Aafiaga o le Orexin O se tagata faʻatau (SB-334867) faʻafefeteina i totonu o le tumutumu o faʻalavelave i luga o amioga masani ma le ava malosi i Wistar rats (2016)

 

lē faʻatino

sini:

Nucleus accumbens (NAcc) o loʻo i ai se sao i vaisu ma amioga faʻaoga. Ina ia mafai ona iloilo le faiga ole orexinergic o loʻo aʻafia ai i lenei mea, na matou faʻaogaina le Orexin A antagonist ma iloilo le aʻafiaga i luga o meaʻai taumafa taumafa ma le ava malosi i rats Wistar.

Mea ma Metotia:

Iole Wistar fa'atosina (n = 54) na vaevaeina i vaega faʻatonutonu ma faʻataʻitaʻiga (maualalo fua ma maualuga fua). I le fa'aogaina o le stereotaxic method, na fa'atulaga ai le cannula ta'iala i le lua e o'o atu i le NAcc. O le fua maualalo (3 ng) ma le maualuga (6 ng) o le Orexin A antagonist (SB-334867) na faʻapipiʻiina, ma o le taumafaina o meaʻai, vai inu ma le ava malosi, ma le lua suʻega filifiliga filifiliga saoloto mo le ava sa faia i le vaega faataitai. O le vaega fa'atonutonu na maua le saline infusion ma isi auala na mulimulita'i e tutusa. O fua na faia i le taimi lava na maeʻa ai le faʻafefe, i le 1 h, 2 h, 4 h, ma mo le aso atoa ma faʻatusalia i le ata ma laulau.

Tali:

O le faʻaitiitia o le faʻaogaina o le vai na matauina i le taimi lava na maeʻa ai le faʻafefe i le 1st h (P <0.05) ma le 2nd h (P <0.01), lea na sili atu i le vaega maualuga fualaʻau faʻatusatusa i le maualalo o fua ma faʻatonuga. Sa mulimulita'i fo'i le inuina o le ava i lea lava faiga. I totonu o fagu e lua filifiliga saoloto, e le'i fa'aalia e iole so'o se mana'o fa'apitoa i le ava malosi.

Faaiuga:

Sa iai le fa'aitiitiga fa'alagolago ile taumafa ole mea'ai ma vai ile iole na togafitia. O lenei mea na fautua mai ai se sao talafeagai mo le orexinergic system i le faʻaogaina o amioga. Ae ui i lea, Orexin A atonu e leai sona sao i le faʻaogaina o vaisu ava e le NAcc nofoaga faʻamanuiaina.

UPU FUA: Nucleus accumbens, mea'ai, Orexin-A antagonist (SB-334867), vai ma le ava malosi

faʻatomuaga

accumbens (NAcc) ua iloa e a'afia ai le fa'aogaina o amioga ma vaisu i vaila'au.[,] Ua aafia foi i le taui ma le faaosofiaga.[] E lua vaega laiti ma'oti ua fa'amatalaina i le NAcc, ma ua aliali mai le tele o fa'aoga i le fa'agaioiga o nei itulagi e lua.[] O le microinjection o vailaʻau faʻamalosi i totonu o le NAcc na faʻaalia ai le faʻatupulaia o le faʻalagolago i le dopamine. Dopamine o se neurochemical o loʻo aʻafia i le faʻasologa o taui. O le pulea e le tagata lava ia o le amphetamine na faʻaalia ai le faʻateleina o lagona taui.[] O isi vaega i totonu o le vaega pito i lalo e fa'aaafia ai amioga fa'atosina, lea e mafai ona feso'ota'i vavalalata ma accumbens. O mea'ai ma vai inu na fa'aalia e a'afia e le tele o vaega o le fai'ai basal, e pei o le lateral hypothalamus,[] nucleus paraventricular, septum pellucidum,[] ma le amygdala basolateral.[] O loʻo i ai le tele o fesoʻotaʻiga neural i le faʻatonutonuina o amioga faʻaogaina. NAcc ua faʻaalia e fesoʻotaʻi lelei i nofoaga autu o le subcortical, e pei o le ventral tegmental area (VTA);[] basolateral amygdala ma isi nofoaga tutotonu.[] O neurotransmitters tetele o loʻo aʻafia i le faʻaogaina o le ava malosi, taui, ma meaʻai na lipotia mai i neural circuits i lenei itulagi.[]

Talu ai nei, o hypocretins, o se vaega o peptides heterogeneous, ua iloa mai le hypothalamus, hypocretin 1 ma 2 (Orexin A ma B), peptides e 32 aa ma 29 aa, faasologa.[] I le amataga, o nei mea na aafia i le faatonutonuina o le taamilosaga o le moe, e pei ona molimauina i le faateleina o le Orexin A na maua i le hypothalamus i le taimi o le gaioiga o le fafagu.[] I le matou falesuesue, na matou iloa ai o Orexin A na faʻateleina meaʻai ma vai inu pe a tui ile NAcc.[] O le antibody orexin o lo'o tu'ufa'atasia e taofia ai le fa'aogaina o mea'ai-fa'alagolago ile 24 itula fa'atosina, ma o le fa'atonuga ole orexin antibody e le mafai ona taofiofia le taumafaina o mea'ai, o lo'o fa'atusalia ai o le orexin antibody e galue i le fatugalemu o le tino ae le o totonu o le tino.] E le gata i lea, na latou faʻamaonia mai o orexins endogenous ei ai le physiological matafaioi i le fafagaina o amioga. E ui o le taimi muamua o Orexins na faʻaalia e aʻafia ai le faʻaogaina o amioga, o le faʻamaoniga o le matafaioi a Orexin A i le fafagaina o amioga ma le faʻaaogaina o le ava ma le fiafia i le ava e faʻamaonia. I a matou suʻesuʻega talu ai, ua matou faʻaalia o Orexin A na faʻateleina meaʻai ma vai inu i isumu anapogi.[] Ina ia faʻamalamalamaina le matafaioi a Orexin A i le gaioiga faʻamalositino, matou te faia lenei seti o faʻataʻitaʻiga i tama tane Wistar na anapopogi i le po, e ala i le tuʻuina atu o le Orexin A antagonist SB-334867 i totonu o le NAcc.[] Sa matou fa'ata'ita'iina fo'i le mea e fiafia i ai le 'ava malosi i isumu ua togafitia e fa'amalamalama ai le a'afiaga o le Orexin A fa'afeagai i luga o le 'ava malosi. O fa'ai'uga o fa'ata'ita'iga i mea'ai, vai ma le 'ava malosi, ma mea e fiafia i ai le 'ava malosi o lo'o talanoaina iinei.

Mea ma Metotia

E limasefulufa po'a Wistar albino (n = 54) mamafa (250 ± 10 g), 3-4 masina le matutua na filifilia mo suʻesuʻega. Sa vaevaeina i latou i ni vaega se tolu viz. Vaega vai, vaega ava malosi ma fagu e lua e filifili fua (n = 18 taitasi). Na vaevaeina i latou i ni vaega laiti se tolu, e pei o. Vaega 1 - Puleaina (Saline infusion); Vaega 2 - La'ititi fua ole SB-334867 (3 ng); Vaega 3 – Tulaga maualuga o le SB-334867 (6 ng, n = 6 taitasi). Sa saunia mea'ai ma vai i vaega uma ad lib, vagana ai le mea na taʻua mo le anapogi i le po.

O manu uma sa fa'anofo ta'itasi i totonu o pa polypropylene, fa'atasi ai ma le fa'amoe lelei ma fa'atumauina i le 12-h le malamalama/pouliuli i le si'osi'omaga e pulea le vevela. O manu na tausia e tusa ai ma taʻiala a le komiti mo le faʻamoemoe o le pulea ma le vaavaaiga o faʻataʻitaʻiga i manu ma taʻiala a le Malo o Initia mo le faʻaogaina o manu suʻesuʻe. Ua fa'amaonia e le Komiti Fa'atonu a Manu Fa'atonu lenei faiga fa'ata'ita'iga.

Fualaau Fa'asaina ma Meatotonu

Saline 0.9%, SB-334867 (Mai: Tocris bioscience) na fa'amuta i le 2% cyclodextran i vai mama. A le fa'aaogaina, o vaifofo e teu i le 4°C e o'o i le 3 vaiaso. Harvard Pico plus (USA) infusion pamu sa fa'aaoga e tiliva ai vaila'au. Sa saunia le vai paipa i fagu inu Palasitika, ma sa saunia fo'i pelleti meaai isumu (Hindustan Unilever Ltd.,). Ethyl alcohol (Absolute) na maua mai (Hayman Ltd., Eastways Park, Witham, Essex, CM83YE, UK) ma faʻafefeteina e fai ai se 10% ava malosi (O lenei faʻatonuga na filifilia i luga o se suʻesuʻega pailate i luga o le manaʻoga o le faʻaogaina o le ava malosi) . Ketamine (NEON Laboratories Limited, Thane, MS) ma le xylazine (Indian immunological Ltd., Hyderabad) na faʻaaogaina mo faʻamaʻi.

Taʻotoga Taʻavale

O tamaʻi Wistar albino rats na faʻamaʻiina e ala i le tuiina o se faʻafefiloi o le ketamine hydrochloride (60 mg / kg), xylazine hydrochloride (6 mg / kg) ma faʻapipiʻi i luga o se masini stereotaxic (Inco, Initia). Sa faia se tipi i luga o le ulu, faʻamaʻi uma i le agaga tipi. Na fa'amama le vaega i le cotton ma le hydrogen peroxyide. O vaega faamaopoopo sa faailogaina i luga o le ulupoo i vaega tutusa e oo atu i le NAcc, faatasi ai ma le faasinomaga a Paxinos ma Watson faiʻai atlas[] (Mai Bregma: Anteroposterior + 2.2 mm, lateral ± 1 mm ma 7.4 mm tūsaʻo). Na faia le pu, ma fa'apipi'i le ta'iala ta'iala uamea (22 gauze) e tusa ai ma fa'asologa o le stereotaxic. O le taimi lava e tu ai le cannula, e fa'amauina i le fesoasoani a sikulima ma nifo. Sa fa'apipi'i i le sitaili ta'iala, ma fa'ataga iole e toe fa'aleleia mo le itiiti ifo i le 7 aso a'o le'i faia le su'ega. Infusion cannula (internal cannula) sa fau mai Septoject stainless steel nila nifo o 30 gauges lea ei ai se hub, faigofie mo le taulimaina.[] Infusion cannula e o'o atu i le 1 mm i tua atu o le cannula ta'iala ta'itasi. Aʻo leʻi amataina faʻataʻitaʻiga na maua uma e iole ni aʻoaʻoga se lua lea na taofia ai i le 24 h anapogi ona maua ai lea o meaʻai, vai, ma le 10% ava malosi. I le taimi o lenei vasega, na aʻoaʻoina ai e iole le anapogi.

Faʻataʻitaʻiga Faʻapitoa

Saline masani ma SB-334867 (i lua doses) na faʻapipiʻiina, i le faasologa, i vaega eseese o isumu pe a uma le 24 h anapogi; isumu e le'i fa'afefeteina (feagai solo) e ala ile cannula fa'amautu. O le infusion na faia e le 10 μl Hamilton syringe e fesoʻotaʻi ma le polyethylene tube ma le cannula totonu. O lenei tui na faʻapipiʻiina i le pamu Harvard. Ona aveese lea o le sitaili na tuu i totonu o le ta'iala. Na fa'apipi'i totonu le cannula i totonu o le ta'iala ma fa'amautu. Ona amata loa lea o le pamu e tuʻuina atu le vaifofo i le itu taumatau ma le agavale o le NAcc le tasi i le isi, 1 μl / min (ina ua uma le faʻaogaina o le cannula i totonu e tuʻu mo le 10 s e faʻatagaina ai le faʻasalalauina o fualaau). E lua tui o le SB-334867 na tuʻuina i le 3 ng (maualalo) ma le 6 ng (maualuga fua). I le faaiuga o le infusion, na aveese le cannula i totonu, ma toe tuʻu le sitaili i le tulaga ma ua matauina le taimi. A mae'a fa'asusu, fa'ato'a fuaina le aofa'i o mea'ai, vai, ma le 10% ava malosi sa tu'uina atu i vaega ta'itasi. O le aʻafiaga o le SB-334867 i luga o le faʻaaogaina na fuaina ma matauina, faʻapitoa i taimi faʻafefe taimi 1, 2, 4, ma 24 h, faasologa. Na aveese pelleti, vai, ma le ava malosi, ma fuafua le aofaʻi o loʻo faʻaaogaina (Aofaʻi na faʻaaogaina = Fuafuaina muamua-tuʻu i luga o le aofaʻi, faʻataʻitaʻiga i le faaiuga o le 1 h).

Ina ua maeʻa le suʻesuʻega, na faʻatauina ai isumu i le faʻamaʻi faʻamaʻi ma faʻamaʻi ese le faiʻai ma faʻasaoina mo le faʻasologa o tala faasolopito. E fitu vaega micron sa tipiina ma pisia i le cresyl violet e faʻamaonia ai le nofoaga o le tui [Ata 1].

Ata 1 

Orexin O se tagata tetee (SB-334867) i totonu o le nucleus accumbens. O pa e fai ma sui, (a) vai ma (b) taumafa o isumu na tui i le SB-334867 i le nucleus accumbens, i le 1st, 2nd, 4th ma le 24 itula taimi faʻatasi ma le fua ole 0 (0.9% saline = Vaega 1) ma le 3 ng SB-334867 ...

Fuainumera Faamaumauga

O suʻesuʻega o faʻamaumauga na faia i le faʻaaogaina o le polokalame faʻafuainumera SPSS version - 16 (SPSS mo Windows, Version 16.0. Chicago, SPSS Inc. USA); na faia le ANOVA auala e tasi e faʻatusatusa ai le amio faʻataunuʻu i le va o vaega. Inter faatusatusa na faia e post-hoc Su'ega a Tukey (Fa'atusa le taumafaina i itula, fa'ata'ita'iga, 1 itula fa'atonutonu le taumafaina o mea'ai vs. 1 h SB-334867 taumafa fa'aogaina). O faʻamaumauga na faʻaalia o le uiga ± masani sese o le uiga P <0.05, na manatu taua.

i'uga

Fa'ata'ita'iga I

Sa fuaina taumafa ma vai (n = 18) i lenei vaega, NAcc cannulated manu (n = 18), na vaevaeina i vaega laiti, Vaega 1 (0.9% saline infusion), Vaega 2 (SB-334867-3 ng), Vaega 3 (SB-334867-6 ng). O vailaʻau na tui faʻatasi i totonu ole NAcc [Faʻamatalaga faʻaalia ile Laulau 1 ma le Ata Ata 1a,1a, ,bb].

Laulau 1 

A'afiaga o le SB-334867 i mea'ai ma le 10% o le ava malosi i le 1, 2, 4 ma le 24 itula (n=6 i vaega taitasi)

Taumafa meaʻai

Pe a faatusatusa i le pulea i le 1 h ina ua uma le SB-334867 togafitiga na faʻaalia ai le faʻaitiitia tele (F [2, 15] = 9.171 p = 0.003) i le taumafa taumafa (fa'atusa le Vaega 1 vs. Vaega 3, p <0.002); ae, e leai se suiga taua na maitauina i le 2 h (F[2, 15] = 0.190 p = 0.829); 4 itula (F[2, 15] = 0.160 p = 0.854); 24 itula fa'auma taimi va'aiga (F[2, 15] = 4.873 p = 0.023) (Vaega 1 vs. Vaega 3, p <0.028; Vaega 2 vs. Vaega 3, p <0.05).

Vaʻaia o le vai

SB-334867 togafitiga na faʻaalia ai le leai o se aʻafiaga i le faʻaaogaina o le vai ile 1 h (F [2, 15] = 0.957 p = 0.406); 2 itula (vai 2 h F[2, 15] = 0.773 p = 0.479); 4 itula (F[2, 15] =0.288 p = 0.753) va'aiga taimi fa'ai'u; ae o le aofaʻi o le 24 itula o le vai na faʻaititia (F[2, 15] = 10.688 p = 0.001) fa'atusatusa ile pulea (Vaega 1 vs. Vaega 3, p <0.002; Vaega 2 vs. Vaega 3, p <0.006).

Fa'ata'ita'iga II

O le ava malosi (10%) ma le taumafaina o mea'ai na fuaina [n = 18, fa'amaumauga i Laulau 2 ma Ata 2].

Laulau 2 

Aafiaga ole SB-334867 ile mea'ai, vai, ma le 10% ava malosi (lua fagu e fiafia i ai) ile 1, 2, 4, ma le 24 itula.
Ata 2 

Vaega fa'asolopito o le nofoaga na tui: Vaega ua pisia Cresyl Violet (7 μ) o le fai'ai isumu o lo'o fa'aalia ai le nofoaga fa'ainu (au uliuli) (×2.5)

NAcc cannulated rats na vaevaeina i ni vaega laiti se tolu, Vaega 1 (0.9% saline n = 6), Vaega 2 (SB-334867-3 ng, n = 6), ma le Vaega 3 (SB-334867-6 ng, n = 6).

10% i'uga inu ava malosi

I le 1 itula ma le 2 h SB-334867 togafitiga na matua fa'aitiitia ai le inu ava malosi ile 1st h (F[2, 15] = 4.457 p = 0.030), (Vaega 1 vs. Vaega 3, p <0.004), 2nd h (F[2, 15] = 11.122 p = 0.001) (Vaega 1 vs. Vaega 3, p <0.001; Vaega 2 vs. Vaega 3, p <0.038). Ae ui i lea, e leai se suiga tele i le inu ava malosi i le 4 h (F[2, 15] = 0.709 p = 0.508) ma le 24 itula (F[2, 15] = 2.631 p = 0.105) vaeluaga, faasologa.

Taumafa meaʻai

I le 1 h ma le 2 h SB-334867 togafitiga tele (F[2, 15] = 4.230 p = 0.035) fa'aitiitia taumafa taumafa (Vaega 1 vs. Vaega 3, p <0.03); (F[2, 15] = 16.558 p = 0.000) (Vaega 1 vs. Vaega 2, p <0.000; Vaega 2 vs. Vaega 3, p <0.021), fa'atusatusa i le pule. E leai ni suiga taua na maitauina ile 4 h (F[2, 15] = 0.070 p = 0.933). Ae, o le aofaʻi o taumafa na faʻaititia (0-24 h) (F[2, 15] = 4.457 p = 0.030) (Vaega 1 vs. Vaega 3, p <0.025).

Fa'ata'ita'iga III

Mea'ai, 10% ava malosi, ma vai [lua fagu e fiafia i ai, Laulau 2] sa fuaina le taumafaina. NAcc cannulated rats na fa'avasegaina i lalo ole Vaega 1 (0.9% saline, n = 6), Vaega 2 (SB-334867-3 ng, n = 6), ma le Vaega 3 (SB-334867-6 ng, n = 6), na tui.

Taumafa meaʻai

SB-334867 togafitiga ile 1 h (F[2, 15] = 5.111, p = 0.02) fa'aitiitia taumafa taumafa (Vaega 1 vs. Vaega 3, p <0.011) ae leai se eseesega taua na matauina i le 2 h, 4 h (F [2, 15] = 0.093 p = 0.911), (F[2, 15] = 0.797 p = 0.469), i le faasologa, ma i le 24 h na faʻaalia uma ai le faʻaititia o meaʻai (F[2, 15] = 12.698). p = 0.001) (Vaega 1 vs. Vaega 2 ma le Vaega 3, p <0.039, p <0.000, fa'asologa), fa'atusatusa i le vaega fa'atonutonu.

Vaʻaia o le vai

SB-334867 togafitiga e leai se suiga i le faʻaaogaina o le vai i soʻo se vaega faʻatasi ma le vaeluaga taimi ile 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) ma le 24 itula (F[2, 15] = 0.513 p = 0.609).

'ava malosi (10%)

SB-334867 togafitiga fa'aitiitia le inu ava malosi ile 1 itula (F[2, 15] = 9.098 p = 0.003), (Vaega 1 vs. Vaega 2 ma le Vaega 3, p <0.004, p <0.008, fa'asologa). Leai se suiga taua i soo se vaega i le 2 h (F[2, 15] = 0.854 p = 0.446), 4 h (F[2, 15] = 0.931 p = 0.416) ma le 24 itula (F[2, 15] = 0.349 p = 0.711), i le faasologa.

Aofa'i vai inu

Leai se suiga taua i soo se vaega, i le 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) ma le 24 itula (F[2, 15] =0.484, p = 0.626).

Talanoaga

O le fa'aogaina o mea'ai ma vai e ala ile neurochemicals ua mae'a su'esu'eina. Faatasi ai ma le tele o mole mole mole ua faʻaalia e aʻafia ai le amio fafaga, e aofia ai le inu ava malosi, o loʻo aʻafia ai foi Orexins.[] O Orexins na muai talitonuina o ni mea e faaosofia ai le taumafaina o meaʻai ma le faʻatonutonuina o gaioiga faʻaogaina; mulimuli ane na maua e afaina ai le moe ma le ala.[] Dube 'ua al. ua fa'aalia o le fa'atonuga tutotonu o Orexins o lo'o iai sona sao fa'aopoopo i amioga fa'ainu, e fa'atotonu i le hypothalamus.[] I la matou faʻataʻitaʻiga o loʻo i ai nei, matou faʻataʻitaʻiina le aʻafiaga o Orexin A antagonist (SB-334867) i le NAcc. O le NAcc ua tu'uina atu i ai se sao taua i vaisu ma gaioiga fa'atatau i le fafagaina.[] Ua aafia foi Orexins i le soalaupulega o lenei gaioiga a le NAcc.[] Ae ui i lea, na faʻaalia e le NAcc ni itumalo se lua faʻasolopito, [] atonu e iai ni eseesega o galuega[] ma o latou galuega na foliga mai e matua felavasa'i.[] I a matou faʻataʻitaʻiga talu ai, na matou iloa ai o le faʻaogaina o Orexin A i totonu o le NAcc e faʻaaoga ai le microinjection technique na faʻateleina ai meaʻai ma vai i itula i le taimi lava na maeʻa ai le faʻapipiʻiina, ae leai se mea e sili ona fiafia i ai le ava pe a tofotofoina e lua filifiliga saoloto.[] O le mea lea, na matou taumafai ai e tui le Orexin A antagonist i totonu o le NAcc ma suʻesuʻeina le faʻaogaina o meaʻai, vai inu ma le ava malosi i isumu, lea na anapogi i le po.

Le faʻaaogaina i le 1st h fa'aitiitia i manu fa'afeagai o le orexin e matua'i togafitia. O a matou suʻesuʻega e faʻamaonia atili ai le matafaioi a Orexin A i le fafagaina o amioga. Ole Orexin receptor type 1 (OX1R) antagonist SB-334867 infusion e faʻaitiitia ai le fafagaina ma le inu. O le Orexin A na faʻaalia i taimi uma le aafiaga faʻaosofia i le fafagaina ma le inu. OX1R antagonist e 10 taimi sili atu le vavalalata mo Orexin A nai lo B.[,]

Orexinergic neurons project to the AccSh and orexin receptors (OX1R and OX2R) are presents in the NAcc, with OX2R expressed to a much extent.[,] Orexin A fa'atuputeleina galu GABAergic ma fa'aititia ai le N-methyl-D-aspartate i totonu o neu tu'u'ese'ese.[] E le gata i lea, o orexins e faaosofia ai le dopaminergic VTA neurons.[] Talu ai ona o le dopaminergic VTA neurons i totonu ma faʻaosofia ai le AccSh GABAergic (inhibitory) neurons, o le faʻailoga o le orexin e mafai ona faʻateleina ai le faʻalavelave faʻapitonuʻu i totonu o le Acc e ala i le faʻateleina o gaioiga neuronal i le VTA, e mafua ai le faʻaleleia atili o amioga faʻataunuʻu. Ae sa feteenai lenei mea e Baldo ma Kelley,[] o le na le maua se aʻafiaga i le fafagaina poʻo le gaioiga o locomotor i totonu-AccSh Orexin A.

Na matou faʻataʻitaʻia le avanoa o Orexin A e fai ma sui o le inu ava malosi [Laulau 2] faatasi ma meaʻai. Mai a matou suʻesuʻega talu ai, na matou faʻamaonia ai e sili atu le fiafia o iole e inu le ava malosi i le 10% fofo lea na faʻamaonia i a matou lava suʻesuʻega talu ai.[] O le mea lea i lenei suʻesuʻega, matou te tuʻuina atu le ava malosi i lenei faʻamaʻi ina ua maeʻa le faʻaogaina o vailaʻau i le NAcc. Na matou maua se faʻaititia tele o le ava malosi i itula na maeʻa ai le faʻaogaina o le Orexin A antagonist. O le faʻaitiitia o meaʻai ma vai na faʻaititia i le vaega maualalo (3 ng) infusion aʻo maualuga i le maualuga o le dose (6 ng) vaega. Ina ia mafai ona fa'ata'ita'i le mea e fiafia i ai le 'ava malosi, na matou tu'uina atu i iole ni tulaga e lua e filifili ai fagu, e tasi le fagu vai ma le isi o lo'o iai le 10% ava malosi na tu'uina atu i le taimi e tasi. I le mae'a ai o le fa'asusuina o le Orexin A antagonist na maua ai se pa'u tele i le taumafa ma le ava malosi. O lenei ituaiga pa'u na maua i le maualalo ma le maualuga, ae fa'atapula'a i le 1st h ina ua uma le infusion. Ae ui i lea, o le faʻaitiitia o meaʻai na sili atu ona iloga pe a faʻatusatusa i le vai poʻo le ava malosi. O lenei faʻamaoniga e maua ai le lagolago mo le aʻafia o le Orexin A i le faʻatonutonuina o meaʻai ae e le lagolagoina le ono aʻafia o Orexin A i le fiafia i le ava malosi.

Lagolagoina tautupe ma le lagolagosua

Matagaluega o Biotechnology, Vaega o le DBT faatupeina poloketi, Ref: Ref: BT/PR14012/MED/30/315/2010 aso 30.09.2010 Malo o Initia.

Feeseeseaiga o Tului

E leai ni feteʻenaʻiga.

Faʻafetai

E faafetaia e le au tusitala le Matagaluega o Biotechnology, Malo o Initia, mo le fesoasoani tau tupe. Kasturba Medical College, Mangalore, Manipal University, mo fale ua saunia.

mau faasino

1. Trojniar W, Plucinska K, Ignatowska-Jankowska B, Jankowski M. Fa'aleaga i le nucleus accumbens atigi ae le'o fa'alavelave fa'alavelave fa'aoso fa'aoso fa'aoso fafaga. J Physiol Pharmacol. 2007;58(Suppl 3):63–71. [PubMed]
2. Marty VN, Spigelman I. Suiga umi i totonu o meatotino membrane, KC currents, ma glutamatergic synaptic currents o nucleus accumbens medium spiny neurons i se faʻataʻitaʻiga iole o le faʻalagolago i le ava. Neurosci luma. 2012;6:86. [PMC free article] [PubMed]
3. Henderson MB, Green AI, Bradford PS, Chau DT, Roberts DW, Leiter JC. O le fa'aosoina loloto ole fai'ai ole nucleus accumbens e fa'aitiitia ai le inu 'ava malosi i isumu e fiafia i le 'ava malosi. Neurosurg Taulai. 2010;29:E12. [PubMed]
4. Stratford TR, Kelley AE. GABA i le nucleus accumbens atigi e auai i le faʻatonuga tutotonu o le fafagaina o amioga. J Neurosci. 1997;17:4434–40. [PubMed]
5. Hernandez L, Lee F, Hoebel BG. Faʻatasi le microdialysis ma le amphetamine infusion i totonu o le nucleus accumbens ma striatum o isumu feoai saoloto: Faʻateleina le dopamine extracellular ma le serotonin. Fai'ai Res Bull. 1987;19:623–8. [PubMed]
6. Hernandez L, Hoebel BG. O le fafagaina ma le faʻamalosia o le hypothalamic e faʻateleina ai le suiga o le dopamine i le accumbens. Amioga Faaletino. 1988;44:599–606. [PubMed]
7. Maejima Y, Sakuma K, Santoso P, Gantulga D, Katsurada K, Ueta Y, et al. Oxytocinergic circuit mai le paraventricular ma le supraoptic nuclei e faʻapipiʻi POMC neurons i le hypothalamus. FEBS Lett. 2014;588:4404–12. [PubMed]
8. Ganaraja B, Jeganathan PS. Aafiaga o le amygdala basolateral ma manua o le hypothalamic ventromedial i luga o le ingestion ma le tofo i le iole. Initia J Med Res. 2000;112:65–70. [PubMed]
9. Narayanan NS, Guarnieri DJ, DiLeone RJ. Metabolic hormones, taʻavale dopamine, ma le fafagaina. Neuroendocrinol i luma. 2010;31:104–12. [PMC free article] [PubMed]
10. Atamai RA. Dopamine, aʻoaʻoga ma faʻaosofia. Nat Rev Neurosci. 2004;5:483–94. [PubMed]
11. Koob GF. Neurocircuitry o vaisu ava malosi: Fa'asologa mai fa'ata'ita'iga manu. Handb Clin Neurol. 2014;125:33–54. [PubMed]
12. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, ​​et al. Orexins ma orexin receptors: O se aiga o le hypothalamic neuropeptides ma le G protein-coupled receptors e faʻatonutonu amioga fafaga. sela. 1998;92:573–85. [PubMed]
13. Liu Y, Zhao Y, Ju S, Guo L. Orexin A faʻapipiʻiina le faʻaaliga o le porotini o le OX1R ma faʻaleleia le faʻateleina o SGC-7901 sela o le kanesa gastric e ala i le ala faʻailoga ERK. Int J Mol Med. 2015;35:539–45. [PubMed]
14. Mayannavar S, Rashmi KS, Rao YD, Yadav S, Ganaraja B. Aafiaga ole orexin-A infusion i totonu o le nucleus accumbens i luga o amioga faʻatupuina ma le ava malosi i tama tane Wistar rats. Initia J Physiol Pharmacol. 2014;58:319–26. [PubMed]
15. Yamada H, Okumura T, Motomura W, Kobayashi Y, Kohgo Y. Faʻasaina o meaʻai e ala ile tui tutotonu ole anti-orexin antibody i isumu anapogi. Biochem Biophys Res Commun. 2000;267:527–31. [PubMed]
16. Smart D, Sabido-David C, Brough SJ, Jewitt F, Johns A, Porter RA, et al. SB-334867-A: O le muamua filifilia ole orexin-1 faʻafefe talitali. Br J Pharmacol. 2001;132:1179–82. [PMC free article] [PubMed]
17. Paxinos G, Watson C. Lonetona: Academic Press; 1998. Le Faiai Iole i Stereotaxic Coordinates.
18. Mayannavar S, Rashmi KS, Deshpande K, Pai SR, Ganaraja B. Saunia o cannula umi mo intracranial micro-infusion o mea neuroactive i manu laiti. Int J Innov Res Sci Eng Technol. 2013;2:6032–8.
19. Uili JT, Chemelli RM, Sinton CM, Yanagisawa M. E ai pe moe?. Orexin i le faatonutonuina o le fafagaina ma le fafagu. Annu Rev Neurosci. 2001;24:429–58. [PubMed]
20. Thorpe AJ, Kotz CM. O le Orexin A i totonu o le nucleus accumbens e faʻaosofia ai le fafagaina ma le gaioiga o locomotor. Fai'ai Re. 2005;1050:156–62. [PubMed]
21. Dube MG, Kalra SP, Kalra PS. O mea'ai taumafa e mafua mai ile pulega tutotonu ole orexins/hypocretins: Fa'ailoaina ole nofoaga ole hypothalamic ole gaioiga. Fai'ai Re. 1999;842:473–7. [PubMed]
22. Kelley AE. Faʻatonuga faʻamalosi o le faʻaosofia o le manaʻo: Matafaioi i le faʻaogaina o amioga ma le aʻoaʻoina o taui. Neurosci Biobehav Rev. 2004;27:765–76. [PubMed]
23. Salgado S, Kaplitt MG. Le Nucleus Accumbens: O se Iloiloga Maualalo. Steeotact Funct Neurosurg. 2015;93:75–93. [PubMed]
24. Ramaswamy C, Ghosh S, Vasudev R. Suiga o mea e fiafia i ai mea'ai e tusa ai ma le tofo ma le aoga o mea'ai pe a mae'a le fa'aleagaina o pitonu'u e lua o nucleus accumbens. Initia J Med Res. 1998;108:139–44. [PubMed]
25. Stratford TR, Kelley AE. GABA i le nucleus accumbens atigi e auai i le faʻatonuga tutotonu o le fafagaina o amioga. J Neurosci. 1997;17:4434–40. [PubMed]
26. Haynes AC, Jackson B, Overend P, Buckingham RE, Wilson S, Tadayyon M, et al. Aafiaga o le tasi ma le tumau intracerebroventricular pulega o orexins i le fafagaina i le isumu. Peptides. 1999;20:1099–105. [PubMed]
27. Muroya S, Funahashi H, Yamanaka A, Kohno D, Uramura K, Nambu T, et al. Orexins (hypocretins) fegalegaleai tuusaʻo ma neuropeptide Y, POMC ma kulukose-tali neu e faʻatonutonu Ca 2 + faʻailoga i se faiga faʻafeiloaʻi i le leptin: Orexigenic auala neuronal i le mediobasal hypothalamus. Eur J Neurosci. 2004;19:1524–34. [PubMed]
28. Cluderay JE, Harrison DC, Hervieu GJ. Tufatufaina o porotini o le orexin-2 tali i totonu o le fatugalemu o le iole. Regul Pept. 2002;104:131–44. [PubMed]
29. Lu XY, Bagnol D, Burke S, Akil H, Watson SJ. Tufatufaina eseese ma le faatonutonuina o le OX1 ma le OX2 orexin / hypocretin receptor messenger RNA i le faiʻai i le anapogi. Horm Behav. 2000;37:335–44. [PubMed]
30. Matini G, Fabre V, Siggins GR, de Lecea L. Fegalegaleaiga a le hypocretins ma neurotransmitters i totonu o le nucleus accumbens. Regul Pept. 2002;104:111–7. [PubMed]
31. Nakamura T, Uramura K, Nambu T, Yada T, Goto K, Yanagisawa M, et al. Ole hyperlocomotion fa'aoso ole Orexin ma fa'ata'ita'iga e fa'atalanoaina e le faiga o le dopaminergic. Fai'ai Re. 2000;873:181–7. [PubMed]
32. Baldo BA, Kelley AE. Amylin infusion i totonu o le rat nucleus accumbens e matua fa'avaivaia ai le gaioiga o le afi ma le fa'aogaina. Am J Physiol Regul Integr Comp Physiol. 2001;281:R1232–42. [PubMed]
33. Mayannavar SK, Shiva RK, Aithal K, Bhat RM, Ganaraja B. O aʻafiaga o faʻamaʻi lua o le nucleus accumbens i luga o amioga faʻataunuʻu i Wistar rats. J Pharm Res. 2013;7:263–6.

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