Mekhoa ea ts'ebetso ea Neural e nang le tšusumetso ea amygdala ea basolateral ho li-intra-accumbens opioid tse khannoang ka mokhoa o ts'oanang le boits'oaro bo matla ba ho fepa mafura ho rat (2015) - BINGE MECHANISM

Behav Neurosci. Sengoloa se ngotsoeng; e fumaneha ho PMC 2015 Dec 1.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

PMCID: PMC4658266

NIHMSID: NIHMS724902

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

inahaneloang

Phuputso e teng hona joale e fuputse karolo ea amygdala ho arolelaneng mokhoa o ikhethileng oa boits'oaro bo tsamaisoang ke ts'ebetso ea opioid ea intra-accumbens (Acb) ho rat. Ho inactivation ea nakoana ea basolateral amygdala (BLA), ka GABAA agonist muscimol tsamaiso e thibela ts'ebeliso e eketsehileng ho latela ts'ebetso ea intra-Acb opioid ea tsamaiso ea khetho ea µ-opioid agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO) Boitšoaro bo botle, haholoholo ha tšebeliso e felile. Tlhaloso e 'ngoe ke hore ho inka ha BLA ka mokhoa o ikhethileng ho thibela ts'ebetso e tsamaisang ts'ebetso ea DAMGO e tsamaeang le tšebeliso (tšebeliso), empa eseng ho rata (mokhoa). Liteko tse teng hona joale li nka monyetla ka karohano ena ea nakoana ea tšebeliso ea tšebeliso ea tšebeliso ea boitšoaro le mekhoa ea ho lekola mesebetsi ea bona e amanang le neural. Kamora ho sebelisa saline ea intra-Acb kapa tsamaiso ea DAMGO, kapa tsamaiso ea muscimol ea BLA kapa ntle le eona, likhoto li ile tsa fuoa monyetla oa ho fumana 2hr tekanyo e lekanyelitsoeng ea lijo tse nang le mafura a mangata. Hang ka mor'a seboka sa ho fepa, likhoto li ile tsa etsoa sehlabelo 'me tsa etsoa ka kelello bakeng sa mokhoa oa tšebetso oa methapo libakeng tse bohlokoa tsa boko tse tsejoang ho laola tloaelo ea ho ja le ho ja. Liphetho li bonts'a hore ts'ebetso ea intra-Acb DAMGO e ekelitse ts'ebetso ea c-Fos ho li-neuron tsa orexin kahare ho sebaka sa potoloho ea hypothalamus le hore keketseho ena ea ts'ebetso e thibetsoe ke BLA muscimol inactivation. Tsamaiso ea Intra-Acb DAMGO e ekelitse ts'ebetso ea c-Fos haholo ka har'a dopaminergic neurons tsa sebaka se potolohileng serethe, ha ho bapisoa le taolo ea letsoai, 'me ho se sebetse ha BLA ho ne ho sena phello keketseho ena. Ka kakaretso, datha tsena li fana ka mabaka a potolohileng a ka 'nang a kopanya tšusumetso ea BLA ea ho khanna ho khanna matla, empa eseng takatso ea lijo, e fepang boits'oaro mohlaleng oa boitšoaro bo khannoang ke matla.

Keywords: boits'oaro bo susumetsang, lits'ebetso le ho sekaseka potoloho, boitsoaro ba laboratori (takatso ea takatso ea takatso ea liphoofolo), Mohlala oa Phoofolo, mokhoa oa ho fepa opioid o fanang ka opioid

Morero oa marang-rang o kenyang letsoho oa ho fepa ka lijo tsa methapo ea methapo e hlahlojoe haholo (; ; ; ), mme liphallelo tsa basolateral amygdala (BLA) li khahlile haholo. Ho se sebetse ka nakoana hoa BLA le GABAA agonist muscimol e thibela keketseho e matla ea ho ja mafura a mangata ka mor'a ts'ebetso ea intraid Acon ea khetho ea--opioid agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO), leha ho le joalo, ho se sebetse ha BLA ha ho na tšusumetso ea ho fepa ho eketsehileng ho tsamaisoang ke ho hlobaela. Tlholo ea lijo tsa 24hr (). Tšusumetso ena ea BLA mabapi le ho tšerehanya mokhoa oa ho fepa ka hedonic e ile ea tsebahala haholo ho bontša hore ho se sebetse ha BLA ho thibele ts'ebeliso e eketsoang ke intra-Acb DAMGO, leha ho le joalo e ile ea sala e eketsehile mekhoa ea mekhoa ea lijo, haholoholo kamora hore tšebeliso ea lijo e felile. Ha sebopeho sa tlhaiso-leseling ea lintlha tsena se fanoe ke , Ho se sebetse ha BLA ho bonahala ho kena-kenana feela le karolo ea tšebeliso ea boitaolo bo mafura a mangata, empa eseng karolo ea mokhoa oa lijo e tsamaisoang ke ts'ebetso ea opioid ea Acb.

Ka nalane, boits'oaro bo nang le moputso bo arotsoe ka har'a takatso ea lijo mohato, o kenyelletsang boits'oaro bo atamelaneng bo kenyelletsang ho khothaletsa monyaka o kang oa lijo le Consummatory mohato, o kenyelletsang boits'oaro bo joalo ka tšebeliso ea lijo (; ). Phapang ena e 'nile ea bonoa ka mashome a lilemo mme e ntse e ratoa le kajeno ha likhopolo tsa khothalletso tse amanang le lijo le meputso e meng li fetoha (; ; ; ; ). Boiteko ba ho hlalosa boikoetliso bo tlasa maemo ana a ikhethileng a boits'oaro bo kenyelelitse mehlala moo kalafo e sitisitseng polelo ea karolo e le 'ngoe ntle le ho susumetsa e' ngoe (; ; ; ). Boithuto ba hona joale bo hlahloba phasolo ea motheo ea mofuta o ikhethileng oa boits'oaro moo karolo ea boipheliso le takatso ea lijo e sa amaneng.

Liteko tse teng hona joale li fupere lits'ebetso tsa neural tsa ts'ebetso tse ka tlas'a takatso ea takatso ea takatso ea phepo le ea phepelo e tsamaisoang ke intra-Acb DAMGO. Taba ea pele,) e ile ea phetoa ho hlahisa sebaka sa tlhahlobo ea bobeli, ho kenyelletsa le tlhoko ea ho fumana tekanyo e nepahetseng ea phepo e lekaneng ho fana ka thuto ea bobeli. Boitekong ba bobeli, kamora 'ngoe ea maemo a mane a fapaneng a kalafo ea lithethefatsi, lithuto tsohle li fuoe monyetla oa ho ja lijo tse nang le mafura a mangata, ho fa sehlopha ka seng kalafo ntle le sehlopha se tšoaroang feela sa DAMGO - ho fihlela satiety (ke hore, lipalo tse boneng tlasa papatso. maemo a lib ho tsoa ho Teko ea 1). Hang ka mor'a seboka sa 2hr sa ho fepa, likhoto li ile tsa etsoa sehlabelo ho hapa mekhoa ea mesebetsi ea neural e amanang le mekhoa ea boitšoaro e bonts'itsoeng. Boitsebiso bo ka morao bo bonts'itse hore ts'ebeliso e felletseng ea ts'ebeliso le mokhoa oa ho ja lijo tsa hopper li etsahala kahare ho metsotso ea 30 ea pele ea seboka sa liteko tse latelang kalafo eohle, leha ho le joalo intra-Acb DAMGO, e sa sebetseng kapa e se na BLA e hlahisa maemo a matla a boitšoaro ba mokhoa oa lijo nakong ea metsotso ea ho qetela ea 90 ea 2hr seboka sa liteko (). Ka hona, mesebetsi ea neural e amanang le tšusumetso ea ho atamela 'me jang e lokela ho emeloa ho likhoto tse amohelang kalafo ea intra-Acb DAMGO ntle le ts'ebetso ea BLA. Ka lehlakoreng le leng, mekhoa ea neural ea ts'ebetso ea likhoto e fumanang kalafo ea intra-Acb DAMGO ka ts'ebetso ea BLA e lokela ho bonts'a tšusumetso e lekanang ho atamela, empa bonts'a tšusumetso e fokotsehileng ho jang.

Ts'ebetso ea Neural e ile ea hlahlojoa libakeng tsa boko tse tsejoang ho tsamaisa takatso ea lijo le boits'oaro bo khahlisang, ho kenyelletsa le sebaka sa ventral tegmental (VTA), dorsal medial hypothalamus (DMH), sebaka se poteletseng sa hypothalamus (PeF), le lateral hypothalamus (LH) (; ; ). Tsamaiso ea Intra-Acb DAMGO e eketsa polelo ea c-Fos ho li-neuron tsa methapo ea methapo ea kutlo mme polelo ena e hloka ho supa ha orexin kahare ho VTA (). Ka kopanelo, lintlha tsena le tse ling li fana ka maikutlo a hore mofuta ona oa ts'ebetso ea phepo e matlafatsoang ke Acb µ-opioid receptor activation o ka bokella li-neurons tsa PeF orexin le ho ntlafatsa ho supa ha orexin kahare ho VTA e ka fetolang mokhoa oa ho tsamaisa tšebetsong oa DA ho Acb le mPFC (). Kameho ea ts'ebetso ea BLA ha e hlokahala ho shebella keketseho ea tšebeliso e phahameng ea mafura-Acb DAMGO, empa eseng tsela e mafura a mangata e tla hlahlojoa.

mekhoa

Likhoto

Linoko tsa banna ba baholo ba mashome a mararo a metso e ts'eletseng tsa Sprague-Dawley (Harlan Sprague-Dawley, Inc., Indianapolis, IN) tse boima ba 300-400 g, li ne li bolokiloe ka bobeli ka koaletsoeng ea Plexiglas kamoreng e laoloang ke maemo a leholimo ka mocheso oa 22 ° C. Likhoto li ne li bolokoa mokolokong o bobebe oa 12-hr, 'me liteko tsohle li ile tsa etsoa nakong ea lebone (0700 -1900) pakeng tsa 1200 le 1500. Ntle le ha ho hlokometsoe ka tsela e 'ngoe, likhoto li ne li na le phihlello ea mahala ea laboratori chow le metsi a nooang le nakong ea liteko tsohle. Lihlopha li na le likhoto tsa 6-8. Ts'ebetso tsohle tsa liteko li entsoe ho ipapisitsoe le protocol e amohetsoeng ke Komiti ea Tlhokomelo ea Liphoofolo le Tikoloho ea Univesithi ea Missouri.

Phekolo

Likhoto li ne li sa anngoe ka motsoako oa ketamine le xylazine (90 mg / kg le 9 mg / kg, ka ho latellana; Sigma, St. Louis, MO), le li-2 sete ea tataiso ea li-cannulas tsa tšepe (23 gauge, 10 mm) li ne li lebisitsoe ho sterotaxically bilaterally kaholimo ho moeli oa konokono ea Acb le khetla ea morao-rao le BLA le ho sirelletsoa lehata ka mabali a tšepe a sa jeleng le leseli le nang le khanya e fumanehang (Phepelo ea meno ea New England, Boston). Kamora ho buuoa, mekhoa ea terata e ile ea kenngoa ka har'a li-cannulas ho thibela ho hlaha. Li-coordinates tsa libaka tsa sepheo li joalo: Acb: AP, + 1.4; ML, ± 2.0; DV, -7.8; BLA: AP, -2.8; ML, ± 4.7; DV, -8.6 (DV hokahanya e emela ho kenngoa ha nale ea 12.5mm sindano e fetisang 2.5mm ventral ea cannula).

didirisiwa

Tlhahlobo ea boitšoaro mabapi le ho iphepa e etsahetse ka phapusing e arohaneng le kamore ea kolone ka liphapusing tse robeli tsa li-Plexiglas (30.5 cm x 24.1 cm x 21.0 cm) (Med Associates, St. Albans, VT). Likhoto li bile le phihlello ea libitum tsa metsi le 35g ea lijo tse fumanehang ntle le moo ho boletsoeng. Likamore tsa ho fepa li ne li kentsoe libalaka tse 'ne tsa infrared locomotor cm ka thoko ho bolelele ba kamore le 6 cm kaholimo. Sekala se ikemetseng sa motho ea jang lijo se ile sa shebella tšebeliso ea lijo. Moralo o eketsehileng oa infrared o kenang monyako oa sesebelisoa sa lijo o bonts'a palo le bolelele ba hlooho e 'ngoe le e' ngoe e kenang sebakeng sa hopper. Botoro ea lijo le botlolo ea metsi li ne li le ka lehlakoreng le leng (likhutlong tse ka thoko) tsa lebota le le leng la kamore, 'me terata ea litšila e tlosoang e ne e le ka tlasa mokatong oa bar. Litekanyo li kenyelletsa ts'ebetso ea locomotor (palo ea likhahla tsa bethe tse otlolohileng), nako ea ho kenella hopper (nako ea khefu ea boriti monyako oa hopper), lipalo tsa hopper (palo ea likheo tsa boriti monyako oa hopper), le kakaretso e sebelisitsoeng ( ligrama tsa lijo tse jeoang). Linako tsa tlhahlobo li ne li kenyelletsa tlhahlobo ea boits'oaro mo likamoreng tsa ho fepa ka software e sebelisang software ea Med-PC (Med Associates Version IV, St. Albans, VT).

Tsamaiso

Microinjection ea lithethefatsi

D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO; Biochemicals ea Phuputso, Natick, MA) le muscimol (Sigma, St. Louis, MO) ka bobeli li qhibilihile ka letsoai la 0.9% e sa sebetseng. Taolo ea koloi e ne e lula e le letsoai la 0.9%. Infusions e ile ea tlisoa ka pompo ea microdrive (Harvard Apparatus, South Natick, MA), e hokahantsoeng ke polyethylene tubing (PE-10), ha likhoto li ntse li tšoaroa ka letsoho. Ho ile ha sebelisoa li-injection tse mashome a mararo a metso e meraro tsa 12.5-mm, li atolosa 2.5 mm ho feta pheletso ea li-cannulas tsa tataiso. Tekanyo ea ente e ne e le 0.32 µl / metsotso bakeng sa Acb le 0.16 µl / min bakeng sa BLA, ha nako eohle ea infusion e le 93 s, e hlahisang lipalo tsa 0.5-µl le 0.25-µl, ka ho latellana. Ho ile ha lumelloa motsotso o le mong bakeng sa phapang.

Design

Leka 1

Ba sebelisa moralo o ka hare ho lithuto, lihlopha tsohle tsa likhoto li fumane motsoako o mong le o mong oa phekolo ea lithethefatsi ka matsatsi a mane a fapaneng a kalafo ka tatellano e lekanang. Liteko tsohle tsa boits'oaro bakeng sa liteko tseo ka bobeli li qalile ha 1 bekeng ea morao-rao kamora kamore ea ho jella lijo tsa Med-Associates. Likhoto li ne li fuoa mokhoa oa ho ja lijong likamoreng tsena tsa 2hr letsatsi le letsatsi ka matsatsi a latellanang a 6. Ho 5th letsatsi, injector ea 10-mm e ile ea kenngoa 'me ea siuoa e le sebaka sa 2 min, e se na molumo o tsoang. Ho 6th letsatsi, ho ile ha kenngoa ente ea 12.5-mm, 'me saline e laoloa bakeng sa 93 s. Ka letsatsi le leng le le leng la liteko, muscimol (20 ng / 0.25 µl / side bilaterally) kapa saline e ne e kenngoa BLA, e lateloa hanghang ke DAMGO (0.25 mg / 0.5 µl / side bilaterally) kapa saline ho Acb, ka hona ho fella ka kalafo tse 'ne tse ka khonehang metsoako. Seboka sa tlhahlobo sa 2hr se qalile hang kamora ho entoa ea ho qetela mme likhoto li fuoe monyetla oa ho fumana lijo tse nang le mafura a mangata. Ho bile le bonyane letsatsi la 1 pakeng tsa matsatsi a kalafo.

Leka 2

Lihlopha tse 'ne tsa likhoto, li sebelisa moralo o pakeng tsa lithuto, e' ngoe le e 'ngoe e na le li-cannulas tse ikhethileng tse lebisitsoeng ho Acb le BLA. Likhoto li ne li fuoa mokhoa oa ho ja lijong ka likamoreng tsena tsa 2hr letsatsi le leng le le leng ka matsatsi a latellanang a 6 mme mekhoa ea ente e ne e ts'oana le Teko ea 1, leha ho le joalo rat e 'ngoe le e' ngoe e ne e tla fumana 1 feela ea 4 mekhoa ea phekolo ea lithethefatsi. Ts'ebeliso ea lijo tse nang le mafura a mangata ka letsatsi la 6th la kalafo ea mantlha e sebelisitsoe ho hanyetsa kabelo ea kalafo ea lithethefatsi ho netefatsa mekhoa e tšoanang ea taolo ea mantlha. Ho 8th letsatsi, liphoofolo li ile tsa fuoa 1 ea 4 kalafo e ka khonehang ea kalafo ea lithethefatsi le ho fihlella 8g ea lijo tse fumanehang habonolo tsa 2hr.

Netefatso ea Nalane ea Ho Bea Cannula

Hang-hang kamora seboka sa phepelo sa 2hr, liphoofolo li ile tsa tlosoa kamoreng ea ho fepa, li sa phekoloe ka ho tebileng ka ketamine le xylazine (90 mg / kg le 9 mg / kg), 'me ea sebelisoa ka kotloloho. Masapo a tlositsoe 'me a qoelisoa ka har'a formalin (10%) bosiu ho 4 ° C ebe e fetisoa ka ho fetisoa ka tharollo ea sucrose (20%) ho 4 ° C. Likarolo tse sa sebetseng tsa "Frozen serial" (50 µm) li ile tsa bokelloa ka bophara ba sebaka sa ente, se behiloe ka li-slide tsa gelatinized, 'me sa hanyetsoa ka cresyl violet. Lifaele tsa polokelo ea Cannula li ile tsa hlahlojoa bakeng sa ho nepahala le data ho litoeba tse nang le cannula e sa sebetseng ha ea ka ea kenyelletsoa tlhahlobisong eo.

Immunohistochemistry

Boreli bo ne bo theotsoe botenya ba 40 µm mme bo bolokiloe ka 0.1M phosphate buffer solution (PB, pH 7.4) ho 4 ° C. Protocol e sa lefelloeng ea li-immunofluorescent ea staching e ne e le ka tsela e latelang: likarolo li ile tsa hlatsuoa (3 × 10 min) ho PBS. Libaka tse sa amaneng le ho tlama li ne li koetsoe ka tharollo ea thibelo [motsoako 10% serum ea poli e tloaelehileng (Lipatlisiso tsa Jackson Immuno, West Grove, PA) le 0.3% Triton X-100 (Sigma) ho PBS) bakeng sa 2 hr. Ka mor'a moo, likarolo tsena li ile tsa kenngoa ka har'a motsoako oa "cock-anti" oa anti-c-Fos (1: 5000; Calbiochem) le khokahano ea likhoho anti-Tyrosine Hydroxylase (VTA) kapa mouse anti-orexin-A (hypothalamus) bosiu. Likarolo li ile tsa hlatsuoa (4 × 30 min) ho PBS e nang le 0.05% Tween-20 (PBST). Ka mor'a moo, likarolo li ile tsa kenngoa lihora tse 2 ka sejoeng se thibelang, se nang le li-antibodies tsa bobeli: Alexa Fluor 555 poli Anti-rabi IgG le Alexa Fluor 488 poli ea Anti-kuku IgG (Invitrogen). Li-antibodies tsohle tsa bobeli li sebelisitsoe molemong oa khothaletso oa 1: 500. Likarolo li ile tsa hlatsuoa (4 × 30 min) ho PBST le PB (2 × 10 min). Likarolo li ne li behiloe holim'a li-slide tse matla haholo (VWR International, USA) ebe li lumelloa ho omella ka mocheso oa kamore ha li ntse li sirellelitsoe leseli. U sebelisa sesebelisoa sa ProLong Anti-fade (Sesebelisoa sa "Antiitrogen") sekhechana se ne se koahetsoe 'me se bolokiloe ka 4 ° C. Metsoako eohle e entsoe ka mocheso oa kamore ntle le ea li-antibodies tsa mantlha tse neng li entsoe ka 4 ° C. Ho laola phapang pitsong ea immunohistochemical, lithane tse tsoang lihlopheng tse fapaneng tsa kalafo li ile tsa amoheloa hammoho. Ntle le moo, lits'oants'o li ne li le sieo litekong tsa taolo ea ho siea li-antibodies tsa mantlha.

Tlhahlobo ea Boitšoaro ba Boitšoaro

Bakeng sa liteko tsa 1, mehato eohle ea ho fepa bakeng sa seboka sa 2-hr ka botlalo le maemong ohle a fapaneng a kalafo e ile ea hlahlojoa ka lintlha tse peli tse kahare ho sehlooho sa ANOVA (kalafo ea Acb X Amygdala), moo maemo ohle e ka bang koloi kapa lithethefatsi. . Bakeng sa liteko tsa 2, mehato eohle ea ho fepa e ile ea hlahlojoa ho sebelisoa lintlha tse peli lipakeng tsa sehlooho sa ANOVA (Acb Treatment X Amygdala Treatment), 'me maemo a ntlha ka' ngoe e kaba koloi kapa lithethefatsi.

Ho bala lits'ebetso, lipono, le tlhahlobo ea lipalo

Bakeng sa tlhahlobo e nyane ea polelo ea immunoreacaction ho hypothalamus (ho kenyelletsa le hypothalamus ea morao-rao, sebaka sa potoloho, dorsomedial hypothalamus) le VTA, likarolo tse tharo tsa likarolo tse tšoanang tsa tekanyetso ho tloha hemisphere e ngoe le e ngoe (6 kakaretso sebakeng ka seng) li ile tsa hlahlojoa tsa ba tsa lekanyetsoa. Litšoantšo tsohle li ile tsa hlahisoa ka sepheo sa 4 × kapa 10 × ka mochine o bapatsang o sebelisa software ea imaging Slidebook 4.3 (Intelligent Imaging Innovations, Denver, CO). Ho latela sebaka se ikhethileng, "fluorescent immunoreacaction" e ka har'a selae sa 40µm e ne e bonts'oa e ka ba c-Fos feela, c-Fos / TH, kapa c-Fos / OrexinA e ngotsoeng, e arotsoe ka mokhoa o ikhethileng. Litšoantšo li ile tsa bontšoa skrineng e felletseng e sebelisang software ea mahala ea domain ea java ea ImageJ (National Institutes of Health, Bethesda, MD, USA), e le ts'ebetso ea ho hlophisa le ho hlahloba litšoantšo e lumelletseng ho ts'oara "neuron" ka 'ngoe ea motho ka mong ba baloa ka mokhoa oa ho se sebetse mahlo. Li-Neurons li ne li khethiloe e le c-Fos feela, peptide feela, kapa e ngotsoe habeli ho latela boteng ba sehlahisoa sa anti anti reaction se ka holimo mokokotlong oa sele.

Libaka tsohle li ile tsa khethoa le ho etsoa 'mapa ho sebelisoa Rat Brain Atlas (Paxinos & Watson, 1998). Sebaka sa Ventral Tegmental le Tyrosine Hydroxylase; likarolo tse khethiloeng li ne li le lipakeng tsa −5.2 le −5.5mm ka pele ho bregma. Boemong bo bong le bo bong, sebaka se nang le lisele tsa tyrosine hydroxylase (TH-IR) le c-Fos-IR li ne li baloa ka bobeli ba li-hemispheres. Hypothalamus le Orexin-A; likarolo tse khethiloeng li ne li le lipakeng tsa -2.8 le -3.3 mm ka pele ho bregma. Sebaka sa hypothalamic (lipakeng tsa -2.8 le -3.3 mm) se fumanoeng se na le orexin-A lisele tse ntle li arotsoe likarolo tse tharo ho tloha medial ho ea lateral. Lisele tsohle tse kahare, tse kantle le tse kantle ho fornix li ne li kenyelelitsoe le sebaka se bohareng se tsejoang e le se haelloang (PeF). Lisele tse nang le mabitso a Orexin-A tse kamorao ho sebaka sena li kenyelelitsoe ho lateral hypothalamus (LH), 'me bao ba mahareng ba fornix ba ne ba le sehlopheng sa medial (DMH), se neng se koahetsoe ke dorsomedial hypothalamus. Li-Neuron li ne li baloa li-hemispheres ka bobeli.

Results

Litlamorao tsohle tsa kalafo li boletsoe ha ho buuoa ka libaka (tsa) tsa tsamaiso ea lithethefatsi kapa koloi (ke hore intra-Acb DAMGO). Ha likhoto tsohle li boetse li fuoa monyetla oa ho ja le ho ja lijo tse nang le mafura a mangata, liphetoho tsohle tse amanang le boits'oaro bo amanang le ho ja (Exp. 1 le 2) le mekhoa ea ts'ebetso ea neural activation (Exp. 2) ehlile ke phello e kopaneng ea moriana ka mong. kalafo le sejo se jeoang.

Boitšoaro ba ho fepa

Leka 1

Tšusumetso ea ho se sebetse ha BLA lits'ebetsong tsa ho fepa mafura a mangata tse tsamaisoang ke tsamaiso ea intra-Acb DAMGO.

Ho sebelisoa

Joalokaha ho bontšitsoe ho Setšoantšo sa 1a, ANOVA e entsoeng mabapi le tlhaiso-leseling ea tšebeliso ea lijo e senotse phello e kholo ea kalafo ea Acb (F (1, 7) = 13.9, p <.01), kalafo ea BLA (F (1, 7) = 8.6, p <.05), le tšebelisano ea kalafo ea Acb × BLA (F (1, 7) = 8.9, p <.05). Tlhahlobo ea post-hoc e senotse hore kalafo ea letsoai ea intra-Acb DAMGO + ea intra-BLA e lebisitse ho maemo a phahameng a ts'ebeliso ea metsi (p <.05) ha e bapisoa le kalafo ka bobeli (intra-Acb saline + intra-BLA saline; intra-Acb saline + intra-BLA muscimol), mme kalafo ea intra-BLA muscimol e thibetse keketseho ena (p <.05).

Setšoantšo sa 1 

Tlhahlobo ea boitšoaro A) Palo ea lijo tse nang le mafura a mangata tse sebelisoang (phihlello ea libitum), B) Kakaretso ea ho kenella ha nako ea tolofelo ea lijo, C) palo e felletseng ea lipalo tsa hopper ea lijo, le lipalo tsa liketsahalo tsa locomotor (ke hore, break breakal boramong). Liphekolo tsa 4 li ile tsa tsamaisoa ho ...
Nako ea ho kena lipakeng tsa hopper

Joalokaha ho bontšitsoe ho Feiga. 1b, ANOVA e entsoeng mabapi le tlhaiso-leseling ea nako ea ho phomola ha lijo e senotse phello e kholo ea kalafo ea Acb (F (1, 7) = 36.3, p <.001), kalafo ea BLA (F (1, 7) = 12.1, p <.05), le tšebelisano ea kalafo ea Acb × BLA (F (1, 7) = 16.5, p <.005). Tlhahlobo ea Post-hoc e senotse hore kalafo ea intra-Acb DAMGO + intra-BLA muscimol e lebisitse ho nako e phahameng haholo ea ho kenya lijo tsa hopper ha e bapisoa le mefuta eohle ea kalafo (p <.001), ha ho na kalafo e 'ngoe e fapaneng haholo le e mong.

Lisebelisoa tsa hopper tsa lijo

Joalokaha ho bontšitsoe ho Feiga. 1c, ANOVA e entsoeng mabapi le tlhaiso ea lijo ea hopper ea lijo e senotse phello e kholo ea kalafo ea Acb (F (1, 7) = 10.6, p <.05), ha kalafo ea BLA e ntse e atamela bohlokoa (F (1, 7) = 3.89, p = .08), le tšebelisano ea kalafo ea Acb × BLA (F (1, 7) = 7.9, p <.05). Tlhahlobo ea post-hoc e senotse hore kalafo ea intra-Acb DAMGO + intra-BLA muscimol e lebisitse ho kenyelletso ea lijo tse ngata haholo ha li bapisoa le mefuta eohle ea kalafo (p <.05), ha ho na kalafo e 'ngoe e fapaneng haholo le e mong.

Ts'ebetso ea locomotor

Joalokaha ho bontšitsoe ho Feiga. 1c, ANOVA e entsoeng mabapi le tlhaiso ea lijo ea hopper ea lijo e senotse phello e kholo ea kalafo ea Acb (F (1, 7) = 23.5, p <.005), empa ha ho na tšusumetso e kholo ea kalafo ea BLA (F (1, 7) = 1.4, p > .05), 'me ha ho na tšebelisano ea kalafo ea Acb × BLA (F (1, 7) = .056, p > .05).

Leka 2

Tšusumetso ea ho se sebetse ha BLA lits'ebetsong tsa ho fepa mafura a mangata le lipaterone tsa ts'ebetso ea neural e tsamaisoang ke tsamaiso ea intra-Acb DAMGO.

Kabelo ea kalafo ea lithethefatsi e ne e lekantsoe ke maemo a mafura a mangata a tsoang ho 6th letsatsi la motheo. Maemo ana a ho ja a ne a le tjena: SAL-SAL, 5.1g; SAL-DAM, 4.9g; MUSC-SAL, 4.9g; MUSC-DAM, 4.8g.

Ho sebelisoa

Joalokaha ho bontšitsoe ho Setšoantšo sa 2a, ANOVA e entsoeng mabapi le tlhaiso-leseling ea tšebeliso ea lijo e senotse phello e kholo ea kalafo ea Acb (F (3, 24) = 26.60, p <.001), empa ha ho na phello ea kalafo ea BLA (F (3, 24) = 0.02, ns) kapa ts'ebelisano 'moho ea kalafo ea Acb × BLA (F (3, 24) = 0.61, ns).

Setšoantšo sa 2 

Tlhahlobo ea boitšoaro a) Palo ea lijo tse nang le mafura a mangata tse tsoang (mola o qhekellehileng o bonts'a phihlello ea 8g); b) palo ea linomoro tsa lijo tsa hopper, c) Kakaretso ea ho kenella ha nako ea tolofelo ea lijo, le d) lipalo tsa mosebetsi oa locomotor (ke hore, likhahla tsa bethe tse otlolohileng). Phekolo ea 4 ...
Lisebelisoa tsa hopper tsa lijo

Joalokaha ho bontšitsoe ho Feiga. 2b, ANOVA e entsoeng ka palo eohle ea lipallo tsa hopper ho pholletsa le nako eohle ea phepo e senotse phello e kholo ea kalafo ea Acb (F (3, 24) = 8.55, p <.01), empa ha ho na phello ea kalafo ea kalafo ea BLA (F (3, 24) = 1.68, ns) kapa ts'ebelisano 'moho ea kalafo ea Acb × BLA (F (3, 24) = 0.39, ns).

Nako ea ho kena lipakeng tsa hopper

Joalokaha ho bontšitsoe ho Feiga. 2c, ANOVA e entsoeng ka nako eohle ea lipallo tsohle tsa hopper ho pholletsa le nako eohle ea phepo e senotse phello e kholo ea kalafo ea Acb (F (3, 24) = 12.45, p = .001), empa ha ho na phello ea kalafo ea BLA (F (3, 24) = .62, ns) kapa ts'ebelisano 'moho ea kalafo ea Acb × BLA (F (3, 24) = 0.07, ns).

Ts'ebetso ea locomotor

Joalokaha ho bontšitsoe ho Feiga. 2d, ANOVA e entsoeng mabapi le ts'ebetso e felletseng ea sebaka sa phepelo ka nako eohle ea phepo e senotse phello e kholo ea kalafo ea Acb (F (3, 24) = 12.93, p = .001), empa ha ho na phello ea kalafo ea BLA (F (3, 24) = .198, ns) kapa ho sebelisana ha kalafo ea Acb × BLA (F (3, 24) = 0.61, ns).

Immunohistochemistry

Sebaka sa Tefo ea Ventral

Joalokaha ho bontšitsoe ho Setšoantšo sa 3a, ANOVA e entsoeng ka lisele tsa c-Fos IR ho VTA e senotse phello e kholo ea kalafo ea Acb (F (3, 24) =, 25.67 p <.001), empa ha ho na phello ea kalafo ea BLA (F (3, 24) = 1.13, ns) kapa tšebelisano lipakeng tsa kalafo (F (3, 24) = 2.80, ns). ANOVA e entsoeng ka liperesente tsa lisele tsa TH-IR tse bonts'ang c-Fos IR e senotse phello ea kalafo ea Acb (F (3, 24) = 6.33, p <.05), empa ha ho na phello ea kalafo ea BLA ka liperesente tsa TH- Lisele tsa IR tse bontšang c-Fos IR (F (3, 24) = .07, ns) ho se sebelisane ha bohlokoa lipakeng tsa kalafo (F (3, 24) = .63, ns).

Setšoantšo sa 3 

a) Palo ea lisele tsa VTA tse hlalosang c-Fos IR; b) Peresente ea lisele tsa VTA TH-IR tse hlalosang c-Fos IR. c) Palo ea lisele tse hlalosang c-Fos-IR sebakeng se poteletseng sa hypothalamus (PeF) d) Peresente ea lisele tsa PeF Orexin-A IR tse hlahisang c-Fos-IR. Phekolo ea 4 ...

Perindowsical hypothalamus

Joalokaha ho bontšitsoe ho Feiga. 3b, ANOVA e entsoeng ho c-Fos IR ho PeF (sebaka se hlahlobiloeng ho setšoantšo sa feiga. 5b) se senotse phello e kholo ea kalafo ea Acb (F (3, 24) = 30.78, p <.001), kalafo ea BLA (F (3, 24) = 30.52, p <.001) le tšebelisano ea kalafo ea Acb × BLA (F (3, 24) = 8.75, p <.01). ANOVA e entsoeng ka liperesente tsa lisele tsa OrxA-IR tse bonts'ang c-Fos IR e senotse phello e kholo ea kalafo ea Acb (F (3, 24) = 55.85, p <.001), kalafo ea BLA (F (3, 24) = 23.52, p <.001), le tšebelisano ea kalafo ea Acb × BLA (F (3, 24) = 14.32, p <.001). Litšoantšong tsa 5a le 5b, litlhahlobo tsa post hoc li bonts'a hore ts'ebetso ea BLA e fokotsa haholo intra-Acb DAMGO e khelositseng polelo ea c-Fos mme e fokotsa palo ea lisele tsa orexin tse hlalosang c-Fos (p <.05).

Dorsomedial hypothalamus

Joalokaha ho bontšitsoe ho Lethathamo 1, ANOVA e etselitsoeng palo ea lisele tsa c-Fos IR ho DMH e senotse phello e kholo ea kalafo ea intra-Acb (F (3, 24) = 20.19, p <.001), empa ha e na phello ea kalafo ea intra-BLA ( T (3, 24) = 1.63, ns) kapa ts'ebelisano 'moho ea kalafo ea Acb × BLA (F (3, 24) = 0.05, ns). ANOVA e entsoeng ka liperesente tsa lisele tsa OrxA-IR tse bonts'ang c-Fos IR e senotse phello e kholo ea kalafo ea Acb (F (3, 24) = 13.39, p <.001), kalafo ea BLA (F (3, 24) = 5.85, p <.05), empa ha ho na tšebelisano ea kalafo ea Acb × BLA (F (3, 24) = .89, p = .36).

Lethathamo 1 

Palo ea lisele tse hlalosang c-Fos-IR (kakaretso) ho hypothalamus ea morao le dorsomedial hypothalamus le liperesente tsa lisele tsa PeF Orexin-A IR tse hlalosang c-Fos-IR (% orexin-A). Mekhoa ea kalafo ea 4 e ile ea tsamaisoa, ho kenyelletsa intra-Acb DAMGO kapa saline (SAL) hang-hang ...

Hamorao hypothalamus

Joalokaha ho bontšitsoe ho Lethathamo 1, ANOVA e etselitsoeng palo ea lisele tsa c-Fos IR ho LH ha e senole phello ea Acb ((F (3,24) = .11, ns) kapa kalafo ea BLA ((F (3, 24 = 6.82, p < .05) mme ha ho na tšebelisano (F (3,24) = .26, ns). ANOVA e entsoeng ka liperesente tsa lisele tsa OrxA-IR tse bonts'ang c-Fos IR ha e senole phello ea bohlokoa ea kalafo ea Acb (F (3, 24) ) = .64, ns), kalafo ea BLA (F (3, 24) = .08, ns), kapa tšebelisano ea kalafo (F (3, 24) = .77, ns.)

Puisano

Tlas'a maemo a phihlello ea mafura a mangata, ho iketsisa ha BLA ho fokolitse tšebeliso ea mafura a mangata e hlahisoang ke intra-Acb DAMGO, ha e ntse e tlohela boitšoaro bo fetelletseng ba boits'oaro bo netefatsang tlaleho ea pejana (). Teko ea bobeli e ile ea hlahloba liketsahalo tsena tse tšoanang, empa ka tlasa maemo a fokolang a phihlello ea lijo tse nang le mafura a mangata, e lumellang lihlopha tsohle tsa kalafo ntle le sehlopha sa kalafo sa intra-Acb DAMGO feela ho fihlela satiety (ke hore, linyeliso tsa chelete e hlokometsoeng tlasa maemo a lipapatso ho Exp. 1). Intra-Acb saline e phekotsoeng liphoofolo, tse nang le ts'ebetso ea BLA kapa e se nang eona, li ja lijo tse nang le mafura a mangata hape li bonts'a maemo a tšoanang a boits'oaro, joalo ka ha ho boletsoe esale pele. Lihlopha tse peli tsa kalafo tse khahlisang ka ho khetheha, tse amohelang intra-Acb DAMGO tse nang le ts'ebetso ea BLA kapa e se na BLA, li jele hoo e ka bang lijo tsohle tse nang le mafura a mangata tse fumanehang kamora ea 30 ea pele ea nako ea liteko tsa 2hr mme li bonts'a mekhoa e ts'oanang ea boits'oaro ea ho kenella lipoping tsa hopper ea lijo, nako ea ho reha ea hopper) ka nako ea ho qetela ea 90 min, joalo ka ha ho boletsoe esale pele. Phekolo ea Intra-Acb DAMGO e mpefalitse palo le nako ea mekhoa ea ho ja lijo tsa hopper ho sa tsotelehe ts'ebetso ea BLA, ha ho bapisoa le lihlopha tse tšoaroang kahare tsa intra-Acb joalokaha ho tlalehiloe pele (). Habohlokoa, joalo ka ha ho bonoa ho liteko 1 le pejana (, ), kalafo ea intra-Acb DAMGO, ntle le ts'ebetso ea BLA, e lebisa maemong a tšebeliso bonyane habeli chelete e fanoeng tlasa maemo a fokolang a phihlello. Ka hona, mekhoa ea neural ea ts'ebetso ea likhoto e fumaneng kalafo ea intra-Acb DAMGO ntle le ts'ebetso ea BLA e lokela ho bonahatsa sepheo sa atamela 'me jang lijo tse ling tse fetang se neng se fumaneha. Ka lehlakoreng le leng, mekhoa ea neural ea ts'ebetso ea likhoto e fumanang kalafo ea intra-Acb DAMGO, e nang le BLA e entsoe, e lokela ho bonts'a sepheo se eketsehileng ho atamela lijo, empa tšusumetso e fokotsang ho jang Lijo tse eketsehileng, ha li bapisoa le likhoto tse tšoaroang ka intra-Acb DAMGO ntle le ts'ebetso ea BLA. Sena ha se bohlokoa feela ho lebaka la moralo, empa tlhaloso ea data ea hajoale. Tekanyo ea lijo e fumanehang ha ea khethoa feela ho boloka maemo a tšebeliso ka har'a mefuta e lekanyelitsoeng ho lihlopha, empa hape le ho netefatsa litoeba sehlopheng se seng le se seng sa kalafo, ntle le sehlopha sa DAMGO-feela, se fihletsoeng kapa se haufi le ho satiation (joalo ka ha ho boletsoe ke Teko ea 1 le e fetileng fumana, bona ).

Tsamaiso ea Intra-Acb DAMGO e eketsehile haholo VTA c-Fos IR maemong a dopaminergic neurons ha e bapisoa le kalafo ea taolo ea letsoai, mme tsamaiso ea intra-BLA muscimol e ne e sena tšusumetso ho keketseho ena. Patlisiso e fetileng e bontša hore keketseho ea c-Fos IR ho VTA mme haholo-holo li-neurons tsa VTA dopamine (DA), e bapala karolo ea mantlha moputsong, khothatsong le bokhobeng ba lithethefatsi (; ; ). Tsamaiso ea litheko tsa dopamine ho litekanyetso tsa lijo tsa lijo tsa Acb e ntse e se na phello tšebelisong e bakoang ke tlala () kapa tšebeliso ea mafura a intra-Acb DAMGO (). Tsamaiso ea Intra-Acb ea dopamine agonists e eketsa tekanyo e tsoelang-pele ea karabelo ea lijo tse matlafatsang, empa ha e na phello ho fepa mahala.). Lintlha tsena le tse ling li fana ka maikutlo a hore mekhoa ea lijo e feteletsang takatso ea lijo e bonoang lihlopheng tsena ka bobeli tsa kalafo e laetsoeng intra-Acb DAMGO, e sa sebetse ka ntle ho tumello ea BLA, e kenelletsoa ke ts'ebetso e eketsehileng ea li-neurons tsa VTA dopaminergic.

Sebopeho sa PeF orexin-Ts'ebetso ea methapo ea kutlo e tsamaisana le mekhoa eo hangata e sebelisoang ho latela litlamorao tse tšoanang tsa kalafo tlasa maemo a phihlello ea lipapatso (, ), ka kalafo ea intra-Acb DAMGO e lebisang tšebeliso e phahameng ho feta kalafo efe kapa efe. Hape re fumane hore intra-Acb DAMGO e eketsa ts'ebetso ea DMH c-Fos ho sa tsotelehe kalafo ea BLA, empa intra-DAMGO feela e eketsang palo ea li-neuron tsa orexin tse hlalosang c-Fos ha li bapisoa le taolo. Leha e nkile karolo ea eona boits'oarong bo susumetsang ba DAMGO (; ), DAMGO ha ea ka ea eketsa haholo ts'ebetso ea LH c-Fos, leha ha ea ka ea lumella liphoofolo ho satiety.

Hypothalamus haesale e nkoa e le setsi sa taolo ea boikemelo ba matla a homeostasis; ho kenyelletsa molao oa ho fepa, ho tsosa le moputso (, ). Li-Neurons tse bontšang orexigenic peptides orexin-A le hormone ea "melanin" (MCH) li tsebahala ka ho pepesa libaka tsa morao tsa hypothalamus (), haholoholo, sebaka sa potoloho. Ts'ebeliso ea lijo tse nang le mafura a mangata a hlokometsoeng ho tsamaisoa ke orexin-A (li-orexin-A tse sebetsitsoeng hantle)) e koetsoe ke tsamaiso ea pele ea opioid antagonist naloxone (), e fana ka tlhahiso ea ho sebelisana ha li-peptide tsa opioid le orexin ho sebeliseng tšebeliso ea lijo tse fumanehang habonolo. Tsamaiso ea Intra-VTA orexin-A e boetse e thabisa li-dopamine neurons (Borgland et al., 2006). Ho thibela ho saena hoa orexin ho VTA ho fokotsa ho fepa hoa lijo tse nang le mafura a mangata a DAMGO (), leha ho le joalo hore na sena se teng ka ho fokotsa boits'oaro ba takatso ea lijo bo ka bakang tšebeliso e eketsehileng ha ho tsejoe. Ka hona, ts'ebetso ea hajoale ea hore ts'ebetso e eketsehileng ea VTA dopaminergic e latelang intra-Acb DAMGO e ne e sa angoe ke ts'ebetso ea BLA, leha e le ho fokotsa ts'ebetso ea PeF orexin, e phahamisa bohlokoa ba boits'oaro ba mekhahlelo ea boipheliso le e khotsofatsang ea boits'oaro. Ntle le moo, datha tsena li fana ka li-hypotheses tse ka lekoang bakeng sa ho hlahloba tšusumetso ea PeF orexin le modumo ea dopaminergic ea methapo ea ts'ebetso ea opioid le mekhahlelo ea phepelo ea phepo.

Boithuto ba hajoale bo sebelisitse phihlello ea lijo tse fokolang (ke hore, ligrama tse fumanehang) ho laola tšusumetso ea maemo a tšebeliso a fapaneng a latelang kalafo e fapaneng ea lithethefatsi. Boithuto bo boetse bo fane ka tlhahlobo ea lona ea lijo tse le 'ngoe; ka hona, monyetla oa ho lula oa hore ho fepa ka lijo tse matlafatsoang ke opioid ho ka tsamaisoa ka mokhoa o tšoanang. Khetho ea lijo tse nang le mafura a mangata e ne e tsamaisoa ke litšobotsi tse fetileng tsa marang-rang a amanang le ona a senotsoeng ke ho fepa ka mafura a mangata ka hare ho Acb DAMGO (; bakeng sa tlhahlobo), haholo karolo ea BLA (, ). Ha ho tsejoe hore na liphumano tse teng hona joale li bua ka mokhoa o itseng lijong tse nang le mafura a mangata, kapa hore na li ka bonoa li sebelisa lijo tse ling. Ho khahlisang, phuputso ea morao-rao e fumane hore le har'a lijo tse matlafatsoang, ho na le phapang e kholo lits'ebetsong tsa c-fos ho pholletsa le libaka tsa bohlokoa tsa taolo ea mesocorticolimbic circ (). Ho tla hlokahala lithuto tsa nako e tlang ho fumana hore na liphetho tsa hona joale li batla li ja lijo tse nang le mafura a mangata.

Ka kakaretso, datha tsena li fana ka leseli la hore na BLA e arabela joang ts'ebetsong ea opioid ea Acb ho khanna ts'ebeliso, empa eseng mekhoa ea boits'oaro, e amanang le lijo tse nang le mafura a mangata. Lintlha li fana ka maikutlo a hore mokhoa oa ts'ebeliso o tsamaisoang ke intra-Acb DAMGO e kanna ea hlahisoa ke ts'ebetso e eketsehang ea li-neuron tsa Pere, ha boitšoaro bo eketsehileng ba mokhoa oa lijo bo bonahala bo amana le ts'ebetso e eketsehileng ea VTA dopaminergic, ha ts'ebetso ea BLA e hlokahala feela ho hlokomela. mohato oa tšebeliso. Lintlha tsena li fana ka kutlwisiso e ntlafalitsoeng ea boits'oaro bo fapaneng ba ho ikatisa kahare ho mohlala o fepehileng hantle. Patlisiso ena e holisa tsebo ea rona ea "neural circry" e bohlokoa ho phepo e khannoang le ho tlisa melemo bakeng sa ho utloisisa mekhoa e mebe ea ho fepa e amehang nts'etsopele ea botenya le boits'oaro ba ho lemalla lijo.

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Setšoantšo sa 4 

Litšoantšo tsa mochini o hlophisitsoeng, tse nkiloeng ho tsoa ho Paxinos & Watson (1998) atlas, e bonts'ang likarolo tsa likorone tse nang le libaka tsa boko tse hlahlobiloeng tse hlalositsoeng sebakeng se putsoa (sebaka se boputsoa) ebe li holisoa ka tlase ka tlase. Libaka: (A) sebaka sa ho kena ka hare sa moea, VTA; (B) sorsomedial ...

Liteboho

Bangoli ba ka thabela ho amohela tšehetso ea lithuso DA024829 ho tsoa Setsing sa Naha sa Tlhekefetso ea Lithethefatsi ho ea MJW.

Mongolo o botlaaseng ba leqephe

Bangoli ba phatlalatsa hore ha ho na likhohlano tsa thahasello.

References

  1. Badiani A, Leone P, Noel MB, Stewart J. Ventral tegmental area opioid mekhahlelo le modulation ea boitšoaro ba ho ingestive. Patlisiso ea Brain. 1995; 670 (2): 264-276. [E fetotsoe]
  2. Baldo BA, Sadeghian K, Basso AM, Kelley AE. Liphello tsa dopamine e khethiloeng ea D1 kapa D2 receptor blockade e ka har'a nucleus e bokella li-subregions ka boitšoaro ba ingestive le mosebetsi o amanang le koloi. Behav Brain Res 2002 Dec 2; 137 (1-2): 165-177. [E fetotsoe]
  3. Baldo BA, Pratt WE, Will MJ, Hanlon EC, Bakshi VP, Cador M. Likeletso tsa khothatso li senotsoe ke mesebetsi e fapaneng ea methapo ea methapo ea methapo ea methapo ea methapo le neuroanatomical. Neurosci Biobehav Moruti 2013 Nov; 37 (9 Pt A): 1985-1998. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  4. Ball GF, Balthazart J. Mohloli o fapaneng oa takatso ea lijo le o felletseng bakeng sa kutloisiso ea rona ea taolo ea neuroendocrine ea boitšoaro ba thobalano? Horm Behav. 2008 Feb; 53 (2): 307-311. karabo ea mongoli 315-8. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  5. Berridge KC. Mehopolo ea susumetso ho "neuroscience" ea boitšoaro. Physiol Behav. 2004 Apr; 81 (2): 179-209. Tlhahlobo. [E fetotsoe]
  6. Berridge KC. Ho `` rata '' le ho 'batla' meputso ea lijo: likarolo tsa boko le likarolo tsa mathata a ho ja. Physiology le Boitšoaro. 2009; 97 (5): 537-550. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  7. Cason AM, Smith RJ, Tahsili-Fahadan P, Moorman DE, Sartor GC, Aston- Jones G. Karolo ea orexin / hypocretin ha ho batloa moputso le ho lemalla: litlamorao tsa botenya. Pholoji le Boitšoaro. 2010; 100 (5): 419-428. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  8. Clegg DJ, Air EL, Woods SC, Seeley RJ. Ho ja ka mokhoa o khahliloeng ke orexin-A, empa e seng mohopolo oa "melanin" o kenang lipakeng. Endocrinology. 2002; 143 (8): 2995-3000. [E fetotsoe]
  9. Craig W. Litakatso le litlatsetso joalo ka litumelo tsa tlhaho. Bulletin ea Tlhaho. 1918; 34: 91-107. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  10. Letsatsi la Y, Ueta Y, Yamashita H, Yamaguchi H, Matsukura S, Kangawa K, Sakurai T, Yanagisawa M, Nakazato M. Orexins, orexigenic hypothalamic peptides, o sebelisana le tsamaiso ea autonomic, neuroendocrine le neuroregulatory. Proc Natl Acad Sci USA. 1999; 96 (2): 748-753. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  11. Dela Cruz JA, Coke T, Karagiorgis T, Sampson C, Icaza-Cukali D, Kest K, Ranaldi R, Bodnar RJ. c-Fos induction ho mesotelencephalic dopamine pathway proipion le dorsal striatum kamora ho ja tsoekere le mafura ka har'a litoeba. Brain Res Bull. 2015 Feb; 111: 9-19. [E fetotsoe]
  12. Masimong HL, Hjelmstad GO, Margolis EB, Nicola SM. Ventral tegmental area neurons ka ho ithuta boits'oaro bo botle le matlafatso a nepahetseng. Tlhahlobo ea selemo le selemo ea Neuroscience. 2007; 30: 289-316. [E fetotsoe]
  13. Hanlon EC, Baldo BA, Sadeghian K, Kelley AE. Keketseho ea litabatabelo tsa lijo kapa boitšoaro bo batlang lijo bo khothalletsoang ke GABAergic, opioid, kapa tšusumetso ea dopaminergic ea li-nucleus accumbens: na ke tlala? Psychopharmacology (Berl) 2004 Mar; 172 (3): 241-247. [E fetotsoe]
  14. Harris GC, Aston-Jones G. Arousal le moputso: dichotomy ts'ebetsong ea orexin. Mekhoa ea Neuroscience. 2006; 29 (10): 571-577. [E fetotsoe]
  15. Ikemoto S, Panksepp J. Ho arohana pakeng tsa likarabo tsa maikutlo le takatso e matlafalitsoeng ke litsoantso tsa litekanyetso tsa libaka tsa boko tse amanang le moputso. Behav Neurosci. 1996 Apr; 110 (2): 331-345. [E fetotsoe]
  16. Jager G, Witkamp RF. Sistimi ea endocannabinoid le takatso ea lijo: bohlokoa ba moputso oa lijo. Nutr Res Rev. 2014 Jun 2; 27 (1): 172-185. [E fetotsoe]
  17. Jennings JH, Ung RL, Resendez SL, Stamatakis AM, Taylor JG, Huang J, Veleta K, Kantak PA, Aita M, Shill-Scrivo K, Ramakrishnan C, Deisseroth K, Otte S, Stuber GD. Ho bona matla a marang-rang a hypothalamic bakeng sa boits'oaro bo botle ba takatso le boits'oaro. Sele. 2015 Jan 29; 160 (3): 516-527. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  18. Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Litloaelano tse tsamaeang tsa ho tsamaisa takatso ea methapo tsamaisong ea hypothalamic ea boima ba 'mele. Litlhahlobo tsa Endocrine. 1999; 20 (1): 68-110. [E fetotsoe]
  19. Kelley AE, Baldo BA, Pratt WE, Will MJ. Corticostriatal-hypothalamic circry le tšusumetso ea lijo: ho kopanya matla, ketso le moputso. Physiol Behav. 2005 Dec 15; 86 (5): 773-795. [E fetotsoe]
  20. Lorenz K. Mokhoa o bapisang ho ithuta mekhoa ea kahare ea botho. Symp. Motsoalle Hlakola Biol. 1950; 4: 221-268.
  21. Nicola SM, Deadwyler SA. Tekanyo ea ho thunya ea li-neuron tsa nucleus e itšetlehileng ka dopamine mme e bontša nako ea boits'oaro ba ho batla koae ka likhoto lenaneong le matlafatsang la keketso ea matlafatso. J Neurosci. 2000 Jul 15; 20 (14): 5526-5537. [E fetotsoe]
  22. Park TH, Carr KD. Mekgwa e sa sebetsanang le methapo ea bongoana ea Fos-e kenyellelitsoeng ke lijo le maemo a phehiloeng kahare ho saline-and naltrexone e tšoeroe ke likhoto. Patlisiso ea Brain. 1998; 805: 169-180. [E fetotsoe]
  23. Ke MJ, Franzblau EB, Kelley AE. Li-mu-opioid tsa nyutlelie li laola ho ja lijo tse nang le mafura a mangata ka ts'ebetso ea marang-rang a boko a fetisitsoeng. J Neuroscience. 2003; 23 (7): 2882-2888. [E fetotsoe]
  24. Ke MJ, Franzblau EB, Kelley AE. Amygdala ke ea bohlokoa bakeng sa ho ja lijo tse nang le mafura a mangata haholo. Neuroreport. 2004; 15 (12): 1857-1860. [E fetotsoe]
  25. Ke MJ, Pratt WE, Kelley AE. Ts'oaetso ea pharmacological ea ho fepa mafura a mangata ho susumetsoa ke ts'usumetso ea opioid ea ventral striatum. Physiol Behav. 2006 Sep 30; 89 (2): 226-234. [E fetotsoe]
  26. Ke MJ, Pritchett CE, Parker KE, Sawani A, Ma H, Lai AY. Boitšoaro ba boits'oaro ba ho nka karolo ha amygdala ho kenella bohareng ba boitšoaro bo tsamaeang le ho tsamaisoa ha intra-kukusanyabens. Neuroscience ea Boitšoaro. 2009; 123 (4): 781-793. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  27. Yamanaka A, Kunii K, Nambu T, Tsujino N, Sakai A, Matsuzaki I, Miwa Y, Goto K, Sakurai T. Orexin lijo tse kenyellelitsoeng tsa lijo li kenyelletsa tsela ea neuropeptide Y. Patlisiso ea Brain. 2000; 859 (2): 404-409. [E fetotsoe]
  28. Zhang M, Kelley AE. Takatso e matlafalitsoeng ea lijo tse nang le mafura a mangata kamora ho hlohlelletsa ho ts'oaroa ha li-striatal mu-opioid: 'mapa oa microinjection le polelo ea fos. Neuroscience. 2000; 99 (2): 267-277. [E fetotsoe]
  29. Zhang M, Kelley AE. Ho ja lischarin, letsoai le ethanol tharollo e eketsoa ke ho kenngoa ha agonist ea mu opioid agoniste. Psychopharmacology (Berl) 2002; 159 (4): 415-423. [E fetotsoe]
  30. Zhang M, Balmadrid C, Kelley AE. Nyuklea e bokella opioid, GABaergic, le dopaminergic module ea lijo tse matlafatsoang: litlamorao tse senotsoeng ke boithuto bo tsoelang pele ba tekanyo ho rat. Behav Neurosci. 2003 Apr; 117 (2): 202-211. [E fetotsoe]
  31. Zheng H, Patterson LM, Berthoud HR. Ho supa ha Orexin sebakeng sa tefo ea moea ho hlokahala bakeng sa takatso ea mafura a mangata e hlahisoang ke ts'usumetso ea opioid ea li-nucleus accumbens. J oa Neuroscience. 2007; 27 (41): 11075-11108. [E fetotsoe]