Liphello tsa ΔFosB e hlaselang maikutlo le ketamine ka ho hlōloa ha sechaba se anedonia e bakoang ke khatello ea kelello ka litoeba (2014)

Psychology ea Biol. Sengoloa se ngotsoeng; e fumaneha ho PMC 2015 Oct 1.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

PMCID: PMC4087093

NIHMSID: NIHMS564517

Moetso oa khatiso oa ho qetela oa mohatisi o fumaneha ho Biol Psychiatry

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

inahaneloang

Background

Khatello e sa feleng ea khatello ea sechaba (CSDS) e hlahisa litloaelo tse tsoelang pele tsa litoeba. Maemong a mangata a boitšoaro, ho ka ba thata ho tseba hore na liphetoho tsena li bontša matšoao a mantlha a khatello ea maikutlo. Re hlophisitse lithuto ho supa litlamorao tsa CSDS mabapi le kutloisiso ea ho putsa, hobane anhedonia (kutloisiso e fokolitsoeng ea moputso) ke tšobotsi e hlalosang ea khatello ea maikutlo ho batho. Re boetse re ile ra hlahloba litlamorao tsa ho hlohlona ha 'mele oa vereFosB kapa ketane ea N-methyl-D-aspartate antagonist, tseo ka bobeli li khothaletsang boikemisetso, ho liphetoho tse tlatselitsoeng ho CSDS ts'ebetsong ea moputso le tšebelisano ea sechaba.

mekhoa

Re sebelisitse matla a ho intlafatsa (ICSS) a makatsang bakeng sa liphetoho tsa ts'ebetso ea moputso oa CSDS. Lice li ile tsa kenngoa ka li-electrodes tsa morao-rao tsa hypothalamic (LH) le likhatiso tsa ICSS li ile tsa lekanngoa kamora nako e 'ngoe le e' ngoe ea 10 letsatsi le letsatsi la CSDS, le ka nako ea 5 ea matsatsi a ho hlaphoheloa. Re boetse re ile ra hlahloba hore na tsamaiso e matla ea ketamine (2.5-20 mg / kg, intraperitoneal) e khutlisa litlamorao tse hlahisitsoeng ke CSDS moputsong kapa, ka litoeba tse arohaneng, ts'ebelisano ea sechaba.

Results

CSDS e ile ea eketsa likhahla tsa ICSS, e bonts'a ho fokotseha ha phello e khotsofatsang ea ts'usumetso ea LH (anhedonia). Phello ena e ananetsoe ke litla-morao tsa BFosB ka litheko tse tsamaellanang le ts'ebetso ea ts'ebetso ea sengoloa sena. Litekanyetso tse phahameng empa eseng tse tlase tsa ketamine e tsamaisoang kamora ho phethoa ha regimen ea CSDS e ile ea thusa ho qoba ho litoeu tse hlotsoeng, leha phello e ne e le ea nakoana. Ketamine ha ea ka ea thibela anhedonia ea CSDS-indied in an testa ea ICSS.

Nahanisisa

Seo re se fumaneng se bonts'a hore CSDS e baka anhedonia e sa khaotseng, mme e tiisa hore ΔFosB oxpxpression e baka khatello ea maikutlo. Li boetse li bonts'a hore ketamine e hlobaetsang e hloleha ho amohela anhedonia ea CSDS ntle le ho fokotsa litlolo tse ling tse amanang le khatello ea maikutlo.

Keywords: hlola, khatello ea maikutlo, anhedonia, intracranial boithati (ICSS), tšebelisano ea kahisano, ketamine, antidepressant

SELELEKELA

Ho sithabela maikutlo ho sa feleng ho ameha ho etiology le pathophysiology ea matšoenyeho le khatello ea maikutlo (-). Leha mathata ana a ntse a eketseha () hape e rata ho phehella hape ho hanela kalafo ea hona joale (,), mekhoa eo khatello ea maikutlo e ba susumetsang e lula e sa utloisisoe hantle (). Mefuta e netefatsang ea khatello ea maikutlo e bohlokoa ho utloisisa hantle litlamorao tsa khatello ea maikutlo, ho hlakisa neurobiology ea mafu a amanang le koluoa, le ho nts'etsapele liphekolo tsa kalafo tse khahlanong le khatello ea maikutlo le tsa antidepressant.

Mefuta ea liphoofolo ea khatello ea maikutlo e itšetleha ka bokhoni ba bona ba ho etsisa kapa ho hlahisa matšoao a mantlha a lefu lena ho batho, ho kenyelletsoa le ho qoba sechaba le anhedonia (maikutlo a fokotsehileng a ho putsa) (,). Matšoenyeho a sa feleng a taolo ea sechaba (CSDS) ke mofuta o sebelisoang hofeta nako o sebelisang matla a boitšoaro bo mabifi ba tikoloho (,) hape e hlahisa matšoao ana a mantlha joalo ka ha ho hlahlojoa liteko tse lekanyang tšebelisano 'moho le khethollo bakeng sa sucrose le meputso e meng ea tlhaho (-). Ntle le moo, litlamorao tsa CSDS li khutlisoa ke tsamaiso e sa foleng ea fluoxetine kapa imipramine (,,), meriana e tloaelehileng ea li-antidepressant e sebelisoa haholo ho phekola mafu a sithabetsang bathong. Ho fapana le hoo, meriana e tloaelehileng e tšoenyang ha e na thuso (). Ka hona CSDS e nkuoa e na le bonnete ba ho aha, sefahleho le tšebeliso ea tebello (). Leha ho le joalo, ho bile le tlhahiso ea hore mekhoa ea CSDS-e qalileng e na le motheo oa bona matšoenyehong (,), mme seo hangata se hlalosoang e le anhedonia litekong tsa khetho ea sucrose se hlile se ka bonts'a neophobia e matlafalitsoeng.

Morero oa mantlha oa lithuto tsa hona joale e ne e le ho hlahloba bokhoni ba CSDS ba ho hlahisa anhedonia, karolo ea mantlha ea mathata a sithabetsang empa eseng a matšoenyeho (). Re sebelisitse matla a ho itšunya-tšunya (ICSS), paradigm eo ho eona litoeba li iketsetsang ts'usumetso ea ts'ebetso ea ts'ebetso ea motlakase, ho hlahloba litlamorao tsa CSDS mabapi le menyetla ea moputso (,). Boitšoaro ba ICSS bo kenyelletsoa litlamong tlasa maemo a bakang maemo a sithabetsang bathong, ho kenyeletsa le ho tlosoa hoa lithethefatsi (-), khatello e sa lebelloang le e sa foleng ea (,), le tsamaiso ea li-agonist tsa kappa-opioid receptor agonists (,). Ka ho khetheha, liphekolo tsena li eketsa lebelo le ho feta leo ts'usumetso e tšehetsang ho arabela, letšoao la anhedonia (). Ntle le moo, paramente ea ICSS e lumella thuto ea liphetoho tse fetotsoeng molemong oa moputso ka nako, 'me e hana taba ea ho tšoenyeha le mabaka a amanang le satiety a ferekanyang liparadiseano tse ling tse sebelisoang ho lekola ts'ebetso ea moputso (mohlala, khetho ea sucrose, thobalano, lithethefatsi tsa tlhekefetso) ().

Ka mokhoa o tšoanang, re ile ra hlahloba bokhoni ba ketamine, mohanyetsi oa li-receptor oa NMDA (), ho fokotsa litlamorao tsa CSDS mabapi le thibelo ea sechaba le likotsi tsa ICSS. Le ha phekolo e tloaelehileng ea li-antidepressant e liehisa katleho ea kalafo (hangata libeke tse 'maloa), liphuputso tsa morao tjena li bonts'a hore tekanyetso e le' ngoe ea ketamine e ka hlahisa likarabo tse potlakileng (leha e le tsa nakoana) ho bakuli ba sithabetseng (-) - Ho kenyeletsa bakuli ba hananang le kalafo (,,,) - le litlamorao-joaloka litlamorao tsa khatello ea maikutlo mefuteng e mengata ea khatello ea maikutlo (-). Ho fumana hore na liketso tse kang tsa kalafo ea ketamine li tsamaisana le litla-morao tsa (ho ithuta- le ho senya) hangata li amanang le bahanyetsi ba NMDA (,) kapa litlamorao tse tšoenyang () re ile ra hlahloba ts'ebetso litekong tsa tlhahlobo ea boithatelo le lithupong tse phahameng tsa maze (EPM). E le mokhoa oa ho lekola hore na ho ka khoneha ho fokotsa litlamorao tsa CSDS ho ICSS, re kenyelletse lithuto tse sebelisang litoeba tsa ΔFosB-overexpressing, tse sa tsotelleng letho (Resilient) ho CSDS ().

LISEBELISOA LE MEKHOA

Liphoofolo le lithethefatsi

Lithunya tsa banna C57BL / 6J (libeke tsa 6-8) li ile tsa rekoa ho Jackson Laboratories (Bar Harbor, ME), le litoeba tsa banna ba CD1 (bareki ba seng ba tlohetse mosebetsi) ba ile ba rekoa ho Charles River Laboratories (Wilmington, MA). Litoeba tse tona tsa banna tse sa sebetseng hantle tse tsoang ho li-vereFosB li hlahisitsoe ho tsoa lifapano tsa NSE-tTA (mohala A) le litoeba tsa TetOP-lineFosB (mola A11), 'me li khutlisetse morao hantle moqolong oa C57BL / 6J, li sebelisa sisteme ea tsamaiso ea mofuta oa tetracycline). Litoeba tsa ΔFosB li phahamisitsoe holim'a metsi a nang le doxycycline (DOX) (100 μg / ml) (Sigma, St. Louis, Missouri), e phehellang polelo ea transgene. Liteko li ile tsa sebetsoa ~ libeke tsa 8 kamora ho khaoloa ha DOX, ha polelo ea transgene ea ΔFosB e le kholo (ΔFosB-ON group) (). Halofo ea litoeba e ile ea sala ho DOX nako eohle ea liteko e le ho laola (asFosB-Control group). Litsuane li ne li na le phihlello ea ho ja lijo le metsi ebile li bolokiloe mochineng o bobebe oa 12-h. Ts'ebetso tsohle li entsoe ho latela melaoana ea National Institutes of Health le McLean Hospital. Ketamine e fumanoe ho Sigma-Aldrich (St. Louis, MO), e qhibilihile ho 0.9% saline (Vehicle), mme e tsamaisoa ka Intraperitoneally (IP) ho 10 ml / kg. Litoeba tsa taolo li fumane kalafo e ts'oanang joalo ka litoeba tse hlotsoeng.

Mekhoa le Liteko tsa Boitšoaro

CSDS e entsoe joalo ka ha ho hlalositsoe pele (,). Litoeba tsa CD1 (baahi) li ile tsa hlahlojoa bakeng sa boits'oaro bo tsitsitseng (lits'oants'o tsa tlhaselo <metsotsoana e 30 bakeng sa liteko tse 3 tse latellanang tsa ho lekola). Ka letsatsi le leng le le leng la matsatsi a 10 a latellanang, toeba e hlasetsoeng (e hlotsoe) e ile ea beoa ka tlung ea toeba ea moahi mme ea fuoa khatello ea khatello ea maikutlo ea 10 min. Kamora seboka sa ho hloloa, litoeba li ile tsa aroloa ka mokoting ka phasalatso ea Plexiglas, e neng e lumella ho pepeseha ha maikutlo ka nako e telele. Litoeba tse hlotsoeng li ne li pepesetsoa moahi e mocha le cage letsatsi le leng le le leng. Litoeba tsa taolo li ne li sebetsoa letsatsi le leng le le leng ebe li bolokoa ka har'a likhaka tse ts'oanang le litoeba tse hlotsoeng, empa li shebane le toeba e ikhethileng. Li-cohorts tse arohaneng li sebelisitsoe bakeng sa liteko tsa ICSS le social interaction (SI).

ICSS e entsoe joalo ka ha ho hlalositsoe pele (,). Ka bokhutšoanyane, litoeba (25-30 g) li ile tsa kenngoa ka li-electrode tse nang le monopolar tse ikemiselitseng ho latela hamorao hypothalamus (LH). Lithaka li ile tsa koetlisoa ka letoto la ho theoha (kapa "ho feta") tsa liteko tsa maqhubu a 1510 mehato ea yuniti), 4 ka letsatsi, ka nako e tlase e sebetsang hona joale. CSDS le lihlopha tsa taolo li ne li na le maqhubu a lekanang a bonyenyane (~ 75 μA). Likhula tsa ICSS (Theta-0) li ile tsa baloa li sebelisa mohala oa mabatooa a lits'oants'o tse loketseng hantle (,). Ka mor'a hore ho thehoe likhechana tsa motheo tsa botsitso (+/− 15% bakeng sa matsatsi a 5 a latellanang; BL1-5), litoeba li ile tsa beoa tlas'a CSDS ka matsatsi a 10 (D1-10). Litsi tsa mantlha li ile tsa aroloa ka lihlopha tse peli ho lekola hore na litlamorao tsa CSDS litsing tsa ICSS li ipapisitse le nako ea nako pakeng tsa seboka sa ho hlola le tlhahlobo ea ICSS: litoeba ka nako e telele (LInt) sehlopha li ile tsa lekoa ho ICSS ~ 16 hrs kamora ho hloloa, athe litoeba sehlopheng sa nakoana sa nakoana (ShInt) li ile tsa lekoa ho ICSS ~ 6 hrs kamora ho hloloa (Setšoantšo sa 1A). Ka mor'a CSDS, litoeba li ile tsa khutlisetsoa mabokoseng a tsona tsa malapeng 'me tsa lekoa ka mor'a ho ts'oaroa ICSS ka matsatsi a 5 (P1-5). Bakeng sa liteko tsa ketamine, litoeba li fumane koloi kapa ketamine (20 mg / kg) 1 hr kamora seboka sa ho qetela sa ho hloloa.

Setšoantšo sa 1 

Matšoenyeho a sa feleng a khatello ea sechaba (CSDS) a eketsa menyetla ea moputso litekong tsa intracranial tsa boithati (ICSS). (A) Moralo oa liteko; LInt = nako e telele (16 hr) lipakeng tsa bout e hlotsoeng le tlhahlobo ea ICSS, ShInt = karohano e khutšoane (6 hr). (B) CSDS ea eketseha ...

Ho hlahloba litlamorao tsa ketamine ho SI, likoloi tse amoheloang litoeba, tekanyetso e tlase (2.5 mg / kg), kapa lethalinyana le phahameng la (20 mg / kg) ea ketamine 24 hrs pele ho letsatsi la pele la CSDS (Letsatsi la 0) kapa 1 hr kamora ho qetela Seboka sa ho hlola (Letsatsi la 10). Lice li ne li tšoaretsoe lebaleng la tšebelisano ka khanya e khubelu bakeng sa 15 min ka matsatsi 8-10 ea CSDS. Mashome a mabeli a metso e mene hr kamora seboka sa ho qetela sa ho hlola (Letsatsi la 11), boits'oaro ba mekhoa ea sechaba ka pel'a sefahleho sa CD-1 se sa kenngoeng ka terakeng ea terata se ile sa hlahlojoa joalo ka ha ho hlalositsoe pele (, ), ka liphetoho tse nyane. Lintlha tsa SI li ne li hlalosoa e le nako eo mouse e sebelisitseng haufi le sebaka se koetsoeng se nang le CD-1 (sepheo sa sechaba) ka nako ea metsotso e 2.5 ha e bapisoa le ha sebaka se koetsoeng se ne se se na letho. Hobane litoeba tsa taolo li qeta nako e ngata li sebelisana le sepheo sa sechaba, palo ea SI ea 1 (nako e lekanang haufi le sepheo sa sechaba ha e bapisoa le sebaka se se nang letho) e sebelisitsoe e le khaolo: Likolo tsa SI> 1 li ne li nkuoa e le "tse nang le khatello ea maikutlo" le lintlha < 1 li ne li nkuoa li "hlaseloa ke khatello ea maikutlo" (). Ho arohana ha litoeba tse hlotsoeng ho etsa litlatsetso tse mamellehang le tse khutsitseng ho ts'ehelloa ke tlhahlobo e pharalletseng ea boits'oaro, neurobiological, le electrophysiological (,).

Maemo a ho qoba ho a qoba a ile a etsoa ka har'a lisebelisoa tsa Gemini qoba (Sesebelisoa sa San Diego, San Diego CA) joalo ka ha ho hlalositsoe pele () le liphetoho tse nyane. Nakong ea boikoetliso, litoeba li ne li fuoe li-1 min acclimation ho komporo ea leseli pele ho marang-rang a lefifi. Hang ha sefapano se entsoe kamoreng e lefifi, litoeba li ne li le maemong a mabeli a latellanang a 2 sec (inescapable) footshocks (0.2 mA), lateloa ke 1 min time-time. Lice li ile tsa fuoa koloi kapa ketamine (20 mg / kg) 1 hr kamora boemo. Mehato e latellanang mohato ka mohato e lekantsoeng li-24 hrs hamorao. Ho lekola litlamorao tsa ketamine ea rona ho litloaelo tse kang ho tšoenyeha, sehlopha sa litoeba tse arohaneng se ile sa fuoa koloi kapa ketamine (20 mg / kg) 24 hrs pele ho liteko tsa EPM. Litoeba li ne li kentsoe bohareng ba moalo o phahameng o kenyellelitsoeng (letsoho le leng le le leng la 33 cm ka bolelele le 5 cm, le matsoho a 2 ka lehlakoreng le leng le koetsoe ke mabota a 16.5 cm a phahameng, maze a phahamisitsoeng ka 81 cm ho tloha fatše) ka leseli le khubelu mme a lumelloa ho phenya bakeng sa 5 min .

Tlhahlobo ea Litekanyetso

Mehato e 'meli le e meraro e pheta-phetoang ANOVA e entsoe bakeng sa CSDS, ICSS, le tlhaiso-leseling ea ho qoba lintho. Li-ANOV tsa bohlokoa li ile tsa hlahlojoa hape ka liteko tsa Bonferroni post hoc. Liphello tsa ketamine ho SI li ile tsa hlahlojoa ka lipapatso tse reriloeng pele (liteko tsa Bonferroni) lipakeng tsa litoeba tse laoloang le tse hlotsoeng kahare ho sehlopha ka seng sa kalafo, ho ipapisitse le mofuta o itseng a priori Khopolo-taba ea hore kalafo ea ketamine e ka fokotsa boitšoaro bo sithabetsang ho litoeba tse hlotsoeng. Litlamorao ho boitšoaro ba EPM li ile tsa hlahlojoa ho sebelisoa t-test ea Seithuti. Liteko tsa SI le EPM li ile tsa buloa vouta 'me tsa laroa ke litsotsi tse foufalitsoeng bakeng sa maemo a kalafo.

LIPOTSO

Litlamorao tsa ho hloloa hoa maemo a bophelo litsing tsa ICSS li ile tsa hlahlojoa kamora karolo e 'ngoe le e' ngoe ea ho hloloa, ho re nolofalletsa ho latela liphetoho ho arabela maemong ohle a CSDS (Setšoantšo sa 1A, B). L data le LInt le ShInt li hlahisoa hammoho ho tsamaisa papiso ea nako le nako ea litlamorao tsa nako ea nako likhethong tsa ICSS (Setšoantšo sa 1B, C). Litlamorao tsa CSDS ka likotlo tsa ICSS li its'etleha ho sehlopha [F (2,22) = 13.53, p<0.001] le letsatsi [F (15,330) = 2.98, p<0.001], le tšebelisano-'moho ea sehlopha se ka thoko sa X letsatsi (p= 0.054). CSDS e eketsehile haholo ho bolela litheko tsa ICSS (tse hlahisitsoeng joalo ka motheo oa%) litonong tse hlotseng tsa LInt le ShInt ha li bapisoa le taolo ka letsatsi la bobeli la ho hloloa (LInt: p<0.05, ShInt: p<0.001). Litoeba tsa ShInt li ne li na le menyako e phahameng ha li bapisoa le litoeba tsa LInt feela ho P1p<0.05) (Setšoantšo sa 1B). Karolo e nyane ea litoeba li ne li tiile ho latela litlamorao tsa CSDS ho anhedonia e ICSS (e sa bonts'ang), e lumellana le liphetho litlhahlobo tse ling (). Kaha ho ne ho se na phapang e fapaneng likhethong tsa ICSS lipakeng tsa litoeba tsa taolo lihlopheng tsa LInt le ShInt (data e sa bontsitsoeng), datha tsena li kopantsoe. Ha data e hlahisoa e le mekhoa e le 'ngoe bakeng sa BL1-5, D1-10, le P1-5 bakeng sa sehlopha ka seng, litlamorao tsa CSDS ka likotlo tsa ICSS li its'etleha ho hloloa [F (2,22) = 9.68, p<0.01], letsatsi [F (2,44) = 21.57, p<0.001], le ts'ebelisano 'moho ea letsatsi la X [F (4,44) = 5.09, p<0.01] (Setšoantšo sa 1C). Ka har'a papiso ea sehlopha ho senotsoe hore likotlo tsa ICSS li eketsehile ho litoeba tsohle tsa LInt le ShInt ho D1-10 le P1-5 ha li bapisoa le BL1-5 (p<0.001). Pakeng tsa papiso ea sehlopha ho senotsoe hore lithibelo tsa ICSS li eketsehile haholo ho litoeba tsa LInt le ShInt tse hlotsoeng ho D1-10 (p<0.001), le litoeba tsa ShInt tse hlotsoeng ho P1-5 (p<0.01), ha e bapisoa le litsamaiso (Setšoantšo sa 1C). Lintlha tse sa tloaelehang ho tsoa ho taolo ea moemeli a le mong le ea hlotsoeng (LInt) e bontša kamoo CSDS e ka bakang phetoho e nepahetseng mesebetsing ea maqhubu a ICSS ho D1-10 ha e bapisoa le BL1-5 (Setšoantšo sa 1D).

Hobane litoeba tse tlatselletsang ho feta osFosB libakeng tse literekeng li ikemiselitse ho CSDS () le maemo a khatello ea maikutlo (), re fane ka maikutlo a hore litoeba tsa ΔFosB-ON, empa eseng iceFosB-Control Control, li tla ikemisetsa ho kotla litlamorao tsa CSDS likhethong tsa ICSS. Ha data e hlahisoa e le mekhoa e le 'ngoe bakeng sa BL1-5, D1-10, le P1-5 bakeng sa sehlopha se seng le se seng, litlamorao tsa ΔFosB overexpression mabapi le liphetoho tsa CSDS-Mediated ho litsing tsa ICSS tse itšetlehileng ka kalafo ea DOX [F (1,4) = 13.25, p<0.05], letsatsi [F (2,8) = 23.89, p<0.001], le kalafo ea DOX kalafo ea letsatsi la X [F (2,8) = 16.40, p<0.01] (Setšoantšo sa 2). CSDS e ile ea eketsa likotsi tsa ICSS ho litoeba tsa ΔFosB-Control ho D1-10 le P1-5 ha e bapisoa le BL1-5 (p<0.001) le ho D1-10 le P1-5 ha li bapisoa le litoeba tsa osBFosB-ON (p<0.05), athe litoeba tsa ΔFosB-ON li ne li khona ho mamella litlamorao tsa anhedonic tsa CSDS. Tlhatlhobo e fetelletseng ea osBFosB ha e na tšusumetso ho maqhubu a fokolang, e netefatsang hore increasedFosB e eketsehang ka boeona ha e ame kutloisiso ea tšusumetso ea LH ().

Setšoantšo sa 2  

Ho hlaseloa ka mokhoa o hlakileng oa ΔFosB ka ho qhekella lithutong ho thibela litlamorao tsa CSDS tlhahlobong ea ICSS. IceFosB-Control litoeba (n = 3), empa eseng iceFosB-ON litoeba (n = 3) e lekoa libeke tsa 8 kamora ho khaotsa ho etsoa ke DoX, ho bonts'a ho eketseha ha likotsi tsa ICSS ...

CSDS e hlahisitse thibelo ea sechaba ho litoeba tse hlotsoeng tse tšoaroang ka koloi kapa tekanyetso e tlase ea ketamine (2.5 mg / kg) (tsa<0.05) empa eseng ho litoeba tse hlotsoeng tse tšoaroang ka tekanyetso e phahameng ea ketamine (20 mg / kg) (Setšoantšo sa 3A); ho bile le phello e kholo ea sehlopha [F (1,60) = 15.75, p<0.001], empa ha ho na tšusumetso e kholo ea tšebelisano ea lethal dose kapa tekanyetso X. Morero oa lintlha tsa SI ka bomong bakeng sa litoeba tse hlotsoeng o bonts'a palo e nyane ea litoeba tse tšoaroang ka koloi (n = 3/12) kapa tekanyetso e tlase ea ketamine (n = 2/10) e bonts'itse botsitso, athe litoeba tse ngata tse tšoaroang le tsona tekanyo e phahameng ea ketamine (n = 8/11) e bontšitse botsitso (Setšoantšo sa 3A, inset). Ha ho na phapang e kholo maetong a maeto kapa velocity nakong ea liteko tsa SI (Setšoantšo sa 3B, C). Lice li ile tsa khutlisetsoa 1 bekeng hamorao ho bona hore na litla-morao tsa kalafo ea chefo e phahameng ea ketamine, joalo ka ha ho lekiloe tlhahlobong ea SI, li ntse li phehella. Ka bobeli lithunya tse hlotseng koloi e amohetseng litoeba tse amohetseng ketamine (20 kg / kg) li bonts'itse phetoho ea sechaba ha e khutla 1 beke hamorao (koloi: p<0.001, ketamine: p<0.05) (Setšoantšo sa 3D); ho bile le phello e kholo ea sehlopha [F (1,36) = 21.10, p<0.0001], empa ha ho na tšusumetso e kholo ea tšebelisano ea lethal dose kapa tekanyetso X. Tsamaiso e le 'ngoe ea ketamine (20 mg / kg) 24 hrs pele ho letsatsi la pele la CSDS ha ea ka ea thibela ho qoba sechaba. CSDS e hlahisitse ho qoba sechaba litoeba tse hlotsoeng tse tšoaroeng pejana ka koloi kapa tekanyetso e phahameng ea ketamine (20 mg / kg) (tsa<0.05) (Setšoantšo sa 3E); ho bile le phello e kholo ea sehlopha [F (1,21) = 1.57, p<0.001], empa ha ho na tšusumetso e kholo ea tšebelisano ea lethal dose kapa tekanyetso X.

Setšoantšo sa 3  

Ketamine e amohela CSDS-e qobelletsoeng ho qoba sechaba. (A) Tekanyetso e phahameng ea (20 mg / kg) empa e seng e tlase (2.5 mg / kg) ea ketamine e fuoeng 1 hr kamora ho hloloa ho hoholo hoa mokokotlo (Letsatsi la 10) e fumana thibelo ea sechaba ho litoeba tse hlotsoeng. Se ka hare: SI ea motho ka mong e na le litoeba tse hlotsoeng ...

Ho bona hore na litlamorao tsa ketamine ho CSDS e kenyellelitsoeng boiketong ba sechaba e ka ba ka lebaka la litlamorao tse matla tsa litekanyetso tsena, re bapisitse ho boloka memori e sa reroeng ka polokelong e ka thoko ea koloi le litoeba tse tsamaisitsoeng ke ketamine. Liroto tsohle tse bonts'itsoeng li ile tsa nyoloha butle-butle matsatsing a tlhahlobo ea memori [F (1,28) = 22.82, p<0.0001] (Setšoantšo sa 4A). Ho ne ho se na phello ea mantlha ea kalafo mabapi le ho boloka memori ea tšabo [F (1,28) = 0.14, ns] kapa letsatsi X ho sebelisana le kalafo [F (1,28) = 0.24, ns]. Ho EPM, ho ne ho se na phapang lipakeng tsa litoeba tse khannoang ka ketamine le ketamine ka nako e bulehileng ea letsoho (t () = 0.61, ns) (Setšoantšo sa 4Bkapa palo ea linomoro tse bulehileng tsa letsoho (t () = 0.34, ns) (ha e bontšoe).

Setšoantšo sa 4  

(A) Ketamine, ka tekanyo e sebetsang (20 mg / kg) e sebelisitsoeng tlhahlobong ea SI, ha e kena-kenane le ho boloka memori ea tšabo litekong tsa thibelo ea passive. Litoeba tsohle, ho sa tsotelehe kalafo ka koloi kapa ketamine 1 hr kamora letsatsi la thupelo, qoba ho kena ...

Mice o ile a fumana ketamine kapa koloi kamora seboka sa ho qetela sa ho hlola, mme a tsoela pele ho etsa liteko tsa ICSS kamora kalafo (D10, P1-5). Mehato ea ICSS e fumanoeng matsatsing a pele ho kalafo (D1-9) e ne e etselitsoe sehlopha ka seng. Mekhatlo e mabapi le D10 le P1-5 e ile ea hlahlojoa ho lekola litlamorao tsa nakoana tsa ketamine. Tekanyetso e tšoanang ea ketamine (20 mg / kg) e ileng ea thusa ho qoba litloholo tse hlotsoeng tekong ea SI ha ea ka ea fumana anhedonia tekong ea ICSS (Setšoantšo sa 5); ho bile le phello e kholo ea sehlopha [F (1,45) = 48.65, p<0.0001], empa ha ho na tšebelisano ea sehlopha X ea bohlokoa kalafo X letsatsi. Ho beoa ha li-electrode tsa ICSS ho ne ho sa khethollehe ho tse bontšitsoeng pejana ().

Setšoantšo sa 5  

Ketamine (20 mg / kg) e tsamaisitsoeng 1 hr kamora ho hloloa ho qetela ha bout ha e thibele litlamorao tsa CSDS tlhahlobong ea ICSS ho D10 kapa P1-5. Bokapele ba botšo bo emela likotsi tse fumanoeng kamora kalafo. Lice li ile tsa hlola matsatsi a 10 (kemiso ea LInt) ...

TŠOHLOA

CSDS e hlahisa anhedonia ho ICSS paradigm ka litoeba. Ka ho khetheha, re bonts'a hore CSDS e fokotsa ts'ebetso e khotsofatsang ea ts'usumetso ea LH, joalo ka ha e lekantsoe ke bophahamo lithutong tsa ICSS (), ka litlamorao tse phehellang ho fihlela matsatsi a 5 kamora post-CSDS. Liphetho tsena li tsamaisana hantle le liphetho tsa lithuto tsa nakong e fetileng literekeng () le hamsters (), e sebelisitseng mekhoa e meng ho qopitsa matla a ho phahamisa bokong. Joalokaha ho lebelletsoe motheong oa mosebetsi o fetileng (), e bonts'itseng hore litoeba tse oxpxpress ΔFosB li tiile ho nts'etsopele ea boiketlo ba sechaba le bofokoli ba ho ikhetholla, re fumane hore litoeba li ne li boetse li inehetse ho litlamorao tse bakelang ho anhedonia tsa CSDS tlhahlobong ea ICSS. Ntle le moo, re ile ra hlahloba thepa e kang antidepressant-like ea ketamine ho CSDS paradigm. Phekolo ea kalafo ea ketamine ka nako e telele ho litoeba tse hlotsoeng ho qoba teko ea SI. Tšusumetso ena e mpe e makatsa ha ho nahanoa ka litlamorao tse ts'oanang tse bonoang feela kamora kalafo e sa foleng le fluoxetine kapa imipramine (,). Leha ho le joalo, ketamine e hlobaetsang e ne e se na phello ho anhedonia litekong tsa ICSS. Liphumano tsa rona li tlatsana le mosebetsi o fetileng o bonts'a hore CSDS e fokotsa khetho ea meputso ea tlhaho (,,), hape u bonts'a hore ICSS ke mokhoa o hlokolosi, o ka tšeptjoang hape o ka rarolloang oa ho bona litlamorao tsa CSDS nakong ea litoeba. Liphetho li boetse li bonts'a hore ketamine e na le litla-morao tse potlakisang khatello ea maikutlo ho ba bang — empa eseng kaofela — CSDS-ikiwa.

Ho paradigm ea CSDS, litoeba tse ka qhekelloang li bonts'a bofokoli ho latela khetho ea sucrose eo hangata e hlalosoang e le anhedonia. Leha ho le joalo, ho na le lintho tse ngata tse thatafatsang tšebeliso ea liteko tsa sucrose joalo ka tekanyo ea anhedonia. Taba ea pele, ba haelloa ke ts'epo: CSDS e tlalehiloe hore ea fokotseha (-), nyollelo (,) kapa ha e na phello (,) ka khetho ea sucrose, ka liphapang tse tšoanang tse tlalehiloeng li sebelisa paradigm e sa foleng ea khatello ea maikutlo (,). Taba ea bobeli, liteko tsa sucrose li ka ferekanngoa le ho hlaka ka tharollo ea sucrose, hobane khatello ea maikutlo e sa feleng e ka baka neophobia (,). Kamora nako, phetoho ea bona ea phetolelo ha e hlake, hobane ha ho na phapang pakeng tsa tharollo e monate lipakeng tsa batho ba nang le khatello e kholo ea khatello ea maikutlo le taolo e phetseng hantle (,), le khatello ea maikutlo le khatello ea maikutlo e sa foleng li ka fella ka ho fokotsa boima ba 'mele kapa ho fumana (,-). Lintlha tsena li fana ka maikutlo a hore tlhahlobo ea ho khetha le liteko tsa tšebeliso ea hau feela li kanna tsa se ke tsa emela mokhoa o nepahetseng bakeng sa ho hlahloba anhedonia. Leha lithuto tsa rona tsa ICSS li sa bue ka hore na liteko tsena tse amanang le sucrose li bonts'a ts'ebetso ea moputso, li tiisa hore kannete CSDS e hlahisa anhedonia.

Monyetla o mong oa tlhahlobo ea ICSS ke hore e nolofalletsa litekanyo tsa letsatsi le letsatsi tsa ts'ebetso ea moputso, e etsa hore ho hlahlojoe ka nepo palo ea CSDS e hlokahalang ho hlahisa anhedonia. Liteko tse phetoang hangata ha li khonehe litekong tsa SI kapa tsa sucrose, hobane boiphihlelo bo ka ama sephetho. Mona re bonts'a hore CSDS e qala ho phahamisa litsotsi tsa ICSS ka karolo ea bobeli ea ho hloloa. Meketjana e lutse e phahame nako eohle ea CSDS le ho fihlela beke e le ngoe kamora ho felisoa, e bonts'a anhedonia e sa khaotseng. Lintho tsena tse phahamisang monyako li tsamaisana le litlamorao tsa kalafo tse ling tse bakang khatello ea maikutlo ho kenyeletsa khatello ea maikutlo e sa reroang (,), ho tlosa lithethefatsi (-), le kappa-opioid receptor agonists (,). Le ha likheo tsa litoeba tsa taolo li ile tsa lula li tsitsitse nakong ea D1-10, ho phahamisoa ka mokhoa o phahameng nakong ea P1-5 e ka ba ka lebaka la ho hlaka ha moralo oa liteko. Ka ho khetheha, litoeba tsa taolo li ne li behiloe kahare ho sefapano ho tloha ho Conspecific nakong ea D1-10, empa (joalo ka lithuto tsohle) li ne li qheletsoe ka thoko nakong ea P1-5. Ho thehiloe hore khethollo ea sechaba ea litoeba tsa batho ba baholo e hlahisa matšoao a amanang le anhedonia ().

Habohlokoa, re bonts'a hore hoa khoneha ho fokotsa anhedonia ea CSDS-e hlahisitsoeng tlhahlobong ea ICSS. Molemo overexpress ΔFosB ka D1-mofuta oa spiny neurons oa striatum () ha li na taba le tlhoko e tlisoang ke CSDS ea likhatiso tsa ICSS. Sena se lumellana le litlaleho tsa pejana tsa hore ha ba na taba le tlhabollo ea boiketlo ba sechaba ea CSDS () le lintšing tsa ho eketseha tsa litlamorao tsa U50488, kappa-opioid receptor agonist e tsejoang ho hlahisa dysphoria (). Bokhoni ba ΔFosB overexpression ho thibela sephetho sa anhedonic tsa CSDS le li-agonists tsa KOR li bontša ho ka ba le phallo e ngata mokhoeng oa limolek'hule, joalo ka ha ho khothaletsoe pele (,). Mochine o mong o ka sebelisang eo ΔFosB e ka sebelisang khatello ea khatello ea maikutlo ka ho kenella ha GluR2 ka har'a nucleus accumbens (NAc), e fokotsang lentsoe glutamatergic (). Le ha litoeba tsa ΔFosB-Control li bonts'a keketseho e kholo ea likotlo tsa ICSS ha li bapisoa le tse bonoang ho litoeba tsa C57BL / 6J, sena e kanna ea ba ka lebaka la semelo se fapaneng sa lits'ebetso tsa mothehi; ehlile litoeba tsa ControlFosB-Control li boetse li tsotella ho qoba ho qhelella ka boiketlo ba sechaba (CSDS)).

Ho ka etsahala hore litlamorao tse bohloko tsa CSDS li kenya letsoho ho phahamisoe litsong tsa ICSS, ho nka hore bohloko bo boholo bo ka eketsa likotsi tsa ICSS (). Ho bonahala eka ha ho na monyetla hore likhahla tse bonoang tsa ICSS li hlahisoe ke bohloko bo le bong, leha ho le joalo, ka mabaka a 'maloa. Taba ea pele, ho pepesetsoa maikutlo a sithabetsang ho kenyeletsa CSDS hangata ho hlahisa analgesia e hatelletsoeng kelellong (,). Taba ea bobeli, likotlo tsa ICSS li ile tsa lula li phahamisitsoe kamora ho felisoa ha ho felisoa, ho bonts'a hore litlamorao tsa CSDS li telele le ho ikemela ha bohloko bo hlobaetsang. Taba ea boraro, litoeba tse "paki" ea ho hloloa sechabeng li bonts'a boits'oaro bo bobe joalo le ha bo sa kopane.). Kamora nako, CSDS e ile ea hloleha ho hlahisa anhedonia ka litoeba tse oxpxpress ΔFosB ka striatum, moo e tsamaeang le khatello ea maikutlo (). Liphetho tsa hona joale li fana ka maikutlo a hore CSDS e hlahisa mekhoa e fapaneng tseleng ea moputso oa boko (,,,) seo se fella ka anhedonic phenotype.

Le ha li-antidepressants tse tloaelehileng li ka khutlisa litlamorao tsa boitšoaro ba CSDS, kalafo e sa feleng e ea hlokahala (,). Hobane ketamine e hlobaetsang e na le litlamorao tse potlakileng tsa mathata ho batho (-), re ile ra lekola hore na kalafo e matla ea ketamine e khutlisetsa litlamorao ho CSDS ho litoeba. Re fumane hore tekanyo e le 'ngoe ea ketamine (20 mg / kg, IP) e baka litlamorao tse tšoanang le tsa (~ 24) tsa litla-morao tse tšoanang le liteko tsa SI kamora ho pepesetsoa CSDS. Sena se lumellana le lithuto tse ngata tse hlalosang litlamorao tse potlakileng (ka mor'a lihora tse seng kae) tsa tekanyetso e entsoeng ka bohlale ea ketamine ho batho (-), esita le ho bakuli ba nang le khatello ea maikutlo e thibelang kalafo (,,,). Ketamine e boetse e na le litlamorao tse potlakileng tsa li-antidepressant mefuteng e meng ea liphoofolo ho kenyeletsoa liteko tse qobelloang tsa ho sesa (FST) le liteko tsa ho emisoa ka mohatla (TST) (,,,,,,), ho ithuta ho hloka thuso paradigm (,,), le khatello e matla ea maikutlo ea khatello ea maikutlo (,,). Ha ho CSDS kapa ketamine e matla e anngoeng ke ts'ebetso ea locomotor, ntho ea bohlokoa ho fana ka litlamorao tse sa tobang ho tlhahiso e kholo ea koloi e ka thatafatsang ho hlalosoa ha datha. Ho nka hore ketamine e hlahisa litlamorao ho litoeba (,), re lekotse monyetla oa hore ketamine e kena-kenane le ho ithuta ho amanang le khatello ea maikutlo le memori. E lumellana le mosebetsi o fetileng (), re fumane hore 20 mg / kg ketamine ha e kena-kenane le ts'ebetso ea tlhahlobo ea thibelo ea bohlola, a fana ka maikutlo a hore litlamorao tse joalo ka lithethefatsi lithutong tsa rona ha li bakoe ke ho senyeha hoa mohopolo. Re boetse re bonts'a hore kalafo e matla ea ketamine e fokotsang ts'ireletso ea sechaba ha e ame boitšoaro ho EPM, leha litlaleho tse fetileng li sa lumellane (,). Hammoho, seo re se fumaneng se fana ka maikutlo a hore litlamorao tsa ketamine litekong tsa SI li ka bapisoa le litlamorao tsa ho ithuta le ho hopola kapa ho tšoenyeha.

Ho khahlisang ke hore ente e le 'ngoe ea 20 mg / kg ketamine 24 hr pele ho letsatsi la e' ngoe ea CSDS e ne e se na tšusumetso ea ho qoba maemo a sechaba, a fana ka maikutlo a ho se khone ho thibela nts'etsopele ea liphetoho tse phetoang tse bakang khatello ea maikutlo hangata bonyane ka tekanyetso e le 'ngoe. Ntle le moo, litlamorao tse kang tsa ketamine litekong tsa SI li ne li sa phehelle: litoeba tse lekiloeng 1 bekeng hamorao ha li a ka tsa bontša ho ts'oaroa ke phetoho ea boiketlo ba sechaba ba CSDS. Ho fumana sena ho lumellana haholo le lithuto tsa bongaka tse fanang ka maikutlo a hore bakuli ba arabelang ketamine e hlobaetsang hangata ba ka khutla ka mor'a matsatsi a 'maloa (,,) le ka litlaleho tsa pele tsa litla-morao tse matla empa tse sa phehelleng tsa kalafo ea ketamine ho FST le TST ka litoeba (,,), leha ho boetse ho na le litlaleho tsa litlamorao tse sa feleng (,,,). Liphapang tsena li ka bakoa ke boholo kapa mofuta oa khatello ea maikutlo (mohlala, khatello ea sechaba ha e bapisoa le FST kapa TST) kapa phapang ea mathata (). Phekolo e phetoang ea ketamine e kanna ea hlokahala ho etsa hore ho be le litlamorao tse ts'epahalang. Haufinyane tjena ho tlalehiloe hore kalafo ea ketamine e pheta-phetoang ho litoeba e ne e hlokahala ho hlahisa mofuta oa nako e telele oa ho tsitsisa maemong a sa tsitsang a khatello ea kelello a sa lebelloang (). Ntle le moo, ho na le bopaki ba hore tsamaiso ea ketamine e sa foleng e etsa hore litlamorao tse joalo ka meriana e se ke ea sebetsa hantle (). Ho na le litlaleho tsa hore infusions khafetsa ho bakuli ba nang le khatello ea maikutlo e hananang le kalafo e ka baka karabelo e tsitsitseng ea antidepressant ha e bapisoa le infusion e le 'ngoe.-). Leha ho le joalo, ts'ebeliso e pharalletseng ea ketamine joalo ka kalafo e ka fokotsoa ke mokoloto oa tlhekefetso le litlamorao tse ling (-). Ho tšoaea nako ea litlamorao tsa ketamine mefuteng ea liphoofolo ho ka thusa ho ntlafatsa mekhoa ea kalafo ea kliniki.

Leha ho bile le litlamorao ho thibelo ea sechaba, ketamine e hlobaetsang e ile ea hloleha ho thibela litlamorao tsa CSDS tlhahlobong ea ICSS. Sena se ne se sa lebelloa ha ho nahanoa ka litlaleho tsa pele tse reng ketamine e khutlisa ho fokotseha ho amanang le khatello ea maikutlo molemong oa khetho ea sucrose (,), le ho eketsa dopamine efflux ho NAc (), phello e hangata e amanang le maikutlo a phahameng (). Ka tsebo eohle ea rona ha ho na litlaleho tsa bokhoni ba li-antidepressants tse tloaelehileng tsa ho khutlisa litlamorao tsa CSDS ho ICSS. Re ke ke ra qhelela ka thoko monyetla oa hore kalafo ea ketamine e ka khutlisetsa anhedonia ea CSDS-tlhahlobisong ea ICSS sebelisa mekhoa e meng ea kalafo (mohlala, litekanyetso tse fapaneng, tsamaiso e phetoang) kapa lits'oants'o tsa litoeba, leha lithuto tse joalo li le kaholimo ho palo ena ea tlaleho tumello ho moralo oa liteko. Leha ho le joalo, lithuto tsa liphoofolo tse kenyelletsang tsamaiso ea ketamine e pheta-phetoang e kanna ea ba le boleng bo fokolang ba ho utloisisa hore na hobaneng lithethefatsi li sebetsa hantle ka mor'a taolo e matla ho batho ().

CSDS e boetse e etsa boits'oaro bo ts'oanang le ts'oaetso joalo ka lits'oants'o tse hlahlobang joalo ka mazaze a phahameng kapa tšimo e bulehileng (,). Leha ho le joalo, karolo ea bohlokoa ea paradigm ea CSDS ke hore e ka khetholla mehato ena e ts'oenyehileng joalo ka matšoao a sithabetsang a kang ho qoba sechaba kapa bofokoli ba khetho ea batho. Haholo-holo, lithibelo tsa kahisano sechabeng le bofokoli ba khethollo ea tšebelisano li tšoaroa hantle le li-antidepressants tse tloaelehileng empa eseng li-anxiolytics (). Ntle le moo, litoeba tse bonts'ang mofuta o tsitsitseng oa maikutlo (ke hore, tse sa thibelo ea ho khesoa sechabeng le bofokoli ba ho rata maemo) li bontša maemo a tšoanang a boits'oaro bo joalo (), joalo ka litoeba tse oxpxpress ΔFosB (). Ka mokhoa o ts'oanang, re bonts'a hore ketamine e matla ea hloho (20 mg / kg) e amme boemo bo le bong ba boitšoaro bo nyenyefatsang (ho qoba maemo a sechaba), empa eseng ba bang (anhedonia, matšoenyeho, ho ithuta le ho hopola), ba fana ka maikutlo a hore boits'oaro bona bo emela libaka tse ikhethang tse laoloang ke karohano e fapaneng empa e le e fetang. makaleng a bokong (). Lisebelisoa tsa limolek'hule tseo ka tsona ketamine e hlahisang litlamorao tse kang tsa antidepressant ha li utloisisoe hantle, empa li ka kenyelletsa liphetoho tsa tšebetso ea glutamate kapa liprotheine tsa liprotheine kahare ho likarolo tsa boko tse kenyeletsang hippocampus le frontal cortex (,,,).

lumela hore baa fokola

Patlisiso ena e ne e tšehelitsoe ka lithuso ho tloha ho National Institutes of Health (MH063266 ho WC; R01MH51399 le P50MH096890 ho EJN; MH090264 ho SJR). RJD e tšehelitsoe ke Grant Grant (T32MH020017) e tsoang Setsing sa Bophelo sa Naha.

Mongolo o botlaaseng ba leqephe

 

LITLHAKISO TSE MALI

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

 

 

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.

 

References

1. Finlay-Jones R, brown GW. Mefuta ea ketsahalo e sithabetsang ea bophelo le qalo ea matšoenyeho le khatello ea maikutlo. Psychol Med. 1981; 11: 803-15. [E fetotsoe]
2. Keller MC, Neale MC, Kendler KS. Kopano ea liketsahalo tse fapaneng tsa bophelo bo fapaneng le mekhoa e fapaneng ea matšoao a sithabetsang. Ke J Psychiatry. 2007; 164: 1521-1529. [E fetotsoe]
3. Kendler KS, Karkowski LM, Prescott CA. Kamano ea ho baka lipakeng tsa liketsahalo tse sithabetsang tsa bophelo le qalo ea khatello e kholo ea maikutlo. Ke J Psychiatry. 1999; 156: 837-48. [E fetotsoe]
4. Kessler RC, Berglund P, Demler O, Jim R, Merikangas KR, Walters EE. Bolelele ba Bophelo le Nako ea Bofetoheli ba Phallo ea Likoluoa ​​tsa DSM-IV ho Phetohelo ea Sechaba ea Comorbidity. Psychology ea Arch Gen. 2005; 62: 593-602. [E fetotsoe]
5. Keller MB, Boland RJ. Litlamorao tsa ho hloleha ho fihlella kalafo e atlehileng ea ho lokisa nako e telele ea ho tepella maikutlo ho sa feleng. Psychology ea Biol. 1998; 44: 348-360. [E fetotsoe]
6. Nemeroff CB. Ho ba haufi le taolo ea khatello ea maikutlo e hanyetsanang le kalafo. J Clin Psychiatry. 2007; 68: 17-25. [E fetotsoe]
7. Krishnan V, Nestler EJ. Neurobiology ea molek'hule ea khatello ea maikutlo. Tlhaho. 2008; 455: 894-902. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
8. Mokhatlo oa American Psychiatric Association. Tlhatlhobo le Buka ea Bophatlalatsi ea Mathata a kelello. 5. Washington, DC: Mokhatlo oa Amerika oa Psychiatric; 2000.
9. Nestler EJ, Hyman SE. Mefuta ea liphoofolo ea mafu a amanang le neuropsychiatric. Nat Neurosci. 2010; 13: 1161-1169. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
10. Golden SA, Covington HE, III, Berton O, Russo SJ. Protocol e emeng bakeng sa khatello ea phetisetso ea sechaba e pheta-phetoang ka litoeba. Nat Protoc. 2011; 6: 1183-1191. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
11. Huhman KL. Mefuta ea likhohlano tsa sechaba: na e ka re tsebisa ka psychopathology ea motho? Horm Behav. 2006; 50: 640-646. [E fetotsoe]
12. Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ, et al. Karolo ea bohlokoa ea BDNF tseleng ea mesolimbic dopamine tseleng ea khatello ea khatello ea sechaba. Mahlale. 2006; 311: 864-868. [E fetotsoe]
13. Krishnan V, Han MH, Graham DL, Berton O, Renthal W, Russo SJ, et al. Ho feto-fetoha ha limolek'hule ho tlatsetsang habonolo le ho hanyetsanang le ho hloloa hoa sechaba libakeng tsa moputso oa boko. Sele. 2007; 131: 391-404. [E fetotsoe]
14. Kudryavtseva NN, Bakshtanovskaya IV, Koryakina LA. Mohlala oa sechaba oa khatello ea maikutlo ho litoeba tsa C57BL / 6J. Pharmacol Biochem Behav. 1991; 38: 315-320. [E fetotsoe]
15. Cao JL, Covington HE, III, Friedman AK, Wilkinson MB, Walsh JJ, Cooper DC, et al. Mesolimbic dopamine neurons bokong ba moputso oa potoloho ea boko bo ka hlaseloang ke ts'ebetso ea tlhaselo ea sechaba le ts'ebetso ea antidepressant. J Neurosci. 2010; 30: 16453-16458. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
16. Covington HE, III, Maze I, LaPlant QC, Vialou VF, Yoshinori ON, Berton O, et al. Ketso ea antidepressant ea histone deacetylase inhibitors. J Neurosci. 2009; 29: 11451-11461. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
17. Chaouloff F. Mehlala ea khatello ea maikutlo lipolotiking tsa khatello ea maikutlo: ba re bolella eng? Cell Tissue Res. 2013: 1-12. [E fetotsoe]
18. Kalueff AV, Avgustinovich DF, Kudryavtseva NN, Murphy DL. BDNF ka matšoenyeho le khatello ea maikutlo. Mahlale. 2006; 312: 1598-1599. [E fetotsoe]
19. Carlezon WA, Jr, Chartoff EH. Intracranial self-stimulation (ICSS) ka litoeba ho ithuta neurobiology ea sepheo. Nat Protoc. 2007; 2: 2987-2995. [E fetotsoe]
20. Der-Avakian A, Markou A. Ho buuoa ka methapo ea kelello ea anhedonia le liphoso tse ling tse amanang le moputso. Mekhoa ea Neurosci. 2012; 35: 68-77. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
21. Barr AM, Markou A, Phillips AG. Tsela ea 'ho senyeha' mabapi le ho khaotsa psychostimulant e le mohlala oa khatello ea maikutlo. Trends Pharmacol Sci. 2003; 23: 475-482. [E fetotsoe]
22. MP ea Epping-Jordan, Watkins SS, Koob GF, Markou A. Dramatic e fokotseha ts'ebetsong ea moputso oa boko nakong ea ho khaotsa nicotine. Tlhaho. 1998; 393: 76-79. [E fetotsoe]
23. Johnson PM, Hollander JA, Kenny PJ. Ts'ebetso ea moputso o fokotsehileng oa boko nakong ea ha nicotine e khaotsa ho litoeba tsa C57BL6: Bopaki bo tsoang lipatlisisong tse ikhethileng tsa ICR (CSS). Pharmacol Biochem Behav. 2008; 90: 409-415. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
24. Liu J, Schulteis G. Bofokoli ba moputso oa bongo bo tsamaisana le ho tlosoa ho tlositsoeng pele ho ts'epahali ho tsoa ho ts'ehetso e matla ea opioid. Pharmacol Biochem Behav. 2004; 79: 101-108. [E fetotsoe]
25. Markou A, Hauger RL, Koob GF. Desmethylimipramine e bontša ho tlosoa hoa koae ho likhoto. Psychopharmacology (Berl) 1992; 109: 305-314. [E fetotsoe]
26. Lin D, Bruijnzeel AW, Schmidt P, Markou A. Ho pepesetsoa ke khatello ea maikutlo e fokolang e sa fetoheng ea khatello ea maikutlo le moputso o latelang oa amphetamine. Neuroscience. 2002; 114: 925-933. [E fetotsoe]
27. Moreau JL, Jenck F, Martin JR, Mortas P, Haefely WE. Phekolo ea antidepressant e thibela anhedonia e sa lebelloang e matla e sa lebelloang joalo ka ha e hlahlojoa ke boits'oaro ba moea oa ho itšunya-tšunya ho likhoto. Eur J Neuropsychopharmacol. 1992; 2: 43-49. [E fetotsoe]
28. DiNieri JA, Nemeth CL, Parsegian A, Carle T, Gurevich VV, Gurevich E, et al. Kutloelo e fetotsoeng ea lithethefatsi tse fanang ka moputso le tse o thusang ho litoeba ka tšitiso e sa sebetseng ea karabo ea cAMP e arolang likarolo tsa protein. J Neurosci. 2006; 29: 1855-1859. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
29. Todtenkopf MS, Marcus JF, Portoghese PS, Carlezon WA., Jr Liphello tsa kappa-opioid ligands ho intracranial ho intlafatsa ho likhoto. Psychopharmacology (Berl) 2004; 172: 463-470. [E fetotsoe]
30. Martin D, Lodge D. Ketamine o sebetsa e le mohanyetsi ea se nang tlholisano oa N-methyl-d-aspartate ho mookotaba oa linokoane ho frro. Neuropharmacology. 1985; 24: 999-1003. [E fetotsoe]
31. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Litholoana tsa khatello ea kelello tsa ketamine ho bakuli ba tepelletseng maikutlo. Psychology ea Biol. 2000; 47: 351-354. [E fetotsoe]
32. Carlson PJ, Diazgranados N, Nugent AC, Ibrahim L, Luckenbaugh DA, Brutsche N, et al. Li-correlates tsa Neural tsa karabelo e potlakileng ea antidepressant ea ketamine ho khatello ea maikutlo e hananang le khatello ea maikutlo: thuto ea pele ea positron emission tomography. Psychology ea Biol. 2013; 73: 1213-1221. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
33. Correll GE, Futter GE. Lithuto tse peli tsa bakuli ba nang le khatello e kholo ea khatello ea maikutlo ba fuoeng li-lowamine tse tlase (subanesthetic) tsa ketamine infusions. Ho utloisa bohloko Med. 2006; 7: 92-95. [E fetotsoe]
34. Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, et al. Teko e eketsang e sa sebetseng ea mohanyetsi oa N-methyl-D-aspartate ea khatello ea maikutlo ea khatello ea maikutlo ea khatello ea kelello. Psychology ea Arch Gen. 2010; 67: 793-802. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
35. Larkin GL, Beautrais Patlisiso ea tlhaho ea tlhaho ea ketamine ea tlase ea khatello ea maikutlo le maikutlo a ho ipolaea lefapheng la tšohanyetso. Int J Neuropsychopharmacol. 2011; 14: 1127-1131. [E fetotsoe]
36. Phelps LE, Brutsche N, Moral JR, Luckenbaugh DA, Manji HK, Zarate CA., Jr nalane ea lelapa la ho ts'epa joala le karabelo ea pele ea antidepressant ho mohanyetsi oa N-methyl-D-aspartate. Psychology ea Biol. 2009; 65: 181-184. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
37. Salvadore G, Cornwell BR, Sambataro F, Latov D, Colon-Rosario V, Carver F, et al. Anterior cingulated desynchronization le tšebetso e kopaneng le amygdala nakong ea mosebetsi oa memori e sebetsang e bolela esale pele karabelo e potlakisang antidepressant ho ketamine. Neuropsychopharmacology. 2010; 35: 1415-1422. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
38. Theko RB, Nock MK, Charney DS, Mathew SJ. Litlamorao tsa ketamine e kenang methapong e hlakileng le e sa totobalang ea ho ipolaea ho khatello ea maikutlo e hananang le kalafo. Psychology ea Biol. 2009; 66: 522-526. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
39. Zarate CA, Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, et al. Teko e sa feto-fetoheng ea mohanyetsi oa N-methyl-D-aspartate ho tepelletseng maikutlong ho hanyetsanang le khatello ea maikutlo. Psychology ea Arch Gen. 2006; 63: 856-864. [E fetotsoe]
40. Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, et al. NMDA receptor blockade phomolong e baka likarabo tse potlakileng tsa boits'ireletso ba kalafo. Tlhaho. 2011; 475: 91-95. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
41. Bechtholt-Gompf AJ, Smith KL, John CS, Kang HH, Carlezon WA, Jr, Cohen BM, et al. Li-CD-1 le litoeba tsa Balb / cJ ha li bonts'e litlamorao tse tšoanang le tsa ketamine litekong tsa katleho e matla ea meriana. Psychopharmacology. 2011; 215: 689-695. [E fetotsoe]
42. Da Silva FC, etsa Carmo de Oliveira Cito M, da Silva MI, Moura BA, de Aquino Neto MR, Feitosa ML, et al. Liphetoho tsa boitšoaro le phello ea pro-oxidant ea tsamaiso e le 'ngoe ea ketamine ho litoeba. Brain Res Bull. 2010; 83: 9-15. [E fetotsoe]
43. Engin E, Treit D, Dickson CT. Anxiolytic- le antidepressant joalo ka thepa ea ketamine mehlaleng ea boits'oaro ea liphoofolo le methapo ea methapo. Neuroscience. 2009; 161: 359-369. [E fetotsoe]
44. Garcia LS, Comim CM, Valvassori SS, Réus GZ, Barbosa LM, Andreazza AC, et al. Ts'ebetso e matla ea ketamine e etsa hore ho be le litlamorao tse kang li-antidepressant litekong tse qobelloang tsa ho sesa 'me e eketsa maemo a BDNF ho hippocampus ea rat. Prog Neuropsychopharmacol Biol Psych. 2008; 32: 140-144. [E fetotsoe]
45. Koike H, Iijima M, Chaki S. Ho kenella ha receptor ea AMPA ka bobeli litlamorao tse potlakileng le tse tsitsitseng tsa antidepressant joalo ka ketamine mefuteng ea liphoofolo ea khatello ea maikutlo. Behav Brain Res 2011; 224: 107-111. [E fetotsoe]
46. Li N, Liu RJ, Dwyer JM, Banasr M, Lee B, Son H, et al. Li-glutamate N-methyl-D-aspartate receptor antagonists li potlakisa ho khutlisa boits'oaro le bofokoli ba synaptic bo bakoang ke ho pepeseha ha khatello ea maikutlo. Psychology ea Biol. 2011; 69: 754-761. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
47. Li N, Lee B, Lui RJ, Banasr M, Dwyer JM, Iwata M, et al. MTOR e thehiloeng ke "synapse" e thehiloe ka tlase ho litlamorao ho potlakileng tsa litla-morao tsa lihanyetsi tsa NMDA. Mahlale. 2010; 329: 959-964. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
48. Lindholm JSO, Autio H, Vesa L, Antila H, Lindemann L, Hoener MC, et al. Litlamorao tse kang tsa li-antidepressant-like tsa lithethefatsi tse glutamatergic, le liakisi tsa AMPA receptor LY 451646 li bolokiloe ka litoeba tsa bdnf (+/−). Neuropharmacology. 2012; 62: 391-397. [E fetotsoe]
49. Ma XC, Dang YH, Jia M, Ma R, Wang F, Wu J, et al. Ketso ea nako e telele ea antidepressant ea ketamine, empa eseng glycogen synthase kinase-3 inhibitor SB216763, ka mohlala o fokolang oa khatello ea litoeba. PloS One. 2013; 8: e56053. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
50. Maeng S, Zarate CA, Jr, Du J, Schloesser RJ, McCammon J, Chen G, et al. Mechine ea lisele e tlatsetsang litlamorao tsa li-antidepressant tsa ketamine: Karolo ea alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Psychology ea Biol. 2008; 63: 349-352. [E fetotsoe]
51. Popik P, Kos T, Sowa-Kucma M, Nowak G. Ho haella ha litlamorao tsa ketamine mefuteng ea khatello ea maikutlo. Psychopharmacology (Berl) 2008; 198: 421-430. [E fetotsoe]
52. Boultadakis A, Pitsikas N. Anesthetic ea ketamine e etsa hore re hopole lintlha tsa nakong e fetileng: nitric oxide synthase inhibitor N-nitro-L-arginine methylester e hanyetsana le bofokoli ba tlhokomeliso ea ketamine. Tlhahlobo ea Tlhaho. 2011; 114: 1345-1353. [E fetotsoe]
53. Wang JH, Fu Y, Wilson FAW, Ma YY. Ketamine e ama ntlafatso ea mohopolo: litlamorao tse fapaneng ho T-maze le paradigms ea thibelo ea litheko ka litoeba. Neuroscience. 2006; 140: 993-1002. [E fetotsoe]
54. Vialou V, Robison AJ, LaPlant QC, Covington HE, Dietz DM, Ohnishi YN, et al. ΔFosB maemong a moputso oa boko e thusa ho sebetsana le khatello ea maikutlo le likarabo tse khahlanong le khatello ea maikutlo. Nat Neurosci. 2010; 13: 745-752. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
55. Kelz MB, Chen J, Carlezon WA, Whisler K, Gilden L, Beckmann AM, et al. Khopolo ea "transcript factor" osFosB bokong e laola maikutlo a koae. Tlhaho. 1999; 401: 272-276. [E fetotsoe]
56. Miliaressis E, Rompre PP, Labiolette P, Philippe L, Coulombe D. Mokokotlo oa li-curve-transt paradigm ka mokhoa oa ho iphelisa. Physiol Behav. 1986; 37: 85-91. [E fetotsoe]
57. Bruchas MR, Schindler AG, Shankar H, Messinger DI, Miyatake M, Land BB, et al. Ho tlosoa ha p383 MAPK ho li-neuron tsa serotonergic ho hlahisa khatello ea maikutlo mefuteng ea khatello ea maikutlo le bokhoba. Neuron. 2011; 71: 498-511. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
58. Muschamp JW, Nemeth CL, Robison AJ, Nestler EJ, Carlezon WA., Jr ΔFosB e ntlafatsa litlamorao tsa cocaine ha e ntse e fokotsa litlamorao tse bakang ts'oaetso ea kappa-opioid receptor agonist U50488. Psychology ea Biol. 2012; 71: 44-50. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
59. Der-Avakian A, Markou A. Neonatal karohano ea bo-mme e eketsa phello e eketsang moputso oa taolo ea amphetamine e matla le phello ea ho hloloa khafetsa ha setjhaba litlamong tsa batho ba baholo. Neuroscience. 2010; 170: 1189-1198. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
60. Kureta Y, Watanabe S. Tšusumetso ea puso ea sechaba ka boits'oaro bo botle ho boikhohomoso ba banna ba liketane tsa khauta. Physiol Behav. 1996; 59: 621-624. [E fetotsoe]
61. Dubreucq S, Kambire S, Conforzi M, Metna-Laurent M, Cannich A, Soria-Gomez E, et al. Cannabinoid mofuta 1 li-receptor tse fumanehang ho li-neurons tse se nang kelello tsa 1 tse laolang boitšoaro ba maikutlo. Neuroscience. 2012; 204: 230-244. [E fetotsoe]
62. Dubreucq S, Matias I, Cardinal P, Häring M, Lutz B, Marsicano G, et al. Disekethara tsa tikoloho ea karolo ea li-cannabinoid mofuta-1 receptors litlamorao tsa maikutlo tsa khatello ea maikutlo ea pheta-phetoang sechabeng litoeba. Neuropsychopharmacology. 2012; 37: 1885-1900. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
63. Croft AP, Brooks SP, Cole J, Little HJ. Ho hlola sechaba ho eketsa ho rata lithethefatsi tsa litoeba tsa C57BL / 10; phello e thibeletsoeng ke mohanyetsi oa CCKB. Psychopharmacology. 2005; 183: 163-170. [E fetotsoe]
64. Hollis F, Wang H, Dietz D, Gunjan A, Kabbaj M. Liphello tsa ho hlola khafetsa sechabeng ka boitšoaro bo bolelele bo kang bo nyahamisang le liphetoho tse khutšoanyane tsa histone ho hippocampus ho likhoto tsa banna tsa Sprague-Dawley. Psychopharmacology. 2010; 211: 69-77. [E fetotsoe]
65. Moreau JL. Ho beha leihlo 'nete ka liphoso tsa hedonic maemong a sa foleng a khatello ea maikutlo. Psychopharmacology. 1997; 134: 357-358. [E fetotsoe]
66. Mokhathala o mong oa khatello ea maikutlo oa Willner P. (CMS) o ile a boela a pheta: concordance e ts'oanang le ea boits'oaro litlamorao tsa CMS. Neuropsychobiology. 2005; 52: 90-110. [E fetotsoe]
67. Bondar NP, Kovalenko IL, Avgustinovich DF, Smagin DA, Kudryavtseva NN. Anhedonia ka moriti oa khatello ea maikutlo ea khatello ea maemo a bophelo, kapa ha maemo a liteko a bohlokoa. Bula Behav Sci J. 2009; 3: 17-27.
68. Faele SE. Lintlha tse laolang mehato ea matšoenyeho le likarabo ho bocha ho panya. Behav Brain Res 2013; 125: 151-157. [E fetotsoe]
69. Berlin I, Givry-Steiner L, Lecrubier Y, Puech AJ. Mehato ea anhedonia le likarabo tsa hedonic ho sucrose ho bakuli ba sithabetsang le ba schizophrenic ha ba bapisoa le lithuto tse phetseng hantle. Eur Psychiatry. 1998; 13: 303-309. [E fetotsoe]
70. Dichter GS, Smoski MJ, Kampov Polevoy AB, Gallop R, Garbutt JC. Ho tepella maikutlong ntle le tumello ha ho arabeloe ka tekano ho Teko e Monate e monate. Ho Tepella Maikutlo. 2010; 27: 859-863. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
71. Dallman MF, Pecoraro N, Akana SF, La Fleur SE, Gomez F, Houshyar H, et al. Ho sithabela maikutlo le botenya: pono e ncha ea "lijo tse khothatsang" Proc Natl Acad Sci USA. 2003; 100: 11696-11701. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
72. Dallman MF, Pecoraro NC, La Fleur SE. Ho sithabela maikutlo le ho ja lijo tse khothatsang: ho ikoetlisa le botenya ba ka mpeng. Brain Behav Immun. 2005; 19: 275-280. [E fetotsoe]
73. Heiskanena TH, Koivumaa-Honkanena HT, Niskanenb LK, Lehtoa SM, Honkalampie KM. Ho sithabela maikutlo le phaello e kholo ea boima: Tlhahlobo e tlang ea 6 ea selemo sa ho tsoa lipetleleng. Compr Psychiatry 2013 [E fetotsoe]
74. Wallace DL, Han MH, Graham DL, Green TA, Vialou V, Iñiguez SD, et al. CREB taolo ea li-nucleus e bokellana ka katleho ea ho itšehla thajana - e hlohlelletsang bofokoli ba boitšoaro. Nat Neurosci. 2009; 12: 200-209. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
75. McLaughlin JP, Li S, Valdez J, Chavkin TA, Chavkin C. Likarabo tsa boitšoaro tse tlisoang ke khatello ea maikutlo tse susumetsoang ke sechaba li kopants'oa ke tsamaiso ea endiozala kappa opioid. Neuropsychopharmacology. 2005; 31: 1241-1248. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
76. Van't Veer A, Carlezon WA., Jr Role oa li-receptor tsa kappa-opioid maemong a khatello le boits'oaro bo amanang le ho tšoenyeha. Psychopharmacology. 2013; 229: 435-452. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
77. Pereira Do Carmo G, Stevenson GW, Carlezon WA, Negus SS. Liphetoho tsa manolo a amanang le bohloko le analgesia mabapi le ho itšunya-tšunya lithutong: lithuto tse ling hape mabapi le boitšoaro bo sithabetsang maikutlo. Bohloko. 2009; 144: 170-177. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
78. Butler RK, Finn DP. Khatello ea kelello e bakiloeng ke khatello ea maikutlo. Prog Neurobiol. 2009; 88: 184-202. [E fetotsoe]
79. Warren BL, Vialou VF, Iñiguez SD, Alcantara LF, Wright KN, Feng J, et al. Mokhoa oa morao-rao oa ho paka liketsahalo tse sithabetsang ho litoeba tsa batho ba baholo. Psychology ea Biol. 2013; 73: 7-14. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
80. Ibrahim L, Diazgranados N, Franco-Chaves J, Brutsche N, Henter ID, Kronstein P, et al. Tsela ea ntlafatso ea matšoao a nyahamisang ho kenngoa ka mokhoa o le mong oa ketamine le keketso ea eketsa: Liphetho ho tsoa bekeng ea 4-beke, bofofu bo habeli, thuto e laoloang ke placebo. Neuropsychopharmacology. 2012; 37: 1526-1533. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
81. Parise EM, Alcantara LF, Warren Bl, Wright KN, Hadad R, Sial OK, et al. Ho pepesetsoa ketamine khafetsa ho etsa hore motho a lule a tsitsitse maikutlong a hae a bocha le a batho ba baholo. Psychology ea Biol. 2013; 74: 750-759. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
82. Yilmaz A, Schulz D, Aksoy A, Canbeyli R. Tšusumetso ea nako e telele ea lethal dose ea anesthetic ea ketamine ka lebaka la ho hloka boitšoaro. Pharmacol Biochem Behav. 2002; 71: 341-344. [E fetotsoe]
83. Garcia LS, Comim CM, Valvassori SS, Réus GZ, Andreazza AC, Stertz L, et al. Tsamaiso e sa foleng ea ketamine e hlahisa litlamorao tse kang li-antidepressant ho litoeba ntle le ho ama maemo a liprotheine tsa boko tsa hippocampal. Basic Clin Pharmacol Toxicol. 2008; 103: 502-506. [E fetotsoe]
84. aan het Rot M, Collins KA, Murrough JW, Perez AM, Reich DL, Charney DS, et al. Ts'ireletso le ho sebetsa hantle ha lethathamo la methapo e kenang ea methapo bakeng sa khatello ea maikutlo e hananang le kalafo. Psychology ea Biol. 2010; 67: 139-145. [E fetotsoe]
85. Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, aan het Rot M, et al. Phello e potlakileng le e telele ea li-antidepressant tsa infusions tse phetoang tsa ketamine khafetsa ho hanyetsanang le khatello ea maikutlo. Psychology ea Biol. 2012; 74: 250-6. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
86. Rasmussen KG, Lineberry TW, Galardy CW, Kung S, Lapid MI, Palmer BA, et al. Li-infusions tsa serial tsa ketamine ea tlase-tlase bakeng sa khatello e kholo ea maikutlo. J Psychopharmacol. 2013; 27: 444-450. [E fetotsoe]
87. de la Peña IJ, Lee HL, de la Peña I, Shin CY, Sohn AR, et al. Ho pepesetsoa lintho tse amanang ho tlatselletsa boikhethelo ba libaka le ho itaola ha motsoako oa NMDA receptor antagonist-benzodiazepine, settil. Behav Pharmacol. 2013; 24: 20-28. [E fetotsoe]
88. Herberg LJ, Rose IC. Matla a MK-801 le bahanyetsi ba bang ba li-receptors tsa NMDA tsa mofuta oa NMDA moputsong oa matla a bokong. Psychopharmacology. 1989; 99: 87-90. [E fetotsoe]
89. Morgan CJA, Mofeez A, Brandner B, Bromley L, Curran HV. Ketamine e sitisa karabo ea karabo ebile e matlafatsa ho baithaopi ba phetseng hantle: thuto ea ho arabela ka tekanyetso. Psychopharmacology. 2004; 172: 298-308. [E fetotsoe]
90. Hancock PJ, Stamford JA. Litholoana tsa stereospecific tsa ketamine ho dopamine efflux le ho fihlela ho li-nucleus tsa ruble. Br J Anaesth. 1999; 82: 603-608. [E fetotsoe]
91. RA ea bohlale. Tšoaea le moputso: lilemo tse anhedonia hypothesis 30 ho ea pele. Neurotox Res. 2008; 14: 169-183. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
92. Morris SE, Cuthbert BN. Tlhahlobo ea Domain ea Patlisiso: Lits'ebetso tsa kelello, li-circuits tsa neural, le boholo ba boitšoaro. Dialogues Clin Neurosci. 2012; 14: 29-37. [Tlhahiso ea mahala ea PMC] [E fetotsoe]