Dopamine tops and downs ka ts'oaetso ea lithethefatsi: mokhoa oa neurodevelopmental (2014)

PMCID: PMC4041845

NIHMSID: NIHMS585222

Marco Leyton, Ph.D.1,2,3,4,* 'me Paul Vezina, Ph.D.5,6

Moetso oa khatiso oa ho qetela oa mohatisi o fumaneha ho Trends Pharmacol Sci

Sheba lihlooho tse ling ho PMC hore Qotsa sehlooho se hatisitsoeng.

inahaneloang

Hangata bokhoba ba ho lemalla bokhoba bo atisoa pele ke mathata bongoaneng le bohlankeng. Bakeng sa batho ba bangata sena se qala ka polelo ea pele ea ho beha kotsing ea ho ba kotsing, ho ba le botsoalle sechabeng le boitšoaro bo hanyetsanang. Re fana ka maikutlo mona hore liponahatso tsena tsa mantlha tse fapaneng li bonts'a bokhoni bo tsotehang ba maikutlo a susumetsang ba ts'ebetso ea ts'ebetso ea dopamine e khothalletsang mokhoa oa boitšoaro. Haeba ts'ebeliso ea lithethefatsi e se e qaliloe, bacha bana ba kotsing ba ka ba le likarabo tse phahameng ho lithahasello tse tsamaeang ka lithethefatsi. Ka maikutlo le tšusumetso ea maikutlo e susumetsoang ke lithethefatsi, litlamorao tsena lia matlafatsa le ho bokella, tse lebisang likarabo tse fetang tse tlisoang ke meputso e meng. Ka nako e ts'oanang, lits'ebeletso tse sa koaeloeng ke lithethefatsi li amahanngoa le ho lokolloa ka tlase ho dopamine, ho eketsa phapang lipakeng tsa meputso ea lithethefatsi le e seng ea lithethefatsi. Ka kopanelo, lits'ebetso tsena tse ntlafatsang le tse thibelang li laola tlokotsi e neng e ntse e le teng ea ho ameha ka lithethefatsi le litakatso tse amanang le lithethefatsi. Liphetoho tsa thibelo le kalafo li tšohloa.

Keywords: Ts'ebeliso e mpe ea lithethefatsi, Ts'ebeliso e mpe ea joala, Moputso, Boemo, Sensitization, Ho khothaletsa Salience, kantle ho naha, Allostasis

Moetso o kopaneng oa neurodevelopmental oa mathata a ts'ebeliso ea lithethefatsi

Bokhoba ba lithethefatsi ke bokuli bo atileng haholo bo amang batho kajeno. Litsenyehelo tsa sechaba, tsa bongaka le tsa moruo li ngata haholo, ha tšebeliso ea lithethefatsi e kenya letsoho ho 12% ea batho ba shoang lefatšeng ka bophara [] le ho lefisa mmuso oa Amerika feela chelete e hakanyetsoang ea $ 400 billion ka selemo [-].

Hobane ke palo e fokolang feela ea batho ba lekang lithethefatsi tsa tlhekefetso ba nang le bothata ba tšebeliso ea lithethefatsi (SUD), ho entsoe boiteko ba ho tseba likarolo tsa neurobiological. Khopolo-taba e 'ngoe eo ho nahanoang hore ke ea nakoana e fetileng ke ea hore menyetla e eketsehileng ea pherekano e bonts'a litšitiso tse tsoang tsamaisong ea mesolimbic dopamine []. Ho sa ntse ho ngangisanoa leha ho le joalo ke hore na mokhoa ona oa ho fetolela tikoloho o itlhahisa e le ho fokotseha hoa tšebetso ea dopamine, joalo ka ts'ebetsong ea mohanyetsi le mehlala ea khaello ea moputso [-], kapa mosebetsi oa dopamine o phahamisitsoeng, joalo ka mehlala ea ts'usumetso ea maikutlo [-]. Moetso oa hona joale oa li-neurodevelopmental o kopanya karolo e 'ngoe le e' ngoe ea likarolo tsena. E hlokomela karolo ea bohlokoa bakeng sa hypo- le hyper-shughuli tsamaisong ea mesolimbic dopamine, 'me e hlakisa hore na e mong le e mong a ka bitsoa joang ka ho khetheha ho batho ba kotsing.

Joalokaha ho akarelelitsoe ka tlase, bopaki bo fetohang bo tsoang lipatlisisong ho bacha ba batho, batho ba baholo ba banyenyane, le liphoofolo tse sebetsang maoatleng ho fana ka maikutlo a hore bacha ba bonts'ang likarabo tsa dopamine tse matlafatsang maikutlong a matla a maikutlong ba na le menyetla e mengata ea ho etsa boits'oaro bo fapaneng, bo batlang meputso. Leha litloaelo tsena li kanna tsa lebisa ho litheko tse fapaneng tse seng tsa lithethefatsi, ts'ebetso ea ts'ebeliso ea lithethefatsi e sitisa ts'ebetso ea dopamine e phahamisitsoeng ho lithahasello tse amanang le lithethefatsi, e lebisang boemong ba lithethefatsi le maikutlo. Litlamorao tsena li matlafatsa likarabo tsa dopamine ea boko ho lithethefatsi le litheko tse tsamaeang le lithethefatsi, ka ho etsa joalo li matlafatsa tlhokomelo ea batho ba kotsing ea ho fumana litheko le ho fumana moriana. Hobane litheko tse se nang lithethefatsi tse sa sebeliseng lithethefatsi ka nako e le ngoe li hokahana le likarabo tse tlase tsa dopamine, sephetho ka kakaretso ke boits'oaro bo hlephileng ba boitšoaro, bo behang sethala sa ho ts'oara lithethefatsi khafetsa le SUD.

Moetso ona o emela ho tloha nthong e le 'ngoe feela likhopolo tsa tlhekefetso ea lithethefatsi (Lethathamo 1). Ka ho kenyelletsa ts'ebetso ea hypo- le hyper-dopamine ka bobeli, le ho kopanya sena le lintlha tse ka tsebahatsang esale pele, mokhoa oa hona joale oa neurodevelopmental o fana ka akhaonto e eketsehileng haholoanyane ea ts'ebetso ea ho lemalla. Hape, re fana ka maikutlo a hore re boemong bo botle ba ho tsebisa nts'etsopele ea maano a phekolo a sebetsang haholoanyane.

Lethathamo 1   

Ho bapisoa ha mefuta ea moputso le khaello ea tšusumetso ea bofokoli ba mofuta oa mofuta oa kopanyo o kopantsoeng mona

Keketseho e potlakileng ea ho batla moputso le karabelo ea dopamine pele ho ts'ebeliso ea lithethefatsi

Letoto la morao-rao la lithuto tsa ho nkela ngoana pele, mafahla, le lithuto tsa morao-rao li tšehelitse qeto e ts'oanang: SUDs tse ngata li bonts'a sephetho sa 'sephetho sa kantle' se nang le tšekamelo ea ho batla menyetla, ho ratana le batho ba bang, le litšekamelo tse hanyetsanang bongoaneng le bonyenyaneng [-]. Lits'ebetso tsa mantlha tse tlatselletsang lipolaong tsena ho nahanoa hore li kenyelletsa maikutlo a holimolimo le a tlase a ho putsa le likotlo tse amanang le kotlo, ka ho latellana [-]. Mohlala, bacha ba nang le mekhoa e metle ea kantle ba etsa liqeto tse kotsi, ba khetha meputso e phahameng khafetsa le haeba tahlehelo e le phahame [-].

Phapang e ikhethang ea ts'ebeliso ea lithethefatsi e boetse e bonoa liphoofolong tsa laboratori, mme ha se tsona kaofela li hlaolelang boits'oaro ba taolo ea lithethefatsi []. E 'ngoe ea litlhaloso tse hlalositsoeng hantle tsa ho ba le ts'ebetso ea lithethefatsi ke tloaelo e kholo ea ho hlahloba tikoloho ea lipale [-]. Har'a liphoofolo tseo tse fumantšang taolo ea lithethefatsi, ke sesebelisoa feela se tla fetoloa ts'ebetsong, joalo ka ha se hlalositsoe ke ho ikemisetsa ho sebetsa ka bongata bakeng sa lithethefatsi, ho mamella liketsahalo tse khelohang ho e fumana, le ho tswela pele ho batla lithethefatsi nako e telele ho feta karolelano [-]. "Lits'ila tsena tse" qobelloang "tse sebelisang lithethefatsi li khetholloa ke ho khetha ho sa tloaelehang le mekhoa e sa potlakileng, joalo ka ho araba pele ho litšito [].

Mekhoa ea boitšoaro e boletsoeng esale pele ea tšebeliso ea lithethefatsi e fapana ka mokhoa o fapaneng le tloaelo ea ho etsa lintho tse ling tse khothatsang le liphapang tse fapaneng le karabelo ea lisele tsa dopamine. Litekong, lisele tse phahameng tsa dopamine e thunya motheong le ho lokolloa ka lebaka la mathata a fapaneng e bolela esale pele tlhahlobo e ncha e ncha [,], phepo e kholo ea tsoekere [,], thuto e khothalletsang haholoanyane [], le phihlello e potlakileng ea ho itaola ka lithethefatsi [,,-]. Bopaki ha bo kopane feela. Dopamine agonists e eketsa likarabo tsa pele ho nako nakong ea liteko tsa ho ts'oaroa le mekhoa e mengata e fapaneng ea ho batla moputso ho kenyelletsa ho batla lithethefatsi (lebokose 1).

lebokose 1

Dopamine le moputso

Boithuto ba liphoofolo bo bontša hore mekhoa e kotsi, e batlang meputso e susumetsoa ke dopamine. Likarolo tse fapaneng tsa boits'oaro bona li ka hlakoloa. Ho ithutoang hamolemo ke ho ikemisetsa ho atamela le ho boloka boikitlaetso ba ho fumana moputso, boits'oaro bo susumetsoang haholo ke phetisetso ea dopamine ho ventral striatum, amygdala, le anterior cingulate [-,-]. Dopamine e boetse e ama tloaelo ea ho arabela pele ho nako linyeoeng tsa meputso [], e bonts'a litlamorao ho striatum [], ho ikemisetsa ho mamella ho lieha bakeng sa moputso o moholo, ho bonts'a litlamorao ho amygdala le orbitofrontal cortex [-,], le puisano ea taolo ea phethahatso le mosebetsi, e bonts'a litlamorao ho cortex ea orbitofrontal []. Boima ba bopaki bo bontša hore dopamine ha e amana haufi le thabo [,].

Ho batho le ho se tšoane ho fapaneng le boits'oarong bo ka amana le phapang ea karabelo ea dopamine. Ho batho ba baholo ba phetseng hantle, karabelo e kholo ea dopamine e sebetsa 'moho ho fapana ka ho batla ntho e ncha [-] le mekhoa e meng e amanang le ho susumetsoa habonolo [-]. Lithutong tsa fMRI, liphetho tse tšoanang lia bonoa. Ha likarabelo tse kholo tsa moputso oa chelete li atoloha haholoanyane, tloaelo ea ho ba le boitšoaro bo kotsing [-]. Ha e le karabelo e kholo litlamong tsa tebello ea chelete, e tla ba le lintlha tse ngata tse nepahetseng tse arabeloang []. Ha karabelo e kholo ho batho ba litso tse betliloeng ka litšoantšo tse tsosang takatso, menyetla ena e tla khethoa likhoeli tse peli hamorao.]. Ha likarabo tse kholo tsa litšoantšo tsa lijo le thobalano li eketseha haholo le ho feta ke ho ba le boima ba ho ikoetlisa le ho etsa thobalano ka mor'a likhoeli tse tšeletseng hamorao.].

Mekhatlo ena e kaholimo ho batho e nahanoa hore e bonts'a litlamorao ho tloha ka ho fetisetsa phetisetso ea dopamine e fetola mekhoa e mengata e ts'oanang [-]. Phepelo ea dopamine e theotsoeng e sitisa khokahano e sebetsang ea corticostriatal [], taolo e holimo-tlase ka cortex le bokhoni ba meputso e amanang le moputso ho kenya ts'ebetsong striatum [-]. Litlamorao tsena tsa neurophysiological li amahanngoa le tloaelo e fokotsehileng ea boits'oaro ea ho arabela ka mokhoa o ikhethileng bakeng sa moputso [-], le boikemisetso bo fokotsehileng ba ho boloka matla a ho fumana meputso, ho kenyeletsa le joala [], koae [] le chelete []. Ts'ebetso ea dopamine e phahamisitsoeng, ka papiso, e eketsa bokhoni ba meputso e amanang le moputso ho tataisa likhetho tsa boits'oaro [], e fokotsa bokhoni ba ho khetholla pakeng tsa moputso o phahameng le o tlase [], hape e etsa hore theolelo ea nakoana ea litheko li fokotsehe, mofuta oa ho qobelloa ho hlalosoang ke khetho bakeng sa meputso e menyenyane e fumanehang hanghang ho feta e meholoanyane, e mahareng haholo]. Ka bongata ba bakuli, bakuli ba lefu la kelello - le nkoang e le lefu la hyper-dopamine - ba na le mathata a mangata a tšebeliso ea lithethefatsi [] athe ba nang le lefu la Parkinson, haeba ho na le letho, ba fokotse litheko tsa tlhekefetso ea lithethefatsi []. Ka sebele, ho tsamaisa bakuli ba Parkinson meriana ea dopamine agonist ho ka tsosa lefu la dysregulation le tsebahalang ka mathata a fapaneng a taolo e mabapi le tšusumetso, ho kenyeletsoa papali ea papali ea kelello, botona le botšehali le tlhekefetso ea lithethefatsi [].

Ketsahalo ea Hyper- le hypo-dopamine kamora ho qala ts'ebeliso ea lithethefatsi

Hang ha tšebeliso ea lithethefatsi e qala, tse ling tsa litlamorao li ka fokotsoa; ke hore, litekanyetso tse tlase tse neng li sa sebetse hantle joale li ka hlahisa karabelo, 'me ka tekanyetso e neng e sebetsa hantle li ka hlahisa likarabo tse kholo. Liphoofolong tsa liphoofolo tse sebetsang, litekanyetso tsa taolo ea lithethefatsi tse pheta-phetoang li ka lebisa keketseho e tsoelang pele ea ts'usumetso ea ts'usumetso ea lithethefatsi, boikemisetso bo boholo ba ho boloka ts'ebetso ea ho fumana moputso oa lithethefatsi, le tokollo e kholo ea lithethefatsi ea dopamine [-].

Maemo a atisang ho hlahisa maikutlo a tšoana le mekhoa ea pele ea tšebeliso ea lithethefatsi ho batho: ho pepesoa makhetlo a mangata ho isa ho tekanyetso e kholo e nkile matsatsi a arohaneng ka pela ts'usumetso e tšoanang ea tikoloho. Ha maemo ana a se a entsoe lipatlisiso tsa batho, maikutlo a susumetsoang ke lithethefatsi a bontšitsoe ho kenyelletsa tokollo ea dopamine e matla ea lithethefatsi le litlamorao tse matla [-]. Sena se hlokometse, le tlasa maemo ana, ha se lithuto tsohle tse bontšang likarabo tse khothatsang. Litekong, litakatso tsa maikutlo li na le monyetla oa ho hola ho tsona tse bonts'ang maemo a holimo ho libaka tse ncha [,]. Ho batho, maikutlo a dopamine a ne a le maholo ho ba nang le lintlha tse phahameng tsa ho batla [].

Tsamaiso e pheta-phetoang ea lithethefatsi le eona e ka baka litlamorao; ke hore, tikoloho e susumetsoang ke moriana e ka hlahisa litlamorao tse ngata tse tšoanang le setheo ka boeona, ho kenyelletsa boitšoaro bo botle, ho lokolloa ha dopamine le ho batla moputso [-]. Maemo a matle bakeng sa ho hlahisa litlamorao tsena tse nang le maemo a ts'oana a tšoana le a a hohelang. Ho feta moo, liphapang tsa batho ka bomong le tsona lia bonahala []. Kamora nako, lits'oants'o tse phahameng tsa ho hlahloba litoeba li kenella haholo mesebetsing ea koae, 'me li kotsing ea ho khutlisetsoa hoa tlhoko-khang ea ho batla lithethefatsi ka mor'a ts'ebetso ea ho felisoa [].

Ho batho le bona, mekhoa ea ho sebelisa lithethefatsi e ka tlisa litlamorao tse tšoanang le tsa lithethefatsi, ho kenyelletsa le ho eketsa moputso [], likhetho tsa sebaka se loketseng [-], takatso e matla ea lithethefatsi e khothalletsoang lithethefatsi [], le ts'ebetso ea dopamine tsela-]. Phapang e ikhethang ea dopamine ea cue-ikiwa] le likarabo tse lakatsang li bonoa [], mme bopaki bo bong bo supa hore sena se ka bonahatsa tšobotsi [].

Litlamorao tse hlahisoang ke cue li bonahala li tšoailoe haholo lithutong tse kotsing ea ho lemalla. Ho batho ba noang haholo ba kotsing ea ho ba le mathata a tšebeliso ea joala, lits'ebetso tse amanang le joala li etsa hore ho be le letšoao le phahameng la elektrone ea electroencephalogram (EEG) Pontšo ea ho se sebetse hantle []. Lithutong tsa fMRI, bacha ba lilemong tse tlase ba bonts'a likarabo tse kholo ho tsebiso ea moputso oa chelete ho feta lithuto tse laoloang ho ventral striatum []. Ka mokhoa o ts'oanang, ha o bapisoa le taolo e phetseng hantle, lithuto tse nang le nalane ea malapa tsa ts'ebeliso ea joala li hlahisa likarabo tse kholo ho li-cices tse amanang le joala tse ka har'a nucleus accumbens le likarolo tse ling tsa mesocorticolimbic circ [-]. Ho joalo, thutong e kholo ea batho ba noang haholo (n = 326), ho ata ha mathata a tšebeliso ea joala, ho hoholo le ho feta ke ts'ebetso ea ts'ebetso ea joala e khothalletsoang [-]. Kamora nako, bopaki bo khahlisang ba pele bo bonts'a hore tatso ea subpharmacological ea biri e lebisa ho likarabo tsa bohlokoa tsa dopamine ho barupeluoa ba nang le nalane ea malapa ea mathata a ts'ebeliso ea joala, empa eseng ho ba noang haholo ba kotsing [].

Ho ba teng vs. ho ba sieo hoa litumelo le maemo a amanang le lithethefatsi ho ka ntlafatsa boikemisetso ba ho arabela liketsahalong tse ling [,-]. Haeba moputso oa tlhaho o fanoa sebakeng seo pele se neng se entsoe ka joala le lithethefatsi, phoofolo e tla bonts'a boitlamo bo kopantsoeng ka moputso ona oa tlhaho [,]. Haeba, hangata, mekhoa ea lithethefatsi e hlahisoa hammoho le monyetla oa ho amohela lithethefatsi, boits'oaro bo batlang lithethefatsi bo khothalletsoa [,,]; haeba moriana o fanoa, polelo ea dopamine [] 'me maikutlo a boitšoaro a lumelloa [-]. Ka lehlakoreng le leng, li-cucamine tse tsamaeang ka ho hlaka ka lebaka la ho se fumane moputso oa lithethefatsi li ka ba le litlamorao tse matla, tsa fokotsa ho lokolloa ha dopamine [], ts'ebetso ea ts'ebetso [,-,-] hammoho le ho nka lithethefatsi le ho khutlisetsoa [-].

Litlamorao tsa ts'usumetso e entsoe ka mokhoa o hlakileng ka ho hloka moputso oa lithethefatsi ha li ithutoe hantle bathong. Leha ho le joalo, bopaki ba morao-rao bo bontša hore ho ka etsoa ts'ebetso ea inhibitory. Mohlala, ha batho ba tsubang ba sa ts'epahalang ba ne ba hlahisoa ka likhoele tsa koae, lintlha tse lakatsang ho eketseha li ile tsa eketseha haholo ka holim'a motheo; tlhahiso ea litheko tse tsamaisitsoeng ka ho hlaka ka lebaka la ho se tsube, ha ho bapisoa, li fokotsehile haholo litakatso tsa tlase []. Bopaki ba litlamorao tsena tse fokotsehileng bo ka bonoa le bokong. Bahloekisi ba kotsing e phahameng ba qalileng tšebeliso ea lithethefatsi ba bonts'a likarabo tse nyane tsa EEG P300 ho litheko tse ntle tse senang thepa tse kang erotica ho feta likhakanyo tse amanang le lithethefatsi []. Lithuto tsa fMRI li ts'ehetsa qeto e ts'oanang: ho bapisoa le taolo e phetseng hantle, lithuto tse kotsing e bonts'a likarabo tse nyane tsa maikutlo a tlase lithutong tse fapaneng tse seng tsa lithethefatsi, mohlomong haholoholo tse nang le manonyeletso a tlase kapele [-; cf, ].

Ho ba teng vs. ho ba sieo hoa lintlha tse amanang le lithethefatsi ho ka boela ha ama boikemisetso ba lisele tsa dopamine ho araba bathong. Mohlala, ha basebelisi ba lithethefatsi tse sa its'epahalleng tse sebelisang lithethefatsi ba kentse cocaine moo ho nang le litheko tse amanang le lithethefatsi (ba kenelletse ts'ebetsong e tloaelehileng ea microen tikoloho ea ho lokisa le ho inhaling phofoine ea koae)], ha e le kholo nalane ea bophelo ea tšebeliso ea lithethefatsi e susumetsang, ke ha karabelo e matla ea litheko tsa dopamine e khothalletsoang. Ha ho bapisoa, ho basebelisi ba ts'usumetso e sa itšetleheng ea liteko tse fumanoeng ha ho na tšusumetso e amanang le lithethefatsi, nalane e telele ea ts'ebeliso ea lithethefatsi e ne e amana le likarabo tse nyane tse hlahisitsoeng ke lithethefatsi tsa dopamine [] (Setšoantšo sa 1). Tlhaloso e 'ngoe ea liphetho tsena ke hore ho ba sieo ha litlhare tse amanang le lithethefatsi dampens dopamine cell reacuction (Setšoantšo sa 2).

Setšoantšo sa 1   

Ho ba teng kapa ho se be teng ha lithethefatsi tsa lithethefatsi ho laola ka mokhoa o fapaneng litokollo tsa dopamine e le ts'ebetso ea nalane ea bophelo bohle ea tšebeliso ea lithethefatsi
Setšoantšo sa 2   

Mohlala oa ts'ebetso ea dopamine le litlamorao tsa boits'oaro ho lithethefatsi

Ka kopanelo, lithuto tse kaholimo li fana ka maikutlo a hore phetisetso e tlase ea dopamine ha ho na mekhoa e amanang le lithethefatsi e ka hlaha lits'ebetsong tse peli. Ea pele ke ts'ebetso eo ho eona phetisetso ea dopamine e tlase haholo ha e bapisoa le likarabo tse bonoang ha litekanyetso tsa lithethefatsi li le teng. Ea bobeli ke ts'ebetso e bonts'ang, e bonts'ang maemo a thibelang (lebokose 2). Ho feta moo, ha se feela hore tsena tse senang lithethefatsi li ka tlisa nako ea ts'ebetso e tlase ea dopamine, takatso ea bona e hohelang e ke ke ea qothisana lehlokoa le litheko tse tsamaeang ka lithethefatsi. Litlamorao tsena li ka ba le litlamorao bakeng sa boits'oaro nakong ea ho tlohela, mme, kannete, ho ba le ts'oaetso e phahameng ea ho batla le ho sebelisa lithethefatsi nakong ea ho tlohela lithethefatsi ho ka bontša lits'ebetso tse tšoanang. Joalo ka ha mebuso ea litsietsi e ka ntlafatsa boleng ba ts'usumetso ea meputso ea tlhaho ea meputso, joalo ka lijo [], bopaki bo qobellehang bo fana ka maikutlo a hore ho batla lithethefatsi ho hlokometsoeng nakong ea ho khaotsa lithethefatsi ho ka bonts'a sekhahla se phahameng sa ts'usumetso ea litheko tsa lithethefatsi ho fapana le ho qoba ho tlosoa.-]. Kahoo, ts'ebeliso ea lithethefatsi nakong ea ho tlohela e ka bonts'a likarolo tsa lits'ebetso tse ntle ho e-na le ts'usumetso e mpe. Ka mekhoa ena, mekhoa ea ho sa sebetse ka lithethefatsi e ka ba ea bohlokoa bakeng sa nts'etsopele ea likarolo tse peli tse akaretsang tsa SUD: ho lieha ho tsoelang pele ha lithahasello tse mabapi le mekhoa e amanang le lithethefatsi le ho ts'oara lithethefatsi le tjantjello ea ho hahamalla lipheo tse amanang le lithethefatsi tse sa hlokahaleng ho atleha.

lebokose 2

Likhakanyo tsa tikoloho le moputso

Nahana u se u nyoloha leralla. Haeba boiphihlelo ba nakong e fetileng bo u rutile hore moputso o hohelang o ka pele, khothatso ea hau ea ho tsoelapele e tla ba holimo, 'me lintlha tse bonts'ang hore moputso o tlang li tla nyolla le ho boloka ts'ebetso ea hau. Litsi tsena tse susumetsang li amana haufi le liphetoho phetong ea dopamine; ke hore, maemo a buloang ka moputso a eketsa boikemisetso ba lisele tsa dopamine ho phatloha hoa mollo ka lebaka la likhakanyo tse laoloang ke meputso [,,]. Ha ho bapisoa, tikoloho e aparetsoeng ka ho hlaka ntle le moputso e ka fumana thepa ea inhibitor [] le bokhoni ba ho thibela ho bala ka dopamine ka mafolofolo le bokhoni ba ho arabela meputsong le likotlo tse amanang le moputso [,]. Ka kopanelo, motsoako ona oa litlamorao o hlahisa likhetho tse matla bakeng sa tikoloho le likharetene tse huloang ke lithethefatsi, tse hohelang batho hole le liketsahalo le liketsahalo tse amanang le lithethefatsi.

Liphuputso tse peli tsa morao-rao li bontša hore lithuto tse kotsing e kholo ea li-SUD li ka angoa habonolo ke litlamorao tsena (Setšoantšo sa 3). Taba ea pele, karabelo e phahameng ka ho fetesisa ea dopamine e ile ea bonoa ho basebelisi ba lithethefatsi ba kotsing e phahameng ea ho lemalla, joalo ka ha ho bapisoa le basebelisi ba kotsi e fokolang, ha ba ne ba lekoa ka litekanyetso tsa lithethefatsi tse teng (joala bo kenelletse ka ho bona seno, ho fofonela, ho latsoa le ho ama)]. Taba ea bobeli, ka lehlakoreng le leng le makatsang, ho lokolloa ka mokhoa o ikhethileng oa dopamine ho ile ha bonoa ho basebelisi ba lithethefatsi ba kotsing e phahameng ea ho lemalla ha ba ne ba lekoa ntle le litokelo tsa lithethefatsi tse teng (d- matlapa aamphetamine a patiloeng ho li-nancaps tsa nondescript) []. Ho lithuto tsena ka bobeli, liphapang tsa sehlopha li ile tsa phehella kamora ho laola tšebeliso ea lithethefatsi bophelo bohle. Kannete ho basebelisi bana ba kotsing e kholo, likarabo tsa dopamine ka ho hloka mekhoa e amanang le lithethefatsi li ne li le tlase haholo ho feta tse bonoang lithutong tse tlase tse kotsing e ts'oanang le nalane ea ts'ebeliso ea lithethefatsi tsa motho []. Maikutlo a joalo a phahamisa monyetla oa hore, ho batho bana ba kotsing e kholo, taolo e laoloang karabelong ea moputso e tsoela pele ka potlako kapa ka mokhoa o pharaletseng. Ka kopanelo, liphumano tse hlahlojoang mona li fana ka maikutlo a hore ho ikopanya ha maikutlo a susumetsoang ke lithethefatsi, maemo, le liphapang tsa motho ka mong lipokellong tsena li ka lebisa bacha ba kotsing ea ts'ebeliso ea lithethefatsi khafetsa, ho theha sethala bakeng sa SUD.

Setšoantšo sa 3   

Dopamine le nts'etsopele ea mathata a ts'ebeliso ea lithethefatsi ho batho ba phahameng haholo

Litlamorao tsa thibelo le kalafo

Ho fapana le pono e le 'ngoe ea bokhoba ba taolo e lebisang ho ts'ebetso ea hyper- kapa hypo-mesolimbic dopamine, mohlala o kopantsoeng mona o kopanya likarolo tsena ka bobeli, ka hona o fana ka sebaka sa ho qala sa neurobiological bakeng sa maano a ho kenella, ho kenyelletsa thibelo (lebokose 3). Mosebetsi oa morao-rao o fana ka lebaka la ho ba le tšepo. Mohlala, ho kenya bacha lilemong ba fuoeng koetliso ea taolo ea tšusumetso ho bontša mathata a ts'ebeliso e fokolang ea lithethefatsi kamora ho latela lilemo tse peli [].

lebokose 3

Dopamine le boits'oaro bo sa susumetseng

Kamano lipakeng tsa boits'oaro bo sa tsitsang, ho lokolloa ha dopamine le ho ba le monyetla o moholo oa tšebeliso e mpe ea lithethefatsi ho ka hasanya meloko eohle. Ntle le keketseho ka mekhoa e meng e metle, litoeba tse sa qhekelloheng li bonts'a tlhokomelo e nyane ea bo-mme [], e lebisang ho ho kenella ho feta tekano, ho kholisa maikutlo a cue, tokollo ea dopamine, le taolo ea lithethefatsi ho bana ba bona [-]. Sebakeng sa tlhaho, liphoofolo tsena li ka ba le monyetla oa ho kopana le liketsahalo tse bohloko. Matšoenyeho ana a boetse a etsa hore dopamine e lokolloe, 'me e ka lebisa ho tšusumetso e telele ea boits'oaro le dopaminergic sensitization ho lithethefatsi tsa tlhekefetso [-], ho mpefatsa ho feta litšekamelo tse neng li le teng pele. Litlamorao tse tšoanang li ka hlaha le ho batho. Ho joalo, bana ba h in olisoang ke malapa a khethiloeng ka boits'oaro bo kantle ba kotsing e kholo ea khatello ea maikutlo, khatello ea maikutlo le ho se tsotelloe, ho ba beha kotsing e kholo ea li-SUDs [].

Ho lula ho le joalo hore na lits'ebetso tse hlalositsoeng kaholimo (litšobotsi tse khethollang (hypert-dopamine function) li nepahetse hang ha ts'ebeliso e mpe ea tahi e tsoetse pele. Ka lehlakoreng le leng, lits'ebetso tse amanang le lithethefatsi li lula li susumetsa ts'ebetso ho batho ba nang le litumelo tsa hona joale, ts'ebetso ena e kholo ho feta e bonoang ka taolo e phetseng hantle, le liphapang tse fapaneng le boholo ba likarabo tsa litheko tsa dopamine tse tlatselletsang ka dopamine ka takatso ea tsona []. Ho latela lipatlisiso tsena, re fana ka maikutlo a hore pele ho nako ho hana phetiso ea dopamine e le sepheo sa kalafo.

Ka nako e ts'oanang, batho ka bomong ba nang le li-SUD tsa morao-rao le tsona ho tlalehiloe ka mokhoa o ts'oanang hore li fokotse ho lokolloa ha striatal dopamine, ha ho bapisoa le taolo e phetseng hantle, ha ho phephetsoa le amphetamine []. Lintlha tse peli li khahla mona. Pele, ho tsohle empa e le ngoe ea lithuto tsena [], amphetamine e ne e fanoa ntle le lits'ebetso tse amanang le lithethefatsi li ba teng (lebokose 4). Taba ea bobeli, ha se batho bohle ba nang le SUDs ba bonts'ang ho fokotseha ha dopamine ea amphetamine ha ba lekoa ha ho se na litheko tse tsamaeang ka lithethefatsi. Karabelo ena e arohaneng e bonahala e na le bohlokoa ba tleleniki: e batlang e le 50% ea lithuto tse bontšang karabelo e tloaelehileng ea dopamine tlasa maemo ana le tsona ke ba arabelang hamolemonyana lithutong tsa boitšoaro tse matlafatsang tse matlafatsang, tse phahamisang menyetla e makatsang ea hore bakuli ba ka hlalosang karabelo ea dopamine ho ho ba sieo hoa mekhoa e amanang le lithethefatsi ho boetse ho khona ho ithuta mekhoa e mecha e amanang le moputso [-]. Ho ntse ho sa hlaka hore na tlhahiso e tlase ea dopamine e bonoang ho bakuli ba bang ba itšetlehileng ka ntho e 'ngoe e bonts'a ho se be teng hoa litumelo tse amanang le lithethefatsi, ho ba kotsing ea phapang pakeng tsa litlamorao tsa ts'ebeliso e mpe ea lithethefatsi, tšobotsi e teng pele, dopamine D2 ea pele le ea post-synaptic receptor super. -Sensitivity, kapa motsoako o mong oa lintlha tsena. Basebelisi, Martinez le basebetsi-'moho [] o lemohile ka mokhoa o makatsang hore batho bana ba ka bonts'a biomarker e bonts'a hore ba ka rua molemo ho tsa kalafo ea boits'oaro haeba ba phekoloa pele le baemeli ba eketsang ts'ebetso ea dopamine ea presynaptic, joalo ka L-DOPA [].

lebokose 4

Dopamine le "bokhoba ba boitšoaro"

Bopaki ba likarabo tsa dopamine tse tlatselletsang boteng ba mekhoa e amanang le ts'ebeliso ea lithethefatsi bo bonoa khafetsa ho batho ba nang le 'litloaelo tsa boits'oaro'. Ha ho bapisoa le taolo e phetseng hantle, batho ba nang le "litloaelo tsa boits'oaro bo amanang le lintho tse ling" (Pathological Gossip, Binge Eating Disorder) ba bonts'a bopaki ba likarabo tsa dopamine tse fetelletseng tsa lijo, meputso ea chelete le matlapa a sa thabiseng a amphetamine [-; cf, ]. Ha tokollo ea dopamine e le kholoanyane, e mpefatsa le ho feta mathata a bongaka.,,-]. Ho lokolloa ha dopamine e tlase ha ho e-so tlaleheloe ho baahi bana. Leha ho le joalo, lingoliloeng tsa papali ea papali ea papali ea fMRI li tlaleha ka bobeli le ho fokotseha ha ts'ebetso ea litheko, 'me likarabo tsena tse fapaneng li bonahala li bonts'a karolo e kholo ea boteng vs. ho ba sieo hoa mekhoa e hlakileng ea ho becha [].

Mekhoa e meng ea phekolo e thehiloeng ho dopamine le eona e tlas'a nts'etsopele. Dopamine D1 le D2 ligands li bontšitse ho se sebetse hantle empa bahanyetsi ba D3 receptor ba bontšitse ka mokhoa o hlakileng hore ba ka khona []. Li-subtypes tse ling tsa li-receptor (D4, D5) ha li sa tla hlahlojoa. Kamora nako, kaha lithethefatsi li bonahala li fumana phallo ea dopamine ka lebaka la litheko tsa lithethefatsi le li-dips ha litheko li le sieo, modulators oa dopamine a ka fana ka kalafo ea noha e lumellanang le mohlala oa hona joale. Tlhahiso ke hore metsoako ena e tla fokotsa keketseho ea dopamine e khutlisetsang ho ts'oara lithethefatsi ntle le ho nyahlatsa phetisetso eohle ea dopamine mme e hlahise tahlehelo e atileng ea litheko [].

Lipolelo tse qetellang

Moetso oa hona joale o kopanya pono ea neurodevelopmental le bopaki ba hore ho ba teng vs. ho ba sieo hoa lits'ebetso tse amanang le lithethefatsi ho ka tlisa taolo ea dopamine hape, ho tataisa lits'ebetso tse susumetsang le ho theha sethala sa tšebeliso ea lithethefatsi khafetsa le SUD. Maikutlo ana a kopantsoeng a bonts'a ts'episo ea ho tataisa maano a thibelo ea pele, 'me a fana ka tlhahiso ea hore tataiso e behang litholoana bakeng sa mekhoa e mecha ea litlhare e ka ba ho nts'etsapele likhakanyo tse matlafatsang bokhoni ba ho ts'oara phaello mesebetsing e amanang le lithethefatsi. Ho matlafatsa boipiletso ba lipheo tsena ho ka thusa ba nang le li-SUD hore ba furalle mekhoa e amanang le lithethefatsi le ho ea ho tse ling tse hlokahalang bakeng sa bophelo bo botle.

​   

Lintlha-khōlō Tsa

  1. Hangata bokhoba ba bokhoba bo tloaelo bo etsoa pele ke boitšoaro ba mathata bongoaneng
  2. Ho ts'oaroa ke letsoalo ho ka bontša likarabo tse eketsehileng tsa dopamine liketsahalong tse ikhethang
  3. Lithethefatsi li utsoa likarabo tsa dopamine, li lebisa boitšoaro ho lithethefatsi
  4. Liketsahalo tse seng lithethefatsi li fetoha tse nyenyefatsang, 'me li ba le matla a ho etsa dopamine
  5. Lithahasello tse thellisitsoeng lia theha sebaka sa ts'ebeliso ea lithethefatsi le lithethefatsi khafetsa

Liteboho

Tlhahlobo ena e ile ea khoneha ka lithuso tse tsoang ho Canadian Institutes for Health Research (MOP-36429 le MOP-64426, ML) le National Institutes of Health (DA09397, PV).

Mongolo o botlaaseng ba leqephe

 

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

 

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