Orexin o arolelana litloaelo tsa ho kopanela liphate ka litoeba tsa banna tsa thobalano, empa ha li bobebe bakeng sa ts'ebetso ea thobalano (2011)

Horm Behav. Sengoloa se ngotsoeng; e fumaneha ho PMC 2011 Aug 1.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

PMCID: PMC2917508

Moetso oa khatiso oa ho qetela oa mohatisi o fumaneha ho Horm Behav

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

Eya ho:

inahaneloang

Hypothalamic neuropeptide orexin e sebelisana le bohloeki, ho robala le boitšoaro bo botle ka tlhaho, ho kenyelletsa takatso ea lijo. Boitšoaro ba botona le botšehali ba monna bo fetoloa ke ba-orexin receptor-1 agonists kapa antagonists, ba fana ka maikutlo a karolo bakeng sa orexin-A ts'ebetsong ena e nang le moputso oa tlhaho. Leha ho le joalo, karolo e ikhethileng ea orexin-A kapa B maemong a fapaneng a boitšoaro ba monna ha e sa tsejoe. Ka hona, lithuto tsa hajoale li sebelisitse matšoao bakeng sa ts'ebetso ea neural activation le liso tse khethehileng tsa cell ho hlahloba maikutlo a hore orexin e bohlokoa bakeng sa tšusumetso ea thobalano le ts'ebetso ho litoeba tsa banna. Taba ea pele, polelo ea cFos ka li-orexin neurons e ile ea bontšoa ke setšoantšo se latelang sa mosali ea amohelang kapa ea sa amoheleng molaetsa ntle le ts'ebetso e tsoelang pele ke likarolo tse fapaneng tsa ho tlolelana. Ka mor'a moo, karolo ea tšebetso ea orexin e ile ea lekoa e sebelisa saporin ea Orexin-B, e ileng ea fella ka hore ho be le lisele tsa 'mele tsa orexin ho hypothalamus. Manonyeletso a ile a etsoa ho banna ba botona le botšehali mme boitšoaro bo latelang ba thobalano nakong ea liteko tse 'ne tsa ho hola. Ba batona ba Lesion ba bonts'itse bofokoli ba ho nyoloha le ho kenella nakong ea liteko tsa pele, empa eseng tse latelang, ba fana ka maikutlo a hore lesapo le thusa ho qala ts'ebetso ea thobalano ho batho ba thobalano, empa e se banna ba nang le boiphihlelo. Ka mokhoa o ts'oanang, marapo ha a ka a ama takatso ea thobalano ho banna ba nang le boiphihlelo, e khethiloeng ke liteko tsa runway. Kamora nako, liteko tse phahameng tsa maze li bonts'itse boitšoaro bo fokotsehileng bo joalo ka banna ba sotlehileng, ho ts'ehetsa karolo ea orexin matšoenyehong a amanang le ho pepesehela basali liphoofolong tsa Naïve. Ka kakaretso, liphumano tsena li bonts'a hore orexin ha e bohlokoa bakeng sa ts'ebetso ea thobalano ea monna kapa sepheo, empa e ka bapala karolo ho tsosa le ho tšoenyeha ho amanang le boits'oaro ba thobalano ho liphoofolo tsa na animalsve.

Keywords: orexin, hypocretin, boitšoaro ba thobalano, ho qopitsa, ts'ebetso ea neural, ts'usumetso, hypothalamus, lipale, ho tsosa, ho tšoenyeha

Selelekela

Orexin, e tsejoang hape ka hore ke hypocretin, ke hypothalamic neuropeptide e bohlokoa bakeng sa boitšoaro ba ho iphepa, (de Lecea et al., 1998; Sakurai et al; 1998, Sakurai, 2006; Benoit et al., 2008) ho tsosa boroko le boroko (Chemelli et al., 1999; Lin et al., 1999, Sakurai, 2007; Furlong le Carrive, 2007; Furlong et al., 2009; Carter et al., 2009). Li-neuron tsa Orexin li etselitsoe sebakeng sa lateral hypothalamic (LHA) le pervivical dorsomedial hypothalamus (PFA-DMH) mme li hlahisa li-neuropeptides tse peli, orexin-A le B (de Lecea et al., 1998; Sakurai et al., 1998). Li-neuron tsa Orexin li bonts'itsoe ho hlahisa likarolo tsa boko tse kenyelletsang ho hokahaneng ha mouoane ho kenyelletsa le locus coeruleus, tuberomammillary nucleus le peduculopontine tegmental nucleus (Peyron et al., 1998; Hagan et al., 1999; Horvath et al., 1999; Baldo et al., 2003). Orexin hape e kentsoe moputso le tšusumetso, e amanang ka ho khetheha le lijo le lithethefatsi tsa tlhekefetso (Aston-Jones et al., 2009a; Aston-Jones et al., 2009b) le li-neuron tsa orexin li bontšitsoe ho rera ho putsa meetso ea boko e amanang le sisteme ea mesolimbic ho kenyelletsa sebaka sa "ventral tegmental" (VTA) le nucleus accumbens (NAc) (Peyron et al., 1998; Fadel le Deutch, 2002; Martin et al., 2002; Baldo et al., 2003). Li-neuron tsa Orexin li kentsoe tšebetsong ke maemo a tloahelehileng a amanang le moputso oa lijo le lithethefatsi (Harris et al., 2005; de Lecea et al., 2006; Choi et al., 2010) 'me ba bontšitsoe hore ba bapala karolo ea boits'oaro bo thehiloeng ho moputso (Choi et al., 2010). Ho feta moo, tsamaiso ea intracerebroventricular (ICV) kapa tsamaiso e kenelletseng ea mohanyetsi oa li-receptor 1 (ORX1) e baka tšusumetso e fokotsang ea lijo tse fumanehang habonolo (Thorpe et al., 2005; Nair et al., 2008), athe ICV orexin-A tsamaiso e ka khutlisa khothatso ena (Boutrel et al., 2005).

Karolo ea orexin mekhoeng e meng e ruisang molemo hajoale ha e hlake, leha lithuto tse 'maloa li kentse karolo ho orexin taolong ea boitšoaro ba thobalano ho likhoto tsa banna. Pele ho kile ha bontšoa hore li-neuron tsa orexin li hlahisoa ka ho kopitsoa ho likhoto tsa banna (Muschamp et al., 2007). Ntle le moo, tsamaiso ea orexin-A sebakeng sa medial preoptic (mPOA) e hlahisitse ts'ebetso ea ts'ebetso ea thobalano e bonahatsoang ke ho fokotseha hoa maqhubu ho nyoloha le ho kenella, le ho eketseha ha maqhubu a litheko le ho kenella (Gulia et al., 2003). Ka lehlakoreng le leng, Tsamaiso ea ICV ea orexin-E susumetsang takatso ea thobalano ka ho fokotsa khetho ea basali, leha e le ho banna feela ba nang le takatso e matla ea thobalano.Bai et al., 2009). Boithuto bo sebelisang bahanyetsi ba ORX1 bo boetse bo bonts'itse data e hanyetsanang, joalo ka tsamaiso ea ORagNUMX antagonist e nyenyefatsang ts'ebetso ea thobalano ka ho eketsa latency ho intromit ntle le ho ama likarolo tse ling tsa boitšoaro ba thobalano (Muschamp et al., 2007), ha Tsamaiso ea ICV ea mohanyetsi oa ORX1 e ne e sena tšusumetso ea khothalletso ea thobalano (Bai et al., 2009). Mmoho lithuto tsena li bonts'a hore taolo ea orexin-A ea khale e ama ts'ebetso ea thobalano le tšusumetso; le ha ho le joalo, orexin ea morao-rao e kanna ea se ke ea bapala karolo ea bohlokoa ho phetheng boitšoaro ba thobalano (Bai et al., 2009). Ka hona, sepheo sa thuto ea hona joale e ne e le ho bona hore na orexin ea bohlokoa e bohlokoa bakeng sa ts'usumetso ea setho sa botona le botšehali.

Taba ea pele, e ile ea khethoa ha ts'ebetso ea thobalano e amanang le ts'ebetso ea thobalano e sebetsoa, ​​ho leka khopolo ea hore methapo ea kutlo ea orexin e kengoa ts'ebetsong ha ho hlahisoa khothalletso e monate. Ho feta moo, joalo ka ha ho bontšitsoe hore boiphihlelo ba thobalano bo susumetsa ts'ebetso ea thobalano (Dewsbury, 1969) le melemo ea ho etsa thobalano (Tenk et al., 2009), ho ile ha khethoa hore na boiphihlelo ba thobalano bo susumetsa ts'ebetso ea "orexin neuron" nakong ea ho hola. Kamora nako, ho ile ha lekoa hore na orexin e bapala karolo ea bohlokoa molemong oa thobalano le ts'ebetso o sebelisa lisele tsa mmele tsa sele tsa li-neuron tsa orexin.

Lisebelisoa le mekhoa

Liroto tsa banna ba baholo ba baholo ba Sprague Dawley (200-250g) li fumanoe ho tsoa Harlan (Indianapolis, IN) kapa Charles River Laboratories (Sherbrooke, Quebec, Canada) mme ba lula ka bonngoe kapa ka bobeli ho latela teko ea motho ka mong (bona ka tlase) ho mekotla ea Plexiglas. Kamore ea kolone e ne e bolokiloe mochineng oa 12 / 12 o khutlisang lebone le lefifi (mabone ho 10 am) mme lijo le metsi li ne li fumaneha ad libitum ntle le nakong ea tlhahlobo ea boitšoaro. Li-rats tsa basali tsa Sprague-Dawley li fumanoe ho tsoa Harlan (Indianapolis, IN) kapa Charles River Laboratories (Sherbrooke, Quebec, Canada) li ile tsa hlahlojoa ka mahlakoreng a mabeli 'me tsa kenngoa ka mokhoa o sa ts'oaneng ka 5% 17-β-estradiol benzoate silular capsular. Ho pheta-pheta ka thobalano ho bakiloe ke liente tsa "subgestaneous" tsa progesterone (500 µg ho 0.1ml ea oli ea sesame) hoo e ka bang 4 h pele ho nako ea kemaro. Ts'ebetso tsohle li amohetsoe ke Likomiti tsa Tlhokomelo ea Liphoofolo Univesithing ea Cincinnati le Univesithi ea Western Ontario mme li lumellana le tataiso e boletsoeng ke Setsi sa Naha sa Bophelo le Lekhotla la Canada mabapi le Tlhokomelo ea Liphoofolo. Liteko tsohle tsa boits'oaro li entsoe nakong ea halofo ea pele ea karolo e lefifi tlasa khanya e khubelu e tlase, ntle le ha ho boletsoe ka tsela e ngoe.

Tlhahlobo ea Boiteko

lithuto tsa polelo ea cFos

Likhoto tsa banna (n = 48) li ne li beoa ka bonngoe mme halofo ea liphoofolo e fumana boiphihlelo ba thobalano ka har'a ntlo ea likhomo nakong ea 5 habeli beke le beke tsa ho emisa. Liteko tsa mating li ile tsa etsoa kahara terakeng ea lapeng ho tlosa polelo e monate le ea cFos e hlahisoang ke ho pepesehela lebaleng le fapaneng la ho ts'oaroa le ho pepesehela litloaelo tse boemo bo amanang le ho tlolelana pele ho nako.Balfour et al., 2004). Mosali ea amohelang molaetsa o ile a kenngoa kahara likhopo tsa lapeng mme banna ba ne ba lumelloa ho nyalana ho fihlela emong e le ngoe kapa bakeng sa metsotso ea 60. Nakong ea tlhahlobo e 'ngoe le e' ngoe boitšoaro ba ho kopanela liphate bo ile ba bonoa. Palo e felletseng ea litheko le maqhubu, hammoho le bophahamo ba pele ba ho nyoloha le ho kenella (nako ea ho tloha ho hlahisoa ha mosali ea amohelang ho ea fihla thabeng ea pele kapa ho kenella), le ho nyaloa (nako ho tloha ho keneng ka pele ho ea pele) (Agmo, 1997). Halofo e setseng ea liphoofolo e ile ea lula e ntse e ts'oarehile ka thobalano. Liphoofolo tsena li ne li bolokiloe ka kamoreng e le 'ngoe le tse tona tse nang le thobalano, li ne li tšoaroa ka letsoho li pepesetsoa monko le melumo e amanang le ho tlolelana. Naïve le liphoofolo tse nang le boiphihlelo li ne li arotsoe hape ka lihlopha tsa liteko tsa 6 (n = 4 ka sehlopha). Lihlopheng tsa 6 naïve le tse nang le boiphihlelo li kenyelelitsoe: Bahlankana ba laolang ba sa pepeseheleng boitšoaro ba thobalano (Home Cage); ba batona ba pepeselitsoe mosali ea sa amohelang molaetsa kahare ho terata ea lapeng bakeng sa metsotso ea 15 (Anestrous Female). Ba batona ba ne ba khona ho etsa lipatlisiso le ho sebelisana, leha ho le joalo ba ne ba sa kopane ka lebaka la khaello ea phetoho ea basali; banna ba pepesehetse monko oa mosali ea amohelang ea behiloeng ka lebokoseng la mesifa ea terata kaholimo ho terata ea lapeng bakeng sa metsotso ea 15 (Estrous Female); e tona e bonts'ang likhoto, empa eseng ho kenella kapa ho hohla ka mokhoa o tšehali le tse tšehali tse ikentseng masapo (Thaba); ba batona ba neng ba bonts'a litheko tse ngata le ho kenella feela (Intromission); le ba batona ba tloaetseng ho tsoaloa hangata. Kamora hora e le 'ngoe ha tlhahlobo e fela, banna ba ile ba etsoa sehlabelo ho hlahlobisisa polelo ea cFos. Lihlopha tse nang le tsebo ea thobalano li ne li ts'oaroa ka methati ea boitšoaro ba thobalano mme ho ne ho se na phapang e kholo lipakeng tsa lihlopha pele ho tlhahlobo ea ho qetela. Ntle le moo, ho ne ho se na phapang e kholo lipakeng tsa naïve le lihlopha tse nang le boiphihlelo ka lipalo tsa litefiso tse eketsehileng le lipallo nakong ea teko ea ho qetela.

Phello: polelo ea cFos

Ba batona bohle ba ne ba sa anngoe ka ho teba ka sodium pentobarbitol (270 mg / mL) mme ba ne ba tlotsoa ka nama ka bongata ka 4% paraformaldehyde (500 mL; PFA). Kamora ho sebelisa litlolo tse tlotsitsoeng ka potlako li ile tsa tlosoa hang-hang 'me tsa emisoa ka nako e le' ngoe ka fixative e le 'ngoe ebe li fetisetsoa 20% sucrose tharollo ea cryoprotection. Li-brains li ne li behiloe ka har'a microtome e sa koaheleng (Microm, Walldorf, Jeremane) likarolong tsa coronal tsa 35 µm mme li bokelleloe likarolong tse tšoanang tsa 4 ka tharollo ea "cryprotectant" (30% sucrose ho 0.1 M PB e nang le 30% ethylene glycol le 0.01% sodium azide) mme e bolokiloe ho −20 ° C ho fihlela e sebetsa.

Immunohistochemistry

Meetso eohle e ne e etsoa ka mocheso oa kamore ka moferefere o bonolo. Likarolo tse phaphamalang tsa mahala li ile tsa hlatsuoa haholo ka 0.1M saline buffered sodium phosphate (PBS). Likarolo li ne li koetsoe ka 1% H2O2 (Tharollo ea setoko sa 30%) ho PBS bakeng sa metsotso ea 10, ebe e ts'oaroa hape hape ka PBS. Likarolo li ne li entsoe ka tharollo ea ho incubation (PBS e nang le 0.1% bovine serum albin le 0.4% Triton X-100) bakeng sa hora ea 1. Mechine ea thibelo ea bokhachane e ile ea etsoa kahare ho tharollo ea ho kenella bosiu ka nako ea mocheso oa kamore. Likarolo tse latelang tsa litšila li ile tsa tšeloa ka PBS, ea kenngoa ka har'a li-slide tse khokhotsoeng 'me tsa koaheloa ka diputyl phthalate xylene (DPX).

cFos / Orexin

Letoto le le leng la likarolo le ile la kenngoa bakeng sa cFos le orexin. Likarolo li ile tsa ts'oaroa bosiu ka mokhoa o tsoakiloeng ke mmutla o lumelang cFos (anti-cFos, sc-52; 1: 10 000, Santa Cruz Biotechnology, Santa Cruz, CA) e lateloang ke ho kenella ka hora ea 1 ka motsoako oa poli ea biotinylated (1: 500 , Vector Laboratories, Burlingame, CA) le avidin horseradish peroxidase tata (1: 1000, kit ya ABC, Vector Laboratories, Burlingame, CA). Likarolo li ne li fuoe metsotso ea 10 ho 0.02% diaminobenzidine (DAB) (Sigma, St. Louis, MO) ho 0.1M phosphate buffer (PB) e nang le 0.012% hydrogen peroxide le 0.08% nickel sulfate, e hlahisang sehlahisoa sa karabelo e putsoa-botsho. Likarolo li ile tsa kenngoa bosiu bo le bong ka motsoako o thibelletsoeng oa 'mele o hlokometseng orexin-A (anti-anti-orexin-A, H-003-30; 1: 20 000, Phoenix Pharmaceuticals, Burlingame, CA) e lateloa ke polokelo ea hora ea 1 e nang le poli ea biotinylated -rabit le ABC, joalo ka ha ho hlalositsoe kaholimo. Kamora moo, likarolo li kenyelelitsoe metsotso ea 10 le 0.02% DAB ho 0.1M PB e nang le 0.012% hydrogen peroxide, e hlahisang sehlahisoa se bosootho bo sootho.

Li-antibodies tsohle li bontšitsoe pele (Chen le al., 1999; Satoh et al., 2004; Solomon et al., 2007). Taolo ea immunohistochemical e kenyelletsa ho siea ha li-antibodies tsa mantlha, tlhahlobo ea letheba la bophirima e bonts'ang lihlopha tse le 'ngoe ka boima bo nepahetseng (cFos), le tahlehelo ea tlhahiso ea orexin ea immunohistochemical le lesapo la orexin B-saporin (orexin).

Boitsebiso ba Lintlha

cFos / Orexin

Li-Neurons tse ngotsoeng bakeng sa orexin kapa orexin le cFos li ne li baloa ka bongata likarolong tse tharo tsa baemeli ka phoofolo e 'ngoe e tsejoang hore e na le lipalo tse phahameng haholo tsa palo ea li-neuronal tsa orexin (Sakurai et al., 1998) spanning −2.3 mm ho −3.6 mm ho tloha bregma (Paxinos le Watson, 1998) (Setšoantšo sa 1), ka ho sebelisa tube ea ho taka e khomaretsoeng microscope ea Leica (Leica Microsystems; Wetzlar Germany), e bonoe ke sefofu se foufetseng lihlopha tsa liteko. PFA-DMH le LHA li ile tsa theoa ho latela sebaka sa fornix (Setšoantšo sa 1a). Liperesente tsa li-neurone tsa orexin tse bonts'ang li-cFos li ile tsa baloa 'me tsa lekanngoa karolo e ngoe le e ngoe bakeng sa phoofolo ka' ngoe, 'me ho baliloe mokhoa oa sehlopha. Bohlokoa ba lipalo lipakeng tsa lihlopha bo ne bo ikemiselitse ho sebelisa ANOVA ea mekhoa e 'meli e nang le boiphihlelo ba botona le botšehali nakong ea teko ea hoqetela e le lintlha tse lateloang ke liteko tsa Fisher tsa LSD tse nang le boemo ba kholiseho ea 95%.

Setšoantšo sa 1 

Sebaka sa li-neuron tsa orexin ho hypothalamus. (A) Sebaka sa antheomine ea li-neurone tsa orexin ho hypothalamus. (Paxinos le Watson, 1998), Bareng ea Scale: 200 µm. (B) Li-neuron tse nang le lebitso le le leng tse bitsoang li-orexin ho PFA-DMH ka phoofolo e laoloang e sa laoloe. (C) Orexin ...

Lithuto tsa Orexin Lesion

Phekolo

Ba batona ba ne ba beoa ka bonngoe mme ba fuoa monyetla o le mong oa tlhahlobo ea pele ho tlhabollo le mosali ea amohelang pele ho thipa lesion le sham. Boitšoaro ba thobalano bo tlalehiloe ka mokhoa o hlalositsoeng kaholimo mme lihlopha li ne li ts'oaroa ho ipapisitse le maemo a boitšoaro ba mating. Likhoto tsa banna li ne li sa sebetse ka isoflurane (Laboralo ea Abbot, St. Laurent, Quebec, Canada) li sebelisa lisebelisoa tsa khase tsa Surgivet Isotec4 (lisebelisoa tsa khase tsa Smiths Medical Vet, Markham, Ontario, Canada) 'me li kentsoe lisebelisoa tsa stereotaxic (Kopf Instrsets, Tujunga, CA) e nang le maske a khase e koahelang nko le molomo Ho ile ha etsoa leqhubu la ho pepesa lehata le leng le la li-lambda le bregma mme li ikemiselitse ho ba maemong. Ho ile ha chekoa lesoba lehata ka har'a lehata ho sebelisa darmel drill (Dremel, Racine, WI) le bophara ba likhalase tsa khalase (40µm bophara, World Precision Instruments Inc, Sarasota, FL) e tlatsitsoeng ke lethaline la toxin orexin-B saporin (IT-20, Advanced Advanced Sistimi ea Ts'ebetso, San Diego, CA; 200ng / µL ho PBS); kapa toxin e sa hlahisoeng ke 'mala oa BLANK-saporin (IT-21, System Targeting System e tsoetseng pele, San Diego, CA; 200ng / µL ho PBS; control sham) li ile tsa theoleloa ho hypothalamus. Toxin ena e lebisitsoeng e bontšitsoe hore e tlamahana le kamano e phahameng ho lisele tse hlalosang orexin receptor 2 (ORX2) hape e na le kamano e tlase haholo bakeng sa lisele tse hlahisang ORX1 (Gerashchenko et al., 2001), 'me ho bontšitsoe ka mokhoa o hlakileng oa ho hlakola li-neurone tsa orexin ho hypothalamus (Frederick-Duus et al., 2007). Li-infusions tsa bilateral tsa 1 µL (2 ka hemisphere) li ile tsa kenngoa litsing tse latelang: AP = −2.8 le −3.2; ML = 0.7 le 0.8; DV = −9.0 (Paxinos le Watson, 1998). Kamora ho kenella ka leng, nale e ile ea siuoa sebakeng sa metsotso ea 3 ho lumella ho ferekana. Li-needle li ile tsa tlosoa butle-butle 'me maqeba a koaloa ka sekhechana sa maqeba. Libeke tse peli kamora ho buuoa ka lesion, banna bohle ba ile ba lekoa bakeng sa boiphihlelo ba thobalano nakong ea liteko tse 'ne tsa ho emisa mme ba beoa tlhahlobo ea tseleng le / kapa tlhahlobo e phahameng ea maze (bona ka tlase). Ho etsoa opereishene libakeng tse tharo tse fapaneng, tse arotsoeng ke libeke tse 'maloa, ho fihlela palo e lekaneng ea liphoofolo ka sehlopha.

Boitšoaro ba Thobalano

Ba batona bohle ba ile ba lekoa bakeng sa boitšoaro ba thobalano nakong ea ha 4 ea ho hola ea basali e ne e etsoa ka letsatsi le leng le le leng la kheiteng ea lapeng. Sebokeng se seng le se seng, ba batona le ba batšehali ba amohela 'mele o le mong kapa ka metsotso e 60, ke mang ea tlang pele. Boitšoaro ba mating bo tlalehiloe joalo ka ha bo hlalositsoe kaholimo mme ho sebetsa hantle ho kopitso ho ne ho bile ho baloa [lipalo tsa li-intromissions / (lipalo tsa lipalo-palo + tsa li-intromissions)]. Phapang ea lipalo ka lipalo tsa ts'ebetso ea thobalano e ne e bapisoa pakeng tsa lihlopha tsa lesion le sham bakeng sa teko e 'ngoe le e' ngoe e sebelisa mokhoa o le mong ANOVA ka ho buoa lesapo e le sesosa le tlhahlobo ea LFD ea Fisher ka boemo ba kholiseho ea 95%, kapa ha ho loketse, liteko tse seng tsa maemo li ne li sebelisoa li sebelisoa ANOVA ea Kruskal-Wallis e le 'ngoe e nang le ts'oaetso ea lesion e le sesosa le tlhahlobo ea Dunn ka boemo ba kholiseho ea 95%. Ntle le moo, datha ea sehlopha ka seng e ne e bapisoa le data ea pele ho ts'ebeliso ea opereishene e sebelisang liteko tsa marang-rang.

Khothatso ea Thobalano: Teko ea Runway

Kamora ho lekoa ka boitšoaro ba thobalano, sehlotšoana sa banna ba nang le thobalano joale ba ile ba lekoa bakeng sa tšusumetso ea thobalano ba sebelisa lisebelisoa tse otlolohileng tsa metlae (MED Associates Inc., St. Albans, VT) (120 cm bolelele; Lopez et al., 1999). Batho ba batona ba lutse molemong oa lisebelisoa tsa mathamo ho feta liteko tse peli tse latelang tsa 10 tse ileng tsa etsoa ka tsatsi lona leo. Ka mor'a moo, ho ile ha etsoa liteko tse peli tsa teko. Nakong ea teko ea pele, phoofolo e susumetsang (e tšehali kapa e motona kapa e motšehali) e ne e beoa ka lebokoseng la sepheo le bapalami ba tlotsitsoeng qetellong ea mmila. Ho ne ho sebelisetsoa fan ho fokotsa monko oa liphoofolo tse hlasimollang tse lebisang ho e motona. Bahlankana ba liteko ba kentsoe ka lebokoseng la ho qala, monyako o ile oa buloa bakeng sa ho fihlella sephethephethe, mme nako ea ho fihla lebokoseng la sepheo e tlalehiloe. Ha ba qeta ho fihlela lebokoseng la sepheo, ba batona ba ile ba fuoa metsotsoana ea 30 hore ba sebelisane le phoofolo e susumetsang e neng e le ka morao ho skrini. Teko ea bobeli e tšoanang e ile ea latela hora ea 1 hamorao. Bohlokoa ba lipalo pakeng tsa linako ho fihlela lebokose la sepheo pakeng tsa teko 1 le liteko 2 li ile tsa hlahlojoa ho sebelisoa liteko tsa t-tiles ka boemo ba kholiseho ea 95% Bohlokoa ba lipalo lipakeng tsa lihlopha bo ne bo ikemiselitse ho sebelisa ANOVA e le 'ngoe ka ts'ebetso ea bongaka e le ntho e lateloang ke liteko tsa Fisher tsa LSD tse nang le boemo ba kholiseho ea 95%.

Ho Ts'oareha Ho Ts'oareha Ho Ts'oenyeha: Ho Phahamisoa Hape Maze

Sehlopha se ka tlase sa banna bao hona joale ba nang le thobalano se ile sa lekoa bakeng sa boits'oaro bo ts'oenyehileng ho bona hore na litlamorao tsa opereishene ea orexin mabapi le ts'ebetso ea thobalano kapa sepheo e bile ka lebaka la liphetoho mokhoeng oa ho tšoenyeha kapa ho tsosa. Ba batona ba ile ba pepesetsoa lisebelisoa tse phahameng tsa maze (EPM; MED Associates Inc., St. Albans, VT) ka kamoreng e khantšitsoeng ka mokhoa o khanyang nakong ea qetellong ea karolo ea khanya. EPM e ne e na le matsoho a 4 e 'ngoe le e' ngoe ea 50 cm ka bolelele ho tloha junipareng e bohareng mme e ne e phahamisitsoe ka 75 cm. Matsoho a mabeli a 'mete a ne a bulehetse tikoloho e kantle' me a mang a mabeli a kentsoe terata ea 40 cm e lefifi. Liphoofolo li ile tsa beoa ho EPM 'me tsa hlahlojoa metsotso e mehlano. Nako e sebelisitsoeng matsohong a bulehileng le a koetsoeng, le linomoro tse felletseng ka letsohong le leng le le leng li ile tsa rekisoa ho sebelisoa lifoto tsa Photobeam. Bohlokoa ba lipalopalo lipakeng tsa lihlopha bo ne bo ikemiselitse ho sebelisa ANOVA e le 'ngoe e nang le lesion e le sesosa se lateloang ke liteko tsa Fisher tsa LSD tse nang le boemo ba kholiseho ea 95%.

Liphetoho le li-cFos tse susumetsang mating

Kamora liteko tsohle tsa boits'oaro, banna bohle ba ne ba sa anngoe haholo ka sodium pentobarbitol (270mg / mL) mme ba ile ba tlotsoa ka mokhoa o phethahetseng ka 500 mL ea 4% PFA bakeng sa netefatso ea lesion joalokaha ho hlalositsoe pejana. Ntle le moo, ho hlahloba litlamorao tsa ho ruruha ha orexin ho polelo ea cFos ea mating, lihlopha tsa banna ba sham le lesion ba holofetse ho fihlela emong e le 'ngoe. Ka hora e le 'ngoe ka mor'a ho emisoa, banna ba ile ba tlotsoa ka nama ka bongata le 4% PFA joalokaha ho hlalositsoe ka holimo. Halofo ea banna ba sehlopheng sena ha baa ka ba tsebisoa mosali 'me ba ile ba tlotsoa ka litlolong tsa lapeng ho sebetsa e le taolo e sa laoloang.

Immunohistochemistry

Li-brains li ne li arotsoe ka ho sebelisa microtome ea ho leqhoa ho likarolo tsa 4 parallel likarolo tsa 35 µm coronal ebe li bolokiloe joalo ka ha ho hlalositsoe kaholimo. Bakeng sa netefatso ea lesion, letoto le le leng la likarolo tse nang le hypothalamus ho tsoa liteko tsohle tsa lesion le ne le ngotsoe lebitso le le leng bakeng sa orexin u sebelisa protocol e tšoanang ea anti-orexin-A le DAB e hlalositsoeng ka holimo. Letoto le le leng la liphoofolo le neng le kopantsoe le ne le entsoe ka li-cFos le orexin joalo ka ha ho hlalositsoe kaholimo.

Tlhatlhobo ea Lesion

Sebakeng se seng le se seng, lipalo tsa orexin neurons immunoreactive bakeng sa orexin li ne li baloa habeli ho PFA-DMH le LHA ka likarolo tsa 3 tse hlalosang lipalo tse phahameng tsa lisele tsa orexin maemong a sa laoleheng a ho buoa, −2.3 mm ho −3.6 mm ho tsoa ho bregma joalokaha ho hlalositsoe ka holimo. Lisele tse etsang karolo ea moea li ne li lekanyetsoa phoofolo ka 'ngoe,' me ho ne ho baloa mokhoa oa sehlopha. Liphoofolo tse sa sebetseng tse sebelisang tharollo ea bongaka (ho tloha liteko tsa cFos) li ile tsa sebelisoa ho khetholla lipalo tsa mantlha tsa methapo ea kutlo ea orexin mme lintlha li hlahisoa e le liperesente ha li bapisoa le ba batona ba sa sebetseng ba bongaka ba taolo (Setšoantšo sa 2). Ba batona ba neng ba e-na le lisele tse ka tlase ho 20% orexin ha li bapisoa le liphoofolo tse sa laoleheng tsa ho buoa li kenyelelitsoe sehlopheng sa lesion. Liphoofolo tse nang le kholo ho feta 20%, empa li le tlase ho 80% li kenyelelitsoe sehlopheng sa karolo ea lesapo. Lisebelisoa tsa Sham li ne li sena liphetoho tse kholo lipalo tsa lisele tsa orexin. Bohlokoa ba lipalo pakeng tsa liphoofolo tse sham, tse lekanyelitsoeng le tse felletseng li ile tsa baloa li sebelisa tlhahlobo e le 'ngoe ea ANOVA le Fisher's LSD ka tekanyo ea boits'epo ea 95%.

Setšoantšo sa 2 

Tlhatlhobo ea Lesion. Litšoantšo tsa moemeli tse bonts'a lisele tsa orexin (A) le MCH (B) ka phoofolo ea sham lesion e kentsoeng le BLANK-saporin. Litšoantšo tse emelang tse bontšang ho lahleheloa ke lisele tsa orexin (C), empa lisele tse sa tsitsang tsa MCH (D) ho phoofolo ea lesapo e kenngoeng ke orexin ...

Tlhaloso ea Lesion

Ho netefatsa hore manonyeletso a thibeloa ho li-neurone tsa orexin, letoto le le leng la likarolo tse nang le hypothalamus le tsoang liphoofolong tsa sham le lesion (n = 20) le ile la kenngoa bakeng sa hormone ea "melanocyte" (MCH), hypeptalamic peptide e nang le sebaka se fetang (ha ho joalo) colocalization) le orexin neurons (Broberger et al., 1998), o sebelisa antibody e phahamisitsoeng ea mmutla e hlokometseng MCH (rabi-anti-MCH, H-070-47; 1: 150 000, Phoenix Pharmaceuticals, Burlingame, CA) le DAB joalo ka ha ho hlalositsoe pejana. Li-neurons tsa MCH li hlahisa ORX1 (Bäckberg et al., 2002) empa eseng ORX2 (Volgin et al., 2004), mme ha e fokotsehe haholo ho latela kalafo ea orexin B-saporin (Frederick-Duus et al., 2007). Lisele tse sa sebetseng tsa MCH li ne li baloa habeli ka likarolo tse peli ka phoofolo e ngoe le e ngoe (sham: n = 7; lesion n = 5), li sebelisa likarolo tse ling ho tse hlahlojoang bakeng sa li-neuron tsa orexin. Lions ha lia ka tsa fokotsa haholo palo ea li-neuron tsa MCH ho PFA-DMH kapa LHA (Lethathamo 1; Setšoantšo sa 2b, d; PFA-DMH: p = 0.47; LHA: p = 0.33). Ntle le moo, polelo ea "cFos" ea mating e ile ea baloa habeli karolong e le ngoe ea baemeli ka phoofolo e ngoe le e ngoe (sham: n = 4; lesion n = 3), ba sebelisa likarolo tse ling ho ba hlahlobisisang li-neuron tsa orexin. Lesions ha e a ka ea ama polelo ea cFos e susumetsang ea ho holofala ho PFA-DMH kapa LHA (Lethathamo 1; PFA-DMH: p = 0.53; LHA: p = 0.82). Qetellong, likarolo tsa baemeli tse sebelisitsoeng bakeng sa lipalo tsa sele ea orexin (liphoofolo: sham: n = 6; lesion: n = 6) li ile tsa qosoa ka Nissl li sebelisa cresyl violet (5 g cresyl violet acetate (C-5042, Sigma, St. Louis, MO), 0.5 g ea sodium acetate trihydrate (S209, Thermo Fisher Science science, Ottawa, Ontario, Canada), 1L habeli e kolobisitsoeng ea metsi ka glacial acetic acid (AX0073-6, EMD Chemicals, Mississauga, Ontario, Canada) ho pH: 3.14). Counts of Nissl stained neurons e ile ea etsoa libakeng tse tloaelehileng tsa tlhahlobo (250 µm × 200 µm) sebakeng se akaretsang sa li-neuron tsa orexin. Lipalo tsa li-neurons tse nang le li-Nissl li ne li sa fapana pakeng tsa lihlopha tsa sham le lesion (Lethathamo 1; PFA-DMH: p = 0.23; LHA: p = 0.33).

Lethathamo 1 

Netefatso ea kotloloho ea lesion: Ho hlahlojoa ha linomoro tsa li-neuron tse emisitsoeng Nissl, MCH kapa ho qaptjoa ha mating ho bontšitse hore ha ho na tahlehelo ea bohlokoa ea li-neuron ka kakaretso, lisele tsa MCH, kapa ho tsofala ho kentsoeng ts'ebetsong ea neural ho PFA-DMH kapa ...

Kaha khaello ea orexin e bonts'itsoe ho kenya letsoho ho narcolepsy ho litoeba (Chemelli et al., 1999), lintja (Lin et al., 1999) le batho (Siegel, 1999; Nishino et al., 2000; Peyron et al., 2000; Thannickal et al., 2000) liphoofolo li ile tsa bonoa ho netefatsa ho ba sieo ha narcoleptic phenotype. Liphoofolo li ile tsa bonoa nakong ea liteko tsohle tsa boitšoaro tse tlalehiloeng thutong ena 'me ha li a ka tsa bontša litšobotsi tsa lefu la ho hlonepha.

Tlhahiso ea cFos e kopantsoeng le tlhoko ea liphoofolo tsa lesion

Lipalo tsa lisele tsa cFos-immunoreactive li ne li baloa habeli kahare ho likarolo tsa 3 ho liphoofolo ka bomong libakeng tse tloaelehileng tsa tlhahlobo sebakeng se bitsoang ventral tegmental area (VTA; 900 × 900 µm), mPOA (400 × 600 µm); nucleus accumbens (NAc) konokono le khetla (400 × 600 µm) le prelimbic, infralimbic le anterior cingulate sub-region tsa medial prefrontal cortex (mPFC) (600 x 800 µm ka sub-region) ke motho ea boneng mahlo ho liteko tsa lihlopha . Litefiso li ne li baloa phoofolo ka 'ngoe,' me ho ne ho baloa mokhoa oa sehlopha. Bohlokoa ba lipalo bo ne bo baloa ho sebelisoa ANOVA ea mekhoa e 'meli e nang le boiphihlelo ba thobalano le lesion e le lintlha tse lateloang ke tlhahlobo ea Fisher LSD e nang le boemo ba kholiseho ea 95%.

Results

Orexin neuron ts'ebetso nakong ea boitšoaro ba thobalano

Keketseho e kholo ea polelo ea cFos ho li-neuron tsa orexin e ile ea bonoa kamora boitšoaro ba thobalano ho PFA-DMH (F(5,31) 63.4; p <0.001; Setšoantšo sa 3a) le LHA (F(5,31) 10.4; p <0.001; Setšoantšo sa 3b), ntle le phello ea bohlola. Haholo-holo, ho liphoofolo tse nang le bohloeki ba ho kopanela liphate le ba nang le boiphihlelo, lihlopha tsohle tsa liteko tsa banna ba bonts'ang litekanyetso tse fapaneng tsa boitšoaro ba thobalano (lipatlisiso tsa mosali ea sa tsotelleng, ho pepesetsoa monko o bohloko oa basali, ponts'o ea ho hlohlona, ​​ho kenella kapa ho ntsoa) ho bontšitse ho kenella ka mokhoa o lekanang oa li-cFos ha li bapisoa le hae. taolo ea likhopo e nang le liperesente tse phahameng tsa lisele tsa orexin tse sebetsang ho PFA-DMH (60-80%) khahlanong le LHA (14-33%), ntle le phapang lipakeng tsa lihlopha tsa liteko. Liphetho tsena li fana ka maikutlo a hore li-neuron tsa orexin li hlahisoa ka mor'a ho pepesehela mosali ea tsosang ntle le ts'ebetso e eketsehileng nakong ea ts'ebetso ea thobalano. Ho feta moo, ts'ebetso ha e ea its'etleha ho ts'usumetso ea ts'usumetso ea ts'usumetso ea basali joalo ka basali ba sa tsebeng ho amohela le ho amohela ba susumetsang ts'ebetso ea banna.

Setšoantšo sa 3 

Li-neuron tsa Orexin ho PFA-DMH (A) le LHA (B) li bontšitse li-cFos tse latelang methati eohle ea boits'oaro ba ho holisa liphoofolo tse ruiloeng le tse nang le boiphihlelo. Selelekela: HC, ntlo ea lapeng AF: mosali ea makatsang; EF, mosali oa mosali; M, Thaba; IM, Ho kenella; E, Phapang. ...

Litlamorao tsa liso tsa orexin

Boitšoaro ba Thobalano

Liso tsa Orexin li hlahisitse ts'ebetso ea ts'ebetso ea boitšoaro ba thobalano (holima latency: F(2,47) 3.962; p = 0.034; intromission latency: H = 9.104; p = 0.011). Nakong ea teko ea pele ea ho tsofala, banna ba lesion ba bonts'a maqhubu a makhuts'oane ho hola le ho kenella ha ba bapisoa le liphoofolo tsa sham (Mount latency: p = 0.03; intencyission latency: p = 0.01; Setšoantšo sa 4a-b) le ho bapisoa le li-latency nakong ea teko ea ho holofala pele ho ts'ebetso (holisa latency: p = 0.02; latencyission latency: p = 0.03; Tlaleho e sa bonts'ang). Ba batona ba nakoana ba lesion ba ne ba sa fapana haholo le banna ba sham, 'me ha ho sehlopha se fapaneng le teko ea pelehi ea ho pepa. Litlamorao tsa ho ruruha ho hoholo le ho kenella morao-rao ho ile ha hlahisoa ka boiphihlelo ba thobalano, kaha ho ne ho se na liphapang lipakeng tsa lihlopha, nakong ea liteko tse latelang (teko ea 4 e bontšitsoeng ho Setšoantšo sa 4a-b). Maiketsetso a maiketsetso (Setšoantšo sa 4c), lipalo-palo (Setšoantšo sa 4dle ho kenella (Setšoantšo sa 4) le bokgoni ba ho qopitsa (Setšoantšo sa 4f) ha ea fapana haholo lipakeng tsa lihlopha nakong ea liteko kapa kahare ho sehlopha se seng le se seng lipakeng tsa teko ea pele ea bocha le tlhahlobo ea pele ho tharollo ea bongaka.

Setšoantšo sa 4 

Mabala a Orexin a khutsufalitse maqhubu a ho hola le ho kenella ho banna ba hlokang thobalano nakong ea teko ea 1. Liso tsa Orexin ha lia ka tsa ama ho ruruha nakong ea teko 4, kamora hore banna ba be le boiphihlelo ba thobalano. (A) Thaba ea Latency. (B) Intencyission Latency. (C) Phapang ...
Teko ea Runway

Mabala a Orexin ha a ka a ama takatso ea thobalano e lekiloeng tlhahlobong e otlolohileng ea baitlami ho banna ba nang le bohlola. Nakong ea liteko tse peli tsa teko, banna ba lesion ba ile ba matha ka lebelo le leholo ho ea ho mosali ea emereng tekong ea bobeli ha a bapisoa le teko ea pele (p = 0.03; Setšoantšo sa 5). Nako e joalo e potlakileng ea ho matha e supa tšusumetso ea thobalano (Lopez et al., 1999). Banana ba nakoana le banna ba sham le bona ba ile ba matha ka lebelo le le leng ho ea ho mosali ea motšehali nakong ea teko ea 2 (p = 0.03), leha sena se ile sa sitoa ho fihlela bohlokoa ba banna ba sham (p = 0.052). Ha ho na sehlopha se ileng sa bonts'a lebelo le eketsehileng la ho mathela ho mosali ea sa kopaneleng kapa e motona nakong ea teko ea 2. Ntle le moo, ha ho phapang e kholo e bonts'itsoeng lipakeng tsa banna ba sham, ba khetholloang le ba lesion ka lebelo ho mathela ho phoofolo efe kapa efe e khothalletsang motho ho se e le teko ea 1 kapa teko ea 2, e bonts'ang ho hloka phapang mesebetsing e akaretsang tseleng ea mapolasi.

Setšoantšo sa 5 

Mabala a Orexin ha a ka a ama takatso ea thobalano ho banna ba nang le boiphihlelo ba thobalano. E bonts'itsoe linako tsa ho fihlela mosali e moholo litekong tsa runway nakong ea liteko ka bobeli 1 le 2. * e bonts'a phokotso e kholo ea nako ea ho fihlela mosali tekong ea 2 ha e bapisoa le ...
Boitšoaro bo kang ho tšoenyeha

Liphetho ho fihlela joale li bontša hore liso li ka nolofatsa ho qaleha ha boitšoaro ba thobalano le liphoofolo tse nang le lefu ka phello e ka bang teng likarabo linthong tse ncha le / kapa boits'oaro bo ts'oenyehileng ha ba batona ba kopana le mosali e mocha. Ka ts'ehetso, banna ba lesion ba bontšitse ho fokotseha ho ts'oana le boits'oaro ho EPM, e bonoang e le peresente e fokotsehileng ea nako e sebelisitsoeng matsohong a koalehileng, (p = 0.012; Setšoantšo sa 6) le liperesente tse eketsehang tsa nako matsohong a bulehileng (p = 0.023; Setšoantšo sa 6) bapisoa le banna ba sham. Liso tse ling ha lia ka tsa ba le phello e ntle. Lintlha tsena li boetse li ts'ehetsa hore lesion e fokotse ts'ebetso e ts'oanang le ho tšoenyeha.

Setšoantšo sa 6 

Matsoafo a Orexin a fokotsetse boits'oaro bo kang ho tšoenyeha ho 'mele e phahameng. Peresente ea nako e sebelisitsoeng matsohong a koetsoeng (ka ho le letšehali) e ne e fokotsehile mme liperesente tsa nako matsohong a bulehileng (ka ho le letona) li ile tsa eketseha ho banna ba sentsoeng. * e bontša phapang ea bohlokoa ...
cFos Tlhahiso

Ho lekola hore na orexin ea morao-rao e kenya letsoho ho keneng ts'ebetsong ea phepelo ea methapo likarolong tse sa sebetseng tsa bokong ba orexin, ho hlahlojoa ha polelo ea cFos ea ho ts'ehetsa ho VF, NAc konokono le khetla, mPOA le mPFC li entsoe. Ho banna ba lesion le ba sham, ho hloa mekoalaba ho matlafalitse li-cFos haholo likarolong tsohle tsa boko tse hlahlobisitsoeng ha li bapisoa le taolo e sa fetoloang (Lethathamo 2). Lesions ha e ame ts'ebetso ea neural activation, joalo ka ha liphoofolo tsa sham le lesion li ne li sa fapana ka polelo ea motheo ea cFos kapa ea mating.

Lethathamo 2 

Mating e kentse li-cFos ka lihlotšoana tsa nakoana, karolo le karolo ea lesion ha e bapisoa le taolo e sa amaneng le maemo a tšoanang a lesion.

Puisano

Lithuto tsena li fuputse karolo ea karolo ea tšebetso ea thobalano molemong oa thobalano le tšusumetso ho rat la monna. Ho fumanoe hore orexin ha e bohlokoa bakeng sa ts'usumetso ea thobalano kapa ts'ebetso. Ho fapana le moo, li-neuron tsa orexin li hlahisoa ke ts'usumetso ea mosali, e sa ikemetseng ka boemo ba lihormone ba mosali le boiphihlelo ba botona. Ho feta moo, ho tlosoa hoa mesifa e ikhethileng ea "orexin" ho fokolitse boits'oaro bo ts'oanang le ho nolofatsa ho qala hoa boitšoaro ba thobalano ho banna ba thobalano. Kahoo, liphetho tsa thuto ena li tšehetsa karolo ea orexin in arousal (de Lecea et al., 2006; Harris le Aston-Jones, 2006; Sakurai, 2007; Boutrel et al., 2009; Furlong le Carrive, 2009; Furlong et al., 2009) le matšoenyeho (Suzuki et al., 2005; Davis et al, 2009; Li et al., 2010), empa u se ke oa tšehetsa karolo ea bohlokoa ea orexin ts'usumetso ea ts'ebetso ea thobalano kapa ts'ebetso.

Liphetho tsa lithuto tsena li hlakisa karolo ea orexin ea morao-rao le lintlha tse fumanoeng tse fumanoeng tsa lithuto tsa pejana tse hlahlobang karolo ea orexin litekatsong tsa botona le botšehali tse sebelisang lisebelisoa tsa pharmacological. Litla-morao tsa Intra-mPOA tsa orexin-A ea tsoelo-pele li lebisitse keketseho ea thobalano le ntlafatso ea ts'ebetso ea thobalano, li fana ka maikutlo a hore orexin e ka sebetsa mPOA ho eketsa ts'usumetso le ts'ebetso ea boitšoaro ba thobalano (Gulia et al., 2003). Leha ho le joalo, ka lehlakoreng le leng, infusions ea ICV ea orexin-Tšusumetso e matla ea thobalano le bootsoa (Bai et al., 2009), leha mohanyetsi oa "orexin receptorist" a sa ka a ba le phello ea ho tsosa takatso ea thobalano (Bai et al., 2009), ho bonts'a orexin ea morao-rao e kanna ea se ke ea bapala karolo ea maikutlo a thobalano. Kamora nako, ORX1 blockade ka liente tsa systemic e bonts'itsoe ho senya ts'ebetso ea kopulate e nyane hanyane (Muschamp et al., 2007). Ho tsoa lithutong tsena tse hanyetsanang, ho ka fihleloa liqeto tse 'maloa. Taba ea pele, ts'ebeliso ea orexin-A ea 'mele e ka ama boits'oaro, empa ORX1 blockade ha e na litlamorao tse ngata, e fana ka maikutlo a karolo e nyane bakeng sa orexin ea mehleng ea khale ho taolo ea boitšoaro ba monna ba thobalano (Bai et al., 2009). Liphetho tsa hajoale li tšehetsa monyetla ona. Boithuto ba hajoale bo sebelisang ho tlosa orexin, ka marang-rang a nang le lesapo le ikhethang le bontša hore orexin ha e bohlokoa bakeng sa ts'usumetso ea thobalano kapa ts'ebetso, tumellanong le se hlokometsoeng ke Bai et al (2009). Ho bohlokoa, leha ho le joalo ho ela hloko hore ho haella ha litlamorao tsa ho ruruha ha maqeba ka ts'usumetso ea thobalano tseleng e kanna ea ba ka lebaka la hore liphoofolo li fumane boiphihlelo ba thobalano pele ho liteko tsa thobalano, ka hona ho hloka ts'ebetso litekong tsa Runway ho kanna ha ba teng ho boiphihlelo ba botona le botšehali ba banna. Liteko tsa nako e tlang li ka sebetsana le lehae lena ka ho leka litlamorao tsa lesapo la orexin le tšusumetso ea thobalano ho banna ba naïve.

Hape hoa etsahala hore li-ligands tse peli tsa orexin le li-subtypes tse peli tsa li-orexin receptors (ORX1 le ORX2; Sakurai et al., 1998) e ka laola boitšoaro ba thobalano ka lehlakoreng le fapaneng. Ka ho sebelisa mekhoa ea leseli ea orexin, ligands tsa li-subtypes ka bobeli tsa li-orexin receptors (orexin-A le B) li felisitsoe thutong ea morao-rao. Li-subtypes tse peli tse amohelang li hlahisoa libakeng tse fapaneng tsa boko (Trivesi et al., 1998; Marcus et al., 2001) 'me ba bontšitsoe ho laola ka mokhoa o ikhethileng molemong oa ho batla cocaine (Smith le al., 2009). Lithuto tse fetileng mabapi le boitšoaro ba thobalano li shebile haholo karolo ea orexin-A le ORX1 (bona puisano ka holimo). Orexin receptor antagonist SB334867 e sebelisitsoeng lithutong ho fihlela joale e hlile e rerile ORX1 e nang le tumellano e phahameng ea orexin-A mme e thehiloe ka tlase haholo ho orexin-B (Sakurai et al., 1998). Ka mokhoa o ts'oanang, orexin-A e sebelisitsoe joalo ka orexin ea kantle ho lithuto tsa nakong e fetileng (Gulia et al., 2003; Bai et al., 2009). Lithuto tsa nako e tlang lia hlokahala ho etsa lipatlisiso mabapi le karolo ea orexin-B le ORX2 taolong ea boitšoaro ba banna ba thobalano.

Boithuto ba hona joale bo lekile litlamorao tsa tahlehelo ea nako e telele ea orexin. Muschamp et al. (2007) o khothalelitse hore phokotso ea nako e telele ea orexin kamora ho fallisoa e ka ikarabella bakeng sa tahlehelo ea ts'usumetso ea thobalano le ts'ebetso. Hypothesis ena e ne e hanyetsoa ke liphetho tsa hajoale hobane li-cell tsa orexin ha lia ka tsa fokotsa ts'usumetso ea ts'ebetso ea thobalano kapa ts'ebetso. Ho ka etsahala hore tahlehelo ea nako e telele ea orexin thutong ea hona joale e kanna ea baka lits'ebetso tsa tefello, leha ho se liphetoho tse fumanoeng ho ts'ebetsong ha ho kenella ka hare ho litho tsa boselamose tse amanang le thobalano. Leha ho le joalo, ho hlakile hore ho fokotseha kapa ho haella ha orexin ha ho thibele boitšoaro ba thobalano. Ntle le moo, liphetho tsa thuto ea hona joale ha li tšehetse karolo e kholo ea orexin ho kenyeng polelo ea cFos ka boitšoaro ba thobalano. Ho thehiloe ka ho hlaka hore orexin e kenya letsoho ts'ebetsong ea li-neurons ho VTA (Korotkova et al., 2003; Borgland et al., 2006; Narita et al., 2006; Vittoz et al., 2008). Leha ho le joalo, lesapo la orexin leseling ha lea ka la thibela ts'ebetso ea maqhubu a ho kenella kahare ho VTA, kapa likarolong tse ling tsa boko tse amanang le moputso tse hlahlobiloeng, le ha ho na le li-fibre tse amanang le orexin tse haufi le li-neuron tse kentsoeng ho banna ba sham. Kahoo, ts'ebetso ea neural activation e kenelletsang matong libakeng tsena tsa boko ha e bonahale e itšetleha ka ketso ea orexin.

Phumano e sa lebelloang ea thuto ea morao-rao e bile litlamorao tsa maqeba a orexin ho tataiseng ho qala ha boitšoaro ba thobalano ho naïve, empa e se liphoofolo tse nang le boiphihlelo. Sena se bonts'itsoe se amana le phokotso ea boits'oaro bo joalo ka ho tšoenyeha. Ka hona, litlamorao tsa ho ruruha ha orexin ka tšusumetso ea thobalano le ts'ebetso e kanna ea ba tsa morao ho litlamorao tsa eona ho tšoenyeha le ho tsosa. Ka sebele lithuto tsa pejana li khothalelitse karolo ea orexin matšoenyehong joalo ka ts'ebetso ea ICV ea orexin-Nako e fokotsehileng ea matsoho a bulehileng a EPM litoeba (Suzuki et al., 2005). Ts'oaetso ea orexin-A khubung ea "patalam" ea "likhofu tsa banna" e fokotse nako e sebelisitsoeng kahare ho kamore e bulehileng ea kamore mme ea fokotsa tlhahlobo ea ntho e 'ngoe le e' ngoe, e bonts'ang hore orexin e ka kenella molatong oa boits'oaro bo kang bo tšoenyang (Li et al., 2010). Ntle le moo, likhoto tsa banna tse hlahelletseng tse bonts'ang likotsi tse eketsehileng tsa ho nka ts'oaetso ea EPM li ekelitse maemo a ORX1 mRNA ho mPFC (Davis et al., 2009). Orexin e boetse e bontšitsoe ho fetola likarabo tsa khatello ea maikutlo (Ida et al., 1999; Ida et al., 2000), le ho tsosa li-receptor tsa orexin ho eketsa ho lokolloa ha corticotrophin relection factor (Al-Barazanji et al., 2001; Singareddy et al., 2006), corticosterone (Ida et al., 2000; Kuru et al., 2000) le hormone ea adrenocorticotropic (Kuru et al., 2000). Barekisi ba Orexin hajoale ba tekong ea bongaka bakeng sa kalafo ea ho hlobaela, lefu leo ​​hangata le kopanang le mathata a ho tšoenyeha (Sullivan le Neria, 2009), 'me ho nahanoa hore lingaka tsa orexin li ka sebelisoa ho phekola mathata a ho tšoenyeha (Mathew et al., 2008). Ha ho fanoa ka 'mele o ntseng o hola oa bopaki ba karolo ea orexin ho tšoenyeha le ho tsosa, ho bonahala eka marapo a orexin a ka thusa ho qala ts'ebetso ea thobalano ho banna ba sa tsebeng ka ho fokotsa likarabo tse kang ho tšoenyeha ho amanang le ho hlahisoa ha tšusumetso ea nalane.

Ts'ebetso ea bohlokoa ea li-neurone tsa orexin e ile ea bonoa kamora ho ts'oara takatso ea thobalano le liphoofolo tse nang le thobalano le liphoofolo tse nang le boiphihlelo ho PFA-DMH le LHA, ka 60-80% le 14-33% ea lisele tsa orexin tse hlalosang li-cFos, ka ho latellana. Ho na le bopaki ba 'mele bo tšehetsang dichotomy ho ts'ebetso ea methapo ea orexin ka har'a sele ea orexin, ha PFA-DMH e kenya letsoho ka mokhoa o makatsang molemong oa ho tsosa le LHA e le bohlokoa bakeng sa boits'oaro bo amanang le moputso (Harris et al., 2005; Harris le Aston-Jones, 2006, Aston-Jones, 2009a). Ka hona, ts'ebetso ea lisele tsa PFA-DMH orexin ka ts'usumetso ea mosali e ts'ehetsa maikutlo a hore orexin e qaliloe ke 'me e bohlokoa bakeng sa ho tsosa, ho kenyeletsa le ho tsosa takatso ea botona kapa botšehali ho banna ba nang le boiphihlelo, le matšoenyeho a amanang le ts'usumetso ea basali e sa tsoa hlaha ho ba batona ba lilemong. Leha ho le joalo, lisele tsa PFA-DMH li ile tsa qobelloa ho ba maemong a ts'oanang le boiphihlelo ba banna le boemo ba lihono tsa mosali, ho fana ka maikutlo a hore lisele tsa PFA-DMH li hlahisitsoe nakong ea mofetoheli ka kakaretso eseng ka kotloloho ke bohlola. Ntle le moo, lithuto tsa rona ha li tšehetse ka botlalo boteng ba palo ea lisele tsa dichotomous orexin ka ha ho bile le ts'ebetso e kholo ea ho ts'oaroa ha LHA ho latela mahlakore ohle a ts'ebetso ea thobalano le ts'ebetso, ho sa tsotelehe hore na boits'oaro bo ne bo amana le moputso. Ka hona, ba batona ba nang le boiphihlelo ba pepeselitsoeng ho mosali ea makatsang ba bontšitse maemo a lekanang a ts'ebetso ea sele ea orexin ho LHA ​​ha a bapisoa le ba batona ba nang le boiphihlelo ba kopaneng le kemiso. Leha ho le joalo, ke sehlopha sa morao-rao se tla etsa mofuta oa boikhethelo bakeng sa ho tlolelana (Tenk et al, 2009); Ho fana ka maikutlo a hore ho kopitsa tloaelo ea kemiso ea motho linthong tsa tlhaho e na le moputso o moholo ho feta likarolo tse ling tsa ho ikatisa. Boithuto ba hona joale ha boa ka ba leka ka ho khetheha karolo ea orexin moputsong oa thobalano; ke ka hona lithuto tsa nako e tlang li hlokahalang ho araba potso eo.

Ka kakaretso, litholoana tsa lithuto tsena li bonts'a hore orexin ha e bohlokoa bakeng sa ts'ebetso ea thobalano kapa sepheo. Sebakeng seo, marang-rang a orexin a ile a bontšoa ho fokotsa ho tšoenyeha, a fana ka maikutlo a hore orexin ea morao-rao e kenyelletsa ho tšoenyeha ho eketsehileng. Ho feta moo, ho tlosoa hoa orexin ho felletse ka mokhoa oa ts'ebetso ea ho qala ts'ebetso ea thobalano ho banna ba nang le thobalano, ho fana ka maikutlo a hore orexin ea mehleng ea khale e ka thibela ho qaleha ha mpa, mohlomong ka ho eketsa matšoenyeho ho arabela tsusumetso ea nalane. Liphumano tsena li hlakisa haholo ho potoloha ha neano ho amehang tšebetsong ea thobalano le matšoenyeho, hape li eketsa 'mele o ntseng o eketseha oa lingoliloeng ka karolo ea orexin molemong oa ho kopanya le ho tšoenyeha.

Liteboho

Patlisiso ena e ne e tšehelitsoe ke lithuso ho tsoa ho National Institutes of Health (R01 DA014591), Canadian Institutes of Health Research (RN 014705), le Litsebi tsa Naha tsa Saense le Boenjiniere ba Canada (Discovery Grant (341710) ho ea LMC.

Mongolo o botlaaseng ba leqephe

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

References

  1. Agmo A. Boits'oaro ba thobalano ea banna. Brain Res Brain Res Protoc. 1997; 1: 203-209. [E fetotsoe]
  2. Al-Barazanji KA, Wilson S, Baker J, Jessop DS, Harbuz MS. Central orexin-A activate hypothalamic-pituitary-adrenal axis mme e hlohlelletsa hypothalamic corticotropin e lokollang ntlha le arginine vasopressin neurones ho likhoto tse hlokolosi. J Neuroendocrinol. 2001; 13: 421-424. [E fetotsoe]
  3. Aston-Jones G, Smith RJ, Moorman DE, Richardson KA. Karolo ea methapo ea kutlo ea methapo ea kutlo ea orexin ts'ebetsong ea moputso le ho lemalla. Neuropharmacology. 2009a; 56 Suppl 1: 112-121. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  4. Aston-Jones G, Smith RJ, Sartor GC, Moorman DE, Massi L, Tahsili-Fahadan P, Richardson KA. Hamorao hypothalamic orexin / hypocretin neurons: Karolo ea ho batla moputso le ho lemalla. Brain Res. 2009b; 1314: 74-90. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  5. Bai YJ, Li YH, Zheng XG, Han J, Yang XY, Sui N. Orexin A attenuates tšusumetso e sa utloahaleng ea thobalano ho likhoto tsa banna. Pharmacol Biochem Behav. 2009; 91: 581-589. [E fetotsoe]
  6. Bäckberg M, Hervieu G, Wilson S, Meister B. Orexin receptor-1 (OX-R1) ts'ireletso ea methapo ea methapo e khethollotsoeng ka lik'hemik'hale tsa hypothalamus: tsepamisa maikutlo ho litheko tsa orexin tse kenyang taolo ea tšebeliso ea lijo le metsi. Eur J. Neurosci. 2002; 15: 315-328. [E fetotsoe]
  7. Baldo BA, Daniel RA, Berridge CW, Kelley AE. Ho arolelana ho arohanngoa ha orexin / hypocretin- le dopamine-beta-hydroxylase-immunoreactive fibers libakeng tsa boko ba litoe tse buellang ho tsosoa, ho susumetsa le khatello ea kelello. J Comp Neurol. 2003; 464: 220-237. [E fetotsoe]
  8. Balfour ME, Yu L, Coolen LM. Boits'oaro ba botona kapa botšehali le litsebi tsa tikoloho tse amanang le likamano tsa botona le botšehali li nolofalletsa tsamaiso ea mesolimbic ka likhoto tsa banna Neuropsychopharmacology. 2004; 29: 718-730. [E fetotsoe]
  9. Benoit SC, Tracy AL, Davis JF, Choi D, Clegg DJ. Mesebetsi ea novel ea li-peptides tsa orexigenic hypothalamic: ho tloha liphatseng tsa lefutso ho ea ho boits'oaro. Phepo e nepahetseng. 2008; 24: 843-847. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  10. Borgland SL, Taha SASF, Fields HL, Bonci A. Orexin A ho VTA e bohlokoa bakeng sa ho kenngoa ha polasetiki ea synaptic le maikutlo a boitšoaro ho cocaine. Neuron. 2006; 49 (4): 589-601. [E fetotsoe]
  11. Boutrel B, Cannella N, de Lecea L. Karolo ea hypocretin ho khanna boits'oaro bo khahlisang le bo nang le sepheo. Brain Res. 2009 [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  12. Boutrel B, Kenny PJ, Specio SE, Martin-Fardon R, Markou A, Koob GF, de Lecea L. Role bakeng sa hypocretin ho loants'ong khatello ea maikutlo le e bakiloeng ke boits'ebetso ba ho batla koae. Proc Natl Acad Sci US A. 2005; 102: 19168-19173. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  13. Broberger C, De Lecea L, Sutcliffe JG, Hoktima T. Hypocretin / orexin- le melanin-tsepamisa mohopolo lisele tse hlahisang li-hormone li theha lipapatso tse fapaneng methapong ea methapo ea methapo e amanang le methapo ea methapo. J Comp Neurol. 1998; 402: 460-474. [E fetotsoe]
  14. Carter ME, Borg JS, de Lecea L. Li-hypocretins tsa bongo le li-receptors tsa bona: babuelli ba matla a manyolo ka ho fetesisa. Curr Opin Pharmacol. 2009; 9: 39-45. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  15. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M. Narcolepsy ho litoeba tsa orexin. : genetics ea limolek'hule tsa molao oa ho robala. Sele. 1999; 98: 437-451. [E fetotsoe]
  16. Chen CT, Dun SL, Kwok EH, Dun NJ, Chang JK. Orexin A-like immunoreactivity bokong ba rat. Neurosci Lett. 1999; 260: 161-164. [E fetotsoe]
  17. Choi DL, Davis JF, Fitzgerald ME, Benoit SC. Karolo ea orexin-A ka tšusumetso ea lijo, boitšoaro bo itšetlehileng ka moputso le ts'ebeliso ea lijo ea neuronal ka likhoto. Khopolo-taba. 2010; 167: 11-20. [E fetotsoe]
  18. Davis JF, Krause EG, Melhorn SJ, Sakai RR, Benoit SC. Likhoto tse atisang ho hlaseloa ke likotsi tsa tlhaho 'me li bontša sepheo se eketsehileng sa moputso oa lijo. Neuroscience. 2009; 162: 23-30. [E fetotsoe]
  19. de Lecea L, Jones BE, Boutrel B, Borgland SL, Nishino S, Bubser M, DiLeone R. Ho lemalla le ho tsosa takatso: likarolo tse ling tsa li-peptides tsa hypothalamic. J. Neurosci. 2006; 26 (41): 10372-10375. [E fetotsoe]
  20. de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS, 2nd, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG. Li-hypocretins: li-peptide tse khethehileng tsa hypothalamus tse nang le ts'ebetso ea neuroexcitatory. Proc Natl Acad Sci US A. 1998; 95: 322-327. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  21. Dewsbury DA. Boitšoaro bo kopanyang ba likhoto (Rattus norvegicus) e le ts'ebetso ea boiphihlelo ba pele ba ho kopitsa. Ntoa ea Behav. 1969; 17: 217-223. [E fetotsoe]
  22. Fadel J, Deutch AY. Likarolo tse ling tsa maqhubu a tšebelisano ea orexin-dopamine: merero ea hypothalamic ea morao-rao sebakeng sa mokokotlo oa ventral. Neuroscience. 2002; 111: 379-387. [E fetotsoe]
  23. Frederick-Duus D, Guyton MF, Fadel J. Lijo tse hlahisitsoeng ka mokhoa o phahameng oa cortical acetylcholine li hloka phetiso ea orexin. Neuroscience. 2007; 149: 499-507. [E fetotsoe]
  24. Furlong TM, Carrive P. Lits'ebetso tsa marang-rang li tsepamisitse maikutlo ho sefofane sa hypothalamus li hlakola karabelo ea pelo le boits'oaro ea maemo a tšabo a maemo empa eseng ea thibelo. Brain Res. 2007; 1128: 107-119. [E fetotsoe]
  25. Furlong TM, Vianna DM, Liu L, Carrive P. Hypocretin / orexin e kenya letsoho ho hlahiseng tse ling empa eseng mefuta eohle ea khatello le maikutlo. Eur J Neurosci. 2009; 8: 1603-1614. [E fetotsoe]
  26. Gerashchenko D, Kohls MD, Greco M, Waleh NS, Salin-Pascual R, Kilduff TS, Lappi DA, Shiromani PJ. Hypocretin-2-saporin lesions ea hypothalamus ea morao-rao e hlahisa tloaelo ea boroko ea narcoleptic-rat. J Neurosci. 2001; 21: 7273-7283. [E fetotsoe]
  27. Gulia KK, Mallick HN, Kumar VM. Sesebelisoa sa Orexin A (hypocretin-1) sebakeng sa medial preoptic se ka baka boitšoaro ba monna ba thobalano ho likhoto. Neuroscience. 2003; 116: 921-923. [E fetotsoe]
  28. Hagan JJ, Leslie RA, Patel S, Evans ML, Wattam TA, Holmes S, Benham CD, Taylor SG, Routledge C, Hemmati P, Munton RP, Ashmeade TE, Shah AS, Hatcher JP, Hatcher PD, Jones DN, Smith MI , Piper DC, Hunter AJ, Porter RA, Upton N. Orexin A activates locus coeruleus cell firing mme e eketsa nyakallo ho rat. Proc Natl Acad Sci US A. 1999; 96: 10911-10916. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  29. Harris GC, Aston-Jones G. Arousal le moputso: dichotomy ts'ebetsong ea orexin. Mekhoa ea Neurosci. 2006; 29: 571-577. [E fetotsoe]
  30. Harris GC, Wimmer M, Aston-Jones G. Karolo bakeng sa li-neurons tsa morao-rao tsa hypothalamic ho oreng moputso. Tlhaho. 2005; 437 (7058): 556-559. [E fetotsoe]
  31. Horvath TL, Peyron C, Diano S, Ivanov A, Aston-Jones G, Kilduff TS, van Den Pol AN. Hypocretin (orexin) ts'ebetso ea ts'ebetso le ts'oaetso ea synaptic ea tsamaiso ea locus coeruleus noradrenergic. J Comp Neurol. 1999; 415: 145-159. [E fetotsoe]
  32. Ida T, Nakahara K, Katayama T, Murakami N, Nakazato M. Lithapo tsa morao-rao tsa "cerebroventricular" tsa "naropeptide" tsa takatso ea lijo, orexin le neuropeptide Y, mesebetsing e fapaneng ea boits'oaro ea litoeba. Brain Res. 1999; 821: 526-529. [E fetotsoe]
  33. Ida T, Nakahara K, Murakami T, Hanada R, Nakazato M, Murakami N. Ho nka karolo ha orexin maemong a khatello literekeng. Biochem Biophys Res Commun. 2000; 270: 318-323. [E fetotsoe]
  34. Korotkova TM, Sergeeva OA, Eriksson KS, Haas HL, Brown RE. Ho khahlisoa ke "neuropreterg" le dopaminergic tsa sebakeng se kenang ka hare tsa mokokotlo ka li-orexins / hypocretins. J Neurosci. 2003; 23 (1): 7-11. [E fetotsoe]
  35. Kuru M, Ueta Y, Serino R, Nakazato M, Yamamoto Y, Shibuya I, Yamashita H. Lekhotla le tsamaeang le orexin / hypocretin le kenya li-axis tsa HPA ka likhoto. Neuroreport. 2000; 11: 1977-1980. [E fetotsoe]
  36. Li Y, Li S, Wei C, Wang H, Sui N, Kirouac GJ. Liphetoho ho boits'oaro ba maikutlo bo hlahisoang ke orexin microinjections karolong ea patencyricular ea thalamus. Pharmacol Biochem Behav. 2010; 95: 121-128. [E fetotsoe]
  37. Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E. Bothata ba ho robala bo ka sitisa narcolepsy ho bakoa ke phetoho ea mofuta oa "hypocretin" (orexin) receptor 2 . Sele. 1999; 98: 365-376. [E fetotsoe]
  38. Lopez HH, Olster DH, Ettenberg A. Khothatso ea thobalano ka hara moetlo oa monna: karolo ea litheko tsa mantlha le boiphihlelo ba bohlasoa. Horm Behav. 1999; 36: 176-185. [E fetotsoe]
  39. Marcus JN, Aschkenasi CJ, Lee CE, Chemelli RM, Saper CB, Yanagisawa M, Elmquist JK. Polelo e fapaneng ea li-receptors tsa orexin 1 le 2 bokong ba rat. J Comp Neurol. 2001; 435: 6-25. [E fetotsoe]
  40. Martin G, Fabre V, Siggins GR, de Lecea L. Ho kenella ha li-hypocretins ka li-neurotransmitters ho li-nucleus accumbens. Regul Pept. 2002; 104: 111-117. [E fetotsoe]
  41. Mathew SJ, theko RB, Charney DS. Tsoelo-pele ea morao-rao ho neurobiology ea mathata a ho tšoenyeha: litlamorao ho lingaka tse ncha. Am J Med Genet C Semin Med Genet. 2008; 148C: 89-98. [E fetotsoe]
  42. Muschamp JW, Dominguez JM, Sato SM, Shen RY, Hull EM. Karolo ea hypocretin (orexin) ka boits'oaro ba monna. J Neurosci. 2007; 27: 2837-2845. [E fetotsoe]
  43. Nka SG, Golden SA, Shaham Y. Phapang e fapaneng ea hypocretin 1 receptor antagonist SB 334867 mabapi le boits'oaro bo phahameng ba ho itaola le ho khutlisetsa lijo tse batlang litlelong. Br J Pharmacol. 2008; 154: 406-416. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  44. Narita M, Nagumo Y, Hashimoto S, Khotib J, Miyatake M, Sakurai T, Yanagisawa M, Nakamachi T, Shioda S, Suzuki T. Ho kenella ka kotlolloho ha lits'ebetso tsa orexinergic ts'ebetsong ea tsela ea mesolimbic dopamine le boits'oaro bo amanang le eona bo hlohlellelitsoeng ke morphine. J Neurosci. 2006; 26: 398-405. [E fetotsoe]
  45. Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E. Hypocretin (orexin) bofokoli ba manonyeletso a batho. Lancet. 2000; 355: 39-40. [E fetotsoe]
  46. Paxinos G, Watson C. Sebaka sa Rat ho Stereotaxic Coordinates. San Diego, CA: Pressic Press; 1998.
  47. Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, Li R, Hungs M, Pedrazzoli M, Padigaru M, Kucherlapati M, Fan J, Maki R , Lammers GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E. Phetoho litabeng tsa tšitiso ea bokhachane le pherekano e akaretsang ea li-peptide tsa hypocretin methapong ea batho ea kelello. Nat Med. 2000; 6: 991-997. [E fetotsoe]
  48. Peyron C, Tighe DK, van den Pol AN, Lecea L, Heller HC, Sutcliffe JG, Kilduff TS. Li-neurons tse nang le hypocretin (orexin) bakeng sa mefuta e mengata ea neuronal. J Neurosci. 1998; 18: 9996-10015. [E fetotsoe]
  49. Sakurai T. Likarolo tsa li-orexin le li-receptor tsa orexin taolong e bohareng ea boits'oaro ba phepo le homeostasis ea matla. Lits'ebetso tsa lithethefatsi tsa CNS Neurol Disord. 2006; 5: 313-325. [E fetotsoe]
  50. Sakurai T. Potoloho ea neural ea orexin (hypocretin): ho boloka boroko le ho tsoha. Nat Rev Neurosci. 2007; 8: 171-181. [E fetotsoe]
  51. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, ​​Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS , Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M. Orexins le li-orexin receptors: lelapa la li-hypothalamic neuropeptides le li-receptors tsa G tsa protheine tse laolang boitšoaro ba phepo. Sele. 1998; 92: 573-585. [E fetotsoe]
  52. Satoh S, Matsumura H, Fujioka A, Nakajima T, Kanbayashi T, Nishino S, Shigeyoshi Y, Yoneda H. FOS polelo ka polelo ea orexin neurons e latelang mascimol perfusion ea sebakeng sa preoptic. Neuroreport. 2004; 15: 1127-1131. [E fetotsoe]
  53. Siegel JM. Narcolepsy: Karolo ea bohlokoa bakeng sa li-hypocretins (orexins) Cell. 1999; 98: 409-412. [E fetotsoe]
  54. Singareddy R, Uhde T, Commissaris R. Litharollo tse fapaneng tsa li-hypocretins ho li-noise-peke le likarabo tse nang le tšabo. Physiol Behav. 2006; 89: 650-655. [E fetotsoe]
  55. Smith RJ, Bona RE, Aston-Jones G. Orexin / hypocretin e tšoaea mochini oa li-receptor oa orexin 1 e laola ho batla-koae hoa mofuta oa cocaine. Eur J Neurosci. 2009; 30: 493-503. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  56. Solomon A, De Fanti BA, Martinez JA. Peripheral ghrelin e kenella le li-neuron tsa orexin ho ho saena hoa glucostatic. Regul Pept. 2007; 144: 17-24. [E fetotsoe]
  57. Sullivan GM, Neria Y. Pharmacotherapy ho khatello ea maikutlo ea morao-rao e sithabetsang: bopaki bo tsoang litekong tse laoloang ka tšohanyetso. Lithethefatsi tsa Curr Opin Inarcher. 2009; 10: 35-45. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  58. Suzuki M, Beuckmann CT, Shikata K, Ogura H, Sawai T. Orexin-A (hypocretin-1) e kanna ea ameha molatong oa boitšoaro bo kang ba ho tšoenyeha. Brain Res. 2005; 1044: 116-121. [E fetotsoe]
  59. Tenk CM, Wilson H, Zhang Q, Pitchers KK, Coolen LM. Moputso oa thobalano ho litoeba tsa banna: litlamorao tsa boiphihlelo ba botona le botšehali ho likhetho tsa sebaka se ikamahantseng le kameho ea setho sa botona kapa botšehali. Horm Behav. 2009; 55: 93-97. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  60. Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, Cornford M, Siegel JM. Palo e fokotsehileng ea li-hypocretin neurons ho narcolepsy ea motho. Neuron. 2000; 27: 469-474. [E fetotsoe]
  61. Thorpe AJ, Cleary JP, Levine AS, Kotz CM. Orexin e laoloang bohareng ke eona e eketsang khothalletso ea li-pellets tse monate ho likhoto. Psychopharmacology (Berl) 2005; 182: 75-83. [E fetotsoe]
  62. Trivesi P, Yu H, MacNeil DJ, Van der Ploeg LH, Guan XM. Tsamaiso ea orexin receptor mRNA bokong ba rat. FEBS Lett. 1998; 438: 71-75. [E fetotsoe]
  63. Vittoz NM, Schmeichel B, Berridge CW. Hypocretin / orexin ka mokhoa o ikhethileng o kenya tšebetsong sebaka sa dopamine neurudomedial ventral tegmental. Eur J Neurosci. 2008; 28: 1629-1640. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  64. Volgin DV, Swan J, Kubin L. single cell RT-PCR gene expression profiling of accac. li-neurons tse bohareng le tse sa khetholloang. J. Neurosci Mekhoa. 2004; 136: 229-236. [E fetotsoe]