / kapa li-nucleus accumbens (NAc) li hlahisa glucagon-like peptide-1 (,), ghrelin (,), leptin (,), insulin (), orexin (), le li-receptor tsa melanocortin (). Ka hona, ha ho makatse hore li-hormone / li-peptide tsena li ka susumetsa likarabo tse khotsofatsang ho lithethefatsi tsa tlhekefetso. Litšebelisano tse joalo li ka hlalosa se fumanoeng ke likarabo tse fumanehang mabapi le litlamorao tse khotsofatsang tsa lithethefatsi mefuteng ea liphoofolo ea botenya (). Ka mokhoa o tšoanang, lithuto tsa batho li fumane kamano e fapaneng lipakeng tsa BMI le tšebeliso e seng molaong ea lithethefatsi () le kotsi e tlase ea mathata a tšebeliso ea lithethefatsi ho batho ba batenya haholo.), ho kenyelletsa le litekanyetso tse tlase tsa nikotine () le matekoane () tlhekefetso. Ho feta moo, lipheo tse fokotsang BMI le tse fokotsang plasma ea insulin le leptin li matlafatsa kutloisiso ea lithethefatsi tsa psychostimulant (), le ts'ebetso ea bongaka ea bariatric bakeng sa botenya e amahanngoa le kotsi e eketsehileng ea ho khutlela hape ho ts'ebeliso e mpe ea tahi le joala (). Ha li kopantsoe hammoho, liphetho tsena li fana ka maikutlo a hore menyetla ea lijo le lithethefatsi e ka ba tlholisano bakeng sa meputso e mengata.

Ho tšabeha ho hoholo pakeng tsa botenya le bokhoba ba kelello ho ka boleloa esale pele ka lebaka la hore lithethefatsi tsa tlhekefetso li kenella mokhoeng o tšoanang oa neuronal o fetolang ts'usumetso le sepheo sa ho batla le ho ja lijo (). Kaha lithethefatsi li kenya ts'ebetsong moputso oa boko ho feta lijo, hona ho thusa ho hlalosa (hammoho le mekhoa ea homeostatic satiety) bokhoni bo boholo ba lithethefatsi ba ho susumetsa tahlehelo ea taolo le boits'oaro bo hatellang. Mekhoa ea Brain DA, e fetotsang karabelo ea boitšoaro lithutong tsa tikoloho, e bapala likarolo tse bohareng tsa botenya (hape le bokhobeng). Dopamine neurons (ka bobeli ho VTA le substantia nigra) ha e fetole moputso feela empa e fana ka tšusumetso le botsitso ba boiteko bo hlokahalang ho fihlela boits'oaro bo hlokahalang bakeng sa ho pholoha. Ho joalo, litoeba tse haelloang ke DA li bolaoa ke tlala, mohlomong ka lebaka la tšusumetso e fokotsehileng ea ho jella lijo, le ho tlatselletsa mosebetsi oa tsona oa bocha ka DA o khutlisetsa ho li fepa le ho li pholosa (). Ho na le tsela e 'ngoe ea DA (tuberoinfundibular pathway) e projeke e tsoang ho hypothalamus ho ea ho pituitary gland, empa ha re e shebe mona hobane ha e so ka e kenella liphellong tse ntle tsa lithethefatsi (), leha e ka angoa ke lithethefatsi tsa tlhekefetso (). Ho fihlela ts'ebetso ea eona, li-neurons tsa DA li amohela likhakanyo tse tsoang libakeng tsa boko tse amehang ka likarabo tsa autonomic (hypothalamus, insula), memory (hippocampus), reactivity ea maikutlo (amygdala), arousal (thalamus), le taolo ea kelello (preortalal cortex) ka mefuta e fapaneng ea li-neurotransmitters le li-peptide (). Ka mokhoa o reriloeng ka nako eo, li-neurotransmitter tse ngata tse amehang mekhoeng ea ho batla lithethefatsi le tsona lia ameha ho jang lijo ().

Ho matšoao ohle a kentsoeng litlamorao tsa lijo le lithethefatsi, DA e bile patlisiso e tebileng ka ho fetisisa. Liteko tsa litoeba li bonts'itse, mohlala, hore lipontšo tsa DA ka li-receptor tsa D1 ka bobeli le li-receptor tsa D2 (D2R) ho dorsal striatum li hlokahala bakeng sa ho fepa le mekhoa e meng e amanang le ho ja (). Mohlala, ha motho a qeta ho fumana moputso oa lijo, ho thunngoa ha li-neuron tsa DA ho VTA ho eketseha ka keketseho e bakang ea tokollo ea DA ho NAc (). Ka ho pepesetsoa khafetsa, li-neurons tsa DA li emisa ho thunya ha li fumana lijo le mollo ho e-na le ho pepesetsoa khothalletso e boletsoeng esale pele ho tlisoa ha lijo (). Ntle le moo, kaha keketseho ea DA e susumetsoang ke ts'usumetso e lebelletsoeng ka theko ea boitšoaro eo phoofolo e ikemiselitseng ho e lefa ho e amohela, sena se tla etsa bonnete ba hore sephethe-phethe (se susumetsoang ke lets'oao la DA) se etsahala pele phoofolo e ja lijo ka botsona. Ho khahlisang, ha cue e sa lebise moputsong oa lijo o lebelletsoeng, ts'ebetso ea neuron ea DA e thibeloa, e fokotsa boleng ba ts'usumetso bakeng sa cue (ho timela). Mefuta ea liphoofolo ea moputso oa lijo le oa lithethefatsi e bonts'itse hore kamora ho felisoa, ts'ebetso ea ts'ebeliso ea lithethefatsi kapa lijo e ka tsosoa ka ho pepesehela cue, moputso kapa khatello ea maikutlo (). Tlokotsi ena ea ho khutlela morao e ithutile haholo mefuteng ea liphoofolo ea tsamaiso ea lithethefatsi mme e bonts'a liphetoho tsa neuroplastic ho alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid le N-methyl-D-aspartate receptor glutamatergic signaling (). Bakeng sa moputso oa lithethefatsi, lithuto li boetse li bontšitse hore ho se leka-lekane pakeng tsa D1 receptor signaling (e ntlafalitsoeng) le D2 receptor signaling (e fokotsehile) ho nolofalletsa tšebeliso ea lithethefatsi e qobelloang (); motho a ka bolela esale pele hore ho se leka-lekane ka tsela e tšoanang ho ka etsa hore batho ba je haholo ntle le ho ja. Monyetla ona o lumellana le tlaleho ea morao-rao moo mohanyetsi ea joalo ka D1 a koetsoeng mme mohanyetsi ea ts'oanang le D2 a kang a eketsa ts'ebetso ea boits'oaro bo batlang lijo ().

Ha li kopantsoe hammoho, liphetho tsena li fana ka maikutlo a hore potoloho ea homeopatic e bile teng ho nka monyetla ka sebaka sa dopaminergic circry ho etsa boits'oaro ba ho iphepa eseng feela ka maemo / thepa e phelisang e sebelisitsoeng qalong ke ts'ebetso ea bohloka empa hape le ts'ebeliso e latelang ea litheko tsa dorsal striatum meahong ea cortical. kenya letsoho ka kotloloho ho kopantseng khothatso le likarabo tsa koloi tse hlokahalang bakeng sa boits'oaro bo lebisitsoeng ho sepheo ().

Litla-morao tsa Neurocircuitry le Boitšoaro

Khothatso e matla ea ho batla le ho sebelisa lithethefatsi ka bokhoba ba tahi ha e kenyeletse ts'oarelo eseng feela ka mokoloto oa meputso empa le lipotoloho tse ling, ho kenyelletsa lipotso tse ling, taolo ea thibelo, taolo ea maikutlo le khatello ea maikutlo, le mohopolo (). Ho ka phetoa khang ea hore mofuta ona oa methapo ea kutlo o sebetsa le mefuta e meng ea botena.

Moputso, Boemo, le Ts'usumetso

Lithethefatsi tsa tlhekefetso li sebetsa ka ho kenya tšebetsong potolo ea moputso oa DA, eo, haeba e sa foleng, ho batho ba tlokotsing, e ka qetellang e lemaletse. Lijo tse ling, haholo-holo tse nang le tsoekere le mafura a mangata, le tsona lia putsa () hape e ka etsa hore e lemale joaloka boits'oaro liphoofolong tse sebetsang.) le batho (). Ho joalo, lijo tse nang le khalori e phahameng li ka khothaletsa ho nona ho feta tekano (ke hore, ho ja tse se nang thipa ho tloha litlhoko tse matlafatsang) le ho baka likamano tse ithutileng lipakeng tsa khothatso le moputso (maemo). Thepa ena ea lijo tse fumanehang habonolo e ne e na le monyetla oa ho iphetola ha lijo e haella, empa libakeng tseo lijo tse joalo li leng ngata li bileng li leng bongata, ke molato o kotsi. Kahoo, lijo tse matlafatsoang, joalo ka lithethefatsi tsa tlhekefetso, li bontša sesosa se matla sa tikoloho, eo ho batho ba tlokotsing ba nang le monyetla oa ho tsamaisa kapa ho mpefatsa ho thehwa ha boits'oaro bo sa laoleheng.

Ho batho, ho kenella ha lijo tse matlafatsoang ho ntsha DA maemong ao a lekanang le litekanyo tsa monate oa lijo.) hape e kenya tshebetsong moputso wa potoloho (). E tsamaellana le lithuto tsa preclinical, lithuto tsa ho nahana ka litšoantšo li boetse li bonts'itse hore li-peptide tsa anorexigenic (mohlala, insulin, leptin, peptide YY) e fokotsa kutloisiso ea ts'ebetso ea moputso oa boko ho moputso oa lijo, athe ba orexigenic (mohlala, ghrelin,) ba e eketsa [bona tlhahlobo ()]. Ho makatsang ke hore, lithuto tse lemalloang le tse batang haholo li bonts'a ts'ebetso e fokolang ea li-circuits tsa meputso ha li fuoa lithethefatsi kapa lijo tse monate, ka ho latellana (). Sena ha se lumellane kaha keketseho ea DA e kholoa ho phethola litheko tse ntle tsa meputso ea lithethefatsi le lijo; ke ka hona likarabo tsa DA tse sa hlakanngoeng nakong ea tšebeliso li lokela ho bolela pheletso ea boitšoaro. Kaha sena ha se se bonoang tleliniking, ho ile ha fanoa ka tlhahiso ea hore ts'ebetso ea DA e tlotsitsoeng ka tšebeliso (ea lithethefatsi kapa ea lijo) e ka baka ts'ebeliso e feteletseng ho lefella karabelo e sa nepahalang ea potoloho ea moputso (). Boithuto ba pelehi bo bonts'ang hore mosebetsi oa DA o fokotsehile ho VTA o fella ka keketseho e kholo ea tšebeliso ea lijo tse nang le mafura a mangata () ho tšehetsa khopolo ena.

Ho fapana le likarabo tsa moputso o phoso nakong ea tšebeliso ea meputso, lithuto tse lemalloang le tse batenya haholo li bonts'a likarabo tse angoang ke likotsi tsa moputso oa lithethefatsi kapa oa lijo. Boholo ba li-DA tsena li eketseha lithutong tse lemaletseng bokhopo bo bolela esale pele botebo ba litakatso tse hlahisitsoeng ke cue (), le ho liphoofolo, li bolela esale pele boiteko boo phoofolo e ikemiselitseng ho bo etsa ho fumana moriana oo (). Ha ho bapisoa le batho ba boima bo tloaelehileng, batho ba batenya ba shebileng litšoantšo tsa lijo tse nang le khalori e ngata (ba susumetsoa ke maemo a bona) ba bonts'itse ts'ebetso e eketsehileng dikarolong tsa moputso le lipotoloho tse khothatsang (NAc, dorsal striatum, orbitofrontal cortex [OFC], cortex ea ka ntle ea ka ntle. [ACC], amygdala, hippocampus, le insula) (). Ka mokhoa o ts'oanang, ho batho ba batenya haholo ba nang le bothata ba ho ja ka ho fetesisa, ho lokolloa ho phahameng ha DA - ha ho pepesetsoa mekhoa ea lijo-ho ne ho amana le ho teba ha lefu lena ().

Likamano tse pharalletseng tsa "glutamatergic" tse amanang le li-neuron tsa DA tse tsoang libakeng tse amehang ts'ebetsong ea moputso (NAc), boemo (amygdala, hippocampus, preortalal cortex), le sesence expression (orbitofrontal cortex) li fetola ts'ebetso ea bona ho latela litšupa tse nang le maemo (). Haholo-holo merero e tsoang ho amygdala, hippocampus, le OFC ho li-neuron tsa DA le ho NAc li ameha likarabo tse fanoeng lijong () le lithethefatsi (). Ho joalo, liphuputso tse nahannoeng li bonts'itse hore ha banna ba sa bateng ba batona ba kopuoa ho thibela takatso ea bona ea lijo ha ba pepesetsoa lijo tsa mofuta oa lijo, ba fokotse ts'ebetso ho amygdala, OFC, hippocampus, insula, le striatum; le ho fokotseha ha OFC ho ne ho amana le ho fokotsa litabatabelo tsa lijo (). Thibelo e ts'oanang ea ts'ebetso ea OFC (le NAc) e ile ea bonoa ho batho ba hlekefetsang koae ha ba kopuoa ho thibela litakatso tsa bona tsa lithethefatsi nakong ea ho pepeseha lithahasello tsa cocaine (). Leha ho le joalo, ha ho bapisoa le litheko tsa lijo, litloaelo tsa lithethefatsi ke lisosa tse matla tsa boits'oaro bo matlafatsang kamora nako ea ho ila. Ka hona, hang ha re tima, boitšoaro bo matlafalitsoeng ke lithethefatsi bo kotsing ea ho khutlisetsoa kelellong ho feta boits'oaro bo matlafatsoang ke lijo (). Ho sa le joalo, khatello ea kelello e tsamaisana le ts'ebeliso e eketsehang ea lijo tse matlafatsang le ho nona ka boima ba mmele le ts'ebetso e mpe ea OFC ho hlahisa meputso ea lijo ().

Ho bonahala eka ts'ebetso ea DA ea ts'ebetso ea striatum ke lithahasello (ho kenyeletsoa maemo a amanang le lithethefatsi) e kenelletse ka takatso (e batlang), joalo ka sesosa sa boitšoaro se ikemiselitseng ho sebelisa moputso oo u o batlang. Ehlile, DA e boetse e etsisa tšusumetso le ho phehella (). Hobane ho ts'oara lithethefatsi e fetoha sesosa se ka sehloohong sa ho lemalla, lithethefatsi tse lemalloang lia tsosoa ebile li susumetsoa ke ts'ebetso ea ho fumana moriana empa li ikarola 'me li sa tsotelle ha li pepesetsoa mesebetsi e amanang le lithethefatsi. Phetoho ena e ithutile ka ho bapisa ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea boteng kapa ho ba sieo ha litlhare tsa lithethefatsi. Ho fapana le ho fokotseha hoa ts'ebetso ea pele ho litlaleho tse tlalehiloeng ho batho ba hlekefetsang koae ha ba sa khothatsoa ke litheko tsa lithethefatsi kapa lithethefatsi [bona tlhahlobo ()], libaka tse ka pele le tse kahare tsa pele (ho kenyeletsoa OFC le Aral ea bohlasoa) li hlahisoa ka ho pepesetsoa takatso e khothalletsang (lithethefatsi kapa litheko) (,). Hape, ha lithuto tse lemaletseng koae li ne li thibela takatso ea takatso ha li pepesetsoa litakatso tsa lithethefatsi, ba neng ba atlehile ba fokotse metabolism ho medial OFC (lits'ebetso tse susumetsang tsa boleng ba matlafatso) le NAc (e bolela moputso) (), e lumellanang le ho kenya letsoho ha OFC, ACC, le striatum khothaletsong e ntlafalitsoeng ea ho fumana lithethefatsi tse bonoang ke ho lemalla. OFC le eona e ameha ka mokhoa o ts'oanang ka ho nka boleng ba ho sesa ka lijo (), ho thusa ho lekola thabo le tebello ea eona e lebelletsoeng e le ts'ebetso ea maemo a eona. Lithuto tse tloaelehileng tsa boima ba 'mele tse buletsoeng mekhoa ea lijo li bonts'itse ts'ebetso e eketsehang ho OFC, e amanang le ho lakatsa lijo (). Ho na le bopaki ba hore OFC e ts'ehetsa le ho fepa ka cue-elicised.) le hore e kenya letsoho ho ho ja ho feta tekano, ho sa natsoe lipontšo tsa tlala (). Ho joalo, lintlha tse 'maloa tsa lipatlisiso li ts'ehetsa kamano e teng lipakeng tsa ho senyeha ha OFC le ho ja lijo tse nang le mathata, ho kenyelletsa le setsoalle se tlalehiloeng lipakeng tsa ho ja tse thibelitsoeng lilemong tsa bocha ba batenya le palo e tlase ea OFC (). Ha ho bapisoa, litla-morao tse ngata tsa kalafi ea OFC li ile tsa bonoa ho bakuli ba nang le bothata ba ho ja 'mele oa balimia le ba kulang.), le tšenyo ea OFC ho litšoene tsa rhesus ho tlalehiloe ho fella ka hyperphagia ().

Ho hlaha ha litakatso tse nang le maemo a mantlha le tšusumetso ea meputso, eo bakeng sa lijo le eona e hlahang ho batho ba phetseng hantle ba sa jang ho feta (), e ne e ke ke ea senya haeba ba ne ba sa kopanngoe le bofokoli bo ntseng bo hola bokong ba kelello ba ho thibela boits'oaro bo bobe.

Boitšoaro Le Matla a ho Hanela Liteko

Bokhoni ba ho thibela likarabo tse itsoelang pele le boitšoaro bo boholo li thusa bokhoni ba motho ba ho hatella boits'oaro bo sa lokang, joalo ka ho sebelisa lithethefatsi kapa ho ja ho feta tekano, ka hona, ho fetola ho ba kotsing ea ho lemalla kapa botenya, ka ho latellana (,). Boithuto ba pelehi le tleliniki bo khothalelitse hore ho senyeha ha lets'oao la DA ho ka nyenyefatsa boits'oaro bo hlalositsoeng ka tlase.

Liphuputso tse entsoeng li bonts'a hore ho fumaneha ho fokotsoeng ha li-receptor tsa D2R ke mokhoa o sa fetoheng oa tšebeliso e mpe ea lithethefatsi le e ka ts'oarang likhoeli kamora ho hlakoloa [ho hlahlojoa ho ()]. Ka mokhoa o ts'oanang, lithuto tsa preclinical li bonts'itse hore ho pepesetsoa lithethefatsi khafetsa ho amana le phokotso ea nako e telele maemong a D2R le ho supa (,). Boemong ba striatum, li-receptors tsa D2 li buisana ka tsela e sa tsamaelaneng e fetolang libaka tse katlase, mme taolo ea tlase ea eona e ntlafatsa boiketlo ba lithethefatsi mefuteng ea liphoofolo.), athe ntlafatso ea eona e kena-kenana le tšebeliso ea lithethefatsi (). Ho feta moo, thibelo ea D2R ea ts'ebetso kapa ts'ebetso ea D1 receptor-e hlalosang striatal neurons (boits'oarong bo supang tseleng e otlolohileng) e ntlafatsa kutloisiso ea moputso oa lithethefatsi (). Phallo ea lets'oao la D2R le eona e bile le tšusumetso ho botenya (,) le ho ja lijo tse qobelloang ka litoeba tsa monokotsoai (). Leha ho le joalo, hore na ho na le lits'ebetso tse tšoanang tsa taolo tse fapaneng tse fokotsehileng ka tsela e tobileng (e fokotsehileng) le e sa tobang joang (ho eketseha) ha botona bo ntse bo sa hlaka.

Phokotso ea D2R ea bokhoba ba tahi le bokhobeng e amahanngoa le ts'ebetso e fokotsehileng libakeng tsa pele tse kenyellelitsoeng ho salience sifa (OFC), ho sibolla phoso le thibelo (ACC), le ho etsa liqeto (dorsolateral prefrontal cortex) (,,). Kahoo, taolo e sa lokelang ea D2R-Mediated DA e bontšang libaka tsena tse ka pele lithutong tse lemalloang le tse feteletseng e ka tlatselletsa boleng bo ntlafalitsoeng ba tšusumetso ea lithethefatsi kapa lijo le bothata ba ho li hanela (,). Ntle le moo, hobane ho senyeha ha OFC le ACC ho tsamaisana le boitšoaro bo qobelloang le ho se ts'oanelehe, ho feto-fetoha ha maikutlo ho sa tloaelehang ha dopamine libakeng tsena ho kanna ha tlatsetsa mekhoeng e qobelloang le e sa qobelloang ea lithethefatsi (ho lemalla) kapa lijo (botenya).

Ka mokhoa o ts'oanang, ho se sebetse ka pele ho libaka tse tlang pele ho nako ho ka baka tlokotsi ea tšebeliso e mpe ea lithethefatsi kapa lijo, tse ka eketsoang le ho feta ke ho fokotseha hoa litheko tsa D2R (ebang ke lithethefatsi kapa khatello ea maikutlo; ha ho hlake hore na lijo tsa 'mele tse jang mahlo li fokotseha ka D2R ). Ehlile re bonts'itse hore lithuto tseo, leha li ne li na le kotsi e ngata ea liphatsa tsa lefutso (nalane e ntle ea lelapa ea joala) e ne e se lino tse tahang, li ne li na le D2R e tloaelehileng, e neng e amana le metabolism e tloaelehileng ea pele () tse ka beng li ba sirelelitse bokhobeng ba joala. Ho khahlisang, phuputso ea morao-rao ea bana ba motho ea nang le bothata ba ho lemalla lithethefatsi tse matlafatsang e fumane hore OFC ea bana ba motho ea lemaletseng bana e ne e le nyane haholo ho feta ea banab'abo ba sa lumelloang kapa lithuto tse laoloang ().

Lintlha tsa monahano oa Brain li boetse li tšehetsa taba ea hore liphetoho tsa sebopeho le tšebetso libakeng tsa bokong tse amehang ho ts'ebetsong (ho kenyeletsa le inhibitory) tšebetso li amahanngoa le BMI e phahameng ho batho ba bang ba phetseng hantle. Mohlala, patlisiso ea ho nahana ka bokhoni ba basali ba tsofetseng e fumane kamano e mpe lipakeng tsa BMI le litaba tse bohlooho (ho kenyeletsoa libaka tse ka pele), tseo ka har'a OFC, li amanang le ts'ebetso e mpe ea motsamaisi (). Boithuto bo bong bo fumane ho fokotseha ho hoholo ha phallo ea mali ka har'a cortex ea pele e amanang le boima bo phahameng lithutong tsa taolo e phetseng hantle (,), le lipatlisiso tsa ts'ebetso ea matla a maiketsetso tse sebetsang li ile tsa tlaleha ts'ebetso e mpe ea boemo bo phahameng ho basali ba batenya (). Ka mokhoa o ts'oanang, lithutong tsa taolo e phetseng hantle, BMI e ne e hokahanngoe hampe le ts'ebetso ea metabolic libakeng tsa pele moo ts'ebetso e ileng ea bolela esale pele lintlha mabapi le liteko tsa ts'ebetso ea botsamaisi (). Ho khahlisang, li-jaers tse atlehileng li kenya letsoho libakeng tsa pele tse kenyelletsoeng taolong ea inhibitory (dorsolateral prefrontal cortex le OFC) ha li ntse li ja (). Lithuto tsena le tse ling li hlahisa khokahano lipakeng tsa tšebetso ea botsamaisi le bokhoba ba ho lemala le botenya / phenotypes, mme lipatlisiso tse ling li tla thusa ho hlakisa lintlha le phapang lipakeng tsa liketsahalo tsena.

Ka ho hlakileng, liphapang tse fapaneng le tšebetso e phahameng li ka baka kotsi ea ho ba le botena hamorao ho batho ba bang (). Ho khahlisang, lipatlisiso tse etsoang ka nqane ho bokhoni ba bana ba ho itaola, ho rarolla mathata le ho etsa lintho tse amanang le bophelo bo botle li senotse bokhoni ba ts'ebetso ea botsamaisi hore bo se ke ba kopanngoa feela le ts'ebeliso ea lithethefatsi empa le ts'ebeliso ea lijo tse matlafatsang tsa khalori e phahameng. le boits'oaro bo ituletseng ().

Tlhokomeliso ea Matšoao a Khethollo

Insula e bohareng e bapala karolo ea bohlokoa litakatsong tsa lijo, koae le koae (-). Bohlokoa ba eona ea ho lemalla bokhoba bo ile ba totobatsoa ha thuto e fumana hore batho ba tsubang ba ileng ba tšoaroa ke stroke se ileng sa senya insula ba khona ho tlohela habonolo ntle le ho tsilatsila kapa ho oela hape (). Insula, haholoholo libaka tsa eona tse ka thoko, e hokahana le likarolo tse fapaneng tsa methapo ebile e ts'ehetsa mesebetsi e fapaneng, e kopanya leseli la boipuso le pono le maikutlo le ts'usumetso le ho fana ka tlhokomeliso ea likeletso tsena (). Tumellanong le khopolo ena, lithuto tse ngata tsa monahano li bonts'a ts'ebetso e hlakileng ea ts'usumetso nakong ea ho lakatsa (). Ka hona, ho boetse ho khothalelitsoe ts'ebetso ea ts'usumetso hape joaloka lebenkele ho thusa ho bolela esale pele ().

Insula hape ke sebaka sa mantlha se phetheselang, se nkang karolo likarolo tse ngata tsa boitšoaro ba ho ja, joalo ka tatso. Ntle le moo, rostral insula (e hokahantsoeng le cortex ea tatso ea mantlha) e fana ka leseli ho OFC e susumetsang pontšo ea eona ea bongata kapa ea moputso oa lijo tse tlang (). Ka lebaka la ho kenella ha mohopolo kelellong e kopanyang ea 'mele, tlhokomelisong ea maikutlo (), le ts'usumetso le maikutlo (), tlatsetso ea ho senyeheloa ha botona ho botenya ha ea lokela ho makatsa. Kannete, ho ba le letsoalo le ka mpeng ho hlahisa ts'ebetso ea ts'ebetso ea kamorao ho ts'ebetso, e leng pontšo ea karolo ea eona ho tsebeng maemo a 'mele (ntlheng ena ea botlalo) (). Ntle le moo, lithutong tse sa tšepahaleng empa eseng lithutong tse monko o monate, ho ba le letsoalo ho ile ha baka ts'ebetso ea ts'ebetso ea amygdala le deactivation ea anterior insula (). Ho haella ha karabelo ea amygdalar lithutong tse batenya ho ka supa temoso e phuthullohileng ea linaha tsa 'mele tse amanang le ho satiety (mpa e felletseng). Leha phetisetso ea tšebetso ea bohloka ke DA e sa hlahlojoe hantle, hoa tsebahala hore DA e nka karolo karabong ea ho latsoa lijo tse matlafatso tse kopantsoeng le ts'ebetso (). Ho joalo, ho batho, ho latsoa lijo tse monate li ile tsa tlatsetsa libakeng tsa seretse le matsoele (,). Ntle le moo, ho tšoaea li-DA ho bonahala ho hlokahala hape bakeng sa ho utloa litaba tsa khalori ea lijo. Mohlala, ha basali ba tloaelehileng ba boima ba latsoa sirapo e nang le likhalori (sucrose), libaka tsa seteraeke le tsa DA li ile tsa qala ho sebetsa, athe ho latsoa tatso e se nang khalori (sucralose) ho kenya ts'ebetso feela ts'ebetso (). Lintho tse nang le botenya li bonts'a ts'ebetso e kholo ho feta lithuto tse tloaelehileng tse laoloang ha u latsoa lijo tsa metsi ka tsoekere le mafura (). Ho fapana le hoo, lithuto tse fumaneng pholoso ea ho ipolaisa tlala (anorexia manthaosa) li bonts'a ts'ebetso e fokolang ha e latsoa ho ikamahanya le maemo 'me e sena mokhatlo oa maikutlo a monate ka ts'ebetso e kenelletseng joalo ka ha ho bonoa lithutong tsa taolo ().

Karolo e Lefifi ea Khopotso e Ntle

Karolo e lefifi ea bokhoba ba tahi e qalile ho khothaletsoa ke Koob le Le Moal () ho hlalosa phetoho eo batho ba lemaletseng lithethefatsi ba nang le eona lipakeng tsa tšebeliso ea lithethefatsi ea pele ho e loketseng, eo ka tšebeliso e sa feleng e hlahisang tšebeliso ea lithethefatsi ho imolla maikutlo a mabe a maikutlo. Haufinyane tjena, Parylak et al a. () ba khothalelitse hore phetoho e tšoanang e ka hlaha tlatsong ea lijo ka lebaka la lijo tsa obesogenic. Ba bontšitse hore litabeng tsa bokhoba ba lithethefatsi le maemong a mang a ho ba le botenya kapa mathata a ho ja, khatello ea maikutlo le maikutlo a mabe (khatello ea maikutlo, ho tšoenyeha) li ka baka lithethefatsi tse tlamang (tlatsong) kapa ho ja lijo ho batho (botenya le mathata a ho ja). Mohlala oa bona o totobatsa bohlokoa ba lipotoloho tse tsamaisang khatello ea kelello le ho ikoetlisa, tse ntlafatsoang kamora ho pepesetsoa lithethefatsi empa le ka mor'a ho fumana lijo tse fumanehang habonolo. Khubu ea mofuta oa bona ke kutloisiso e ntlafalitsoeng ea amygdala e atolositsoeng le ho tšoaea ho eketsehileng ka corticotropin-releasing factor le corticotropin-releasing factor amanang le peptides, tse arabelang karabelo ho khatello.

Ka mokhoa o tšoanang, tlhokomeliso ea hore habenula e buisana le thibelo ea VTA DA neuron e thunya ha moputso o lebelletsoeng o sa fumanehe () e boetse e tlama tikoloho ena ho kenya letsoho ho li-circry tse joalo tse sa sebetseng. Kahoo, kutloisiso e ntlafalitsoeng ea habenula, ka lebaka la ho pepesehela lithethefatsi ho sa feleng, e ka baka ts'ebetso e kholo ho lithahasello tsa lithethefatsi mme hape e ka kenya letsoho metseng ea dysphoric nakong ea ho tlohela. Ka sebele, ts'ebetso ea "habenula" ea morao-rao, litšoantšong tsa liphoofolo tsa lithethefatsi tsa koae kapa tsa heroin, e amahantsoe le ho khutlela morao (,). Habenula e boetse e kenella moputsong oa lijo: li-neuron tse ka har'a rostromedial tegmental nucleus, tse amohelang karolo e kholo ho tsoa habenula, projeke ho li-neurons tsa VTA DA mme li kenngoa ka mor'a ho hloka lijo (). Liphumano tsena li tsamaisana le karolo ea habenula ea morao-rao ho arabisanang le karabelo lipotsong tse tlatselletsang kapa lipulong tse kang tse etsahalang nakong ea lijo kapa ho tlohela lithethefatsi.

Kakaretso le Liphello

Boko ba motho ke sistimi e rarahaneng ea likokoana-hloko e hlophisehileng mohahong o hlophisitsoeng oa likhokahano tse sebelisanang, tseo ka linako tse ling li bitsoang bowtie (), moo sekoti se fokotsang sa lisebelisoa tse ngata tse nang le bokhoni se ka fetolela palo e nyane ea lits'ebetso pele se nyolla hape ho fapana ka tlhahiso. Boitšoaro bo jang bo hlahisa mohlala o motle oa boqapi bona moo hypothalamus e leng thipa e bohareng ea methapo ea methapo (Setšoantšo sa 2A) le midbrain DA nuclei (VTA le substantia nigra) le libaka tsa bona tsa boiketsetso (NAc; amygdala; hippocampus; dorsal striatum; and pre mapemaal, motor, and temporal cortices) li emela lefapha le bohareng bakeng sa sistimi e amanang le tsusumetso e kantle ea kantle (ho kenyeletsoa lithethefatsi le lijo), hammoho le matšoao a kahare a ka hare (ke hore, tlala, lenyora) (Setšoantšo sa 2B). Lisebelisoa tsena tse peli li ka talingoa e le mehlala ea meaho e meholo e hlophisitsoeng (), eo mokokotlo oa DA o tšehetsang matšoao a kahare a arolelanoang ka ho supa lipontšo tsa hypothalamic (Setšoantšo sa 2C). Moetso ona o thusa ho hlalosa mehlala e holisang ea lintlha tsa ho ikopanya lipakeng tsa botenya le bokhoba, tseo tse ling tsa tsona li ileng tsa hlakisoa tekong ena.

Setšoantšo sa 2 

Setšoantšo se reriloeng sa meralo ea ho haha ​​ka kelellong ea bongoana joalo ka mohlala oa (A) matla homeostatic (metabolic) le (B) dopamine li-system (moputso) tse sebetsang. Boko ba motho, joalo ka litsamaiso tse rarahaneng tsa bioloji, bo tsebahala ka meaho e raliloeng ...

Kahoo, maano a tsoang mokhoeng o atlehileng oa thibelo le kalafo a ka ba molemo ho botenya. Patlisiso ea nako e tlang sebakeng sena e lokela ho kenyelletsa maano a sechaba le melaoana ho fokotsa ho fumaneha ha lijo tsa obesogenic (ho thibela thekiso ea eona, ho eketsa litšenyehelo tsa eona), ho eketsa phihlello ea li-suppforcers tse ling (lijo tse phetseng hantle tse ka qothisanang lehlokoa le theko ea lijo tse nang le khalori e ngata le phihlello ea lijo tsa 'mele tse fumanehang). ts'ebetso), le ho ntšetsa pele thuto (ho nka monyetla ka likolo, malapa le sechaba). Ka mokhoa o ts'oanang, lipatlisiso tsa kalafo li ka tsepamisa maikutlo ho maano a kliniki le a sechaba ho fokotsa thepa e matlafatsang ea lijo le ho theha / ho matlafatsa thepa e tlisang melemo ea lingoliso tse ling (kenyeletsa meputso ea sechaba, ts'ebetso ea 'mele, maemo a tšohanyetso) ho ithuta mekhatlo e mecha), fokotsa khatello ea maikutlo le ho ntlafatsa mohopolo (boikoetliso ba 'mele, kalafo ea kelello), le ho matlafatsa boits'oaro bo akaretsang (kalafo ea kelello le ea boits'oaro). Likarolo tsa phetolelo tse hlahang ho hlokomela sebopeho se atileng sa maloetse ana li bonts'a mokhoa o le mong feela oa tlhahlobo ea nako e tlang e fumanoeng tlhahlobisong ena (Lethathamo 1).

Lethathamo 1 

Tse ling tsa lipotso tse bulehileng tsa lipatlisiso tsa nako e tlang mabapi le lintlha tse tlatsetsang tsa botenya

E ntse e bolela hore litšokelo tse peli tse kholo tse ka thibeloang bophelong ba sechaba (ho tsuba le botenya) li kenyeletsa potoloho ea moputso e khothalletsang batho ho sebelisa meputso leha e le hore e kotsi bophelong ba bona. Litharollo tsa lefu lena la lefu lena le tla hloka, ho kenyelletsa mekhoa e ikemetseng, mananeo a pharalletseng a bophelo bo botle a khothaletsang liphetoho tse bohlale tikolohong.

lumela hore baa fokola

Patlisiso ena e ne e tšehelitsoe ke National Institutes of Health (Lenaneo la Lipatlisiso la Intramural la Setsi sa Naha sa Ts'ebeliso ea Tahi le Tahi).

Mongolo o botlaaseng ba leqephe

 

Bangoli ha ba tlalehe litabeng tsa lichelete kapa litabeng tse ka 'nang tsa e-ba le thahasello.

 

References

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