Tsela e ncha ea ho bapala papali ea chelete-e tšoanang le boitšoaro boemong ba litoeba tsa laboratori: ho sebelisa mochine oa ho itšireletsa ka boeena e le motlakase o matla (2014)

Stephanie E. Tedford^1,2*, Nathan A. Holtz^1,2, Amanda L. Persons^{1,2 †} 'me T. Celeste Napier^1,2,3

• ¹Lefapha la Pharmacology, Setsi sa Boitšoaro bo Tiileng le Bokhopo, Setsi sa Bongaka sa Rush University, Chicago, IL, USA
• ²Lefapha la Pharmacology, Setsi sa Bongaka sa Rush University, Chicago, IL, USA
• ³Lefapha la Psychiatry, Setsi sa Bongaka sa Rush University, Chicago, IL, USA

Ho becha ka tsela ea tlhaho ke pontšo e 'ngoe ea mathata a taolo a susumetsang. Lisosa tsa likokoana-hloko tsa mathata ana li lula li le thata ebile kalafo e se ea bohlokoa. Mefuta ea liphoofolo ea mathata a ho laola litšusumetso ke sesebelisoa sa bohlokoa sa ho etsa lipatlisiso bakeng sa ho utloisisa boemo bona le bakeng sa nts'etsopele ea meriana. Ho nahana ka mekhoa e joalo e rarahaneng hoa nyahamisa, empa ka ho e hloa, bo-rasaense ba boetse ba phetela liphoofolo likarolo tse mahlonoko tsa papali ea chelete. Karolo e ngoe ea papali ea chelete ke ho etsa liqeto tsa theko / melemo eo ho eona motho a lekanyang litšenyehelo tse lebelletsoeng le melemo e lebelletsoeng ea ketso e itseng. Kotsi / moputso, ho nka qeto le ho lieha ho etsa liqeto ho latela boikitlaetso kaofela li emela likhetho tsa theko / melemo. Litšobotsi tsena li ithutoa bathong mme li fetoletsoe ho protocol ea liphoofolo ho lekola mekhoa ea ho etsa liqeto. Ka setso, se matlafatso se sebelisoang lithutong tsa liphoofolo ke lijo. Mona, re hlalosa kamoo ho itšunya-tšunya ho maiketsetso ho ka sebelisetsoang litšenyehelo / ho etsa liqeto tsa ho etsa liqeto le ho lekola lithuto tsa rona tsa morao-rao tse bonts'ang mekhoa ea phekolo ea meriana e fetotsang boits'oaro bona literekeng tsa laboratori. Re fana ka maikutlo a hore mefuta ena e ka ba le bohlokoa ba ho hlahloba lisebelisoa tse ncha bakeng sa bokhoni ba ho khothaletsa le ho thibela likarolo tsa boitšoaro ba papali ea chelete.

Selelekela

Bothata kapa papali ea chelete e mpe, ho kenyelletsa boemo bo fetelletseng bo bitsoang ts'ebeliso ea ho becha ea pathological, e tšoauoa ka boits'oaro boo hangata bo phehellang nako e telele. Bothata ba papali ea chelete bo ka ba le phello e mpe boiketlong ba motho, boitsebisong le licheleteng. Lilemong tse mashome a mabeli tse fetileng, menyetla ea papali ea chelete e eketsehile ka phetoho ea melao le kenyelletso ea libaka tse ncha (mohlala, papali ea chelete ea inthanete). Ka hona, keketseho ea bothata ba ho becha e ntse e eketseha. Ha ho na kalafo e lumelletsoeng ke FDA bakeng sa bokuli bona, ka hona, ho bohlokoa ho utloisisa mekhoa ena hantle ho ntlafatsa mekhoa ea phekolo e sebetsang.

Bothata ba papali ea chelete ke ntho e rarahaneng, e kenyelletsang ho etsa liqeto tse sa potlakang (Alessi le Petry, 2003; Dixon et al., 2003; Holt et al., 2003; Kraplin et al., 2014) e hlahisoang ke litlhahlobo tse mpe tsa theko / melemo. Tlhahlobo ea bongaka ea ho nka liqeto, e atisang ho sebelisa lipatlisiso le lisebelisoa tse sebetsang tse sebelisang khomphutha, e bile karolo ea bohlokoa ho tsebeng liqeto tse bohlale tsa ho etsa liqeto ho li-pathologies tse fapaneng ho kenyeletsoa le ba bechang ba li-pathological (Ledgerwood et al., 2009; Madden et al., 2009; Mikalczuk et al., 2011; Petry, 2011; Miedl et al., 2012). Litlhahlobo tsa kliniking hangata li etsoa ho ipapisitsoe le lintho tse tharo tse fapaneng, ho feta ka bongata, likarolo tsa ho etsa liqeto / ho etsa melemo, ho kenyelletsa tse latelang: (i) palo ea menyetla ea ho fumana moputso (kotsi / ho etsa liqeto), (ii) ho lieha ho fihlella pele ho tlisoa ha moputso (ho etsa liqeto tse liehang), le (iii) palo ea boiteko bo hlokahalang ho fumana moputso (ho etsa liqeto tse thehiloeng boitekong). Mesebetsi e mengata e se e hlahisitsoe ho lekola likarolo tsena tsa bohlokoa tsa ho etsa liqeto tse fokolang ho utloisisa haholoanyane mekhoa e amanang le papali ea chelete. Mesebetsing ena, taba e khetha pakeng tsa moputso o monyane le o moholo, e 'ngoe le e' ngoe e amanang le maemo a itseng a karabelo. Ho etsa liqeto tsa kotsi / moputso (ke ho re, theolelo ea litheko), lithuto li khetha pakeng tsa moputso o monyane o hlahisoang nako le nako maemong a phahameng (mohlala, monyetla oa 100% oa ho fumana $ 10) le moputso o moholo o hlahisoang ka menyetla e fapaneng (mohlala, 10-80 % monyetla oa ho amohela $ 100). Lithutong tsa bongaka le tsa pele ho nako, ho ba sieo hoa moputso o lebelletsoeng ke ketsahalo e khathollang e emisang likarabo tse lumellanang tsa 'mele (Douglas le Parry, 1994; Papini le Dudley, 1997). Khetho ea khetho e kholo, e "kotsi" ho feta e nyane, khetho e itseng e nkuoa e bonts'a liqeto tse fokolang tsa ho etsa qeto / ho etsa moputso, mme ho tlalehiloe mabaka a 'maloa a batho a bonts'ang ts'usumetso e ntlafalitsoeng (Reynolds et al., 2004; Rasmussen et al., 2010; Dai et al., 2013). Ha ho etsoa liqeto tse thehiloeng moahong (ke ho re, theolelo ea ho lieha, khetho e potlakileng), moputso o monyane o hlahisoa kamora hore khetho e khethoe, athe moputso o moholo o fanoa kamora ho lieha ho fapaneng, (mohlala, $ 10 joale kapa $ 100 ka libeke tsa 2). Batho ka bomong ba bonts'ang boikemisetso bo phahameng ba bonts'a khetho ea meputso e fumanehang hang (leha e le nyane), meputso e liehang (leha e le kholo) leha khetho ea morao e ka ba molemo ho motho ka mong (Crean et al., 2000; Reynolds et al., 2004; Bickel et al., 2012). Ha u etsa liqeto tse thehiloeng boitekong, sehlooho se khetha pakeng tsa moputso o nyane o fuoang ho latela boiteko bo fokolang, kapa moputso o moholo o hlahisoang kamora hore ho sebelisoe matla a maholo. Mosebetsing ona, ho khethoa ka bomong bakeng sa boikitlaetso bo matla / khetho e kholo ea meputso le "ntlha" eo motho ka mong a fetohelang ka tlase ho boiteko bo tlase / khetho e nyane ea moputso. Boithuto ba ho nka liqeto tse thehiloeng boitekong ho bathati ba batho ha li sa lokela ho etsoa, ​​empa e tla ba tsa thahasello e kholo ho lekola ts'ebetso ea kelello ho bongata bona.

Liprotheine tse nkang liqeto tse sebelisitsoeng litekong tsa bongaka li ka fetoloa ho ithuta ho nka liqeto litekatsing tsa laboratori, 'me mehlala ena e bohlokoa bakeng sa ho hlahloba likarolo tsa boits'oaro ba methapo ea kutlo le methapo ea kutlo. Likhoto, ho etsa liqeto ho ka hlahlojoa ka ho beha phoofolo ka phapusing ea maemo a sebetsang, le ho lumella phoofolo hore e khethe pakeng tsa lows tse peli (kapa tse peli tse hulang nko) tse fumanehang ka nako e le 'ngoe. Mokhoa o hlophisitsoeng oa moputso bakeng sa ho matlafatsoa ho nepahetseng mesebetsing ena ea litentara ke lijo (Stopper le Floresco, 2011; Eubig et al., 2014). Re tšohla mona mokhoa o mocha o sebelisoang laboratoring ea rona o sebelisang ho susumetsa ka mokhoa o tobileng oa ts'usumetso ea meputso ea boko (ho intlafatsa ho intša; ICSS) ho lekola litšenyehelo / ho etsa liqeto ka litheko le tlatsetso ea li-neurotransmitters tsa monoaminergic ha ho etsoa liqeto (Rokosik le Napier, 2011, 2012; Tedford et al., 2012; Batho et al., 2013).

Ho Iphetisa ka Matla

Matlafatso ea ts'ebetso ke ts'usumetso, eo ha e etsoa ka ts'ebetso e itseng, e eketsang menyetla ea ho pheta ketso eo. Intracranial self-stimulation (ICSS) ke ts'ebetso eo ho eona liphoofolo li ithaopisang motlakase libakeng tsa boko tse tsejoang hore li kenya letsoho tšebetsong e ntle. ICSS e ile ea ithutoa ka lekhetlo la pele ho li-1950 ha James Olds le Peter Milner (Ba baholo le Milner, 1954) ba entse qeto ea hore likhoto li khutlele sebakeng ka lebokoseng moo li fumanang tšusumetso ea motlakase libakeng tse amanang le moputso bokong. Ba lumelletse likhoto hore li sebetse bakeng sa tšusumetso ea kelello ea motlakase (EBS) ka ho arabela manipulandum (mohlala, ho tobetsa lever, ho phethola lebili) (Ba baholo le Milner, 1954). Ho sibolloa hoa mokhoa ona ho kentse letsoho ho etsa 'mapa oa meputso kelellong eohle, mme ha ho ntse ho na le likarolo tse ngata tsa boko tse ka sebelisoang ho ts'ehetsa ICSS (Ba baholo le Milner, 1954; Bohlale le Bozarth, 1981; Bohlale, 1996), ho tlalehiloe hantle hore ho ts'oaroa ha moriana oa mali oa moriana (MFB) ho khothaletsa tlhahiso e matla le e tšepahalang ea boitšoaro (Corbett le Wise, 1980; Pirch et al., 1981; McCown et al., 1986; Tehovnik le Sommer, 1997). Litefiso tsa hona joale tsa tšusumetso li ka fetoloa ho ama boleng bo matlafatsang ba EBS mme ka hona e fetole boitšoaro ba ICSS. Litekanyetso tsena li kenyelletsa botebo (ke hore, amperes) ea motlakase oa hona joale le maqhubu a hona joale (ke hore, hertz). Ho phahamisoa maemong ka bobeli ka tloaelo ho fella ka ho eketseha ha li-neuron tse loketseng moputso, ekaba ka ho eketsa palo ea li-neurons tse susumetsoang ke ts'usumetso (amperes) (Keesey, 1962; Wise et al., 1992) kapa ka ho eketsa khafetsa moo palo e lekantsoeng ea methapo ea mollo (hertz) (Bohlale le Rompre, 1989; Bohlale, 2005). Ts'ebetso ea matla a hona joale a fetolang palo ea li-neuron tse sebetsitsoeng, ke hore, matla a maholo a hona joale a amang palo ea li-neuron ho feta maqhubu a manyane. Kahoo, ha paramente ena e lula e bolokiloe khafetsa, palo ea baahi ba methapo ea kutlo e thabisoang ke EBS e batla e ts'oana ho sa tsotellanoe ka maqhubu a hona joale. Khetla e fapaneng ea khetho ea li-protocol tsena ke maqhubu a hona joale, kaha khetho ena e re lumella ho theola sekhahla sa ho thunya sa sehlopha se le seng sa li-neuron se nang le litlamorao tse nyane ka nako kapa sebaka sa ho kopanya. Ka ho theola maemo ana a EBS, re thehile meetso e meholo ea liqeto tsa ho etsa liqeto / melemo tse sebelisang ICSS (Rokosik le Napier, 2011, 2012; Tedford et al., 2012; Batho et al., 2013). Sesebelisoa sena se emetse ho tloha ka mokhoa o matla o khothalletsang (joalo ka lijo) mesebetsing e lekolang ho nka liqeto litoeba. ICSS e ka fana ka menyetla e 'maloa ea ho leka ho feta mekhoa ea moetlo oa setso. Ho tataisa karabo ea lijo bakeng sa lijo, ho ja lijo tsa letsatsi le letsatsi hangata hoa thibeloa (Feja le Koch, 2014; Hosking et al., 2014; Mejia-Toiber et al., 2014). Ts'ebetso ena e ka ferekanya mehato ea sephetho, kaha ho na le ho pharalla ho matla lits'ebetsong tsa methapo ea kutlo tse fetotsoeng nakong ea lithibelo tsa lijo tse sa feleng le tseo tse etsang qeto ea ho nka liqeto tse potlakileng (Schuck-Paim et al., 2004; Minamimoto et al., 2009). Ntle le moo, liphoofolo tse matlafatsoang ke lijo li thatafala le ho feta nakong eohle ea thuto, e fokotsang boleng ba matlafatso ea lijo (Bizo et al., 1998), leha phello ena e ka its'etleha ka boholo bo matlafatsang (Roll et al., 1995). Ho fapana le ts'ebeliso ea lijo, boleng bo matlafatsang ba EBS bo lula bo tsitsitse nakong eohle ea thuto, e lumella tlhahlobo e pharaletseng le e lumellanang ea boitšoaro (Trowill et al., 1969). Karolo ena e lumella hore linako tsa liteko li hlahe khafetsa ho pholletsa le letsatsi, tse ka ba molemo ha u ithuta ka litlamorao tsa kalafo ea meriana, haholo kalafo e sa foleng ea lithethefatsi. Lithuto tsa rona tse theotsoeng tsa litheko (tse hlalositsoeng ka tlase) li ne li etsoa makhetlo a 'maloa ka letsatsi ho pholletsa le kalafo ea dopamine agonist (pramipexole). Re fana ka maikutlo a hore molemo ona oa ts'ebetso o sebetsa haholoanyane ho batho mme ka hona o fana ka liphetho tse ntlafalitsoeng tsa phetolelo. Ho fihla joale, lithuto tse tšoanang tse hlahlobang litlamorao tsa dopamine agonist mabapi le ho etsa liqeto tse sa tsotelleng li sebelisa moputso oa lijo li lekantse feela kalafo ea lithethefatsi tse mpe (St Onge le Floresco, 2009; Zeeb et al., 2009; Madden et al., 2010; Johnson et al., 2011; Koffarnus et al., 2011) 'me e tla ba ho khahlisang haholo ho bapisa sephetho sa boits'oaro se latelang kalafo ea lithethefatsi e mpe le e sa foleng lipakeng tsa li-femele tsena tse fapaneng. Le ha ICSS e fana ka menyetla e 'maloa holim'a matlafatso ea lijo, ICSS e boetse e fana ka likotsi tse' maloa. Mohlala, ICSS e hloka ts'ebetso ea bongaka e hlaselang le ho hlaphoheloa, 'me methapo ea hlooho e sa pheleng hantle e ka fella ka tahlehelo ea lithuto ho pholletsa le boitšoaro ba kemiso. Leha ho na le mathata ana, re lumela hore ICSS ke mokhoa o mong o ka sebelisang matlafatso ea lijo hape o hlahisa melemo e mengata ea ho matlafatsa lijo mesebetsing ena ea boits'oaro.

Lits'ebetso tsa ho etsa liqeto / ho etsa melemo li hloka hore ho khethoe lipakeng tsa likhetho tse amanang le meputso e fapaneng. Ka hona, li-reinforcer tse sebelisitsoeng mesebetsing ena li lokela ho bonts'a bokhoni ba ho hlahisa liphetoho tse joalo ka moputso o moholo mme ka morao ho moo likhoto li tlameha ho khetholla lipakeng tsa "encorcercer" (SR) le khetho e kholo ea li -forforcer (LR). Ts'ebetsong tse sebelisang matlafatso ea lijo, sena se fihlelloa ka ho fetola palo ea lijo tse fumanehang kamora karabo. Ho ICSS, EBS e ka fetoloa ka ho feto-fetoha ha matla a ho ts'oaroa ha matla kapa maqhubu a hona joale. Setšoantšo 1 e bonts'a karabo ea khatiso ea lever e fumanoeng ha matla a hona joale a fapana (ke hore, maqhubu a hona joale a ne a tšoaroa khafetsa; setšoantšo 1A) kapa ha maqhubu a hona joale a fapaneng (ke hore, botebo ba hona joale bo ne bo lula bo ts'oaroa; setšoantšo 1B). Ha paramente e ngoe le e ngoe e fetotsoe, likhoto li bonts'a lever e lekanyelitsoeng ea boleng bo bonyenyane ba EBS mme e bonts'a litekanyetso tse matla tsa khatello ea boleng bakeng sa litekanyetso tse kholo tsa EBS, e fana ka tlhahiso ea hore boleng ba matlafatso ba ts'usumetso e kholo bo feta (ntle le hore matla kapa maqhubu a hona joale a thehiloe). EBS ka hona e ka qaptjoa bakeng sa boikemelo bo nyane le bo boholo bo hlokahalang bakeng sa protocol ea ho etsa liqeto. Melemo ena ea matlafatso e ka khethoa ho likhakanyo ka bonngoe ka ho hlahisa li-curve tse tsitsitseng tsa khatello ea karabelo ea phoofolo e ngoe le e ngoe (Rokosik le Napier, 2011, 2012). Ntle le moo, khetla ea palo ea baahi e ka hlahisoa ho tsoa ho sehlopha sa likhoto moo boleng ba boleng ba SR le LR bo ka khetholloang (Tedford et al., 2012; Batho et al., 2013). Mokhoa ona oa morao-rao o fana ka mokhoa o sebelisang nako e nepahetseng hape o tšepahalang oa ho fumana SR le LR. Letotong la bobeli la lithuto, re sebelisitse mokhoa o mongata oa ho sebelisa matla kapa maqhubu a mangata ho theha litekanyetso tsa SR / LR mosebetsing oa ho fokotsa litheko (ho bolela, kotsi / ho etsa liqeto). Liphetoho ho boleng ba hona joale ba matlafatso (ke hore, maqhubu a hona joale a ne a tšoaroa khafetsa) le litekanyetso tsa maqhubu a hona joale (ke hore, matla a hona joale a neng a ts'oaroa a sa ts'oaneng) ka bobeli li hlahisa boitšoaro ba bohlokoa ba litheko ho likhoto (Litšoantšo. 1C, D). E ipapisitse le karolo ea moeli oa khokotso e thellang, maqhubu a hona joale a ne a ikemiselitsoe ho ba motheo o nepahetseng oa boleng bo matla ba ho matlafatsa. Hang ha ho se ho fumanoe hore likhoto li ka khetholla pakeng tsa maqhubu a tloaelehileng a hona joale a sebelisoang bakeng sa SR le LR, li ka lekoa ho e 'ngoe ea li-paradigms tsa ho etsa liqeto tsa ICSS: (i) kotsi / ho etsa liqeto ka sepheo (Rokosik le Napier, 2011, 2012), (ii) ho nka liqeto tse thehiloeng ho lieha (Tedford et al., 2012), kapa (iii) ho etsa liqeto tse thehiloeng boitekong (Batho et al., 2013).

 

Setšoantšo sa 1. Liphello tsa litekanyetso tsa ts'usumetso ea boko ho ts'ebetso ea khatello ea-lever le ho theola monyetla. Litekanyetso tse peli tsa EBS tse lekiloeng e ne e le matla a hona joale le maqhubu a hona joale. Rats lever e hatelletsoe bakeng sa EBS (ka kemiso e tsitsitseng ea 1 ea ntlafatso) eo ho eona metsotso e meng le e 'ngoe ea 2, paramente e le' ngoe ea EBS e ile ea qhekelloa mme karolo e 'ngoe e ne e lula e ts'oaroa. (A) Phokotso ea matla a hajoale. Matla a hajoale ho tloha 10 ho isa 350 μA a hlahisitsoe ka tatellano e hlophisitsoeng (n = 6); maqhubu a hajoale a ne a tšoaretsoe 100 Hz. (B) Phokotso ea maqhubu a hona joale. Meetso ea hajoale ho tloha 5 ho 140 Hz e hlahisitsoe ka tatellano e hlophisitsoeng (n = 3); matla a hajoale a ne a tšoaroa khafetsa ka tekanyo e neng e etselitsoe motho a le mong le e ikemiselitseng lithutong tsa pele tsa thupelo. Ho thefula boholo ba hona joale kapa maqhubu a hona joale ho hlahisitse mekhoa e ts'oanang ea karabelo ea khatiso ea lever. Lintlha li bontšoa e le mokhoa oa ho hloka nako bakeng sa likarolo tse tharo tse latellanang tse latellanang. Likhoto li ile tsa koetlisoa kamora nako ea ho fokotsa litheko le boleng ba sesebelisoa se nyane le se seholo bakeng sa phoofolo e 'ngoe le e ngoe ka ho etsa likhakanyo tse matla tsa hona joale tsa maqhubu le maqhubu a hona joale a fumanoeng ho EBS vs. ea litekanyetso tse phahameng tsa khatello ea li-lever-Press, ka ho latellana. Ho tebisa boholo ba botebo ba hona joale (C) kapa maqhubu a hona joale (D) fella ka ho theola matlafatso a maholo (LR) ha monyetla oa ho tsamaisoa o fokotsehile (ke hore, ho fokotseha ha khetho ea liperesente e amanang le LR mabapi le likhetho tse felletseng). Lintlha li bontšoa e le mokhoa oa ± sem ka letsatsi la ho theola le ho sebelisa matla a hajoale le matsatsi a 2 a theolelo u sebelisa maqhubu a hona joale. Setšoantšo se fetotsoeng ho tloha Rokosik le Napier (2011) mme e hatisoe hape ke tumello ho tsoa ho mohatisi.

Ho netefatsa tšebeliso ea ICSS ho lekola mehato ea ho susumetsa le ho etsa liqeto

Nts'etsopele ea mefuta e mecha ea liphoofolo e hloka ho nahanisisoa ka hloko mabapi le ho nepahala. Kahoo, ha re rala mesebetsi ena ea ho nka liqeto ka ICSS, re ikitlaelletse ho netefatsa sefahleho le ho aha, le ho netefatsa menyetla ea bonnete.

Ho nepahala ha sefahleho ho bolela boholo ba ha tlhahlobo e bonahala e lekanya ntho e etselitsoeng eona. Moralo oa mosebetsi o mong le o mong oa ho nka liqeto o amanang le ICSS o ne o ipapisitse le liprotheine tsa hajoale tse sebelisitsoeng bathong bakeng sa ho lieha le ho theola monyetla (Rasmussen et al., 2010; Leroi et al., 2013) le mesebetsi e meng e amanang le ho etsa liqeto (Treadway et al., 2009; Buckholtz et al., 2010; Wardle et al., 2011). Ho batho, mehato ea litšenyehelo / ho etsa liqeto ka melemo e nkiloe ho kopa batho ho khetha pakeng tsa likhetho tse 'maloa tse fumanehang ka maemo a itseng a ikhethileng (ke hore, kotsi, ho lieha, kapa boiteko). Re etsisa boemo bona ka ho hlahisa likhoto tse nang le lists tse peli tse atolositsoeng ka nako e le ngoe, moo khetho ea mofuta o mong e amanang le moputso o monyane kapa o moholo o isitsoeng tlasa maemo a itseng a tšohanyetso. Ka hona, e 'ngoe le e' ngoe ea liqeto tsa rona tsa ho nka liqeto tse nketsoeng ICSS e bonts'a ho nepahala ha sefahleho.

Ho aha bonnete ho bolela bokhoni ba paradigm ba ho lekola ka nepo seo se rerang ho se lekanya. Ho kotsi / moputso le ho nka liqeto tse thehiloeng ho lieha, khetho ea moputso o moholo e ea fokotseha ha menyetla ea ho phumisoa e theotsoe, kapa ho lieha ho lebisoa ho tliso ea moputso ho eketsoa ka ho latellana. Ka ho etsa liqeto tse thehiloeng boitekong, batho ka bomong ba bonts'a khetho ea pele bakeng sa boikitlaetso bo matla / moputso o moholo ha boiteko bo amanang le moputso o moholo bo nkuoa bo utloahala. Phetoho molemong oa boikitlaetso bo tlase / moputso o monyane o bonoa ha boiteko bo phahameng bo se ba sa tšoaneloe ke tšebeliso ea matla. Ho tlalehiloe hantle hore litoeba li bonts'a mekhoa e ts'oanang ea kotsi / moputso, ho nka nako le ho etsa liqeto tse thehiloeng boitekong ho bapisoa le batho (Rachlin et al., 1991; Buelow le Suhr, 2009; Jimura et al., 2009), mme re hlokometse lifaele tsena ho o mong le o mong oa mesebetsi ea rona (Rokosik le Napier, 2011, 2012; Tedford et al., 2012; Batho et al., 2013) (mohlala, bona setšoantšo 2).

 

Setšoantšo sa 2. Litlamorao tsa pramipexole ho tsebiso ea kotsi / moputso ho sebelisa mosebetsi oa ho fokotsa litheko. Chronic (Chronic) PPX e fokotsa litheko ho PD-like (A) le taolo ea sham (B) likhoto. Ka bokhutšoanyane hlalosa mosebetsi, PD-like (n = 11) le taolo ea sham (n = 10) likhoto li ile tsa koetlisetsoa mosebetsi oa ho fokotsa litheko ho sebelisoa ICSS. Monyetla o amanang le ho tsamaisoa ha matla a maholo (LR) o hlahisitsoe ka tatellano ea pseudo-randomized. Hang ha boitšoaro bo tsitsitseng bo bonoa, likhoto li ile tsa alafshoa ka mehla ka liente tsa 2 mg / kg (±) PPX ka matsatsi a 13. Tlhahisoleseling e bontsitsoeng e ile ea bokelloa ho tloha nakong eo re hlokometseng phello ea tlhapi ka letsatsi la ho qetela la kalafo (ke hore, 6 h post injosal) mme e bapisoa le baseketsetsi ba boitlamo ba pelehi (BL). Ho bontšoa ke khetho ea liperesente ea LR (ke hore, tekanyo ea khetho ea mahala) khahlanong le monyetla oa hore LR e tlisoe. A rmANOVA ea tsela tse peli le post hoc Newman-Keuls o senotse keketseho e kholo ho khetho ea% ea batho ba sa tsitsang, LR e latelang kalafo e sa foleng ea PPX (*p <0.05) bakeng sa lihlopha tse peli tse kang tsa PD le tsa sham rat. Le ha lipalo tsa sehlopha li bonts'a keketseho e bakiloeng ke PPX ea ho etsa liqeto tse tlase tsa ho ipeha kotsing / ho putsa, likhoto tse peli sehlopheng ka seng li bonts'itse keketseho e ka tlase ho 20% ho tloha qalong ho monyetla o tlase o lekiloeng; ka hona, likhoto tse ling li ne li bonahala li sa tsotelle bokhoni ba moriana ho fetola litheolelo. Setšoantšo se fetotsoeng ho tloha ho Rokosik le Napier (2012) mme e hatisoe hape ke tumello ho tsoa ho mohatisi.

Ho nepahala ha ponelopele ho bolela bokhoni ba mehlala ho bona esale pele likamano tsa nako e tlang, mme re beha hore mefuta ea rona e ka sebelisoa ho noha bokhoni ba kalafo ea meriana e ncha ho fetola liqeto tsa litšenyehelo / melemo. Ka mantsoe a mang, ka ho bontša bopaki ba mohopolo ka ho pheta-pheta litlamorao tsa baemeli ba litlhare tsa meriana litabeng tsa ho etsa liqeto tse seng li thehiloe bathong, re etsa tlhahiso ea hore meetso ea rona e ka ba le tšebetso ea ho bolela esale pele hore na litlhare tse ling li ka sebetsana joang le boits'oaro bona tleliniking . Mohlala, seteishene sa bakuli ba nang le lefu la Parkinson (PD) ba alafshoang ka kalafo ea dopamine agonist se bonts'a ho ata ha boitšoaro ba papali ea chelete (Weintraub et al., 2010) le litheolelo tse nyolohang tsa ho etsa liqeto tse mabapi le ho lieha (Matlo a et al., 2010; Milenkova et al., 2011; Voon et al., 2011; Leroi et al., 2013; Szamosi et al., 2013). Kahoo, laboratori ea rona e ile ea ikemisetsa ho etsa mohlala oa PD literekeng le ho ithuta ka litlamorao tsa pramipexole, ngaka e tloaetseng ho sebelisoa ea dopamine e amanang le boits'oaro ba papali ea chelete (Weintraub et al., 2010), mabapi le litšenyehelo / ho etsa liqeto ka melemo ho ratoa o sebelisa mosebetsi oa ho fokotsa litheko (kotsi / ho etsa liqeto) (Rokosik le Napier, 2012). Ho etsa joalo, likhoto li ne li fetoleloa e le "PD-like" ka ho khetha maselinyana a dopaminergic litheko ka hara dorsolateral striatum dessyecik infusions tse peli tsa 6-OHDA, ha likhoto li ntse li fumana infusions tsa koloi ea 6-OHDA (Rokosik le Napier, 2012). Li-neurons ka har'a dorsolateral striatum ea 6-OHDA ea likhoto tse tšoeroeng feela li bontša ho fokotseha ha tyrosine hydroxylase (Rokosik le Napier, 2012), letšoao la dopamine. PD-like rats e bonts'a likhathatso tsa makoloi tse tšoanang le batho ba nang le PD ea methapo ea pele, e ka khutlisetsoang tekanyo-ka kotloloho ka kalafo ea pramipexole. Tekanyetso ea pramipexole eo re e tsamaisitseng ho ithuta ho etsa liqeto tsa kotsi / moputso e fokotsa bofokoli ba makoloi, ka hona e bohlokoa kalafong (Rokosik le Napier, 2012). Le ha re sa bone phapang mokhoeng oa ho beha “kotsi” ”pakeng tsa likhoto le taolo e kang PD, kalafo e sa foleng ea pramipexole e eketsa khetho ea LR e kotsi lihlopheng ka bobeli tsa litoeba ha menyetla ea ho beleha e ne e le nyane (Litšoantšo. 2A, B), e bonts'a hore pramipexole e etsa hore ho be le kotsi e nyane / ho etsa liqeto. Lintlha tsena li lumellana le lithuto tse lekotseng litlamorao tsa pramipexole ho batho (Spengos et al., 2006; Pizzagalli le al., 2008; Riba et al., 2008). Leha ho le joalo, re fana ka netefatso ea ponelo-pele ea mehlala ea rona ea pentšele ho bonts'a li-activator tse ling tse ka kopanyeletsang litšenyehelo / liqeto tsa ho etsa liqeto bathong.

Re boetse re lekile mirtazapine, anti-depressant atypical, mosebetsing oa ho etsa liqeto. Litla-morao tsa boitšoaro le tšebeliso e mpe ea lithethefatsi li arolelana litšobotsi tse ngata tse akaretsang, ho kenyelletsa ho nka liqeto tse nyane, le lithuto tse ncha ho batho le liphoofolo tse seng tsa batho li bontša hore mirtazapine e sebetsa hantle ho fokotsa boits'oaro bo khothalletsoang ke lithethefatsi tse hlekefelitsoeng (mohlala, opiates le psychostimulants) esita le tse amanang. ka ho oela hape nakong ea ha ho etsoa thipa (bakeng sa tlhahlobo, bona Mabitla et al., 2012). Lintlha tse bokelletsoeng ho tsoa mosebetsing oa rona oa ho nka liqeto tse mabapi le ICSS o bonts'ang hore mirtazapine e fokotsitse boikhethelo bakeng sa boikitlaetso bo matla / LR, e fetohela boitekong bo tlase / SR, e fana ka maikutlo a hore palo ea boiteko bo hlokahalang bakeng sa LR e ne e se e sa "lekane" eona, ”kapa hore boleng ba moputso oa LR bo fokotsehile (Batho et al., 2013). Liphetho tsena li fana ka maikutlo a hore e kanna ea ba ho khahlisa ho ithuta ka litlamorao tsa ho nka liqeto kamora nako ea ho etsa liqeto tse boima litabeng tsa papali ea chelete ka tleliniking.

fihlela qeto e

Ka kakaretso, re sebelisitse ICSS e le mokhoa o matlafatsang mesebetsing e meng e mengata ea lipale e etselitsoeng ho lekanya karohano, empa leha ho le joalo e akaretsa, lintlha tsa theko / ho etsa liqeto tse bonts'itsoeng bothateng ba papali ea chelete. Mehato ena e ka sebelisoa ho hlahloba phano ea monehelo oa likarolo tse fapaneng tsa neuroanatomical subistates le li-neurotransmitter bothateng ba papali ea chelete. Mesebetsi e kopanetsoeng le ICSS e fana ka monyetla o mong oa ts'ebeliso ea lijo maemong ana a rarahaneng a sebetsang. Re lumela hore bonnete ba mesebetsi ena bo bonts'a hore ba ka thusa ho hlahlobisisa lithethefatsi bakeng sa bokhoni ba tsona ba ho kenya litšusumetso tsa taolo e matla, joalo ka ho becha ka mathata le ho thusa ho tseba lithethefatsi tse fokotsang mathata ana.

Tlhōlisano ea Tlhaloso

Dr. Napier o fumane tšehetso ea lipatlisiso ho tsoa ho Setsi sa Naha sa Bophelo, Michael J. Fox Foundation le Setsi sa Naha sa Lipapali Tse Ikarabellang. Ngaka Napier o amohetse matšeliso bakeng sa tse latelang: ho buisana le setsi sa thuto sa bophelo bo sa lefelloeng le liofisi tsa molao mabapi le litaba tse amanang le tlhekefetso le taolo ea litšusumetso; Ho bua ka litlatsetso libokeng tsa holo ea toropo ea sechaba, likolo tse phahameng tsa sechaba, tse sa etsetseng phaello, le likopano tsa litsebi tsa makhotla a lithethefatsi; ho fana ka litekolo tsa thuso bakeng sa Likolo tsa Naha tsa Bophelo le mekhatlo e meng; lipuo le lithutong tsa thuto e phahameng. Ngaka Napier ke setho sa Illinois Alliance mabapi le Ho Becha Mathata, mme o fana ka likeletso tsa litsebi mabapi le nts'etsopele ea meriana ho Cures Under Research Foundation. Ngaka Holtz, Dr. Persons, le Mme Tedford ba phatlalatsa hore lipatlisiso li entsoe kamora ho se be le kamano efe kapa efe ea khoebo kapa ea lichelete e ka nkuoang e le khohlano e ka bang teng ea phaello.

lumela hore baa fokola

Mosebetsi ona o tšehelitsoe ke Setsi sa Naha sa Lipapali se Ikarabellang, Michael J. Fox Foundation, Daniel F. le Ada L. Rice Foundation, le USPHSGs NS074014 ho T. Celeste Napier le DA033121 ho Stephanie E. Tedford le T. Celeste Napier .

References

E hlophisitsoeng ke:

Patrick Anselme, Univesithi ea Liège, Belgium

Hlahloba by:

Christelle Baunez, Setsi sa Scientific Research, Fora
Yueqiang Xue, Setsi sa Saense ea Bophelo ba Saense ea Tennessee, USA