Zoyeserera za Neural zomwe zimayambira pamayendedwe amygdala am'magazi omwe amachititsa kuti opioid ayendetsedwe moyenera motsutsana ndi machitidwe okhudzana ndi kudya mafuta kwambiri mu khola (2015) - BINGE MECHANISM

Behav Neurosci. Zolemba zolemba; ilipo mu PMC 2015 Dec 1.

Lofalitsidwa mu mawonekedwe omaliza omaliza monga:

PMCID: PMC4658266

NIHMSID: NIHMS724902

Mtundu womaliza wa chosindikiza wa nkhaniyi ukupezeka pa Behav Neurosci
 

Kudalirika

Kafukufukuyu akufufuza ntchito ya amygdala pokambirana njira yodyetsa yodyetsa yogwidwa ndi intra-accumbens (Acb) opioid activation mu khola. Kupangidwanso kwachisawawa kwa amygdala (BLA), pogwiritsa ntchito GABAA agonist muscimol administration kumateteza kuchuluka kwa mankhwala osokoneza bongo pambuyo pa intra-Acb opioid administration ya μ-opioid agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO). makhalidwe amatha, makamaka atatha kumwa. Kutanthauzira kumodzi ndiko kuti kusokoneza kwa BLA kumateteza mwatsatanetsatane ntchito zowonjezera zomwe zimayambitsa kugwiritsidwa ntchito kwa DAMGO, koma osati zovuta (kuyandikira) makhalidwe. Zomwe zikuchitika panopo zimapindula ndi chisokonezo chachisokonezo chachisanu ndi chizolowezichi komanso njira zoyenera kuchita pofuna kufufuza zochitika zawo za neural. Potsata intra-Acb saline kapena DAMGO administration, popanda BLA muscimol administration, makoswe anapatsidwa 2hr kupeza chakudya chochepa cha mafuta ambiri. Pambuyo pake panthawi yopatsa chakudya, makoswe amaperekedwa nsembe ndipo ubongo amayesedwa kuti azitsatira njira zogwiritsira ntchito neural kudutsa m'madera ovuta a ubongo omwe amadziwika kuti aziwongolera zokhazokha komanso zoyenera kudya. Zotsatira zikuwonetsa kuti intra-Acb DAMGO administration yowonjezera c-Fos kulumikizidwa mu orexin neurons mkati mwa malo ozizira a hypothalamus ndikuti kuwonjezeka kwa kuchitidwa kumatsekedwa ndi BLA muscimol ntchito. Ma intra-acb DAMGO administration yowonjezera c-Fos kuyambitsidwa mkati mwa dopaminergic neurons ya ventral tegmental dera, poyerekeza ndi kayendedwe ka saline, ndipo kuyendetsa BLA sikunathandize pa kuwonjezeka uku. Zonsezi, detayi imapereka maofesi oyendetsa magetsi omwe angagwirizane ndi mphamvu ya BLA poyendetsa galimoto, koma osati zokhutiritsa, kuyambitsa makhalidwe abwino mu chitsanzo cha khalidwe lodyetsa mwadongosolo.

Keywords: khalidwe lolimbikitsidwa, machitidwe ndi kusanthula dera, khalidwe la ma laboratory (zokhumba / zotsutsa), Animal Model, opioid kudyetsa neural activation pattern

Kugawidwa kwa intaneti komwe kumapereka kwa intra-accumbens (Acb) opioid feeded mediated kudyetsedwa kwambiri (; ; ; ), komanso zopereka za amygdala zowonjezereka (BLA) zakhala zosangalatsa kwambiri. Kusintha kwadongosolo kwa BLA ndi GABAA Agonist muscimol imateteza kuwonjezeka kwamtundu wambiri wa mafuta pambuyo pa intra-Acb ulamuliro wa μ-opioid agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO). 24hr chakudya chosowa (). Izi zimapangitsa kuti bungwe la BLA likwaniritse njira yowonjezeramo zakudya za hedonic zomwe zikuwonetseratu kuti ntchito ya BLA inaletsa kugwiritsa ntchito mankhwala osokoneza bongo opangidwa ndi intra-acb DAMGO, komabe kuchoka kwa chakudya chawonjezeka kwambiri, makamaka atatha kudya. Ngakhale kutanthauzira kwathunthu ndi kutanthauzira kwa detayi kwaperekedwa , Kuwonetsa BLA kumawoneka kuti kumangowonongeka ndi kayendedwe kake ka machitidwe odyetsa mafuta, koma osati njira yogwiritsira ntchito chakudya choyendetsedwa ndi opioid activation of Acb.

Zakale, makhalidwe opindulitsa apangidwa m'gulu kukhutira gawo, lomwe limaphatikizapo makhalidwe okhudzana ndi njira zoyenera kuchita pofuna kupeza zopindulitsa monga chakudya, ndi zimatha gawo, lomwe limaphatikizapo makhalidwe monga kudya chakudya (; ). Kusiyanitsa kumeneku kwachitika kwa zaka makumi ambiri ndipo kumakhalabe wotchuka masiku ano monga ziphunzitso zokhuza zokhudzana ndi chakudya ndi mphotho zina zimasintha (; ; ; ; ). Kuyesera kufotokozera thupi la pansi pa magawo osiyanawa a khalidwe lolimbikitsako kwaphatikizapo mafanizo omwe mankhwala amalepheretsa kufotokozera gawo limodzi popanda kutsogolera ena (; ; ; ). Kafukufuku wamakono akufufuzira zaumulungu zenizeni za khalidwe lapadera la chizolowezi chodyetsa pamene gawo lokhalitsa ndi lokhazika mtima pansi linasokonezedwa.

Zomwe zikuchitika panopa zafufuzira zokhudzana ndi zochitika zokhudzana ndi zochitika zokhudzana ndi zofuna zowonongeka ndi zopatsa mphamvu zomwe zimayendetsedwa ndi intra-Acb DAMGO. Choyamba, kupeza koyamba () anaphatikizidwa kuti atsimikizidwe kuti ayesetse kuyesa kachiwiri, kuphatikizapo kufunika kokwanira kudya zakudya zochepa kuti apereke phunziro lachiwiri. Muyeso yachiwiri, kutsata njira zisanu ndi zinayi zochizira mankhwala, maphunziro onse anapatsidwa mwayi wochuluka wa zakudya zamtundu wapatali, kupereka gulu lililonse la mankhwala kupatula gulu lachipatala lokhalitsidwa ndi DAMGO, kuti lifike pamasewera ena (mwachitsanzo, akuwonetsedwa pansi pa malonda zofunikira kuchokera ku kuyesa 1). Pambuyo pake panthawi yopatsa 2hr, makoswe anaperekedwa nsembe kuti agwire zochitika za neural zomwe zikugwirizana ndi machitidwe a khalidwe. Deta yam'mbuyomu yawonetsetsa kuti njira yonse yodyera komanso zakudya zoyendetsera chakudya zimapezeka mkati mwa gawo loyamba la 30 la gawoli popita kuchipatala, komabe intra-Acb DAMGO, yopanda ntchito ya BLA kapena yopanga chakudya, imapangitsa kuti anthu azikhala ndi chakudya chokwanira pamapeto a 90 min Phunziro la 2hr (). Choncho, ntchito za neural zogwirizana ndi zolimbikitsa ku yandikira ndi idyani ziyenera kuimiridwa mu makoswe omwe akulandira mankhwala a intra-acb DAMGO popanda ntchito ya BLA. Mosiyana ndi zimenezi, njira zamakono zomwe zimakhala ndi makoswe omwe amalandira mankhwala a intra-Acb DAMGO ndi BLA kuyambitsa ziyenera kuwonetsa mofanana yandikira, koma zikuwonetseratu zotsitsimula kuti idyani.

Zochitika za Neural zinayang'aniridwa m'madera a ubongo omwe amadziwika kuti amatsutsana ndi zovuta zokhudzana ndi zofuna zawo, kuphatikizapo ventral tegmental area (VTA), dorsaal hypothalamus (DMH), malo osokonekera a hypothalamus (PeF), ndi lateral hypothalamus (LH) (; ; ). Ma intra-acb DAMGO maulamuliro amachulukitsa c-Fos kufotokozera mu zizindikiro za hypothalamic neurons ndipo mawu awa amafunika orexin kuzindikiritsa mkati mwa VTA (). Zonsezi, zotsatizanazi ndi zina zimasonyeza kuti njirayi yothandizira kudyetsa kupyolera mwa Acb μ-opioid receptor activation ingagwiritsire ntchito PeF orexin neurons ndikupangitsa orexin kuzindikiritsa mkati mwa VTA zomwe zingayambitse DA efflux ku Acb ndi mPFC, kuyendetsa kayendedwe ka kudya (). Zotsatira za kuchitidwa kwa BLA kukhala kofunikira kuwona kuwonjezeka kwa intra-Acb DAMGO kwambiri mafuta ogwiritsidwa ntchito, koma osati kwambiri mafuta njira zoyenera, adzafufuzidwa.

Njira

makoswe

Amuna makumi atatu mphambu asanu ndi limodzi achikulire a Sprague-Dawley (Harlan Sprague-Dawley, Inc., Indianapolis, IN) olemera 300-400 g, adagwiritsidwa mwa awiri awiri mu malo osungirako zinthu omwe amadziwika ndi malo ozungulira nyengo yotentha ya 22 ° C. Makoswewo ankasungidwa pa 12-hr kuwala-mdima, ndipo kuyesera konse kunkachitika panthawi ya kuwala (0700 -1900) pakati pa maola a 1200 ndi 1500. Pokhapokha ngati taona, makoswe anali ndi mwayi wopita ku laboratory chow ndi madzi akumwa kale ndi kuyesa. Magulu anali ndi rats 6-8. Njira zonse zoyesera zinachitidwa mogwirizana ndi mapulogalamu obvomerezedwa ndi University of Missouri Institutional Animal Care ndi Komiti Yogwiritsira ntchito.

Opaleshoni

Makoswe ankatsitsidwa ndi ketamine ndi xylazine (90 mg / kg ndi 9 mg / kg, motsatira Sigma, St. Louis, MO), ndi 2 magulu a zitsulo zosapanga zitsulo (23 gauge, 10 mm) ankawotchedwa sterotaxically Pakati pa malire a chigawo cha Acb ndi chigoba cha BLA ndi BLA ndipo amatetezedwa ku chigaza ndi zitsulo zosapanga dzimbiri komanso zowonongeka (Dental Supply New England, Boston). Pambuyo pa opaleshoni, zida za waya zinayikidwa mu guide cannulas kuti zisawonongeke. Kukonzekera kwa malo otetezedwa ndi awa: Acb: AP, + 1.4; ML, ± 2.0; DV, -7.8; BLA: AP, -2.8; ML, ± 4.7; DV, -8.6 (DV coordinate ikuimira kuyika kwa 12.5mm injection ya singano yomwe imapangitsa 2.5mm kukhazikika kwa chingwe).

zida

Kuyesera kachitidwe ka kudya kunkachitika m'chipinda chosiyana ndi chipinda cha colony mu 8 Plexiglas (30.5 cm × 24.1 cm × 21.0 cm) kudyetsa zipinda (Med Associates, St. Albans, VT). Makoswe amatha kupeza malonda a madzi libitum ndi pafupifupi 35g ya zakudya zokoma kupatula pomwe tawonetsa. Kudyetsa zipinda kunali ndi zipangizo zinayi zapakati pazipangizo zapakati pa 6 cm kupatula kutalika kwa chipinda ndi masentimita 4.3 pamwamba. Zomwe zimapangidwira pang'onopang'ono kuti chophimba chakudya chiziyang'anitsitsa kugwiritsidwa ntchito kwa chakudya. Dera linalake lopangidwa ndi ma chinsalulo lomwe linayambira pakhomo la chakudya chodyeramo chakudya linatsimikiza kuti nambala ndi nthawi ya mutu uliwonse kulowa m'dera lamtunda. Chophimba chakudya ndi botolo la madzi zinali pambali imodzi (moyang'anizana ndi ngodya) za khoma limodzi la chipinda, ndipo tayi yowonongeka inali pansi pa malo osanja. Kuyeza kwake kunaphatikizapo ntchito yokonza mapulogalamu (kuchuluka kwa mazenera osakanikirana), kutalika kwa malo olowera kumtunda (kutalika kwa dothi losweka pakhomo la chimbalangondo), zolembera zam'madzi (chiwerengero cha mphukira pakhomo la chimbalangondo), ndi kuchuluka kwa ndalama ( magalamu a zakudya zowonongeka). Nthawi yoyezetsa magazi inali ndi kuyang'anitsitsa khalidwe muzipinda zodyera ndi kompyuta yomwe imayendetsa mapulogalamu a Med-PC (Med Associates Version IV, St. Albans, VT).

Kayendesedwe

Dokotala Microinjection

D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO; Research Biochemicals, Natick, MA) ndi muscimol (Sigma, St. Louis, MO) zonse zinasungunuka mu 0.9% saline wosabala. Kuyendetsa galimoto nthawi zonse kunali kovuta 0.9% saline. Mankhwala opatsirana amaperekedwa ndi mpweya wa microdrive (Harvard Apparatus, South Natick, MA), wogwiritsidwa ntchito pogwiritsa ntchito polyethylene tubing (PE-10), pamene makoswe anali atasamalidwa bwino. Zida makumi atatu ndi zitatu za 12.5-mm zimagwiritsidwa ntchito, kutambasula 2.5 mm kupitirira mapeto a zowonongeka. Mlingo wa jekeseni unali 0.32 μl / min kwa Acb ndi 0.16 μl / min kwa BLA, ndi nthawi yonse yokhala ndi 93, zomwe zimachititsa 0.5-μl ndi 0.25-μl mabuku, motero. Mphindi imodzi yowonjezera inaloledwa kuti itengeke.

Design

Yesani 1

Pogwiritsa ntchito mapangidwe apakatikati, magulu onse a makoswe adalandira limodzi mwa mankhwala anayi a mankhwala osokoneza bongo pa masiku anai ochizira opaleshoni. Kuyesera kwa makhalidwe onsewa kunayambitsa 1 sabata pambuyo pa opaleshoni muzipinda zowawonongera chakudya cha Med-Associates. Makoswe anapatsidwa mwayi wodyeramo zakudya m'zipinda izi za 2hr tsiku lililonse pa 6 masiku otsatira. Pa 5th tsiku, 10-mm injector inalowetsedwa ndipo yasiyidwa m'malo a 2 min, popanda kupopera mphamvu. Pa 6th tsiku, 12.5-mm injection inalowetsedwa, ndipo saline imaperekedwa kwa 93 s. Patsiku lililonse la mayeso, muscimol (20 ng / 0.25 μl / mbali palimodzi) kapena saline amalowetsedwa mu BLA, kenako amatsatira DAMGO (0.25 mg / 0.5 μl / mbali palimodzi) kapena saline mu Acb, motero amachititsa mankhwala anayi kuphatikiza. Phunziro la 2hr linayamba mwamsanga kulandira katemera kotsiriza ndipo makoswe anapatsidwa kulandira zakudya zogulira mafuta. Panali osachepera tsiku la 1 pakati pa masiku achipatala.

Yesani 2

Magulu anayi a makoswe, pogwiritsira ntchito mapangidwe apakati, omwe ali ndi mapepala awiri omwe akugwirizana ndi Acb ndi BLA. Mphungu zinapatsidwa mwayi wopezera chakudya m'zipindazi za 2hr tsiku ndi tsiku pa 6 masiku otsatizana ndi njira zojambulira zinali zofananako ndi kuyesera 1, komabe ngongole iliyonse ikanalandira 1 yokha yosakaniza mankhwala a 4. Kugwiritsira ntchito zakudya zamtengo wapatali pa tsiku la 6th la mankhwala oyambirira kunagwiritsidwa ntchito poyesa kuchepetsa kusamalitsa mankhwala opatsirana mankhwala kuti atsimikizire njira zofanana zowonetsera mankhwala. Pa 8th tsiku, zinyama zinapatsidwa 1 ya 4 mankhwala otheka omwe amapezeka ndi kupeza kwa 8g chakudya chokoma kwa 2hr.

Kuzindikiritsa kwake kwachembedwe ka kuikidwa kwachitsulo

Pambuyo pake panthawi yopatsa 2hr, nyama zimachotsedwa m'chipinda chodyetsa, zowonongeka kwambiri ndi ketamine ndi xylazine (90 mg / kg ndi 9 mg / kg), ndipo transcardial perfused. Ubongowo unachotsedwa ndi kumizidwa mu formalin (10%) usiku umodzi pa 4 ° C ndipo kenaka imatetezedwa podutsa njira yotsatira sucrose (20%) pa 4 ° C. Zigawo zowonongeka (50 μm) zinasonkhanitsidwa kudera lonse la jekeseni, zowonongeka ndi zithunzi zajelatinized, komanso zowonongeka ndi cresyl violet. Mapulogalamu osungirako zikhomo ndiye anayesedwa chifukwa chachindunji ndi deta kuchokera ku makoswe ndi misomali yosalongosoka sizinaphatikizidwe mu kufufuza.

Immunohistochemistry

Ubongowo unadulidwa pa 40 μm makulidwe ndi kusungidwa mu 0.1M phosphate solution solution (PB, pH 7.4) pa 4 ° C. Ndondomeko yowonongeka yopanda mavitamini yowonongeka yaumadzi ndi yotere: Zigawo zinatsukidwa (3 × 10 min) mu PBS. Malo osadziwika omangirira anali otsekedwa pogwiritsa ntchito njira yothetsera [osakaniza 10% seramu yeniyeni ya mbuzi (Jackson Immuno Research, West Grove, PA) ndi 0.3% Triton X-100 (Sigma) mu PBS)] kwa 2 hr. Kenaka, zigawozo zidakonzedwa pamsakaniza wokhala ndi rabbit anti-c-Fos antibody (1: 5000; Calbiochem) ndi nkhuku yotsutsana ndi Tyrosine Hydroxylase (VTA) kapena mbola anti-orexin-A (hypothalamus) usiku uliwonse. Zigawo zinatsukidwa (4 × 30 min) mu PBS zomwe zili ndi 0.05% Tween-20 (PBST). Kenaka, zigawo zidakonzedwa chifukwa cha maola a 2 m'kati mwachitsulo chosakanikirana, ndi zakudya zowonjezereka: Alexa Fluor 555 mbuzi Anti Anti-rabbit IgG ndi Alexa Fluor 488 mbuzi Anti-nkhuku IgG (Invitrogen). Ma antibodies onse apachilendo amagwiritsidwa ntchito pa 1: 500. Zigawo zinatsuka (4 × 30 min) mu PBST ndi PB (2 × 10 min). Zigawozo zinakwera pamwamba pa slide (VWR International, USA) ndipo analola kuti aziuma pa firiji pamene ankatetezedwa kuchokera ku kuwala. Pogwiritsira ntchito kampani ya ProLong Anti-fade mounting kit (Invitrogen) magawowo anali ataphimbidwa ndi kusungidwa ku 4 ° C. Zokwanira zonsezi zinkachitidwa kutentha kutentha kupatulapo ma antibodies oyambirira omwe ankatengedwa pa 4 ° C. Pofuna kusintha mitundu yosiyanasiyana ya immunohistochemical reaction, minofu ya magulu osiyanasiyana ochiritsira inagwirizanitsidwa palimodzi. Kuwonjezera apo, kudetsa kunalibe pokhapokha poyesa kuyesa kuyesa ndi kusalidwa kwa ma antibodies oyambirira.

Kusanthula Kosintha kwa Zinthu

Kuyesera 1, njira zonse zodyera pa nthawi ya 2-hr komanso magawo osiyanasiyana a mankhwalawa anafufuzidwa ndi zigawo ziwiri mkati mwa mutu wa ANOVA (Acb Treatment X Amygdala Treatment), ndi magawo a chinthu chilichonse kukhala galimoto kapena mankhwala . Kuyesera 2, njira zonse zodyera zinafufuzidwa pogwiritsa ntchito zigawo ziwiri pakati pa-ANOVA (Acb Treatment X Amygdala Treatment), ndi magawo pa chinthu chilichonse kukhala galimoto kapena mankhwala.

Kuwerengera ndondomeko, kujambula, ndi kusanthula ziwerengero

Pofufuza kuchuluka kwa matenda osamvetseka m'thupi mwa hypothalamus (kuphatikizapo lateral hypothalamus, malo ovuta, dorsomedial hypothalamus) ndi VTA, magawo atatu a minofu kuchokera ku dziko lonse (6 total per region) anafufuzidwa ndi kuwerengedwa. Zithunzi zonse zinapangidwa kudzera muzithunzithunzi za 4 × kapena 10 × ndi makina osokoneza bongo omwe amagwiritsira ntchito pulogalamu yamakono yotchedwa Slidebook 4.3 (Intelligent Imaging Innovations, Denver, CO). Malingana ndi dera lomwelo, kutentha kwa thupi kosapangidwira m'madzi mkati mwa chidutswa cha 40μm chinali chithunzi cha c-Fos, c-Fos / TH, kapena C-Fos / OrexinA yolemba njira, yosiyana ndi malo okhazikika. Zithunzizo zinkasonyezedwa pazenera zonse pogwiritsa ntchito mapulogalamu a ufulu wa java omwe amawagwiritsa ntchito a java, a ImageJ (National Institutes of Health, Bethesda, MD, USA). anawerengedwa mu mafashoni akhungu. Ma Neuroni amagawidwa monga c-Fos okha, peptide okha, kapena kawiri-yolembedwa pambali pa kukhalapo kwa pamwamba pamtundu wa mankhwala opangira mankhwala mu khungu la maselo.

Madera onse adasankhidwa ndikujambulidwa pogwiritsa ntchito Rat Brain Atlas (Paxinos & Watson, 1998). Ventral Tegmental Area ndi Tyrosine Hydroxylase; magawo omwe adasankhidwa anali pakati pa -5.2 ndi -5.5mm anterior kwa bregma. Pa mulingo uliwonse, dera lokhala ndi maselo a tyrosine hydroxylase (TH-IR) ndi c-Fos-IR amawerengedwa m'ma hemispheres onse. Hypothalamus ndi Orexin-A; magawo osankhidwa anali pakati pa -2.8 ndi -3.3 mm anterior kwa bregma. Dera la hypothalamic (pakati pa -2.8 ndi -3.3 mm) lomwe limapezeka kuti lili ndi orexin-A maselo abwino adagawika magawo atatu kuyambira medial mpaka lateral. Maselo onse mkatikati, mkati, ndi m'mbali mwa fornix adaphatikizidwa ndi dera lapakatikati lotchedwa perervical (PeF). Maselo olembedwa ndi Orexin-A ofananira ndi dera lino adaphatikizidwa ndi lateral hypothalamus (LH), ndipo amankhwala ochokera ku fornix anali mgulu lamankhwala (DMH), lomwe linali ndi dorsomedial hypothalamus. Ma Neurons amawerengedwa m'magawo onse awiriwa.

Results

Zotsatira za mankhwala onse zanenedwa ponena za malo (s) a mankhwala kapena mankhwala oyendetsa galimoto (ie intra-Acb DAMGO). Monga makoswe onse anapatsidwa mwayi wokhala ndi zakudya zochepa zamtundu wa mafuta, kusintha konse kwa makhalidwe odyetserako (Exp. 1 ndi 2) ndi machitidwe a neural activation (Exp. 2) ndizogwiritsidwa ntchito pamodzi ndi mankhwala onse mankhwala ndi zakudya zowonongeka.

Kudyetsa khalidwe

Yesani 1

Mphamvu ya BLA kuyambitsanso makhalidwe abwino odyetsa mafuta omwe amachitidwa ndi intra-acb DAMGO administration.

Kugwiritsa ntchito

Monga momwe taonera Fanizo la 1a, ANOVA yomwe imagwiritsidwa ntchito pazidziwitso za zakudya zimasonyeza kuti zotsatira za mankhwala a Acb (F (1, 7) = 13.9, p <.01), chithandizo cha BLA (F (1, 7) = 8.6, p <.05), ndi kulumikizana kwa chithandizo cha Acb × BLA (F (1, 7) = 8.9, p <.05). Kusanthula kwaposachedwa kunavumbula kuti mankhwala amchere a intra-Acb DAMGO + intra-BLA amathandizira kuti azigwiritsa ntchito kwambiri (p <.05) poyerekeza ndi mankhwala onse owongolera (intra-Acb saline + intra-BLA saline; intra-Acb saline + intra-BLA muscimol), ndipo chithandizo cha intra-BLA muscimol chidaletsa kuwonjezeka uku (p <.05).

Chithunzi 1 

Kuwongolera khalidwe: A) Zambiri za zakudya zamtengo wapatali zomwe zimadya (ad libitum access), B) chiwerengero cha chakudya chokwanira chambiri, C) Chiwerengero chazolowera zakudya, ndi zochitika zapakhomo zimakhala zofunikira (mwachitsanzo kupuma kwazitsulo). Mankhwala a 4 anaperekedwa ...
Nthawi yowonjezera chakudya chokwanira

Monga momwe taonera Fanizo la 1b, ANOVA yomwe imapangidwira nthawi yowonjezera chakudya yowonjezera deta yasonyezera zotsatira zazikulu za mankhwala a Acb (F (1, 7) = 36.3, p <.001), chithandizo cha BLA (F (1, 7) = 12.1, p <.05), ndi kulumikizana kwa chithandizo cha Acb × BLA (F (1, 7) = 16.5, p <.005). Kusanthula kwa post-hoc kunawulula kuti intra-Acb DAMGO + intra-BLA muscimol chithandizo chidapangitsa kuti pakhale nthawi yokwanira yolowetsa chakudya poyerekeza ndi mankhwala ena onse (p <.001), popanda chithandizo china chilichonse chosiyana kwambiri ndi chimzake.

Zowonjezera zakudya

Monga momwe taonera Fanizo la 1c, ANOVA yomwe inkapangidwira pakhomo la chakudya chowongolera chakudya, inasonyeza zotsatira zazikulu za mankhwala a Acb (F (1, 7) = 10.6, p <.05), pomwe chithandizo cha BLA chinkayandikira (F (1, 7) = 3.89, p = .08), ndi kugwirizana kwa mankhwala a Acb × BLA (F (1, 7) = 7.9, p <.05). Kusanthula kwa post-hoc kuwulula kuti intra-Acb DAMGO + intra-BLA muscimol chithandizo chidapangitsa kuti pakhale chakudya chambiri poyerekeza ndi mankhwala ena onse (p <.05), popanda chithandizo china chilichonse chosiyana kwambiri ndi chimzake.

Ntchito yowonongeka

Monga momwe taonera Fanizo la 1c, ANOVA yomwe inkapangidwira pakhomo la chakudya chowongolera chakudya, inasonyeza zotsatira zazikulu za mankhwala a Acb (F (1, 7) = 23.5, p <.005), koma palibe zotsatira zazikulu zamankhwala a BLA (F (1, 7) = 1.4, p > .05), ndipo palibe kulumikizana kwa chithandizo cha Acb × BLA (F (1, 7) = .056, p > .05).

Yesani 2

Mphamvu ya BLA kuyambitsanso machitidwe abwino odyetsa mafuta ndi njira zowonongeka za neural zoyendetsedwa ndi intra-Acb DAMGO administration.

Kugwiritsa ntchito mankhwala osokoneza bongo kunali kosayerekezereka ndi magulu a mafuta olemera kwambiri kuchokera ku 6th tsiku loyambira. Maseŵera awa okhudzidwa ndi awa: SAL-SAL, 5.1g; SAL-DAM, 4.9g; MUSC-SAL, 4.9g; MUSC-DAM, 4.8g.

Kugwiritsa ntchito

Monga momwe taonera Fanizo la 2a, ANOVA yomwe imagwiritsidwa ntchito pazidziwitso za zakudya zimasonyeza kuti zotsatira za mankhwala a Acb (F (3, 24) = 26.60, p <.001), koma palibe zotsatira za chithandizo cha BLA (F (3, 24) = 0.02, ns) kapena mgwirizano wa mankhwala a Acb × BLA (F (3, 24) = 0.61, ns).

Chithunzi 2 

Kuwongolera khalidwe: a) Mitengo yambiri ya mafuta yowonongeka (mzere wotsutsa umasonyeza kuchepa kwa mwayi wa 8g); b) Chiwerengero cha zolembera zakudya, c) chiwerengero cha chakudya chokwanira chambiri, komanso d) Zochita zogwira ntchito zimakhala zofunikira (mwachitsanzo, kupuma kwazitsulo). Mankhwala a 4 ...
Zowonjezera zakudya

Monga momwe taonera Fanizo la 2b, ANOVA yomwe inkaperekedwa pafupipafupi kudutsa gawo lonse la chakudya, inasonyeza kuti zotsatira za mankhwala a Acb (F (3, 24) = 8.55, p <.01), koma palibe chithandizo chamankhwala a BLA (F (3, 24) = 1.68, ns) kapena mgwirizano wa mankhwala a Acb × BLA (F (3, 24) = 0.39, ns).

Nthawi yowonjezera chakudya chokwanira

Monga momwe taonera Fanizo la 2c, ANOVA yomwe yachitidwa pa nthawi yonse ya zolembera kudutsa gawo lonse lodyetserako chakudya, inasonyeza zotsatira zazikulu za mankhwala a Acb (F (3, 24) = 12.45, p = .001), koma palibe zotsatira za mankhwala a BLA (F (3, 24) = .62, ns) kapena mgwirizano wa mankhwala a Acb × BLA (F (3, 24) = 0.07, ns).

Ntchito yowonongeka

Monga momwe taonera Fanizo la 2d, ANOVA yomwe inachitidwa pa ntchito yonse yothandizira pakhomo la chakudya, inasonyeza zotsatira zazikulu za mankhwala a Acb (F (3, 24) = 12.93, p = .001), koma palibe zotsatira za mankhwala a BLA (F (3, 24) = .198, ns) kapena kugwirizana kwa Acb × BLA mankhwala (F (3, 24) = 0.61, ns).

Immunohistochemistry

Ventral Tegmental Area

Monga momwe taonera Fanizo la 3a, ANOVA yochitidwa pa maselo a c-Fos IR mu VTA idawulula zotsatira zabwino za chithandizo cha Acb (F (3, 24) =, 25.67 p <.001), koma palibe zotsatira za chithandizo cha BLA (F (3, 24) = 1.13, ns) kapena kulumikizana pakati pa chithandizo (F (3, 24) = 2.80, ns). ANOVA yochitidwa ndi kuchuluka kwa maselo a TH-IR omwe akuwonetsa c-Fos IR idawulula zotsatira za chithandizo cha Acb (F (3, 24) = 6.33, p <.05), koma palibe zotsatira za chithandizo cha BLA pa kuchuluka kwa TH- Maselo a IR omwe akuwonetsa c-Fos IR (F (3, 24) = .07, ns) kulumikizana kopanda tanthauzo pakati pa chithandizo (F (3, 24) = .63, ns).

Chithunzi 3 

a) Chiwerengero cha maselo a VTA akufotokoza c-Fos IR; b) Peresenti ya maselo a VTA TH-IR akufotokozera c-Fos IR. c) Chiwerengero cha maselo akulongosola c-Fos-IR pamalo ovuta a hypothalamus (PeF) d) Peresenti ya PeF Orexin-A maselo a IR akufotokozera c-Fos-IR. Mankhwala a 4 ...

Perifornical hypothalamus

Monga momwe taonera Fanizo la 3b, ANOVA yopangidwa pa c-Fos IR ku PeF (dera lomwe lafotokozedwa pa Fanizo la 5b) linasonyeza zotsatira za mankhwala a Acb (F (3, 24) = 30.78, p <.001), chithandizo cha BLA (F (3, 24) = 30.52, p <.001) ndi kulumikizana kwa chithandizo cha Acb × BLA (F (3, 24) = 8.75, p <.01). ANOVA yochitidwa pa kuchuluka kwa maselo a OrxA-IR omwe akuwonetsa c-Fos IR idawulula zotsatira zazikulu za chithandizo cha Acb (F (3, 24) = 55.85, p <.001), chithandizo cha BLA (F (3, 24) = 23.52, p <.001), ndi kulumikizana kwa chithandizo cha Acb × BLA (F (3, 24) = 14.32, p <.001). M'mazithunzi 5a ndi 5b, posachedwa kusanthula kukuwonetsa kuti kuyimitsidwa kwa BLA kumachepetsa kwambiri intra-Acb DAMGO idapangitsa c-Fos kufotokoza ndikuchepetsa kuchuluka kwa maselo a orexin akuwonetsa c-Fos (p <.05).

Dorsomedial hypothalamus

Monga momwe taonera Gulu 1, ANOVA yoyendetsedwa ndi kuchuluka kwa maselo a c-Fos IR mu DMH idawulula zotsatira zabwino zamankhwala a intra-Acb (F (3, 24) = 20.19, p <.001), koma palibe chithandizo chamankhwala a intra-BLA ( F (3, 24) = 1.63, ns) kapena mgwirizano wa mankhwala a Acb × BLA (F (3, 24) = 0.05, ns). ANOVA yochitidwa pamlingo wa maselo a OrxA-IR omwe akuwonetsa c-Fos IR idawulula zotsatira zofunikira za chithandizo cha Acb (F (3, 24) = 13.39, p <.001), chithandizo cha BLA (F (3, 24) = 5.85, p <.05), koma palibe kulumikizana kwa chithandizo cha Acb × BLA (F (3, 24) = .89, p = .36).

Gulu 1 

Chiwerengero cha maselo akuwonetsa c-Fos-IR (chiwerengero) mu lateral hypothalamus ndi dorsomedial hypothalamus ndi chiwerengero cha PeF Orexin-A IR maselo akulongosola c-Fos-IR (% orexin-A). Mankhwala a 4 anaperekedwa, kuphatikizapo intra-Acb DAMGO kapena saline (SAL) mwamsanga ...

Pambuyo hypothalamus

Monga momwe taonera Gulu 1, ANOVA yoyendetsedwa ndi kuchuluka kwa maselo a c-Fos IR mu LH sanawonetse zotsatira za Acb ((F (3,24) = .11, ns) kapena chithandizo cha BLA ((F (3, 24 = 6.82, p < .05) ndipo palibe kulumikizana (F (3,24) = .26, ns). ANOVA yomwe idachitika pamaselo a OrxA-IR maselo omwe akuwonetsa c-Fos IR sanawulule chilichonse chokhudza chithandizo cha Acb (F (3, 24 ) = .64, ns), chithandizo cha BLA (F (3, 24) = .08, ns), kapena kulumikizana kwamankhwala (F (3, 24) = .77, ns.)

Kukambirana

Pogwiritsa ntchito mikhalidwe yowonjezera mafuta, BLA inachepetsa kuchuluka kwa mafuta omwe amapangidwa ndi intra-Acb DAMGO, pamene kusiya njira yowonjezera chakudya kumayendetsa khalidwe, kutsimikizira lipoti lapitalo (). Chiyeso chachiwiri chinayang'ana zochitika zomwezi, koma ndi zochepa zomwe zimawathandiza kudya zakudya, kupatsa magulu onse achipatala kupatula intra-Acb DAMGO yokha yogwiritsidwa ntchito pokhapokha, kuti afike poyambira (mwachitsanzo, idyani ndalama zomwe zimayang'aniridwa pansi pa zilembo za Exp. 1). Intra-Acb saline ankachitira nyama, popanda BLA, kapena kudya popanda kudya, ankadyera zakudya zofanana kwambiri ndi mafuta ndipo ankawonetsera makhalidwe omwewo, monga ananenedweratu. Magulu awiri ochiritsira omwe ali ndi chidwi, omwe amalandira DAMGO omwe ali ndi BLA kapena popanda ntchito, amawononga pafupifupi zakudya zonse zamtengo wapatali zomwe zilipo m'kati mwa 30 min ya masewero a 2hr ndipo amawonetsa njira zofanana ndi ziwerengero zamakono (ie nambala Zowonjezeredwa za zakudya zopangira chakudya, chakudya cholowera chakudya cham'mbuyo) pamapeto omaliza a 90 min, monga ananenedweratu. Kuchuluka kwa mankhwala a DAMGO kuwonjezereka ponseponse nambala komanso nthawi ya chakudya chowongolera zakudya kumayendetsedwe mosasamala kanthu koyambitsa BLA, poyerekeza ndi magulu awiri omwe amagwiritsidwa ntchito m'thupi mwawo monga momwe ananenedwa kale (). Chofunika kwambiri, monga momwe tawonera mu kuyesa 1 ndi kale (, ), mankhwala osokoneza intra-Acb DAMGO, popanda kuika BLA, amatsogolera kumagulu opitirira kawiri kuchuluka kwa ndalama zomwe zimaperekedwa pokhapokha ngati zili zochepa. Choncho, maukonde a neural mu makoswe omwe adalandira mankhwala a intra-Acb DAMGO popanda BLA kukhazikitsidwa ayenera kufotokoza zonse zolimbikitsa yandikira ndi idyani chakudya china kuposa zomwe zinalipo. Mosiyana ndi zimenezi, njira zamagetsi zomwe zimalandira mankhwala a intra-Acb DAMGO, ndi BLA, sizinapangidwe, ziyenera kuwonetsa kuti yandikira chakudya, koma zochepa zolimbikitsa kuti idyani chakudya chowonjezera, poyerekeza ndi makoswe otetezedwa ndi intra-Acb DAMGO popanda ntchito ya BLA. Izi ndi zofunika kwambiri osati zongoganizira zokhazokha, koma kutanthauzira deta yamakono. Kukula kwa chakudya kunasankhidwa osati kungokhala ndi magulu ochepa m'magulu angapo, komanso kutsimikizira makoswe mu gulu lililonse lachipatala, kupatula gulu la DAMGO okha, lomwe linafika kapena likuyandikira satiation (monga yatsimikiziridwa ndi Mayesero 1 ndi kale zofufuza, mwaona ).

Ma intra-acb DAMGO administration yowonjezera VTA c-Fos IR mu dopaminergic neurons poyerekeza ndi chithandizo cha mankhwala a saline, ndi ma intra-BLA muscimol administration sankakhudza kuwonjezeka kumeneku. Kafukufuku wammbuyo amasonyeza kuti kuwonjezeka kwa c-Fos IR mu VTA makamaka makamaka, VTA dopamine (DA) neurons, imakhala ndi gawo lalikulu pa mphotho, chilimbikitso, ndi mankhwala osokoneza bongo (; ; ). Kusamalira antchito a dopamine kupita ku Acb kumapangitsa kuti zakudya zokhudzana ndi zakudya zokhudzana ndi njala zisawonongeke koma sizikhala ndi zotsatira zowonongeka ndi njala () kapena ma intra-acb DAMGO mafuta oyamwa (). Ulamuliro wa intra-Acb wa agopisi wa dopamine ukuwonjezeka pang'onopang'ono-kuyanjanitsa kuyankha kwa chakudya chowongolera, koma alibe mphamvu pa kudya kwaulere (). Deta iyi ndi ena amati njira yowonjezera yokhutiritsa chakudya chokhudzidwa ndi machitidwe omwe amapezeka m'magulu onse ochiritsira omwe amachitidwa intra-Acb DAMGO, ndi popanda BLA kupanga ntchito, akukhala pakati pa ntchito yowonjezera mu VTA dopaminergic neurons.

Chitsanzo cha PeF orexin-A neuronal ntchito ikufanana ndi njira zomwe zimagwiritsidwa ntchito potsatira zotsatirazi zochiritsira zofanana ndi zovuta zopezeka pafupipafupi (, ), ndi mankhwala a intra-Acb DAMGO omwe amachititsa kuti azigwiritsa ntchito kwambiri kuposa mankhwala ena alionse. Tinapezanso kuti intra-Acb DAMGO yowonjezera ntchito ya DMH c-Fos mosasamala kanthu za mankhwala a BLA, koma intra-DAMGO yokha idawonjezera kuchuluka kwa orexin neurons kufotokoza c-Fos poyerekeza ndi machitidwe. Mosasamala kanthu za udindo wawo ku khalidwe lodyetsa la DAMGO (; ), DAMGO sanawonjeze kwambiri ntchito ya LH c-Fos, ngakhale sanalole kuti nyama zifike pamtima.

The hypothalamus yakhala ikudziwika kuti ndi malo odziwitsira mphamvu zowonongeka kwa mphamvu; kuphatikizapo kudya malamulo, kudzutsa, ndi mphotho (, ). Ma Neurons akufotokoza orexigenic peptides orexin-A ndi ma melanin-kuchuluka kwa hormone (MCH) amadziwika kuti amakhala ndi malo ochepa a hypothalamus (), makamaka, malo osokonekera. Kugwiritsa ntchito zakudya zamtengo wapatali zomwe zikuwonetsedwa kuti zimayendetsedwa ndi orexin-A () imatsekedwa ndi oyang'aniridwa ndi ophioid antagonist naloxone (), kutanthauza kuyanjana kwa opioid ndi orexin peptides potengera chakudya choyenera. Intra-VTA orexin-Uchiyanjano umakondanso dopamine neurons (Borgland et al., 2006). Kuletsa orexin kuzindikiritsa mu VTA kumachepetsa kudya kwa DAMGO kwa zakudya zamtengo wapatali (), komabe mpaka pano kupyolera m'makhalidwe abwino omwe angapangitse kuchulukitsira ntchito sikudziwika. Choncho, pakali pano kupeza kuti kuchuluka kwa VTA dopaminergic ntchito pambuyo pa intra-Acb DAMGO sikunakhudzidwe ndi kukhazikitsidwa kwa BLA, ngakhale kuti kuchepetsa ntchito ya PeF orexin, kumabweretsa kufunika kokhala ndi khalidwe labwino komanso zovuta zokhudzana ndi khalidwe la kudya. Kuonjezera apo, deta imeneyi imapereka zifukwa zomveka zoganizira zovuta za PeF orexin ndi VTA dopaminergic modulation pa njira opioid amayendetsa ndikudya chakudya.

Kafukufuku wamakono adagwiritsa ntchito zakudya zochepa (ie magalamu omwe alipo) kuti athetse mphamvu zosiyana siyana pakutsata mankhwala osiyanasiyana. Phunziroli linapewanso kuyesa kwa chakudya chimodzi; Choncho, zowonjezerabe kuti kudya kwa opioid komwe kumayendetsa zakudya zina zowonongeka kungayambidwe mofananamo. Kusankhidwa kwa zakudya zapamwamba kwambiri kunayendetsedwa ndi mapangidwe akale a malo omwe amagwiritsidwa ntchito omwe akuwonetsedwa kuti azitsatira kwambiri intra-Acb DAMGO mafuta odyetsa kwambiri (; kubwereza), makamaka udindo wa BLA (, ). Sizidziwika ngati zochitika zenizenizi ndizozowonjezera zakudya zam'mafuta kwambiri, kapena kuti ziwonetsedwe pogwiritsa ntchito zakudya zina. N'zochititsa chidwi kuti kafukufuku waposachedwapa anapeza kuti ngakhale pakati pa zakudya zopatsa thanzi, pali kusiyana kwakukulu pa c-fos njira zowonjezera kudera lopangira zakudya zoyenera za mesocorticolimbic circuit (). Zotsatira zamtsogolo zidzafunikanso kuti mudziwe ngati zowonjezera zowonjezera zowonjezera zokhudzana ndi mafuta ambiri.

Mwachidule, detayi imapereka ndondomeko yowona momwe BLA ikuyankhira poyambitsa opioid ya Acb kuti igwiritse ntchito mogwiritsira ntchito, koma osati makhalidwe oyenerera, okhudzana ndi zakudya zapamwamba. Deta imasonyeza kuti khalidwe lakumwa loyendetsedwa ndi DAMGO ya intra-Acb lingakhale chifukwa cha kuchuluka kwa ntchito za orexin-A neurons ku PeF, pomwe njira zowonjezera zakudya zimawoneka kuti zikugwirizana ndi ntchito yowonjezera VTA dopaminergic, ndi kuchitidwa kwa BLA kumafunika kuti muzisunga ndi mowa gawo. Deta izi zimapangitsa kumvetsetsa bwino makhalidwe awiri okhudzana ndi kudyetsa matenda omwe amapezeka m'thupi mwachitsanzo. Kafukufukuyu akuwonjezera chidziwitso chathu cha oyang'anira dera la neural omwe amachititsa kuti anthu azidya moyenera komanso kuti azitha kumvetsetsa makhalidwe omwe amachititsa kuti munthu azikhala wochuluka kwambiri komanso kuti azidya zakudya zolimbitsa thupi.

​

Chithunzi 4 

Zojambula pamizeremizere, zosinthidwa kuchokera ku ma Paxosos & Watson (1998) ma atlas, akuwonetsa magawo okhala ndi zigawo zomwe zidafufuzidwa madera aubongo ofotokozedwa mdera labuluu (imvi) ndikukula pansipa. Madera: (a) malo amtunda, VTA; (b) dorsomedial ...

Zothokoza

Olembawo akufuna kuvomereza thandizo la thandizo la DA024829 ku National Institute of Drug Abuse ku MJW.

Mawu a M'munsi

Olembawo amanena kuti palibe kutsutsana kwa chidwi.

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