Ann NY Acad Sci. Sengoloa se ngotsoeng; e fumaneha ho PMC 2011 Jul 22.
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inahaneloang
Stressis e 'ngoe ea lisosa tse ka sehloohong tsa ts'ebeliso e mpe ea lithethefatsi, haholo-holo ho oeleng hape boits'ebetsong ba ho batla lithethefatsi. Le ha ho le joalo, mekhoa e bakang tšebelisano lipakeng tsa khatello ea maikutlo le tšebeliso e mpe ea lithethefatsi ha e hlake. Ka lilemo tse ngata, lithuto li shebile karolo ea karolo ea moputso oa dopaminergic ts'ebelisong ea lithethefatsi. Liphetho tsa rona li bonts'a hore ts'ebetso ea dopaminergic e eketsehang e susumetsoa ke maikutlo a lithethefatsi le khatello e fapaneng ea maikutlo ka tsela e ka fokolisang tsela ea "ventc subiculum-nucleus accumbens" (NAc). Leha karolo ea NE ea ts'ebetso ea khatello ea maikutlo e tsebahala haholo, ho nka karolo ha eona ts'ebelisong e mpe ea lithethefatsi ho amohetse tlhokomelo e nyane. Tlhahlobo ena e lekola mekhoa e fapaneng eo ka eona bahatelli ba ka fetolang tsela e kenelletseng ea bokantle ba moea, le hore na liphetoho tsena li ka tlisa liphetoho joang boits'oarong ba taolo ea lithethefatsi. Haholo-holo re tla shebana le litumellano tse peli tsa mantlha tsa NAc, amygdala ea basolateral le subralulum ea hippocampus, le tšebelisano ea bona le systemus coeruleus-norepinephrine.
Patlisiso mabapi le ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebeliso ea lithethefatsi hampe ka moetlo e shebile haholo molemong oa moputso oa dopaminergic ho nts'etsopele ea bokhoba, ka ho hatisa haholo liphetoho tsa neural libakeng tse nang le moputso tse khothalletsoang nakong ea bokhoba, ho khutla hape le ts'ebeliso ea bohloka. 1, 2. Tsamaiso e pheta-phetoang ea lithethefatsi tsa tlhekefetso ho lumeloa hore e baka karabelo ea methati ho potoloho ea neural e amehang ho sebetsanang le moputso oa tlhaho, mme mekhoa e tlisoang ke liphetoho tsena tse nyarosang e bile sehlooho sa lipatlisiso tse ngata 3. Sisteme ea mesolimbic e thehiloeng ka karolo ke sebaka sa ventral tegmental (VTA) le li-nucleus accumbens (NAc) ke karolo ea bohlokoa ea potoloho ea moputso oa boko. Mesolimbic dopamine e ea ameha ts'ebetsong ea meputso ea tlhaho le e amanang le lithethefatsi, e buisana le likarolo tsa hedonic tsa meputso e ntle. 4, hape e sebetsa e le lets'oao la ho ithuta la ho matlafatsa boitšoaro 5. Ho entsoe mohlala oa phetoho ea boko e etsahalang nakong ea ts'ebetso ea ts'ebeliso ea bokhoba ba joala e hlalosang tlokotsi e phehellang ea ho khutla hape, le kamora nako e telele kamora hore ts'ebeliso ea lithethefatsi e felile. Ho joalo, liphetoho tse tlisoang ke lithethefatsi ka har'a polasetiki ea synaptic tsamaisong ea mesolimbic, haholo-holo VTA le NAc, le karolo e ka etsahalang ea li-receptor tsa dopamine nts'etsopele ea li-neuroadaptations tsena, e bile sepheo sa lithuto tse 'maloa. Phallo ea phetisetso ea phetisetso ea synaptic libakeng tse mahareng le ka mor'a ho pepesetsoa lithethefatsi e nkile karolo ea bohlokoa ho khutliseng lithethefatsi le ho khutlisetsoa kahare ho eona. 1. Kahoo liphetoho tsa morphological le li-synaptic tsa mefuta e 'maloa ea lisele tsa neuronal libakeng tsa maoto a bokong li ka ikarabella bakeng sa ts'ebeliso ea nako e telele ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea taolo 6. Ha joale ho thehiloe hantle hore karolo e thata ka ho fetisisa ea ho phekola bokhoba ba lithethefatsi ha se ho tlosa lithethefatsi, empa ho thibela ho oela hape 7, 8. Ho khutlela mokhoeng oa ho lemalla lithethefatsi hangata ho amana le ho lakatsa lintho tse tsamaisanang le boitšoaro ba ho batla lithethefatsi. Ho 'nile ha fanoa ka maikutlo a hore esita le ka mor'a libeke, haeba e se likhoeli tsa ho tlohela, ba lemaletseng litheko tsa kelello ba susumetsoa ke lithahasello tsa tikoloho tse amanang le lithethefatsi tse sebetsang e le tšusumetso ea kantle ho takatso ea bona 9-11.
E 'ngoe ea lintho tse ngata tse tsejoang hore li kenya letsoho ho tloheleng ts'ebeliso e mpe ea lithethefatsi ke khatello ea maikutlo. Ho joalo, liphuputso tse ngata tsa bongaka hammoho le liphoofolo li bontšitse karolo e ka sehloohong ea khatello ea ts'ebeliso e mpe ea lithethefatsi le ho khutla hape 12. Leha ho le joalo, mekhoa ea motheo ea kamano ena e lula e sa hlaka. Khatello ea kelello le psychostimulants li-sensitize, tse nang le khatello ea maikutlo tse lebisang ho karabelo e phahameng ho li-psychostimulants le mahlakore a mabe. Ntho e 'ngoe e tloaelehileng eo karolo ea khatello ea maikutlo le ts'usumetso ea lithethefatsi ke ho itšetleha ha bona ka matla maemong a potolohileng. Ehlile, liphoofolo tse pepesitsoeng khatello ea maikutlo maemong a itseng li bonts'a liphetoho tsa boitšoaro maemong a ts'oanang 13, 14, le psychostimulant sensitization e kholo ha liphoofolo li hlahlojoa tikolohong e le 'ngoe eo moriana o hlahisitsoeng ho eona 15, 16. Sebaka se kentsoeng ts'ebetsong tse itšetlehileng ka maemo ke sebopeho sa moea sa hippocampus (vSub). VSub e kenya letsoho maemong a tšabo a itšetlehileng ka maemo 17 hammoho le lits'ebetso tse ling tse amanang le maemo 18-20. VSub hape ke sebopeho sa bohlokoa ho karabelo ea mmele e amanang le khatello ea maikutlo 21 le karabelo ea hyperdopaminergic ho amphetamine 22, 23. Sebopeho se seng sa bohlokoa se amanang le khatello ea maikutlo ke basolateral amygdala (BLA). Ts'ebetso ea methapo kahare ho amygdala e angoa haholo ke khatello ea maikutlo, ho pepeseha khatello ea maikutlo le ts'ebetso e khahlisang. 24, 25. Plastiki ea Synaptic ka har'a amygdala e boetse e anngoe ke ho pepesetsoa khatello ea maikutlo 26. Habohlokoa, BLA e boetse e kenella ho oeleng hape ho lithethefatsi, haholoholo ka ho kopanya litšusumetso tsa khatello kelellong e amanang le lithethefatsi. 27. Ntle le moo, BLA e fana ka phetoho e matla ho vSub 28. Tlhahlobo ea hona joale e tla shebana le balekane ba babeli ba bohlokoa ho NAc mme e hlalose karolo ea bona ea ho khutla lithethefatsi, boits'oaro ba lithethefatsi le kamano ea bona ho khatello.
Mokhoa oa moputso oa dopamine
Hajoale ho tsebahala hore mesolimbic dopaminergic neurons e na le likarolo tse fapaneng tsa ts'ebetso. Dopaminergic neurons li ka aroloa ka lihlopha tse peli ho latela tšebetso ea tsona: li sebetsa ka boithatelo, li tsamaellana le mosebetsi oa bongata ba li-neuron tsa DA, le li-neurons tse sa sebetseng 29. Ho li-neuron tsa DA tse thulang hang feela, mokhoa oa ho thunya o bonoa o le teng lipapatsong tse peli tsa ts'ebetso: mokhoa o potlakileng o sa tloaelehang oa "tonic" oa ho thunya, le mokhoa o phatlohileng oa "phasic" 30, 31. Mokhoa o phatlohileng oa ho thunya o hlohlelletsoa ke takatso e kantle e amanang le moputso liphoofolong tse phelang li falimehile, kapa ka ho susumetsa batho ba amanang le bona 5, 22. E 'ngoe ea li-efferents tsa mantlha tsa mesolimbic DA ke NAc. Kahoo, ts'ebetso e sa sebetseng ea ho thunya e tla fetolela maemo a DA a tummeng ea NAc athe mohlala oa ho thunya o nka karolo e kholo ea phasic, e khutsitseng ea tlhaka ea dopamine ka har'a phokotso 32. Mekhoa ena e 'meli ea ho thunya e susumetsoa ke mefuta e fapaneng ea barekisi ho VTA. Ts'ebetso ea ho thunya ho hoholo e tsamaisoa ke ho lokolloa ha glutamate ho VTA ke pedunculopontine tegmentum (PPTg) 32, 33, athe palo ea baahi e thunya e kopanyang tokollo ea tonic ka dopamine e susumetsoa ke ts'ebetso ea tsela e sa tobang e kenyeletsang VSub-NAc-ventral pallidum-VTA (Setšoantšo sa 1). Tsela ena e netefalitsoe ke bokhoni ba kynurenicacid ente ho NAc le ente ea lehae ea muscimol / baclofen (agonists e ikhethang ea GABAA / B receptors) ka hare ho potral pallidum ho thibela litlamorao tsa ts'ebetso ea vSub ho thunya ha neuron ea DA 32. Ho khahlisang, mekhoa eo e 'meli ea ho thunngoa e bontšitsoe hore e sebetsa ka mokhoa o kopanetsoeng ho susumetsa karabelo e nepahetseng ea boitšoaro. Kahoo, re bontšitse hore palo ea li-neurons tsa DA e thunya ka boithatelo e lekola palo ea lisele tse ka tsamaisoang ho phatloha ho hoholo 22. Ka hona, susumetso e eketsang ts'ebetso ea vSub e eketsa ho eketseha ha karabelo ea tsamaiso ea DA ketsahalong e itseng ea phasic.
Subralulum le khatello ea maikutlo / ho khutla hoa lithethefatsi
VSub ke tlhahiso ea mantlha ea hippocampus, e romella likhakanyo libakeng tse ngata tse amanang le maoto le matsoho, haholo-holo NAc 34. VSub e kenella mekhoeng e fapaneng e itšetlehileng ka maemo-a amanang le boemo ba tšabo 17, 19, ho timela 35, tlhokomeliso ea lithethefatsi 12 le khatello ea maikutlo 36.
Boithuto bo bonts'itse hore ts'ebetso ea vSub e fokotsa ts'ebetso ea koae le ho ts'oaroa ke cueine, e totobatsang bohlokoa ba vSub ts'ebetsong ea ho batla lithethefatsi 37. Ho khothalelitsoe maikutlo a lithethefatsi ho etsa mohlala oa litakatso tsa lithethefatsi tse etsahalang nakong ea ts'ebetso ea bokhoba 38 hape e ka bapala karolo ea bohlokoa ho khutlisetsong hape le ho khutla hape lithutong tse khaotsoeng ke lithethefatsi. Ho joalo, moelelo oa taba o tsebahala o bapala karolo e kholo ho nahanisiseng ka boitšoaro bo nkang lithethefatsi 37. Boitšoaro ba lithethefatsi bo hlalosoa e le taolo e pheta-phetoang ea li-psychostimulants, tse kang cocaine kapa amphetamine, e hlahisang karabelo e phahameng ho tsamaiso e latelang ea lithethefatsi 39. Boikutlo bona ba boitšoaro bo bapisoa le takatso e matla ea lithethefatsi e bonoang ho batho ba sebelisang lithethefatsi hampe 38. Boitšoaro ba boitšoaro bo botle ho amphetamine bo hlahisoa, bonyane ka karolo, ho ea eketseha ea mesolimbic DA neuron drive, e itšetlehileng ka tsela ea vSub-NAc. Ha e le hantle, ho qaptjoa ha vSub ho likhoto tse amphetamine tse khutlisetsang ts'ebetso ea baahi ba DA ho ea maemong a basal, mme ho felise karabelo ea boits'oaro bo matla ba ho amphetamine 23. Ho feta moo, sensitization ea koae e etsa hore ho be le nako e telele tseleng ea vSub-NAc e itšetlehileng ka ts'ebetso ea D1-receptors 40. Lithuto tsena kaofela li tšehetsa karolo e kholo ea vSub ho khothaletsong ea lithethefatsi.
Lithethefatsi tsa tlhekefetso li na le likarolo tse tšoanang tsa boko joalo ka ba amehang karabong ea khatello ea maikutlo. Matšoenyeho a ka hlalosoa e le tšitiso ts'ebetsong ea tlhokomelo ea homeostatic, le karabelo ea khatello ea maikutlo e bakang liphetoho tse feto-fetohang tse fetotsoeng ke mabaka a tikoloho. 41. Boithuto bo bongata bo bontšitse karolo e ntseng e eketseha ea vSub likarabo tse fapaneng tsa khatello ea maikutlo 42. Kahoo, lesapo la hippocampal le hokahane le maemo a eketsehang a plasma ea hormone ea adrenocorticotropic (ACTH) le corticosterone tlasa maemo a khatello. 43le khatello e fokotsehileng ea liphoofolo 44. E 'ngoe ea likarabo tse kholo tsa khatello ea kelello ea vSub ke ho fokotseha, ka litsela tse ngata, karabelo ea li-axoth tsa hypothalamic-pituitary-adrenal (HPA). 45. Ntle le moo, ho bontšitsoe libaka tse ling tse amanang le li-limbic system tse amanang le "cortex" ea pele-pele, amygdala le NAc. 45. Sena se fana ka maikutlo a hore tlhaiso-leseling ea maoto e ka ama ts'ebetso ea mekhoa ea homeostatic le ho imeloa kelellong ha khatello ea kelello ho ka kenyelletsa ho se sebetse hantle potong ena.
Sisteme ea locus coeruleus-norepinephrine (LC-NE) ke e 'ngoe ea litsamaiso tse kholo tse kenyelletsang khatello ea maikutlo. Ebile, corticotropin-releasing factor, e leng hormone e tla susumetsa tokollo ea ACTH nakong ea khatello ea maikutlo, e bonts'itsoe ho kenya ts'ebetso ts'ebetso ea LC-NE ho arabela mathata a ikhethang 46. Kahoo, ho vivo 47 le in vitro 48 lithuto li bontšitse hore tsamaiso ea CRF e bakile keketseho ea sekhahla sa ho thunya LC ka nako e le ngoe le keketseho ea NE efflux 47. VSub e fumana bolulo bo hlahelletseng ba NE ho tsoa LC 49, 'me NE e ka hlahisa ts'ebetso ea li-neuron tsa vSub 50. Ho litoeba, vSub e hlalosoa e na le letsoalo le phahameng ka ho fetesisa la beta-adrenergic receptors ka popelong ea hippocampal 51. Ka hona, ts'ebetso ea li-receptor tsa beta ka ho lokolloa ha NE ho kena vSub e kanna ea etsa hore ho be le phello e matla ea maikutlo ka ho eketsa likarabo ho kenyelletso ea karolo ea glutamatergic e amanang le vSub 52, 53.
Khatello ea kelello le tšebeliso e mpe ea lithethefatsi li arolelana likarolo tse ngata tse tloaelehileng; ka ho khetheha bokhoni ba ho susumetsa dopamine hammoho le tokollo ea norepinephrine libakeng tsa maoto 54 le kamano e matla ea bona le maemo, ba susumetsa vSub. Ho feta moo, khatello ea maikutlo e kenella ka maikutlo le li-psychostimulants. Kahoo phoofolo e pepesitsoeng khatello ea maikutlo e tla bonts'a karabelo e phahameng ho amphetamine ha e hlahisoa ke taolo e latelang ea moriana, ka lehlakoreng le leng 16. Re bontšitse hore khatello ea methapo ea khatello ea kelello e bakileng ts'oaetso ea khatello ea khatello ea khatello ea maikutlong e bakile keketseho ea ts'ebetso ea baahi ho VTA, le hore keketseho ena e khutlisoa ke ho kenella ha sodium-Channel inhibitor tetrodotoxin (TTX) ho vSub 55. Protocol ea 2hr restrot e sebelisitsoeng thutong e fetileng e hlalositsoe ho susumetsa boits'oaro ba boits'oaro ho amphetamine 56. Kahoo, ts'ebetso ea palo ea baahi ba VTA e eketsehang e etsahala moketjaneng o nang le karabelo ea boits'oaro bo botle ho amphetamine; karabelo e boetse e khutlisoa ke ts'ebetso ea vSub 55.
Ha re e nka hammoho, lintlha tsena li bonts'a hore hyperactivity ea DA e hlalositsoeng kamora ho pepeseha ha khatello ea maikutlo kapa maikutlo a kelello ka lebaka la keketseho ea ho thunya ha tonic ea li-neurons tsa VTA DA mme e its'etleha ho hyperactivity tseleng ea vSub-NAc. Ts'ebetso ea vSub ka norepinephrine e ka ba mochine o le mong o ka eketsang ts'ebetso e kholo tseleng ea vSub e sebetsang ho NAc.
Norepinephrine le khatello ea maikutlo / ho oela hape hoa lithethefatsi
Norepinephrine (NE) ke e 'ngoe ea li-neurotransmitter tse ngata ka ho fetisisa bokong' me e bapala karolo ea bohlokoa ho khetho e khethehileng 57 kakaretso e akaretsang 58, le khatello ea maikutlo59, 60. Sisteme ea norepinephrine e simoloha haholo ho locus coeruleus mme, joalo ka ha ho hlalositsoe kaholimo, e na le karolo ea mantlha karabelong ea bahatelli. Kahoo, mefuta e mengata ea khatello ea maikutlo e tla eketsa ts'ebetso ea ho thunya ea li-neuron tsa LC 61 hammoho le ho eketsa phetiso ea NE libakeng tse ngata tsa LC 62. Karolo ea NE ho ts'ebeliso e mpe ea lithethefatsi e sa le nako e telele e sa tsotelloe, kaha mokhoa oa moputso oa dopamine e bile sepheo sa lithuto tse ngata lefapheng lena. Leha ho le joalo, ho lokolloa ha NE ho tlalehiloe ho ama ho khutlisetsoa hoa boits'oaro ba ho batla lithethefatsi 63. Ka hona, Sisteme ea LC-NE e bontšitsoe hore e qalile nakong ea ho tlohela lithethefatsi 64 mme ho fanoe ka maikutlo a hore karolo ea thepa e matlafatsang ea morphine e lemalloang ea lithethefatsi e tsoa karolong e 'ngoe ea bokhoni ba eona ba ho fokotsa khatello ea khatello ea maikutlo le mokhathala o amanang le tokollo ena. 65. Ntle le moo, lithuto tsa litheknoloji tse sebelisang alpha2 adrenergic autoreceptor agonists li totobalitse karolo ea NE ho khutlisetsong khatello ea maikutlo bakeng sa ho batla lithethefatsi 66, le bahanyetsi ba alpha-2adrenergic ba hlohlelletsa keketseho ea ts'ebetso ea tebello ea dopamine e itšetlehileng ka dopamine. 67.
Ntle le ho kenya tšebetsong sistimi ea LC-NE ka kotloloho, bahatelli ba ka kenya tšebetsong meaho e meng ho projeke ea LC, joalo ka BLA. Habohlokoa, sebopeho se le seng se bapala karolo ea bohlokoa karolong ea maikutlo ea karabelo ea khatello ke BLA 68. Kahoo, maikutlo a sithabetsang a kang footshock kapa mohatla o tsitsitseng oa ts'ebetso ea amygdala 69, 70. Ntle le moo, polasetiki ea synaptic ka hare ho amygdala e boetse e angoa ke khatello e fapaneng ea khatello 24, 26. Ho feta moo, ba sa foleng le ba ho hlobaela, khatello ea maikutlo e bakile keketseho ea tšebetso ea li-neuron tsa BLA 71. Leha ho le joalo, phetisetso ea ts'ebetso ea methapo ea LC ke BLA ha e ea otloloha, ka ts'ebetso ea ts'ebetso ea methapo e bohareng ea amygdala (CeA) le mookotaba oa bethe ea stria terminalis (BNST) e tla susumetsa tokollo ea CRF libakeng tsa dendritric pericoerulear 72. Kahoo, BLA e romela litlatsetso tse thabisang ho CeA 70, sebopeho se tla kenya tšebetsong sisteme ea LC-NE ka ho lokolla CRF 48. Kamano lipakeng tsa Sistimi ea LC-NE le BLA lia iphetetsa. Ka hona, ntle le ho romela tumellano e sa tobang ho LC, BLA e amohela likhakanyo tse tobileng tse tsoang ho locus coeruleus, 'me tokollo ea NE e etsoa ke LC e hlophisa tšebetso ea li-recensor tsa BLA neuronsvia alpha-le beta-adrenergic 73 (Setšoantšo sa 2).
BLA e bapala hape karolo ea bohlokoa ea ho khutlela boits'oarong ba ho batla lithethefatsi, hobane ho inactivation ea nucleus ena ho ama ho khutlisetsoa ka maemo ntle le ho fetola phello ea tsamaiso ea lithethefatsi. 74. Ho feta moo, tlhahlobo ea phumano e bonts'itse hore ho na le tšebelisano e matla pakeng tsa sisteme ea dopaminergic le BLA e kenyang ho thunya ha methapo ea kutlo ho tsoa ho li-neuron tse tsoang NAc tse tla khothaletsa boitšoaro bo batlang moputso 75.
Likenyelletso tse tsoang BLA le vSub li hlalositsoe hore li fetohe ka li-neuron tse tšoanang tsa NAc 28. Khokahano pakeng tsa BLA le vSub le eona e hlalositsoe 28 ho fana ka maikutlo a hore BLA le vSub li ka sebelisana 'moho ka boikemelo ba tsona mabapi le ho hokahana ha tsona ho NAc. Joalokaha ho boletsoe kaholimo, vSub e khothalletsoa ho kopanya litlamorao tsa khatello ea maikutlo karolong e 'ngoe ka tsela ea vSub-NAc. Ntle le moo, vSub e fumana litlatsetso tse ngata tse tsoang libakeng tse amanang le khatello ea maikutlo tse kang Sisteme ea LC-NE, hammoho le BLA 28. Haufinyane re fumane hore ho hlohlelletsa sisteme ea LC-NE le BLA activate vSub neuronal shughuli 50, le khatello ea maikutlo e matla le e sa foleng e etsa hore ho be le keketseho ea tšebetso ho tsebiso tseo tse peli 24, 76. Ka hona, hypothesis e le 'ngoe e susumetsang maikutlo a lithethefatsi le ho fetoloa ha eona ka khatello ea maikutlo ho ka kenyelletsa ts'ebetso ea vSub-NAc tsela ke LC-NE system le / kapa BLA e lebisang keketseho ea ketsahalong ea palo ea DA, e arabelang karabelo e eketsehang ea boitšoaro ho li-psychostimulants .
fihlela qeto e
Ho khutlela mokhoeng oa ho batla lithethefatsi ho latela mabaka a mangata a fapaneng: tikoloho ea tikoloho e kenyang vSub, ho khutlisetsoa ho cue-cue e kenyelletsang BLA, le liketsahalo tse sithabetsang tse etsang hore ho be le potoloho e pharalletseng e kenyeletsang vSub le BLA. Liketsahalo tse sithabetsang le tlhekefetso ea lithethefatsi li na le likarolo tse tloaelehileng. Ka bobeli li kenyelletsa sensitization, e leng ketsahalo e itšetlehileng ka maemo e kenyelletsang hyperactivation ea sisteme ea mesolimbic DA. VSub ke sebopeho sa bohlokoahali se bapalang karolo e kholo ho hokahanya karabelo liketsahalong tse sithabetsang le boits'ebetsong ba ho batla lithethefatsi. Re na le bonnete ba hore vSub, haholo-holo tsela ea vSub-NAc, e ikarabella bakeng sa tšebeliso e mpe ea tsamaiso ea DA ho arabela khatello le maikutlo a bokhoba ba lithethefatsi. Sebopeho sena se fumana likenyelletso tse peli tsa mantlha tse tsejoang hore li qaptjoa ke li khatello tse fapaneng tsa maikutlo le tse amehang ts'ebetsong ea ho batla lithethefatsi: Sisteme ea LC-NE le BLA.
Ho utloisisa ka nepo hore na tsamaiso ea lithethefatsi e ka etsa hore motho a boele a ts'oare lithethefatsi le ho batla lithethefatsi, ho bohlokoa ho ithuta liphetoho tse amanang le pathophysiological tse etsahalang mokhatlong oa tsamaiso ea khatello ea maikutlo. Tlhahisoleseling e joalo e bohlokoa ho tataisa pharmacotherapy ea nakong e tlang le kalafo bakeng sa ho lemalla, ka ho kenella ha pharmacological sebakeng se le seng kapa tse 'maloa tsa potoloho ena, joalo ka vSub kapa BLA.
References