Umphumo we-Orexin Umphikisi (SB-334867) ukumnika kwi-nucleus ehlangene nokuziphatha kunye nokukhethwa kotywala kwizilwanyana ze-Wistar (2016)

 

Abstract

Injongo:

I-Nucleus accumbens (NAcc) inendima ekukhohliseni nasekuziphatheni kokutya. Ukuze sivavanye inkqubo ye-orexinergic ebandakanyekayo koku, sifake umchasi we-Orexin kwaye savavanya isiphumo ekuthathweni kolwelo lokutya kunye nokukhethwa kotywala kwiimpuku zeWistar.

Impahla nenkqubo:

Inbred Wistar iimpuku (n = 54) zahlulwa zibe ngamaqela olawulo kunye novavanyo (idosi ephantsi kunye nedosi ephezulu). Ukusebenzisa indlela ye-stereotaxic, i-cannula yesikhokelo yamiselwa kwindawo yamazwe amabini ukufikelela kwi-NAcc. Idosi ephantsi (3 ng) kunye nedosi ephezulu (6 ng) ye-Orexin A antagonist (SB-334867) yafakwa, kunye nokusetyenziswa kokutya, ukuthathwa kwamanzi kunye nokusela utywala, kunye novavanyo olukhethiweyo lweebhotile simahla lokukhetha utywala lwenziwa kwi iqela lokulinga. Iqela lolawulo lifumene ukufakwa kwe-saline kwaye ezinye iindlela ezilandelwayo zazifana. Imilinganiselo iqhutywe ngokukhawuleza emva kokuxilwa, kwi-1 h, 2 h, 4 h, kunye nosuku lonke kwaye imelwe kumfanekiso kunye neetafile.

iziphumo:

Ukuncipha kokungena kwamanzi kubonwe ngokukhawuleza emva kokungena kwi-1st h (P <0.05) kunye ne-2nd h (P <0.01), eyayingaphezulu kwiqela ledosi ephezulu xa kuthelekiswa nedosi ephantsi kunye nolawulo. Ukusela utywala kwakulandela indlela efanayo. Kwiibhotile ezimbini ezikhethiweyo ezikhululekile, iigundane azizange zibonise ukhetho oluthile lotywala.

Isiphelo:

Kwakukho ukucutha okuxhomekeke kwithamo ekuthathweni kokutya kunye nolwelo kwiimpuku ezinyangweyo. Oku kucebise ngendima enokwenzeka yenkqubo ye-orexinergic ekuziphatheni kokutya. Nangona kunjalo, i-Orexin A isenokungabi nanxaxheba ekumodareyitheni likhoboka lotywala liziko elinomvuzo le-NAcc.

AMAZWI ANGAPHAMBILI: I-Nucleus accumbens, ukutya, i-Orexin-A antagonist (SB-334867), amanzi kunye notywala

intshayelelo

i-accumbens (NAcc) yaziwa ngokuchaphazela indlela yokuziphatha yokungena kunye nokuba likhoboka lezinto.,] Ikwabandakanyeke emvuzweni nakwinkuthazo.] Imimandla emibini eyahlukileyo ichaziwe kwi-NAcc, kwaye kuvele ukuhlangana okuninzi ekusebenzeni kwale mimandla mibini.] Isitofu seMicroijection yeziyobisi ezikhobokisayo kwi-NAcc ibonise ukonyuka okuxhomekeke kwithamo kumanqanaba e-dopamine. I-Dopamine yi-neurochemical ebandakanyekayo kumvuzo wokujikeleza. Ukuzilawula kwe-amphetamine kwi-Intranuclear kubonise ukonyuka kwemvakalelo yomvuzo.] Ezinye iindawo ezikummandla ongaphantsi kweekhorotiki nazo zinempembelelo kwindlela yokuziphatha yokungenisa, enokuthi inxulunyaniswe ngokusondeleyo ne-accumbens. Ukutya kunye nokuthathwa kwamanzi kuboniswe ukuba kuphenjelelwe ngamacandelo amaninzi engqondo ye-basal, njenge-lateral hypothalamus, [] i-nucleus yeparaventricular, i-septum pellucidum,[] kunye ne-basolateral amygdala.] Kukho uthungelwano olubanzi lwe-neural kulawulo lokuziphatha kokutya. I-NAcc ibonakaliswe ukuba ixhunywe kakuhle kumaziko angaphantsi kwe-subcortical, njenge-ventral tegmental area (VTA);[] i-basolateral amygdala kunye namanye amaziko.] Ii-neurotransmitters ezinkulu ezibandakanyekayo ekuhlengahlengisweni kotywala, ukuvuzwa, kunye nokutya kwabikwa kwi-neural circuits kulo mmandla.]

Kungekudala, i-hypocretins, iqela leepeptide ezingafaniyo, zichongiwe kwi-hypothalamus, i-hypocretin 1 kunye ne-2 (i-Orexin A kunye ne-B), i-peptides ene-32 aa kunye ne-29 aa, ngokulandelanayo.] Ekuqaleni, ezi zinto ziye zabandakanyeka kulawulo lomjikelo wokuvuka kokulala, njengoko kungqinwa kukunyuka kwe-Orexin A efunyenwe kwi-hypothalamus ngexesha lesigaba esisebenzayo sokuvuka.] Kwibhubhoratri yethu, sifumene ukuba i-Orexin A yonyusa ukutya kunye nokuthatha ulwelo xa itofwe kwi-NAcc.] I-antibody elawulwa ngumbindi ye-orexin inqanda ukutya okuxhomekeke kwi-24 h iigundane ezizila ukutya, kunye nokulawulwa kwe-intraperitoneal ye-orexin antibody ayikwazanga ukucinezela ukusetyenziswa kokutya, imele ukuba i-orexin antibody isebenza kwinkqubo ye-nervous central kodwa kungekhona kwi-peripheral tissue.] Ngaphezu koko, baye baqinisekisa ukuba i-orexins engapheliyo inendima ye-physiological ekuziphatheni kokutyisa. Nangona ekuqaleni ii-Orexins zaye zachatshazelwa ukuba zichaphazele indlela yokuziphatha kokutya, ubungqina bendima ye-Orexin A ekuziphatheni kokutyisa kunye nokusela utywala kunye nokukhethwa kotywala ngumzobo. Kuphononongo lwethu lwangaphambili, siye sabonisa ukuba i-Orexin A yonyusa ukutya kunye nokutya okunomanzi kwiimpuku ezizila ukutya.] Ukuze kucaciswe indima ye-Orexin A kumsebenzi wokutya ngokungathandabuzekiyo, siye saqhuba le seti yovavanyo kwiigundane ze-Wistar eziyindoda ezizila ukudla ubusuku bonke, ngokufaka umchasi we-Orexin A u-SB-334867 kwi-NAcc.] Siphinde savavanya ukhetho lotywala kwiigundane eziphathwayo ukuze sicacise umphumo we-Orexin Umchasi ochasene notywala. Iziphumo zovavanyo lokutya, amanzi kunye nokusela utywala, kunye nokukhethwa kotywala kuxoxwa ngazo apha.

Impahla nenkqubo

Amashumi amahlanu anesine eempuku ze-Wistar albino (n = 54) ubunzima (250 ± 10 g), iinyanga ezi-3-4 ubudala zakhethwa ukuba zifundwe. Bohlulwa bangamaqela amathathu oko kukuthi. Iqela lamanzi, iqela lotywala kunye neqela elikhethiweyo leebhotile ezimbini (n = 18 nganye). Zahlulwa zaba ngamacandelwana amathathu, oko kukuthi. Iqela le-1 - Ukulawula (i-Saline infusion); Iqela le-2 - I-dose ephantsi ye-SB-334867 (3 ng); Iqela le-3 - Umthamo ophezulu we-SB-334867 (6 ng, n = 6 nganye). Ukutya kunye nolwelo lwanikezelwa kuwo onke amaqela i-ad lib, ngaphandle kwalapho kukhankanyiweyo ngokuzila ukutya ebusuku.

Zonke izilwanyana zahlaliswa ngabanye kwii-polypropylene cages, kunye neebhedi ezifanelekileyo ze-husk kwaye zigcinwe kwi-12-h ukukhanya / umjikelezo omnyama kwindawo elawulwa yiqondo lokushisa. Izilwanyana zagcinwa ngokwezikhokelo zekomiti ngenjongo yokulawula kunye nokubeka iliso kwiimvavanyo kwizilwanyana kunye nezikhokelo zikaRhulumente waseIndiya zokusetyenziswa kwezilwanyana zaselebhu. IKomiti yeZiko yezokuziphatha yezilwanyana yamkele le nkqubo yophononongo.

Iziyobisi kunye nezixhobo

I-Saline 0.9%, i-SB-334867 (Ukusuka: i-Tocris bioscience) yachithwa kwi-2% ye-cyclodextran emanzini ayinyumba. Xa zingasetyenziswa, izisombululo zigcinwe kwi-4 ° C ukuya kwiiveki ezi-3. Impompo yokufakela yeHarvard Pico plus (USA) yasetyenziswa ukuhambisa ichiza. Amanzi etephu anikezelwa ngeebhotile zePlastiki zokusela, kunye neepellets zokutya zeempuku (Hindustan Unilever Ltd.,) zanikezelwa. I-Ethyl alcohol (Absolute) yathengwa (Hayman Ltd., Eastways Park, Witham, Essex, CM83YE, UK) kwaye ihlanjululwe ukwenza i-10% yotywala (Olu gxininiso lukhethwe ngokusekelwe kwisifundo somqhubi malunga nokukhetha koxinzelelo lotywala) . I-Ketamine (i-NEON Laboratories limited, i-Thane, i-MS) kunye ne-xylazine (i-Indian immunological Ltd., i-Hyderabad) yayisetyenziselwa i-anesthesia.

Inkqubo yoNyango

Iigundane ze-Wistar ze-albino ze-Anesthetized ngokujova umxube we-ketamine hydrochloride (60 mg / kg), i-xylazine hydrochloride (6 mg / kg) kwaye ifakwe kwi-stereotaxic apparatus (Inco, India). Kwasikwa entlokweni, kwakhutshwa iintsholongwane ngokupheleleyo ngomoya wotyando. Le ndawo yacocwa ngomqhaphu nehydrogen peroxide. Amanqaku okulungelelanisa aphawulwe kukhakhayi kwiindawo ezihambelanayo ukufikelela kwi-NAcc, ngokubhekisele kwi-Paxinos kunye ne-Watson brain atlas[] (Ukusuka eBregma: Anteroposterior +2.2 mm, i-lateral ± 1 mm kunye ne-7.4 mm ethe nkqo). Umngxuma we-Burr wenziwa, kwaye i-cannula ye-stainless steel guide (i-22 gauze) yafakwa ngokuhambelana ne-stereotaxic coordinates. Emva kokuba i-cannula isendaweni, ikhuselekile ngoncedo lwezikrufu kunye ne-acrylic yamazinyo. I-cannula yesikhokelo yayifakelwe i-stylet, kwaye iimpuku zavunyelwa ukuba ziphinde ziphinde ziphinde ziphinde ziphinde ziphinde ziphinde ziphinde ziphinde ziphile ubuncinane iintsuku ezisi-7 phambi kovavanyo. I-infusion cannula (i-cannula yangaphakathi) yenziwe ukusuka kwinaliti yamazinyo ye-Septoject yensimbi engenasici yeegeyiji ezingama-30 ezinehabhu, elungele ukuphathwa.] I-cannula ye-infusion yandisa nge-1 mm ngaphaya kwe-cannula yesikhokelo. Ngaphambi kokuqala kovavanyo zonke iimpuku zafumana iiseshoni zoqeqesho ezimbini apho zazigcinwe kwi-24 h ukuzila emva koko zafumana ukutya, amanzi, kunye ne-10% yotywala. Ngethuba le seshoni, iigundane zafunda ukuzila ukudla.

Inkqubo yovavanyo

I-saline eqhelekileyo kunye ne-SB-334867 (kwiidosi ezimbini) zafakwa, ngokulandelanayo, kumaqela ahlukeneyo amagundane emva kokuzila ukutya kwe-24 h; iimpuku ezingachazwanga (ezihamba simahla) ngokusebenzisa icannula yesikhokelo ekhuselekileyo. I-infusion yenziwa nge-10 μl yesirinji ye-Hamilton edibene netyhubhu ye-polyethylene kunye ne-cannula yangaphakathi. Le isirinji yayifakelwe impompo yaseHarvard. Emva koko i-stylet efakwe kwi-cannula yesikhokelo yasuswa. I-cannula yangaphakathi ifakwe kwi-cannula yesikhokelo kwaye ikhuselekile. Emva koko impompo yaqaliswa ukuhambisa isisombululo kwicala lasekunene nelasekhohlo le-NAcc enye emva kwenye, i-1 μl/min (emva kokufakwa kwe-cannula yangaphakathi ekhohlo malunga ne-10 s ukuvumela ukusasazwa kwechiza). Amanani amabini e-SB-334867 afakwe kwi-3 ng (i-dose ephantsi) kunye ne-6 ng (i-dose ephezulu). Ekupheleni kokufakwa, i-cannula yangaphakathi yasuswa, kwaye i-stylet yabuyiselwa kwindawo kunye nexesha laphawulwa. I-post infusion, ngokukhawuleza isixa esilinganiselweyo sokutya, amanzi, kunye ne-10% yotywala yanikezelwa ngokwamaqela ahlukeneyo. Umphumo we-SB-334867 ekusetyenzisweni ulinganiswe kwaye waqatshelwa, ngokucokisekileyo ngexesha le-infusion intervals 1, 2, 4, kunye ne-24 h, ngokulandelanayo. Iipellets ezisele, amanzi, kunye notywala zaye zasuswa, kwaye imali esetyenzisiweyo yabalwa (Isixa esisetyenzisiweyo = Isixa esilinganisiweyo-esele sishiye ubuninzi, umz. ekupheleni kwe-1 h).

Emva kokugqitywa kophononongo, iimpuku zabingelelwa ngedosi ebulalayo ye-anesthesia kwaye ingqondo yakhutshelwa ngaphandle kwaye yagcinelwa ukusetyenzwa kwe-histological. Amacandelo asixhenxe emicron aye acandwa kwaye adyojwa ngecresyl violet ukuqinisekisa indawo yokufakelwa [Umzobo 1].

Umzobo 1 

I-Orexin Umphikisi (SB-334867) kwi-nucleus accumbens. Imivalo imele, (a) amanzi kunye (b) nokutya kokutya kweegundane ezifakwe kwi-SB-334867 kwi-nucleus accumbens, kwi-1st, 2nd, 4th kunye nexesha le-24 h kunye nedosi ye-0 (0.9% saline = Iqela le-1) kunye ne-3 ng SB-334867 ...

Uhlalutyo lweSatisati

Uhlalutyo lwedatha lwenziwa kusetyenziswa i-software ye-SPSS version ye-statistical - 16 (SPSS yeWindows, Version 16.0. Chicago, SPSS Inc. USA); indlela enye ANOVA yenziwa ukuthelekisa ukuziphatha kokugqiba phakathi kwamaqela. Ukuthelekisa phakathi kwenziwa ngu i-post-hoc Uvavanyo lukaTukey (Ukusetyenziswa kweyure xa kuthelekiswa ngokwahlukileyo, umz. i-1 h yokulawula ukutya kokutya vs. 1 h SB-334867 enyangwayo yokutya). Idatha yachazwa njengentsingiselo ± impazamo eqhelekileyo yentsingiselo P <0.05, ithathwa njengento ebalulekileyo.

iziphumo

Uvavanyo I

Ukusetyenziswa kokutya kunye namanzi kuye kwalinganiswa (n = 18) kweli qela, izilwanyana ezifakwe kwi-NAcc (n = 18), zahlulwe zaba ngamacandelwana, iQela 1 (0.9% i-saline infusion), iQela 2 (SB-334867-3 ng), iQela 3 (SB-334867-6 ng). Iziyobisi zafakwa ngokulinganayo kwi-NAcc [Idatha eboniswe kuyo 1 Table kunye noMzobo Umfanekiso1a,1a, ,bb].

1 Table 

Impembelelo ye-SB-334867 ekutyeni kunye ne-10% yokusela utywala ngexesha le-1, i-2, i-4 kunye ne-24 hn=6 kwiqela ngalinye)

Ukutya

Xa kuthelekiswa nokulawula kwi-1 h emva kokuba unyango lwe-SB-334867 lubonise ukwehla okukhulu (F [2, 15] = 9.171 p = 0.003) ekuthathweni kokutya (oko kukuthi iQela 1 vs. Iqela lesi-3, p < 0.002); kanti, akukho tshintsho lubalulekileyo luphawulwe kwi-2 h (F [2, 15] = 0.190 p = 0.829); 4 h (F[2, 15] = 0.160 p = 0.854); Ixesha le-24 h emva kwexesha lokungena (F [2, 15] = 4.873 p = 0.023) (Iqela 1 vs. Iqela 3, p < 0.028; Iqela 2 vs. Iqela 3, p <0.05).

Ukuthatha amanzi

Unyango lwe-SB-334867 lubonisa ukuba akukho mpembelelo ekungeneni kwamanzi kwi-1 h (F [2, 15] = 0.957 p = 0.406); I-2 h (amanzi 2 h F [2, 15] = 0.773 p = 0.479); 4 h (F[2, 15] =0.288 p = 0.753) izithuba zexesha le-postinfusion; kodwa umthamo wamanzi we-24 h uthotyiweyo (F[2, 15] = 10.688 p = 0.001) xa kuthelekiswa nolawulo (iQela 1 vs. Iqela le-3, p < 0.002; Iqela 2 vs. Iqela 3, p <0.006).

Uvavanyo II

Utywala (10%) kunye nokusetyenziswa kokutya kwalinganiswa [n = 18, idatha kwi 2 Table kwaye Umzobo 2].

2 Table 

Iziphumo ze-SB-334867 ekutyeni, emanzini, kunye ne-10% yokusela utywala (ukukhethwa kweebhotile ezimbini) kwi-1, 2, 4, kunye ne-24 h ixesha
Umzobo 2 

Icandelo le-Histological lendawo etofiweyo: Icandelo elinebala le-Cresyl Violet (7 μ) yobuchopho bempuku ebonisa indawo yokutofa (utolo olumnyama) (×2.5)

Iigundane ze-NAcc ze-cannulated zahlulahlulwe zaba ngamacandelwana amathathu, iQela 1 (0.9% saline n = 6), Iqela 2 (SB-334867-3 ng, n = 6), kunye neQela 3 (SB-334867-6 ng, n = 6).

I-10% yeziphumo zokuthatha utywala

Kwi-1 h kunye ne-2 h SB-334867 unyango lunciphise kakhulu ukusetyenziswa kotywala kwi-1st h (F[2, 15] = 4.457 p = 0.030), (Iqela 1 vs. Iqela 3, p < 0.004), 2nd h (F[2, 15] = 11.122 p = 0.001) (Iqela 1 vs. Iqela 3, p < 0.001; Iqela 2 vs. Iqela 3, p < 0.038). Nangona kunjalo, akukho tshintsho lubalulekileyo ekusetyenzisweni kotywala kwi-4 h (F [2, 15] = 0.709 p = 0.508) kunye ne-24 h (F[2, 15] = 2.631 p = 0.105) ngamaxesha, ngokulandelanayo.

Ukutya

Kwi-1 h kunye ne-2 h SB-334867 unyango kakhulu (F [2, 15] = 4.230 p = 0.035) i-attenuated food intake (Iqela 1 vs. Iqela le-3, p < 0.03); (F [2, 15] = 16.558 p = 0.000) (Iqela 1 vs. Iqela 2, p < 0.000; Iqela 2 vs. Iqela 3, p <0.021), ngokulandelanayo, xa kuthelekiswa nolawulo. Akukho zinguqu zibalulekileyo ziphawulwe kwi-4 h (F [2, 15] = 0.070 p = 0.933). Nangona, ukutya okupheleleyo kuncitshisiwe (0-24 h) (F [2, 15] = 4.457 p = 0.030) (Iqela 1 vs. Iqela 3, p <0.025).

Uvavanyo III

Ukutya, i-10% yotywala, kunye namanzi [ukukhethwa kweebhotile ezimbini, 2 Table] ukusetyenziswa kwalinganiswa. Iigundane ze-NAcc ezifakwe kwi-cannulated zahlulwa njengeQela loku-1 (0.9% saline, n = 6), Iqela 2 (SB-334867-3 ng, n = 6), kunye neQela 3 (SB-334867-6 ng, n = 6), zatofwa.

Ukutya

Unyango lwe-SB-334867 kwi-1 h (F [2, 15] = 5.111, p = 0.02) i-attenuated food intake (Iqela 1 vs. Iqela le-3, p <0.011) kodwa akukho ntlukwano ebalulekileyo yabonwa kwi-2 h, 4 h (F [2, 15] = 0.093 p = 0.911), (F[2, 15] = 0.797 p = 0.469), ngokulandelanayo, kunye ne-24 h zombini i-dose ye-antagonist ibonise ukuncipha kokutya (F [2, 15] = 12.698 p = 0.001) (Iqela 1 vs. Iqela lesi-2 kunye neQela lesi-3, p <0.039, p <0.000, ngokulandelanayo), xa kuthelekiswa neqela lolawulo.

Ukuthatha amanzi

Unyango lwe-SB-334867 aluvelisi utshintsho kumanzi angena kulo naliphi na iqela kunye nexesha le-1 h (F [2, 15] = 0.584 p = 0.578), 2 h (F[2, 15] = 0.662 p = 0.530), 4 h(F[2, 15] = 1.655 P = 0.224) kunye ne-24 h (F[2, 15] = 0.513 p = 0.609).

Utywala (10%) ukuthathwa

SB-334867 unyango attenuated utywala ukungenisa kwi-1 h (F [2, 15] = 9.098 p = 0.003), (iQela 1 vs. Iqela lesi-2 kunye neQela lesi-3, p <0.004, p <0.008, ngokulandelanayo). Akukho tshintsho olubalulekileyo kulo naliphi na iqela kwi-2 h (F [2, 15] = 0.854 p = 0.446), 4 h (F[2, 15] = 0.931 p = 0.416) kunye ne-24 h (F[2, 15] = 0.349 p = 0.711), ngokulandelanayo.

Ukuthatha ulwelo ngokupheleleyo

Akukho tshintsho lubalulekileyo kulo naliphi na iqela, ku-1st h (F[2, 15] = 2.064 p = 0.161), 2nd h (F[2, 15] =1.023 p = 0.383), 4th h (F[2, 15] =1.205 p = 0.327) kunye ne-24 h (F[2, 15] =0.484, p = 0.626).

ingxoxo

Ukumodareyithwa kokutya kunye nokuthathwa kwamanzi ngamachiza ahlukeneyo e-neurochemicals kuye kwaqwalaselwa. Phakathi kweemolekyuli ezininzi zabaviwa eziye zabonakaliswa ukuba zichaphazela indlela yokuziphatha yokutya, kubandakanywa nokusela utywala, i-Orexins nayo iyabandakanyeka.] Ii-Orexins ekuqaleni zazikholelwa ukuba zivuselela ukutya kunye nokulawulwa komsebenzi wokugaya; kamva zafunyaniswa zichaphazela ubuthongo kunye nokuvuka.] Dube okqhubekayo. baye babonisa ukuba ulawulo oluphakathi lwe-Orexins lunendima yokumodareyitha ekuziphatheni kokutya, ngokuyintloko igxile kwi-hypothalamus.] Kuvavanyo lwethu lwangoku, sivavanye umphumo we-Orexin A antagonist (SB-334867) kwi-NAcc. I-NAcc inikwe indima ebaluleke kakhulu kwiziyobisi kunye nemisebenzi enxulumene nokondla.] IiOrexins nazo ziye zabandakanyeka kulamlo lwesi senzo se-NAcc.] Nangona kunjalo, i-NAcc ibonise izithili ezibini ezahlukileyo ngokwembali,] enokuthi inomahluko wokusebenza[] kwaye imisebenzi yazo yabonakala ihambelana ngokubonakalayo.] Kwiimvavanyo zethu zangaphambili, sifumene ukuba ukufakwa kwe-Orexin A kwi-NAcc kusetyenziswa ubuchule be-microinjection kwandisa ukutya kunye nokuthatha kwamanzi kwiiyure nje emva kokuxutywa, kodwa kwakungekho kukhetha okuthile kotywala xa kuvavanywa ngokukhetha iibhotile ezimbini simahla.] Ngoko ke, sazama ukufaka i-Orexin Umphikisi kwi-NAcc kwaye sahlalutya ukutya okudliwayo, ukusela amanzi kunye nokusela utywala kwiigundane, eziye zazila ubusuku bonke.

Ukusetyenziswa kwi-1st h yehlile kwizilwanyana eziphathwa ngokuchasa i-orexin kakhulu. Uphononongo lwethu lungqina ngakumbi indima ye-Orexin A ekuziphatheni kokutyisa. Uhlobo lwe-1 ye-receptor ye-Orexin (i-OX1R) i-SB-334867 infusions inciphisa ukutya nokusela. I-Orexin A isoloko ibonisa impembelelo evuselelayo ekondleni nasekuseleni. Umchasi we-OX1R une-10 amaxesha amakhulu obudlelwane be-Orexin A kune-B.,]

Iprojekthi ye-Orexinergic neurons kwi-AccSh kunye ne-orexin receptors (i-OX1R kunye ne-OX2R) zikhona kwi-NAcc, kunye ne-OX2R ebonakaliswe kakhulu.,] I-Orexin A yanda imisinga ye-GABAergic kunye nokuncipha kwemisinga ye-N-methyl-D-aspartate kwii-accumbens neurons ezizimeleyo.] Ukongeza, ii-orexins zichulumancisa i-dopaminergic VTA neurons.] Ekubeni i-dopaminergic VTA neurons i-innervate kwaye ivuyise i-AccSh GABAergic (inhibitory) neurons, ukubonakaliswa kwe-orexin kunokwandisa ngakumbi ukuvinjelwa kwendawo kwi-Acc ngokwandisa umsebenzi we-neuronal kwi-VTA, okukhokelela ekuphuculeni ngakumbi ukuziphatha kokugqibela. Kodwa oku kwachaswa nguBaldo noKelley,] ongakhange afumane siphumo sokutyisa okanye kumsebenzi welocomotor nge-intra-AccSh Orexin A.

Sivavanye ukuba kungenzeka ukuba i-Orexin A isebenze njengemodyuli yokusela utywala [2 Table] kunye nokutya. Ukususela kwisifundo sethu sangaphambili, safumanisa ukuba iigundane zikhetha ukusela utywala kwisisombululo se-10% esiye saqinisekiswa kwisifundo sethu sangaphambili.] Ke ngoko kolu phononongo, sibonelele ngotywala kolu dilution kulandela ukufakwa kwechiza kwi-NAcc. Sifumene ukuhla okubonakalayo kokusela utywala kwiiyure nje ezilandela ukufakwa kwe-Orexin A antagonist. Ukuhla kokutya kunye nokuthathwa kwamanzi kwakungaphantsi kwi-dose ephantsi (i-3 ng) iqela lokuxhamla ngelixa laliphezulu kwi-dose ephezulu (6 ng) iqela. Ukuze uvavanye ukhetho lotywala, sinikeze iigundane ngeemeko ezimbini zokukhetha ibhotile, apho ibhotile enye yamanzi kunye nenye equlethe i-10% yotywala yanikezelwa ngaxeshanye. Ukulandela ukunyuswa kwe-Orexin Umchasi ochasayo uvelise ukuhla okubonakalayo kokutya kunye nokusela utywala. Olu hlobo lokuhla lufunyenwe kwidosi ephantsi kunye nephezulu kodwa ithintelwe kwi-1st h emva kokufakwa. Nangona kunjalo, ukuhla kokutya kwakuphawulwe ngakumbi xa kuthelekiswa namanzi okanye utywala. Obu bungqina bunika inkxaso yokubandakanyeka kwe-Orexin A kulawulo lokutya nokuba kukutya kodwa akuxhasi ukuba nokwenzeka kokubandakanyeka kwe-Orexin A ekukhetheni utywala.

Inkxaso yezeMali kunye nenkxaso

ISebe le-Biotechnology, Inxalenye yeprojekthi ye-DBT exhaswa ngemali, Ref: Ref: BT/PR14012/MED/30/315/2010 yomhla we-30.09.2010 uRhulumente waseIndiya.

Iimbambano Zomdla

Akukho zimbambano zomdla.

Imibulelo

Ababhali banombulelo kwiSebe leBiotechnology, uRhulumente waseIndiya, ngenkxaso yemali. IKholeji yezoNyango yaseKasturba, eMangalore, kwiYunivesithi yaseManipal, kwizibonelelo ezibonelelweyo.

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