Bopaki ba Neuroimaging ea Ho Fetoha Mosebetsi oa Fronto-Cortical le Striatal ka mor'a hore nako e telele ea Cocaine e ikemetse ka botsitso (2011)

Neuropsychopharmacology. 2011 Nov; 36 (12): 2431-2440.

E hatisitsoe Inthaneteng 2011 Jul 20. doi:  10.1038 / npp.2011.129

PMCID: PMC3194070

Sehlooho sena se bile teng e boletsoeng ke lihlooho tse ling ho PMC.

Eya ho:

inahaneloang

Bokhoba ba cocoaine hangata bo etsoa maemong a liteko moo litoeba li ithutang ho itaola (SA) lithethefatsi. Leha ho le joalo, hore na mefuta ena e pheta liphetoho tse sebetsang joang tse fumanoeng lithutong tsa kliniki tsa ts'ebeliso ea bokhoba ba koae e ntse e sa tsejoe. Re sebelisitse matla a ts'ebetso ea matla a khoheli (MRI) ho lekola ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea likhopo ho likhoto tse tlas'a ts'ebetso ea nako e telele ea ho sebelisa koae ea SA. Haholo-holo re ile ra lekanya bophahamo ba mali a "basal" Lithuto tse pepesitsoeng ke cocaine tse bonts'itsoeng li fokolitse bCBV libakeng tse ling tsa conto-cortical, li-nucleus accumbens, ventral hippocampus le thalamus. Sehlopha sa cocaine se boetse se bonts'itse karabelo e sebetsang ea amphetamine libakeng tse kenang kahare, phello e neng e amana haholo le tšebeliso ea koae ka botlalo. Kamano e sa lumellaneng pakeng tsa bCBV ho reticular thalamus le karabelo e ka pele e hlahisoang ke amphetamine e fumanoe lithutong tsa taolo empa eseng sehlopheng sa cocaine, ho fana ka maikutlo a hore ts'oaetso ea inhibitory e pakeng tsa potoloho ena ea tlhokomelo e ka fokotsoa ke lithethefatsi. Habohlokoa le ho feta, tlhahlobo ea histopathological ha e a ka ea senola liphetoho tse kholo tsa bethe ea microvascular bokong ba lithuto tse pepesitsoeng ke koae, e fana ka maikutlo a hore liphetho tsa monahano li ke ke tsa hlalosoa feela ka tšenyo e bakiloeng ke koae. Liphetho tsena li fana ka maikutlo a hore koae ea cocaine e sa foleng, e atolositsoeng le e atolositsoeng e hlahisa li-liphetoho tse hlakileng tse amanang le tšebeliso ea lithethefatsi liphoofolong tsa laboratori.

Keywords: cocaine, fMRI, phMRI, dopamine, bokhoba ba lithethefatsi, rat

SELELEKELA

Tšebeliso ea koae e sa foleng e hlahisa liphetoho tse sa feleng tsa neurobiological tseo ho nahanoang hore li etsa tahlehelo ea taolo ea tahi le lithethefatsi tse hlalosang ts'ehetso ea koae (Koob et al a, 1998). Lithuto tsa neuroimaging tsa batho li se li qalile ho hlakisa mofuta oa liphetoho tsena le kamano ea bona le boits'oaro bo itseng kapa matšoao. Bafuputsi ba bangata ba cocaine ba fokotsehileng le ho pepeseha ho "metabolite" ka nakoana.Strickland et al a, 1993; London et al a, 1999; Volkow et al a, 1992). Ts'ebetso e senyehileng ea libaka tse ka pele e hokahane le bofokoli bo sa khaotseng ba neuropsychological le taolo e sa lekanyetsoang ea ho sebelisa lithethefatsi tse khahlisang khafetsa (Strickland et al a, 1993; Kalivas, 2004). Lithuto tsa Positron emission tomography (PET) tse khethiloeng ka D2 dopamine (DA) ligands li bontšitse hore lithuto tse nang le tahi ea koae li bonts'a phokotso e phehellang ho D2 Ho fumaneha ha li-DA (Volkow et al a, 1993; Martinez et al a, 2004) le ho fokotsa boikarabello ba dopaminergic ho li-nucleus accumbens le likarolo tse ling tsa 'potoloho ea moputso' (Volkow et al a, 1997), e lumellanang le maikutlo a fokotsehileng a matlafatso ea tlholeho e bonoang lithutong tsena (Volkow et al a, 2007). Patlisiso ea morao-rao e bonts'a hore ts'ebetso e fetotsoeng e sebetsang ea li-circuits tsa catecholamine e ka baka tšitiso e sa sebetseng ea ts'ebetso ea cortical e bonoang ho batho ba hlekefetsang koae, e fumanoang e bonts'a mekhoa e meng ea mekhoa ea neuroadaptational e amanang le linaha tse lemalloang (Tomasi et al a, 2010; Gu et al a, 2010).

Tlhekefetso ea cocoaine e etsoa hangata ntle le litekong tsa liteko moo likhoto li koetliselitsoeng ho itaola (SA) lithethefatsi. Ka ho sebelisa mekhoa e fapaneng ea SA, baetsi ba liteko ba khonne ho hlahisa likarolo tse 'maloa tse tsebahalang tsa bokhoba ba lithethefatsi, ho kenyelletsa le ho batla lithethefatsi ho tlamang (Vanderschuren le Everitt, 2004), ts'ebeliso e sa laoloang ea lithethefatsi (Ahmed le Koob, 1998), le khothatso e eketsehileng ho SA sethethefatsi (Paterson le Markou, 2003). Litšobotsi tsena li etsa hore mefuta ena e be sesebelisoa sa teko sa ho nepahala ha sefahleho ho hlahloba liketsahalo tsa neuroplastic tse amanang le tšebeliso ea lithethefatsi tsa boithaopo (Roberts et al a, 2007). Leha ho le joalo, litlatsetso tse ikhethang tsa ts'ebeliso ea lithethefatsi tsa koae, joalo ka karabelo ea DA ea libaka tse sotlehileng tse hlokometsoeng lithutong tsa PET (Volkow et al a, 1993; Martinez et al a, 2004), ha li bonahale li etsisoa ka mokhoa o lekaneng ke mekhoa ea setso ea nako e khuts'oane ea "cocaine SA" e fumanehang khafetsa, moo ho e-na le hoo e 'khothatsang' (ke hore, ho eketseha) likarabo tsa dopaminergic hangata li bonoa (Narendran le Martinez, 2008). Ho feta moo, boholo ba mefuta ena bo ikopanya le liphetoho tse 'maloa tse amanang le thuto ea methapo e sa tsejoeng.

Thutong ea hona joale, re sebelisitse matla a tlhaho a ho bonolela (MRI) ho etsa 'mapa oa basal le oa ho etsa hore boko bo sebetse ka har'a mofuta oa li-cocaine SA. Protocol ea nako e telele (52), e atolositsoeng (12 h) protocol ea SA e ile ea sebelisoa ho bontša litšobotsi tsa tekanyo e phahameng, tlhekefetso e sa foleng ea koae ho batho (Gawin le Ellinwood, 1988; Briand et al a, 2008). Ho ile ha tsebisoa nako ea ho itlopa joala khafetsa ho theola litlamorao tse mpe tsa lithethefatsi le ho netefatsa tšusumetso e matla ea ho ikoetlisa litekanyetso tse phahameng tsa cocaine (Roberts et al a, 2007). Kamora nako ea detoxation ea matsatsi a 10, re ile ra lekanya bophahamo ba methapo e fokolang ea methapo ea methapo ea methapo (bCBV), sesupo se sa nepahalang sa ho phomola hoa ts'ebetso ea boko (Gaisler-Salomon et al a, 2009; Small et al a, 2004), le ho lekola botjha ba sisteme ea dopaminergic ka ho etsa karabo e sebetsang e hlahisitsoeng ke DA-renaser amphetamine a sebelisa protocol ea CBV e thehiloeng holima litlhare MRI (phMRI) (Gozzi et al a, 2010; Schwarz et al a, 2004). Correlation e lekola pakeng tsa likarabo tsa ho phomola (bCBV) le amphetamine-evoked (rCBV) ho entsoe ka sepheo sa ho khetholla tahlehelo ea methapo ka har'a lipotoloho tse laolang ho hloa le ho ba le ts'ebetso ea karabelo ea libaka tse itseng tsa boko. Qetellong, poso ea setopo litlhahlobo tsa histopathological li ile tsa etsoa ho lekola tlatsetso e ka bang teng ea litlamorao tse otlolohileng tsa methapo le methapo ea koae ea nako e telele ho tse fumanoeng.

LISEBELISOA LE MEKHOA

Liteko li entsoe ho latela melaoana ea Mataliana e laolang boiketlo ba batho le ts'ireletso. Li-protocol li ile tsa hlahlojoa hape ke komiti ea tikoloho ea tlhokomelo ea liphoofolo, ho latela tataiso ea Melao ea Mosebetsi oa Tlhokomelo ea Liphoofolo (NIH XXUMX-86, 23 e ntlafalitsoeng).

Cocaine SA

Lisebelisoa tsa koae SA

Likhoto tse neng li ntse li sebelisoa ka har'a cocaine SA li ile tsa lekoa likamoreng tsa basebetsi joalokaha ho hlalositsoe pele (Moretti et al a, 2010). Kamore e 'ngoe le e' ngoe ea liteko (Med Associates, St Albans, VT) e ne e kentsoe leseli la cue le behiloeng kaholimo ho lever e 'ngoe, le modumo oa molumo oa 2900-Hz. Pompo ea ho kenella e ne e hokahantsoe ka catheter e tsoang kantle ho sutu ea mokelikeli o le mong oa motlakase (Instech Laboratories, Plymouth Assembly, PA). Phumano ea data le paramethara ea tšebetso li ne li laoloa ke software ea Med-PC (Med Associates).

Ts'ebetso ea Cocaine SA

Kakaretso ea likhoto tsa banna tsa 30 tsa banna tsa Lister-Hooded (Charles-River, Margate, Kent, UK) tse boima ba 275-300 g li ne li bolokiloe ka bonngoe ka phapusing ea taolo ea mocheso le mongobo-metsi le metsi a fumanehang ad libitum. Liphoofolo e ne e le lijo tse thibetsoeng ho pholletsa le liteko ho boloka boima ba 'mele ba 300 g (± 10 g).

Kamora ho fihla ha bona, likhoto li ile tsa tumisoa bakeng sa beke ea 1 'me ka mor'a moo tsa kenngoa ka catheter mothapong oa jugular joalo ka ha ho hlalositsoe pele (Moretti et al a, 2010). Kamora nako ea phomolo ea matsatsi a 7, likhoto li ile tsa isoa kamoreng e sebetsang. Ts'ebetso ea Cocaine SA e qaliloe tlasa kemiso e sa fetoheng (FR) 1 ea matlafatso. Mochini o mong le o mong oa khatiso ho lever o sebetsang o ne o amahanngoa le ho tšeloa ha metsi ka cocaine ml ea hydrochloride (0.1 mg / ml, e lekanang le 3 μg ka infusion le 300 mg / kg ka likhoto tse boima ba 1 g) hammoho le khanya ea nako e le ngoe ea khothatso khanya le ho nyamela ha leseli la kamore ka li 300 s. Mechine ea khatiso ho lever 'e sa sebetseng' ha e na litlamorao tse reriloeng. Ts'oaetso e 'ngoe le e' ngoe ea lithethefatsi ('nehelano ea moputso') e ne e lateloa ke ho huloa ha lever ea 20-s. Likarolo tsa pele tsa 'koetliso' tse tharo li ile tsa emisoa kamora ho ts'oaroa ha 20 kapa 50 h ho tloha qalong ea seboka. Likarolong tse latelang tsa 2, nako ea phihlello ea cocaine e ekelitsoe ho 30 h (12-1800 h), tekanyetso ea yuniti e fokotsoe ho 0600 μg / infusion (0.150 ml ea 0.1 mg / ml tharollo ea cocaine, e tsamaellanang le 1.5 mg / kg ka likhoto e boima ba 0.5 g), 'me butle-butle FR e ile ea nyolohela ho 300 (mananeo a 3-4) mme qetellong ea ba 6 (linako tse setseng tsa 5).

Lintho tse lahlehetsoeng ke "catheter patency" kapa li bonahala li sa phele hantle (ke hore, li bonts'itse matšoao a tšoaetso) li tlositsoe thutong (lithuto tsa 11 ka botlalo). Linako tse pheta-phetoang tsa 48-72 h li ile tsa hlahisoa ka matsatsi a 16 (seboka 14, 72 h), 23 (sebopeho 18, 72 h), le 31 (seboka 23, 48 h) ho fokotsa kotsi ea ho ts'oaroa ke cococaine e bakoang haholo. Session 30 e ile ea lateloa ke nako e teletsana (matsatsi a 5) ea ho itlopa lijo e lateloang ke likarolo tse peli tse eketsehileng. Lits'oaetso tse joalo li ile tsa hlahisoa ka lebaka la tlhokeho ea ho lumellanya nako ea tlhahlobo ea MRI scan le SA protocol ea palo e kholo ea lithuto tse hiriloeng. Nako ea matsatsi a 10 ea ho natefeloa ha lihlahisoa kahara kharetene ea lapeng e ile ea hlahisoa pele ho teko ea monahano.

Tsamaiso ea Vehicle SA

Sehlopha sa likhoto tsa 14 se sebelisitsoe e le sehlopha sa lits'ireletso tsa basement Lithuto tsena li kentsoe ka catheter ea jugular mme ea fuoa koetliso e ts'oanang le lits'ebetso tsa SA (ho kenyeletsoa palo, nako ea lithuto tsa SA, le ho ila) joalo ka ha ho hlalositsoe kaholimo, ntle le ts'ebeliso ea koloi (saline, 0.1 ml) sebakeng sa cocaine nakong ea ts'ebetso mananeo.

Litšoantšo tsa Magnetic Resonance

Litokisetso tsa liphoofolo

Lithuto tse entsoeng ka ho qhekelloa li entsoe matsatsi a 10 kamora seboka sa ho qetela sa SA. Litokisetso tsa liphoofolo le lipallo tsa MRI li kile tsa hlalosoa ka nepo ka botlalo (Gozzi et al a, 2010; Schwarz et al a, 2004). Ka bokhutšoanyane, likhoto li ne li sa anngoe ka 3% halothane, li-tracheotomised, li bile li entsoe ka moea o mobetsang ka mochine oa phefumoloho. Meketsoana ea methapo ea botšehali le mothapo oa liphoofolo li ne li kanngoe 'me liphoofolo tsa holofala le D-tubocurarine. Kamora ho buuoa, boemo ba halothane bo ile ba beoa ho 0.8%. Mocheso oa 'mele oa lithuto tsohle o ne o bolokoa maemong a' mele 'me khatello ea mali a arterial (MABP) e ne e lula e beiloe leihlo ka ts'ebetso ea methapo ea basali.

Phumano ea setšoantšo sa MR

Lethathamo la nako la Anatomical le fMRI le fumanoe tsamaisong ea Bruker Avance 4.7 Tesla. Liphoofolo li ne li behiloe haufi le ts'ehetso e entsoeng ka tloaelo, 'me' Rat Brain 'e kobehileng quadrature tse peli-loop e amohela li-coil (Bruker, Ettlingen, Jeremane) e ne e behiloe holim'a lehata la phoofolo ebe e tsepamisoa ho ea e tšoereng. Mohlokomeli oa liphoofolo o ile a kenngwa ka har'a resonator ea linonyana tsa linonyana tse 72 mm (Bruker) e neng e sebelisetsoa phetisetso ea radiofrequency feela. Likhoele ka bobeli ke likarolo tse tloaelehileng tse fanoang ke moetsi.

AT2Bolepo ba anatomical -weighted bo ile ba fumanoa bo sebelisoa ka tatellano ea RARE (TR = 5461 ms, TEeff= 72 ms, RARE factor 8, FOV 40 mm, 256 × 256 matrix, 20 contiguous 1 mm slices) e lateloang ke tlhahlamano ea nako ea li-nako (TR)eff= 2700 ms, TEeff= 111 ms, RARE factor 32, dt = 27) e nang le tšireletso e lekanang ea sepakapaka, e fana ka boholo ba pixel bo sebetsang ba ≈1 mm3. Nako eohle ea ho fumana nako ea mananeo a MRI e ne e le 58 min (lipapatso tsa 128) bakeng sa lihlopha tsena ka bobeli.

Ka mor'a litšoantšo tse hlano tse boletsoeng, 2.67 ml / kg ea moemeli ea fapaneng Endorem (Guerbet, Roissy CdG Cedex, France) o ile a kenngoa bakeng sa ho etsa hore liphetoho tsa molumo oa FMRI li utloe ka molumo oa mali a chisi (cCBV) (Mandeville et al a, 1998; Schwarz et al a, 2003). D-amphetamine (0.5 mg / kg) e ile ea tsamaisoa kahare ho 25 min ka mor'a ho entoa ha moemeli ea fapaneng, mme data ea MRI e fumanoe ka nako ea 25 min kamora phephetso. Motsoako oa -amphetamine o ile oa khethoa ho latela tse fetileng Ka vivo lithuto (Schwarz et al a, 2004; Gozzi et al a, 2011). Tekanyo e netefatsa ts'ebetso e matla ea boko, ha e hlahise likarabo tsa 'siling' rCBV (Micheli et al a, 2007), hape e tsosa likarabo tsa nakoana tsa MABP tse lefshoang hae ka kotloloho tlasa anesthesia ea halothane (Gozzi et al a, 2007; Zaharchuk et al a, 1999).

Boitsebiso ba Lintlha

Basal CBV

Lintlha tsa letoto la li-bCBV tsa nako le nako tsa teko e 'ngoe le e' ngoe li ile tsa hlahlobisisoa ka har'a mofuta oa mohala oa mantlha (Worsley et al a, 1992). Lithuto tsa motho ka mong li ile tsa fetoloa ka mokhoa oa tlhaho hore e be le seteraeke sa litekanyetso tsa "template" ea MRISchwarz et al a, 2006a). Liphetoho tse matla tsa matsoho li ile tsa fetoloa bCBV (t) motheong o bohlale oa pixel joalo ka ha ho hlalositsoe pele (Chen et al a, 2001; Mandeville et al a, 1998). Nako ea li-bCBV e ile ea balelloa holim'a fensetere ea nako ea 4.5-min ho qala 6.8 min kamora ho hlaba ente ea moemeli. Meetso ea bCBV e bolelang lithuto ka bomong e entsoe ka ho lekanya linako tsa 10 tsa nako ka nako. Ho ile ha tsebisoa hore bothata bo fokotsoa ka melaSchwarz et al a, 2003). Lipalopalo tsa sehlopha se bohlale sa Voxel li ile tsa etsoa ho sebelisoa FSL (Smith et al a, 2004) sebelisa infotial Bayesian infusions, e nang le 0.7 mm spatial smoothing, a Z monyako> 1.6, le monyako oa bohlokoa oa sehlopha se lokisitsoeng oa p= 0.01.

karabelo ea phMRI ho D-amphetamine

Liphetoho tse matla tsa lets'oao la MRI li ile tsa fetoloa hore e be frogional CBV (rCBV) joalo ka ha ho hlalositsoe pele (Mandeville et al a, 1998) 'me ea fallisoa ho ikarabella bakeng sa ho tlosoa hoa moemeli ea fapaneng letamong la mali (Schwarz et al a, 2003). Ha e sa khopisoe, nako ea tatellano ea nako ea rCBV bakeng sa phephetso ea amphetamine e baliloe ho koahela prechallenge ea 12.5-min le 24-min postchallenge Window. Lipalopalo tse bohlale tsa Voxel li ile tsa etsoa ho sebelisoa FEAT ka sepakapaka sa 0.7 mm le ho sebelisa ts'ebetso ea mohlala (Supplementary Figure S1) ho hapa setšoantšo sa nakoana sa karabo ea amphetamine-induction rCBV (Schwarz et al a, 2006b). Ho bapisoa ha sehlopha sa maemo a holimo ho ile ha etsoa ka tšenyo ea multilevel Bayesian le ho thibeloa Z> 1.6 e nang le moeli oa bohlokoa oa sehlopha se lokisitsoeng p= 0.01. E le ho leka ka kotloloho mohopolo oa phetoho e nchafalitsoeng ea litheko ho D-amphetamine likhotong tsa koae, 3D binary mask of main subcortical area (striatum, thalamus, hippocampus, hypothalamus the striatum, ventral pallidum, BNST, and amygdala) e entsoe ho sebelisoa pokello ea digital ea maqhubu a boko ba rat (Schwarz et al a, 2006a) hape e sebelisoa ho hlophisa tatellano ea nako ea rCBV pele ho tekolo ea boemo bo holimo ea FSL. Ts'ebetso ena e eketsa matla a lipalo a tlhahlobo ka ho fokotsa palo ea lipapiso tse ngata (Huettel et al a, 2004). Ho etsa lipatlisiso mabapi le phello ea tikoloho ka mokhoa o se nang khatello ea maikutlo le ho ahlola phokotso e akaretsang karabong ea amphetamine ho pholletsa le kelello, tlhahlobo e tšoanang e ile ea phetoa liteisheneng tsa data tsa RCB tse senang mask (Supplementary Figure S5). Boholo ba thahasello (VOI) e bolela boleng ba bCBV le linako tsa phephetso ea amphetamine li nts'itsoe joalokaha ho hlalositsoe pele (Schwarz et al a, 2006a; Gozzi et al a, 2008). Phapang ea lipalo tsa bCBV e bolelang e ile ea hlahlojoa ho sebelisoa tlhahlobo e le 'ngoe ea ANOVA e lateloang ke teko ea Fisher bakeng sa lipapiso tse ngata.

Tlhahlobo ea likamano

Limmapa tsa likarabo tsa bCBV tse kopantsoeng le likarabo tsa RCBV tse hlahisitsoeng ka D-amphetamine lithutong tsohle li ile tsa baloa kahare ho sebopeho sa GLM sehlopheng sa sehlopha mabapi le bCBV libakeng tse emetseng tse sebelisang FSL (Schwarz et al a, 2007a, 2007b). Likhetho tse 'maloa tsa li-VOIs li ile tsa khethoa ho latela liphetho tsa limmapa tsa bCBV (medial prefrontal, insular, orbitofrontal, somatosensory cortex, caudate putamen, nucleus accumbens, reticular thalamus, and posteroventral thalamus). Bakeng sa VOI ka 'ngoe, sebopeho sa moralo se ne se entsoe ka "regressor" e nkang sehlopha se bolelang lets'oao la bCBV ka hara sebopeho sa anatomical le se seng se nang le vevis ea bCBV ea zero N lithuto sehlopheng se tsoang mohloling o khethiloeng oa litšupiso. The ZLitšoantšo tse ts'oaroang hantle li ne li baloa ka lipapatso tse nkang khokahano e ntle le e fosahetseng ka karabelo ea pontšo, 'me li ne li thibelloa ka Z> 1.6 le moeli oa bohlokoa oa sehlopha se lokisitsoeng p= 0.01. Lithane tsa regression regression tsa bCBV le likarabo tsa RCBV li ile tsa baloa ka ho rera bCBV le ho bolela karabelo ea rCBV ho amphetamine ho lithuto ka bomong, tsa morao li hlahisoa e le karabelo e mpe holim'a fensetere ea 20 min (4-24 min postinjection) nako.

Histopathology

Tekolo ea histopathological e entsoe ka 10 cocaine taba le li-8 tse khethiloeng ka mokhoa o khethiloeng joalo ka ha ho hlalositsoe pele (Barroso-Moguel et al a, 2002). Kamora liteko tsa MRI, likhoto li ile tsa bolokoa tlasa anesthesia e tebileng (halothane 5%), 'me 15-min aortic perfusion ea media e hlophisitsoeng (10% buffered formalin) e entsoe, e etelletsoe pele ke ts'ebetso ea 5-min ea saline. Litlolo tse senyehileng li ile tsa tlosoa 'me tsa bolokoa ka tharollo ea ho lokisa bakeng sa 24-72 h. Ho loha brain ka nako eo ho ne ho etsoa ho sebelisoa matrix ea boko (ASI Equipment) e etselitsoeng likhoto tse boima ba 200-400 g. Mehlala ea lisele e ne e kentsoe parafini e kenelletseng, e arotsoe ka mahlakore a tšesaane a 5-μm, mme e entsoe ka lesela la hematoxylin-eosin le Luxol Fast Blue (Scholtz, 1977). Libaka tse sekasekiloeng le bokong tse ileng tsa hlahlojoa e ne e le cingate le preortal cortex, caudate putamen, Corpus callosum, hippocampus (C2), cerebellum (lisele tsa purkinje), le substantia nigra. Tlhahlobo e entsoe ke litsebi tse peli tsa thuto ea liphoofolo tse sa boneng hantle.

LIPOTSO

Bothata bo sa foleng ba Cocaine SA

Lithuto tsohle li qetile lithuto tsa 33 cocaine SA ka katleho ka nako e telele ea matsatsi a 52. Lenaneo la SA le sebelisitse netefatso ea ho ja koae ka nako e telele le ho phehella.Setšoantšo sa 1). Tekanyo e tloaelehileng ea ho kopanya ea koae ea SA ka karolelano e ne e le 1138.4 ± 33.3 mg / rat. Mechini ea khatiso ea maemo a mabeli le tšebeliso ea koae e ne e bonahala e tsitsitse nakong eohle ea liteko, leha maemo a morao-rao a ne a supa a fokolang empa e le a bohlokoa (p<0.03, F = 4.62) mokhoa o lebisang ho keketseho e akaretsang ea k'hok'heine ka nako ha likarolo tsohle tse ts'oanang li bapisoa (mananeo a 4-31, FR 3-5, linako tsa ho itlopa joala 48-72 h) (Setšoantšo sa Tlatsetso S2).

Setšoantšo sa 1 

(a) Palo ea mechine ea khatiso ea lever e tlalehiloeng sehlopheng sa cocaine SA (N= 19) le taolo (saline SA, N= 14) ka har'a likarolo tsa SA. Ts'ebetso ea Cocaine SA e qaliloe tlasa tekanyetso e tsitsitseng ea (FR) 1 kemiso ea ho matlafatsa. Lithuto tse tharo tsa pele tsa thupelo ...

Basal CBV

Bakeng sa ho etsa lipatlisiso ka litlamorao tsa taolo ea koae e sa foleng ho ts'ebetso ea kelello ea basal, re ile ra lekanya bCBV ho cocaine SA le ho laola lithuto mme ra hlophisa libaka tse bonts'ang phapang e kholo lipakeng tsa lihlopha. Likhoto tse nang le cocaine ea SA li bontsitse bCBV e fokotsehile haholo libakeng tse fapaneng tsa boko ha li bapisoa le likhoto tsa taolo (Litšoantšo 2 'me Le3) .3). Phello e ne e hlaheletse kahare ho methapo ea methapo ea methapo kapa ea pele, ea cingrate, orbitofrontal cortex, septum, ventral hippocampus, tikoloho ea mantlha ea li-nucleus accumbens, hammoho le libakeng tsa raphe nuclei le reticular thalamic. Ha ho phapang pakeng tsa CBV ka botlalo lipakeng tsa lihlopha tse ileng tsa bonoa (p= 0.23, Seithuti t-etete). Ha ho khokahano e fumanoeng pakeng tsa bCBV le tšebeliso ea koae ka botlalo ho li-VOIs tsohle tse hlahlobiloeng (P> 0.16, li-VOIs kaofela).

Setšoantšo sa 2 

Ts'ebetso ea anatomical ea libaka tse bonts'ang bCBV e tlase haholo ho litoeu tse sa tsamaiseng k'holeseterole (cocaine SA; N= 20) vs lithuto tsa taolo (koloi SA; N= 14; Z> 1.6, khalemelo ea sehlopha p= 0.001) sebakeng se emeng ka nepo ...
Setšoantšo sa 3 

BBBV ho moemeli oa li-anatomical tsa 3D (VOIs, Schwarz et al a, 2006a) cocaine SA (N= 20) le lithuto tsa taolo (saline SA; N= 14). AcbC, konokono ea li-nucleus accumbens; AcbSh, khetla ea lisele tsa nyutlelie; Amy, amygdala; Cg, cingrate cortex; ...

Karabo e sebetsang ho D-Amphetamine

E le ho etsa liphuputso tse amanang le dopaminergic reacaction, cocaine SA le likhoto tsa taolo li ile tsa qholotsoa le DA-releaser amphetamine, 'me boteng ba liphetoho tse sebetsang ka boholo ba karabelo ea RCBV e hlahisitsoeng ke lithethefatsi li ile tsa hlahlojoa ka lipalo-bohlale tsa voxel. E lumellana le lithuto tse fetileng (Schwarz et al a, 2004), amphetamine e hlahisitse ts'ebetso e matla ea libaka tse subcortical le cortical ka lihlopha tsena tse peli tsa lithuto (Supplementary Figure S3). Likhoto tse pepesitsoeng nako e telele k'hok'heine e bontšitse karabelo e sebetsang ho amphetamine striatum ha e bapisoa le likhoto tsa taolo (Setšoantšo sa 4 le Setšoantšo sa Tlatsetso S3). Tšusumetso e boetse e bonahetse ho li-profiles tsa nako tsa rCBV tse sa sebetsoang (Supplementary Figure S4). Litekong tse sebelisoang ke k'hok'heine e ithekisang, bophahamo ba karabelo ea maikutlo ho amphetamine bo fumanoe bo lumellana haholo le tšebeliso ea koae ea koae (cumulative cocaine) (p= 0.03, Setšoantšo sa 4). Liphetoho tse eketsehileng tsa karabelo e sebetsang ea amphetamine li ile tsa bonoa ho sensory-motor le orbitofrontal cortex (Supplementary Figure S3 le S5).

Setšoantšo sa 4 

Pono ea Orthogonal (a: ho potoloha, b: coronal, c: sagittal) ea likaroloana tsa kelello tsa subcortical tse bonts'ang karabelo ea RCBV e fumanoang ho D-amphetamine ho likhoto tse sa tsamaiseng k'hok'heine (cocaine SA; N= 20) vs lithuto tsa taolo (koloi SA; N= 14; ...

Tsamaiso ea amphetamine e hlahisitse keketseho ea nakoana ho MABP (Supplementary Figure S6). Phello e ne e sa tsamaellane ka nakoana le karabelo e sebetsang, 'me e ne e le hantle ka har'a phallo ea mali e kenang kahare ho eona moo likarabo tsa vasopress li busellelitsoeng hantle lapeng ntle le ho hlahisa liphetoho tsa bohlokoa tsa RCBV (Gozzi et al a, 2007; Zaharchuk et al a, 1999). Likhase tsa mali tsa arterial (leqaCO2 leqaO2) li ne li lekantsoe pele le kamora lethathamo la nako la fMRI (Supplementary Table S1). Ha ho phapang ea lipalo-palo ea bohlokoa ho bolela pele kapa ho fumana thepa ka mora paCO2 boleng bo lipakeng tsa lihlopha bo fumanoe (p> 0.1, lihlopha tsohle; tsela e le 'ngoe ANOVA).

Kamano lipakeng tsa Ketsahalo ea Basal le e Ts'osang

Boitekong ba ho theha khokahano lipakeng tsa tšebetso ea basal le e tsoetseng pele le ho etsa lipatlisiso taolong ea taolo ea linaha tsena tse peli, re lekantse khokahano lipakeng tsa bCBV le karabelo e hlahisitsoeng ke amphetamine taolong le liphoofolong tse rekisoang ke koae. Ha ho khokahano lipakeng tsa bCBV le likarabo tsa amphetamine tse tlisoang ke RCBV tse fumanoeng sehlopheng sefe kapa sefe ho tse ling tsa libaka tse hlahlojoang, ntle le li-remicular tsa morao-rao tsa morao-rao tse senolang, lithutong tsa taolo, likamano tse sa lumellaneng le amphetamine-indedu RCBV ho Fronto Libaka tse ikhethileng (Litekanyetso tsa tlatsetso S7 le S8). Ha ho khokahano e joalo e neng e le teng sehlopheng sa cocaine SA (Supplementary Figure S8).

Histopathology

Tlhahlobo ea histopathological ea taba e tšoeu le e putsoa, ​​likarolo tsa glial le mahareng, hammoho le likarolo tse ngata tsa macro- le methapo, ependymal, le meningeal ha lia ka tsa totobatsa liso leha e le life tsa methapo ea methapo, ea methapo kapa e menyenyane. Ka ho khetheha, ha ho na matšoao a phallo ea methapo ea methapo kapa ea atrophy, ho fetoha ha fiber, necrosis le edema ea methapo ho ile ha bonoa libakeng tsohle tsa kelello tse sa hlahlojoang, leha e le liphetoho lipakeng tsa bethe ea microvascular le capillary (ke hore, basal membrane dilation kapa rupture, hemorrhage, endothelial thickening kapa wall fibrosis, thrombi kapa occlusions, le necrosis kapa vacuolution of endothelial cell).

TŠOHLOA

Litokomane tsa thuto tsa hona joale tse sa feleng, tse fumanehang tsa koae ka har'a Rot, li hlahisa liphetoho tse tšoanang le tse fumanoeng litekong tsa batho ba lemaletseng koae. Ka ho khetheha, re hlokometse hore bCBV e fokotsehile haholo, letšoao la ts'ebetso ea ho phomola bokong, libakeng tse nang le tlatsetso ea mantlha mesebetsing e hlokolosi ea taolo le taolo ea thibelo (libaka tsa fronto-cortical), ho lakatsa le tebello (libaka tsa fronto-hippocampal), le moputso (mesolimbic libaka). Ntle le moo, cocaine SA e ne e amana le ho fokotsoa ha maikutlo a khutlang ho dopaminergic, le boteng ba liphetoho tse sebetsang lipakeng tsa inhibitory interplay lipakeng tsa reticular thalamus le ts'ebetso ea libaka tsa fronto-cortical. Liphetho tsa rona li fana ka bopaki bo khahlisang ba liphetoho tse ngata tšebetsong ts'ebetso ea boko ka mor'a ho ja lijo tse sa tsitsang le tse ithaopetsang tsa koae tse sebetsang hantle joaloka tšebeliso ea lithethefatsi tse kenelletseng liphoofolong tsa laboratori.

Tlhekefetso e sa feleng ea cocaine hangata e etsoa maemong a boitšoaro moo litoeba li koetliselitsoeng ho itlhahisa ka boithaopo. Mona, re sebelisitse protocol ea nako e telele, e atolositsoeng ea cocaine SA nako e telele ea ho itlopa lijo (Parsons et al a, 1995; Wilson et al a, 1994; Wilson le Kish, 1996) ho etsisa litšobotsi tsa tekanyetso e phahameng, tlhekefetso e sa foleng ea koae ho batho. Litaba tsa nako e telele tsa SA li tlalehiloe hore li hlahisa likarolo tsa bohlokoa tsa ho lemalla koae ka ho kenyeletsa ts'ebeliso e mpe ea lithethefatsi leha ho na le litsietsi tsa tikoloho (Vanderschuren le Everitt, 2004), le tebello e phahameng ea ho khutlela bothateng ba ho batla lithethefatsi (Deroche-Gamonet et al a, 2004). Protocol e sa foleng e sebelisitsoeng (e koahelang ≈10% ea motho ea holileng ea pheleu ea lenaka, Sharp le La Regina, 1998) e lumella ho etsisa baahi ba bakuli ba nang le nalane ea bohlokoa (> likhoeli tse 6) tsa bokhoba ba k'hok'heine joalo ka ba tloaetseng ho ingolisa lithutong tsa kelello tsa batho, ka hona ba eketsa bohlokoa ba phetolelo ea liphihlelo tsa rona. Ntle le moo, ts'ebeliso ea phihlello e atolositsoeng ea k'hok'heine (ke hore, ⩾6 h) e tsejoa ka ho khetholla likarolo tse ikhethang tsa boits'oaro ba ts'ebeliso ea lithethefatsi, joalo ka liphetoho tse sa khaotseng tsa ts'ebetso ea kelello (Briand et al a, 2008; George et al a, 2007), khothatso e eketsehileng ea koae (Paterson le Markou, 2003), le ho nyoloha hoa tšebeliso ea lithethefatsi (Ahmed le Koob, 1998). Nako le nako khafetsa ea ho itlopa joala ka mokhoa o qobelloang ho ile ha hlahisoa ho fokotsa litlamorao tse mpe tsa lithethefatsi le ho netefatsa tšusumetso e tsitsitseng ea ho itaola litekanyetso tse phahameng tsa koae (Roberts et al a, 2007). Leha tšebeliso ea koae ka botlalo e fumanehang ka protocol ea hona joale e phahame ho feta e bonoang ka lipapatso tsa phihlello ea nako e khuts'oane, boleng bo fumanoeng bo hole haholo le moeli oa chefo e mpe (Mantsch et al a, 2004; Wee et al a, 2007), e hlalosang ho haella ha lefu le bolaeang le bonoang thutong ena.

Ha ho bapisoa le protocol ea moeli e se nang meeli, moo ts'ebeliso ea lithethefatsi e bonts'a palo e phahameng le e tlase ea infusions ka matsatsi a alternating (Wilson et al a, 1994), protocol e atolositsoeng ea ho fihlella e sebelisitsoeng mona e netefalitse SA ea litekanyetso tse phahameng tsa cocaine. Ho fapana le se tlalehiloeng ke lihlopha tse ling (Ahmed le Koob, 1998; Ferrario et al a, 2005; Wee et al a, 2007), ha rea ​​ka ra hlokomela bopaki bo sa reroang ba keketseho ea litekanyetso, leha mokhoa o lebisang kekeng ea keketseho ea koae ka makhetlo a latellanang o ne o bonahala (Supplementary Figure S2).

Moeli o mong oa mofuta o sebelisitsoeng ke hore o ne o sa kenyeletse litekanyo tsa boits'oaro ba ts'ebeliso ea lithethefatsi leha ho na le litlamorao (mohlala, 'ho hana kotlo' Deroche-Gamonet et al a, 2004), tšobotsi eo motho a e nkang e le mokhoa oa bohlokoa oa ho khetholla bokhoba ho batho (Mokhatlo oa Mahlale oa Amerika, 2008). Hobane sebopeho sena se teng ka har'a ca. 20% ea likhoto tse pepesitsoeng koae (cocaine) (Deroche-Gamonet et al a, 2004; Ahmed, 2010), liphetoho tse nahanoang tse etselitsoeng mosebetsi oa hona joale li kanna tsa kenyelletsa monehelo o tsoang mananeng a lithuto tse bonts'ang ts'ebetso ena. Leha ho le joalo, hore na tšobotsi ena e khetholloa ke liphetoho tse sebetsang tse arohaneng le tse totobisitsoeng thutong ena li ntse li tlameha ho tsejoa.

Nako ea ho hlapela ea letsatsi la 10 e ile ea hlahisoa pele ho lipatlisiso tsa ho nahana ho laola litla-morao tse matla tsa koae le ho fokotsa tšitiso e ka bang teng lipontšong tsa khatello ea methapo e matla methating ea ts'ebetso ea boko. Boholo ba liphetoho tse amanang le neurochemical le boits'oaro tse ka amanang le ho tlosoa ka mokhoa o tsitsitseng li na le tšimoloho e potlakileng, tlhoro lipakeng tsa 6 le 72 h kamora ho felisoa ha phihlello ea lithethefatsi, mme hangata li khaotsa matsatsing a 2-7 ho tloha sebokeng sa ho qetela sa cocaine (Baumann le Rothman, 1998; Harris le Aston-Jones, 1993; Malin et al a, 2000; Mutschler le Miczek, 1998; Markou le Koob, 1992). Ka hona ha ho na monyetla oa hore lintlha tse fumanoeng li na le litlatsetso tse kholo ho tsoa ho ts'ebetso ea nakoana ea neurobiological e amanang le ho ila koae ka matla. Ka lehlakoreng le leng, liphetoho tse sebetsang tsa ts'ebetso li lebelletsoe ho kenyelletsa monehelo o tsoang lits'ebetsong tse telele tsa neuroadaptational (ke hore, ho kenyelletsa takatso ea koae) e bonts'itsoeng ho aha ka mor'a ho khaotsa koae (Lu et al a, 2004), mme tseo ke tsa bohlokoa ba phetolelo kaha li ka amana le tekano ea ho khutla.

Mehato ea MRI ea bCBV e lumella 'mapa oa liqeto tse phahameng tsa ts'ebetso ea ho phomola ea bokong e lumellanang hantle le metabolism ea matla a potoloho le phallo ea mali a mokelikeli (Gaisler-Salomon et al a, 2009; Pholo et al a, 2001; Gonzalez et al a, 1995). Lintlha tsa rona li bonts'a boteng ba bCBV e fokotsehileng ka har'a gyrus, cortex ea pele, orbitofrontal cortex, hammoho le libakeng tsa striatal le hippocampal tsa lithuto tsa cocaine SA. Phello ea pele-pele e tumellanong e ntle haholo le lipatlisiso tsa bongaka tsa ho lemalla koae, moo mesebetsi e fokolisitsoeng ea pele le e amanang le bophelo e hlokometsoeng kamehla (Strickland et al a, 1993; Tumeh et al a, 1990; London et al a, 1999; Volkow et al a, 1992, 1988) mme ea fumanoa e hokahana le ho senyeha hoa kelello, ho qobelloa, le tahlehelo ea taolo e thibelang likokoana-hloko tse amanang le lithethefatsi e ka lebisang ho oeleng hape (Goldstein et al a, 2010; Kalivas et al a, 2005; Kalivas, 2004; Hong et al a, 2010; Strickland et al a, 1993). Habohlokoa, bofokoli ba kelello bo hlokometsoe ho likhoto tse lumelletsoeng ho fihlella (empa eseng moeli) phihlello ea koae (Briand et al a, 2008; George et al a, 2007), ketsahalo e neng e kenyelletsa mohopolo oa ho sebetsa le mesebetsi e hlokolosi (mesebetsi e 'meli e itšetlehileng ka cortex) hammoho le mehato ea ho lemoha ntho (mosebetsi o itšetlehileng ka hippocampus). Ho kenya letsoho ha lits'ebetso tsa hippocampal hape ho tsamaisana le karolo e phethoang ke sebopeho sena sa boko maemong a memeng le mohopolong, mesebetsi e 'meli e fetotsoeng ke ts'ebeliso ea koae' me ho lumeloang hore e bapala karolo ea litakatso tsa cue-elicited (e hlahlojoe ke Koob le Volkow, 2010). Ka mokhoa o ts'oanang, bCBV e fokotsehileng bokong ba li-nucleus e ne e se ntho e sa lebelloang, ka lebaka la khokahano e tsitsitseng pakeng tsa ts'ebetso ea fronto-cortical le ventrostriatal DA cell e thunya le ho lokolla (Kalivas et al a, 2005; Batho et al a, 2007). Ho latela sena, lithuto tsa morao-rao tsa PET tsa morao-rao li bonts'itse maemo a tlase a DA ea semmuso ho batho ba lemaletseng koae ka koae.Martinez et al a, 2009) 'me lipatlisiso tsa morao-rao li senotse ts'ebeliso ea tsoekere ea glucose libakeng tse nang le ts'ebeliso e sa foleng ea koae, e leng tšobotsi e ileng ea phatlalatsoa haholo ka ho pepesetsoa hoa koae (Porrino et al a, 2007).

Phokotso ea bCBV ea Focal e ile ea boela ea bonoa ho reticular thalamic le raphe nuclei. Tse fumanoeng tsa pele li lumellana le lithuto tsa batho tse amang maikutlo tse bonts'a phetoho ea methapo ea methapo ea kutlo ea "GABAergic" thalamus ea batho ba hlekefetsang koae.Volkow et al a, 1998) le bopaki ba morao-rao ba electrophysiological ba boemo ba ho ipha matla ba libaka tsa reticular thalamic kamora ts'ebetso ea ho itlopa joala ea koae.Urban et al a, 2009). Ho khahlisang ke hore, ha serotonin e fana ka ts'ebetso e tobileng ho li-neurons tsa GABAergic ho reticular thalamus (McCormick le Wang, 1991), ts'ebetso e fokotsehileng ea li-nuclei tsena le tse bonoang libakeng tsa raphe li ka tsamaellana ka tsela e sebetsang le karolo ea potoloho e le 'ngoe e nang le sekoli.

Ha ho khokahano pakeng tsa tšebeliso ea koae ka botlalo le bCBV ha e fumanoe ho efe kapa efe ea li-VOIs tse hlahlobiloeng. Ho haella ha khokahano ho ka bonts'a tšoaetso e fapaneng ea motho ka mong litlamorao tsa moriana, kapa ho ka amana le palo e phahameng ea ts'ebeliso ea koae e ka fetisang palo e hlokahalang ho hlahisa liphetoho tse kholo tsa bCBV.

Boitekong ba ho tsebahatsa tokiso ea fMRI ea karabelo e theohileng ea dopaminergic e bonoang lithutong tsa PET tsa motho (Volkow et al a, 1990, 1993; Martinez et al a, 2004) hape re fumane karabo ea tšebetso e hlahisitsoeng ke DA-renaser amphetamine re sebelisa protocol ea phMRI (Schwarz et al a, 2004; Bifone le Gozzi, 2010). Lithuto tse 'maloa tsa phMRI li fane ka bopaki bo matla ba hore karabelo ea hemodynamic e hlahisoang ke amphetamine e bonts'a litlamorao tsa dopaminergic (e hlahlobuoe ka har'a Knutson le Gibbs, 2007). Mohlala, amphetamine e bonts'itsoe ho fana ka keketseho ea BOLD kapa rCBV libakeng tse nang le li-ventrostriatal tse nang le DA tse tsamaellanang hantle le li-concentaptic tsa DA (Dixon et al a, 2005; Ren et al a, 2009; Khetho et al a, 2006; Schwarz et al a, 2007b; Pele et al a, 2007). Ntle le moo, likarabo tsa RCBV tse hlahisang amphetamine li felisoa libakeng tse senyehileng tsa DA (Chen et al a, 1997, 1999), phello e ka khutlisoang kamora ho fetisoa ha sele ho fetal kapa stem (Bjorklund et al a, 2002; Chen et al a, 1999). Kahoo, kakaretso ea lintlha tsena e bonts'a likarabo tsa amphetamine tse susumetsang tsa RCBV li ka sebelisoa ka mokhoa o nepahetseng e le lets'oao la li-neurotransmission tsa DA. Ka har'a sebopeho sena, boteng ba karabelo ea RCBV e bonts'itsoeng ho amphetamine sehlopheng sa cocaine SA se supa karabelo e fokotsehileng ea ts'ebetso ea dopaminergic ea ts'ebetso e ts'oanang ho se bonoang lithutong tsa PET bathong (Narendran le Martinez, 2008). Tlhahiso ena e fana ka lekhetlo la pele khokahano e hlakileng ea neuroimaging ea e 'ngoe ea lipontšo tse hlakileng tsa kliniki ea bokhoba ba k'hok'heine, eo ho lumeloang hore e bapala karolo ea bohlokoa ho' hypohedonia 'le boithabiso bo tlalehiloeng ke batho ba lemaletseng lithethefatsi nakong ea ho tlohela nako e telele (Volkow et al a, 1997). Sephetho sena se ngola ngollano e ka bang ea bohlokoa lipakeng tsa liphetoho tsa bongaka le tsa kalafo tse bakoang ke k'hok'heine tsamaisong ea DA, e leng karolo e sa bonahaleng e hlophisitsoe ka nepo ke litloaelo tsa setso tsa ts'oaetso ea cocaine, moo ho 'matlafalitsoeng' (ke hore, ho eketsehang) likarabo tsa dopaminergic hangata li bonoa. (e hlahlojoe ke Narendran le Martinez, 2008). Joalo ka karabelo tse tšoanang tsa bohato ba leholimo ha li a ka tsa bonoa lithutong tse nang le methapo e sebelisang nako e khuts'oane ea matsatsi a 5)Febo et al a, 2005; Reese et al a, 2004; le Gozzi, sephetho se sa phatlalatsoang, datha tsa rona li fana ka maikutlo a hore, hore tšobotsi ena e ka fetoloa ka litoeba, ho ka hlokahala nako e telele le ho atolosoa litekanyetso tse phahameng tsa cocaine. Habohlokoa, ho ne ho sa bonoe liso tsa microscopic tse ntle ka har'a methapo ea methapo ea methapo le methapo ea kutlo. Sephetho sena ke sa bohlokoa, kaha se lumella ho fana ka tlhahiso e ka bang teng ea ts'ebetso e sa tloaelehang ea ts'ebeliso ea methapo ea methapo methapong ea hemodynamic ea ts'ebetso ea boko e entsoeng (ke hore, bCBV le rCBV).

Tlhahlobo ea likamano lipakeng tsa likarabo tsa ho phomola le amphetamine-evoked (rCBV) e senole kamano e sa lumellaneng pakeng tsa bCBV libakeng tse khutsitseng tsa thalamic le amphetamine-induction activation ea pele lithutong tsa taolo, empa eseng sehlopheng sa cocaine. Boithuto ba nakong e fetileng bo bontšitse hore ho thibela mosebetsi oa reticular thalamic ho ka matlafatsa fronto-cortical dopaminergic neurotransmission (Jones et al a, 1988), ho fumana ho tsamaellana le khokahano e sebetsang ea libaka tsena (Paxinos, 2008) le segalo se phahameng sa GABAergic ea reticular thalamic nucleus (Paxinos, 2008). Joalo ka ha ho nahanoa ka ntho e tlang pele ho "netus" e khutlelang morao e bapala potoloho e ikhethileng bakeng sa mekhoa ea ho tsotella (Zikopoulos le Barbas, 2006), re kholoa hore tahlehelo ea khokahano pakeng tsa tšebetso ea basal le e tsoakiloeng e bonoang sehlopheng sa cocaine SA e ka amana le khaello e elang hloko ea likhoto tse lumelletsoeng ho fihlella koae (Briand et al a, 2008; George et al a, 2007). Karolo e tlatsetsang bakeng sa khatello ea methapo ea khatello ea kelello ea koae e ts'ehetsoa ke lithuto tsa morao-rao tse bontšang ho hokahana ha thalamo-cortical ho ba hlekefetsang koae tlasa maemo a phomolo (Gu et al a, 2010) le ha o etsa mosebetsi oa ho lemoha (Tomasi et al a, 2007). Leha ho le joalo, ha litekanyo tsa khokahano e sa bonts'e mokhatlo oa ho qhekella, lipatlisiso tse ling li tlamehile ho hlakisa mofuta oa sona.

Ka kakaretso, re fana ka bopaki ba tšebetso e fetotseng ea boko ho likhoto tse bileng teng nako e telele ho tse ling tsa cocaine SA. E tsamaellana le liphumano tse fumanoeng tsa kliniki, liphoofolo tse pepesitsoeng ke koae li senotse ts'ebetso ea ts'ebetso ea kelello libakeng tse nang le phepo le litla-morao, le karabelo e fumanehang libakeng tse qholotsoang ke phephetso le tlhaselo ea DA-releaser amphetamine, e amanang haholo le tšebeliso ea koae ka kakaretso. Ho lumellana ha liphumano tsena le mehato e khahlisang ho bakuli ba lemaletseng koae ho ts'ehetsa ts'ebeliso ea lipapatso tsa nako e telele le tse atolositsoeng tsa SA ho ratoa le lipatlisiso tsa litumelo tsa motsoako oa koae.

lumela hore baa fokola

Re leboha Valerio Crestan le Giuliano Turrini ka tšehetso ea bona e ntle ea theknoloji ho mehato ea phMRI, le Pamela Rodegher oa Histolab, Verona, Italy, ka litokisetso tsa nalane.

Notes

Bangoli bohle ke basebetsi ba GlaxoSmithKline. Bangoli ba phatlalatsa hore, ntle le chelete e fumanoeng e tsoang ho mohiri oa bona oa mantlha, ha ho tšehetso ea lichelete kapa puseletso e seng e fumanoe ho motho e mong le e mong kapa mokgatlo lilemong tse fetileng tsa 3 bakeng sa lipatlisiso kapa tšebeletso ea litsebi 'me ha ho na litaba tsa lichelete tse ka nkuoang e le ho theha khohlano e ka bang teng khoebong.

Mongolo o botlaaseng ba leqephe

Tlhahisoleseling ea tlatsetso e tsamaea le pampiri ho websaeteng ea Neuropsychopharmacology (http://www.nature.com/npp)

Boitsebiso bo Eketsehileng

Setšoantšo sa tlatsetso S1

Setšoantšo sa tlatsetso S2

Setšoantšo sa tlatsetso S3

Setšoantšo sa tlatsetso S4

Setšoantšo sa tlatsetso S5

Setšoantšo sa tlatsetso S6

Setšoantšo sa tlatsetso S7

Setšoantšo sa tlatsetso S8

Litlhaloso tsa Tlatsetso ea Tlatsetso

Letlapa le tlatsetsang S1

References

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