Li-receptors tsa "Opioid" ka hare ho lihlopha tsa libaka tsa Striatum Mediate Pair Bond Formation ka Mekhoa e Ts'oanang ea Moputso (2015)

J Neurosci. 2013 May 22;33(21):9140-9. doi: 10.1523/JNEUROSCI.4123-12.2013.

Pheta SL1, Dome M, Gormley G, Franco D, Nevárez N, Hamid AA, Aragona BJ.

inahaneloang

The prairie vole ke mofuta o mong oa bophelo bo botle ba batho ba phoofolo eo e leng mohlala o motle oa liphoofolo bakeng sa lithuto tsa neurobiology ea khokahano ea sechaba. Boithuto bo joalo bo bontšitse hore ts'ebetso ea ts'ebetso ea meputso nakong ea lipuisano ea sechaba e nolofalletsa ho theha maqhama a mabeli. Ka har'a potoloho ena, li-μ-opioid receptors (MORs) li tloaetse boitšoaro bo khotsofatsang ka tlhaho ka tsela e arohaneng; Li-MORs tse fumanehang ho pholletsa le striatum (dorsal striatum, NAc konokono, le khetla eohle ea NAc) li ameha lits'ebetsong tse akaretsang tsa ts'usumetso, athe tse fumanehang ka kotloloho ho dorsomedial NAc shell Mediate hedonics (mme li bitsoa "hedonic hotspot"). Morero oa thuto ea hona joale e ne e le ho bona hore na li-MOR kahare ho litekanyetso tsena tse ikhethileng li ikamahanya le litlamo tsa maqhama a mabeli. Pele re sebelisitse li-receptor autoradiography ho bapisa methapo e tlamang ea MOR lipakeng tsa libaka tsena. Ho kopanya ha MOR ho ne ho phahame haholo ka har'a polokeho ea NAc le dorsomedial NAc ha e bapisoa le khetla ea ventc NAc. Ka mor'a moo re ile ra sebelisa tlhahlobo eo re e khethang ea balekane ho bona hore na li-MOR tsa maemong ana a fapaneng li ikamahanya le maemo. Blockade of MORs using 1 or 3 μg of Hd-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 ka hare ho dorsal striatum e fokotsehile ho ruruha nakong ea ho phomola le ho thibela khetho ea molekane. Ka lehlakoreng le leng, blockade ea MORs ka har'a dorsomedial NAc shell e ile ea thibela khetho ea molekane ntle le ho hlahisa boits'oaro ba mating, athe libaka tse ling li ne li sa amehe. Ka hona, li-MOR tse kahare ho dorsal striatum mediate molekane oa ho khetha ka ho senyeha ha mating, athe tse ho dorsomedial NAc khetla li bonahala li le matlale pakeng tsa bonono ka ho theha li-hedonics tse tsamaeang le ho tlolelana.

Selelekela

Pholo e monate ea sechaba se le sengMicrotus ochrogaster) ke mohlala o motle oa phoofolo bakeng sa ho ithuta neurobiology ea khokahano ea sechaba (Young le al., 2005). Balekane ba tlamang ba Prairie vole ba theha litlamo tse ikhethileng tse qalang ka ho khetha pele bakeng sa molekane ea tlohellang. "Tlhahiso ena ea molekane" e amahanngoa le litšebelisano tse ntle tsa sechaba (Williams et al., 1992; Winslow et al., 1993) tse laoloang ke potoloho ea moputso (Aragona le Wang, 2009). Taba ea bohlokoa ke hore, "potoloho ena" e na le lits'ebetso tse sebetsanang le tšebetso tsa hedonic tse tsamaisang botle ba tšusumetso ea tikoloho, 'me li hokahane le boits'oaro bo batlang sepheo (Dickinson le Balleine, 2010; Leknes le Tracey, 2010). Mohlala, hedonics e nepahetseng e bohlokoa bakeng sa boits'oaro ba takatso ea lijo (Cacioppo et al., 2004; Watson et al., 2010), ho kenyelletsa le ea setsoalle (Komisaruk et al., 2010). Mokhoa o bohlokoa oa neural oa ho kopanya li-hedonics tse ntle ke ts'ebetso ea μ-opioid receptors (MORs) (Panksepp et al., 1980; Bakshi le Kelley, 1993; Pecina le Berridge, 2000) kahare ho karolo ea dorsomedial ea nucleus accumbens (NAc) khetla (ke hore, hotspot ea hedonic), subportion ea striatum e nang le litšobotsi tse ikhethang tsa ts'ebetso / li-anatomical (Pecina le Berridge, 2005; Britt le McGehee, 2008; Smith le al., 2010; Britt et al., 2012; Watabe-Uchida et al., 2012).

Leha batsamaisi ba neano ba moputso ba tloaetse ho khothaletsoa ho hloaea boits'oaro bo monate sechabeng (Trezza et al., 2011), "Moputso" ha se mohopolo o kopanetsoeng oa kelello; ho fanoe ka maikutlo a hore "moputso" o ka kenyelletsa bonyane likarolo tse tharo tsa kelello: hedonics, susumetso le ho ithuta (Berridge le Robinson, 2003). Haholo-holo liphuputso tsa moputso oa lijo li bontsitse hore li-MOR li abiloe hohle ka likarolo tse khothatsang tsa meputso ea lijo ka mokhoa o ikhethileng (Kelley le Berridge, 2002). Haholo-holo, ho ts'oaroa ha li-MORs nakong eohle ea striatum (dorsal striatum, NAc konokono, le leqhetso lohle la NAc) e eketsa mmuso ka kakaretso o susumetsang (Bakshi le Kelley, 1993; Zhang le Kelley, 2000; DiFeliceantonio et al., 2012), athe tlhoko ea MOR feela ka hara khetla ea dorsomedial NAc e arabella likarabo tse ntle tsa hedonic tse amanang le tšebeliso ea lijo tse matlafatsoang haholo (Kelley et al., 2005; Pecina le Berridge, 2005; Smith le Berridge, 2007). Sesebelisoa sena sa anatomical se ka sebelisoa e le sesebelisoa sa ho lekola li-neurochemical le neuroanatomical correlates tse arolelanang mefuta e meng ea moputso, joalo ka sebopeho sa khokahanyo.

Phuputsong ea hajoale, re sebelisitse 'mapa ona o thehiloeng hantle oa tšebetso oa MOR molao oa moputso ho tseba hore na likarolo tse ikhethang tsa striatum, ka hona, mohlomong likarolo tse ikhethang tsa kelello tsa moputso, li laola sebopeho sa khetho ea molekane. Boithuto bona bo bohlokoa haholo hobane haufinyane ho fanoa ka maikutlo a hore li-MOR ka har'a dorsal striatum, empa eseng NAc, li bohlokoa molemong oa khetho ea balekane hobane blockade ea MORs ka har'a dorsal striatum, empa eseng ka har'a khetla ea ventral NAc, e thibetse khetho ea molekane.Burkett et al., 2011). Leha ho le joalo, thuto ena e fetileng ha ea ka ea hlahloba karolo ea li-MORs ka har'a khetla ea dorsomedial NAc (ke hore, sebaka se bohlokoa bakeng sa hedonics). Kahoo, thutong ea hona joale, re sebelisitse pharmacology ea receptor autoradiography le litekanyetso tsa boitšoaro tse lebisitsoeng setsing ho bapisa ho nka karolo ha li-MORs kahare ho libaka tse 'ne tsa striatum ka popelong ea balekane ba ratoang.

Lisebelisoa le mekhoa

Lintho.

Lithuto tsa liteko tsa balekane ba khethiloeng e ne e le li-voes tsa basali ba baholo ba rorisoang Univesithing ea Michigan (Resendez et al., 2012). Ho ne ho sebelisoa lipalesa tsa banna ba baholo e le liphoofolo tse matlafatsang. Lintho li ile tsa khoesoa 'me tsa bolokoa ka moo ho hlalositsoeng pele (Resendez et al., 2012). Ts'ebetso tsohle li entsoe ho latela tataiso ea tlhokomelo ea liphoofolo Univesithing ea Michigan. Litlhokomelo tsa basali ba baholo le li-voalk tse sebelisoang bakeng sa ho tsamaisoa ha litora tsa MOR li ile tsa kenngoa Univesithing ea Florida State ka laboratoring ea Dr. Zouxin Wang, mme lits'ebetso tsohle li ile tsa tsamaisoa ho latela litaelo tsa tlhokomelo ea liphoofolo tsa Yunivesithi ea Florida State.

Receptor autoradiography.

Lintho li ile tsa bolaoa ka ho senyeheloa kapele, le masapo a basali ba basali ba sa tsebeng ho robala (n = 5) le likamano tsa botona le botšehali tsa basali tse ka sebelisang thobalano (n = 5) e tlositsoe, hang-hang hoamisoa leqhoeng le omileng, 'me e bolokoe −80 ° C (Aragona et al., 2006; Lim et al., 2006; Resendez et al., 2012). Li-brains li ne li arotsoe ka selikeng sa 15 μm ka likarolo tse 'ne tsa serial' me li bolokiloe ho −80 ° C ho fihlela e sebetsoa (Liu et al., 2010). MOR autoradiography (DAMGO; PerkinElmer, catalog #NET 902; ngata #3615807) e entsoe joalo ka ha ho hlalositsoe pele (Resendez et al., 2012). Filimi ea Kodak BioMAx MS e ile ea beoa holim'a li-slide 'me ea pepesetsoa likhoeli tsa 6 (Resendez et al., 2012). Kamora ho qeta nako ea ponaletso, litšoantšo tsa lifilimi li ile tsa nkuoa ho sebelisoa sekepe sa Scan moe 1000XL Microtek. Matsoalo a MOR a tlamang kahare ea dorsal striatum, NAc konokono, khetla ea dorsomedial NAc, le khetla ea "ventc" (Feie. 1A,B) e ile ea hlahlojoa le NIH ImageJ 64 (Bales et al., 2007b). LIHOLO tse tlamang tsa tikoloho ka 'ngoe li ne li lekanngoa ka likarolo tse' ne tsa serial rostral coronal (pele ho corpus callosum fusing) (Aragona et al., 2006) hammoho le likarolo tse 'ne tsa serial coronal caudal to callosum fusions (ha kamohelo ea kantle e lumellana le ventricle). Libaka tsena tse matla le tse khahlisang li ne li kenyellelitsoe tikolohong ka 'ngoe ea sebaka seo.

Matšoao a anatomical a ka holimo a rostral le caudal striatum a ile a khethoa hore a lumellane le a neng a hlalositsoe pele ho li-voles (Aragona et al., 2006) hammoho le tse hajoale li sebelisetsoa ho hlalosa sebaka sa NAc hedonic hotspot ka likhoto (Richard et al., 2013). Mathata a bolelele ba libaka tsohle tse khahlisang a ne a nkuoe ho tsoa lipampiring tsa litaba tse tšoeu (boitlamo ba kahare) (Olazabal le Monyane, 2006). ImageJ 64 e ne e boetse e sebelisoa ho hlahisa litšoantšo tse kopantseng tsa bophahamo ba MOR bo kopanyang ba basali ba bahlano ba marena a rorisang kahare ho rostral le caudal striatum (Feie. 1C,D). Litšoantšo li entsoe ka ho paka likarolo tsa "rostral" kapa "caudal" tse sebelisoang ho sekaseka karolo e 'ngoe le e' ngoe ea basali ba rorisang basali (n = 20; Likarolo tsa 4 / mosali) ebe letsoalo le kopanyang le ile la hakanyetsoa hohle litšoantšo.

Stereotaxic cannulation.

Li-voiri tsa prairie tsa basali li ne li sa anngoe ka motsoako oa ketamine (100 mg / kg) le xylazine (10 mg / kg) mme li kentsoe cannula ea tataiso ea 26-gauge bilateral e lebisitsoeng ho dorsal striatum (+ 1.6 mm A / P; ± 1.5 mm. M / L; −3.0 mm D / V), NAc konokono (+ 1.6 mm A / P; ± 1.2 mm M / L; −3.5 mm D / V), kapa NAc khetla (+ 1.7 mm A / P; ± 1 mm M / L; dorsomedial: −4.2 mm D / V; ventral: −4.5 mm D / V) (Aragona et al., 2003; Burkett et al., 2011). Lithuto tsohle li ile tsa fuoa 10 mg / kg ketoprophen hang kamora ho sebetsoa le 24 h kamora nako mme ba fuoa 3-5 d hore ba fole ka hara ntlo ea bona ea likhoho le balekane ba bona ba likhohlopo.

Liteko tsa ho ratana le ho tloaelana.

MORA ea tsamaiso ea maqhama a kopantsoeng e ile ea hlahlojoa ho sebelisoa litlatse tse laeloang ke litlhahlobo tsa bongaka tse amanang le litheko tsa balekane (Liu le Wang, 2003; Cushing et al., 2008). Kamora ho sebetsoa ka thipa, lithuto tsa basali li ile tsa emisoa ka estrogen ka 2.0 μg estradiol benzoate ea 3 d pele ho kopanoa le monna (Fowler et al., 2005; Burkett et al., 2011). Ka letsatsi la teko, mokelikeli oa kokoana-hloko ea motsoako oa maiketsetso (aCSF) (n = 11) kapa aCSF e nang le 1 kapa 3 μg ea mohanyetsi ea itseng oa MOR Hd-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) (Sigma-Aldrich) (Burkett et al., 2011; Trezza et al., 2011) e kentsoe ho e 'ngoe ea libaka tse' ne tsa striatum (dorsal striatum n = 6-10; Mantlha ea NAc n = 5-6; sorsomedial NAc shell: n = 4-8; ventral NAc shell: n = 8-9).

Hang-hang ka mor'a ho entoa, lithuto tsa basali li ile tsa beoa ka sejelong se nang le monna e motšo (eo ho thoeng ke "molekane") mme a lumelloa ho lula hammoho le molekane oa 24 h, eo ka ts'epo e etsang hore ho khethoe molekane.Williams et al., 1992). Li-6 h tsa pele tsa cohabitation li ile tsa hlahlojoa bakeng sa palo e felletseng ea likamano tsa botona le botšehali, 'me ke lithuto feela tse ileng tsa kenella nakong ena tse kenyelitsoeng thupelong (Carter le Keverne, 2002; Aragona et al., 2003; Liu le Wang, 2003; Curtis le Wang, 2005a). Ho hlaseloa ke moea oa mating ho hlalositsoe e le ho ba teng hoa tatellano ea liketsahalo tse latelang: ho nyoloha, ho kenella ka hare le ho itlhophisa libakeng tsa botona. Lordosis e hlokahala bakeng sa e tona hore e holise hantle le ho kenella kahare ho mosali, mme boits'oaro bona bo ile ba hlahlojoa hape nakong ea ha e hlaba mali. Ha ho phapang lipakeng tsa palo eohle ea liphoofolo tse ileng tsa ts'oaroa lipakeng tsa lithuto tse amohetseng CTAP ho dorsal striatum (χ2 = 3.79, df = 2, p = 0.15), mantlha ea NAc (χ2 = 0.55, df = 2, p = 0.76), kapa khetla ea NAc (χ2 = 1.29, df = 4, p = 0.86) (Lethathamo 1). Metsotsoana ea pele ea 10 ea hora e 'ngoe le e ngoe nakong ena ea 6 h e boetse e fuoe lintlha tsa ho lekola nako ea boits'oaro bo kopanetsoeng (lipatlisiso tsa boiketsetso le ho ikopanya le batho ba bang) hammoho le khafetsa ea mosebetsi oa locomotor (lifapano tsa likhopo) nakong ea ho phomola.

Tafole 1.

Ratio ea lihlooho tse amanang le sehlopha ka seng sa kalafoa

Kamora nako ea boiketlo ba 24 h, liteko tsa khetho ea molekane li ile tsa etsoa ho sebelisoa lisebelisoa tse fetotsoeng tsa khetho ea molekane (Ahern le e Mocha, 2009; Burkett et al., 2011). Ka bokhutšoanyane, lisebelisoa tsa ho rata molekane li ne li entsoe ka likarolo tse tharo tse lekanang hantle tse arotsoeng ke lithibelo tse itseng. Balekane ba banna ba ne ba khokhotheloa ka nqeng e le 'ngoe, athe banna ba tummeng (bao ho thoeng ke "basele") ba ne ba khangoa ka mokhoa o hlophisitsoeng ka kamoreng e ka thoko (Donaldson et al., 2010; Keebaugh le Monyane, 2011). Qalong ea tlhahlobo, lithuto tsa basali li ne li beoa kahare ea seporo mme li lumelloa ho phenya-palama ka bolokolohi pakeng tsa likarolo tsa 3 h (Curtis et al., 2001; Bales et al., 2007a). Khetho ea bohlokoa ea molekane e khethiloe ke ho bapisa lipalo (bona ka tlase) nako e sebelisitsoeng ho ikopanya le balekane ho fihlela nako e sebelisitsoeng ho kopana le ba sa tsebeng (Cho et al., 1999; Cushing et al., 2003; Bales et al., 2007a). Ho beoa ha Cannulae ho netefalitsoe ke ho theha methapo ea boea e halikiloeng likarolong tsa 40 μm sebelisa Leica cryostat (CM1850). Ke feela lithuto tse nang le lipalo tse nepahetseng tse sebelisitsoeng bakeng sa ho hlahlojoa. Ho beoa hohle ha striatal ho ne ho le likarolong tse kholo tsa mookotaba (ke hore, libaka tse neng li netefalitsoe esale pele hore li bohlokoa bakeng sa thero ea maqhama a mabeli) (Aragona et al., 2006).

Lipalopalo.

ANOVA e nang le tsela e le 'ngoe e ne e sebelisoa ho bapisa letsoalo la MOR lipakeng tsa libaka tse' ne tsa striatum (Heinz et al., 2005). E entsoe t teko e sebelisitsoe ho bapisa letsoalo le tlamang la MOR lipakeng tsa sebaka sa rostral le sa caudal sa sebaka ka seng. Ho ile ha sebelisoa ANOVA ea mefuta e 'meli (sebakeng sa mefuta e fapaneng) ho bapisa letsoalo le tlamang la MOR lipakeng tsa li-voes tsa prairie le meadow (Insel le Shapiro, 1992). ANOVA e neng e sebelisoa ka tsela e le 'ngoe e ne e sebelisoa ho bapisa liphapang lipakeng tsa khafetsa lipakeng tsa lihlopha tsa kalafo le nako eohle ea ho ikopanya (molekane oa motho ea kopanang le eena)Burkett et al., 2011). ANOVA ea mekhoa e 'meli (kalafo ea nako ea kalafo) e sebelisitsoe ho bona hore na thibelo ea MORs e amme boitšoaro bo kopanetsoeng kapa ts'ebetso ea locomotor nakong ea 6 h ea pele ea cohabitation (Curtis et al., 2001; Aragona et al., 2003). ANOVA ea litsela tse peli (kalafo × kamore) e boetse e sebelisetsoa ho bona hore na thibelo ea MOR e amme nako e sebelisitsoeng kamoreng e ngoe le e ngoe ea lisebelisoa tsa khetho ea molekane. Li-ANOVA tsohle li ile tsa lateloa ke Tukey's post hoc tlhatlhobo. Khetho ea molekane e ne e ikemiselitsoe ka lipara t teko ka ho bapisa nako ea nako e sebelisitsoeng ho ikopanya le molekane le ea osele (Cushing et al., 2003; Curtis le Wang, 2005a). Qetellong, χ2 e sebelisitsoe ho bapisa palo eohle ea lithuto tse amanang le sehlopha sa kalafo. Maemong ohle, bohlokoa ba lipalo bo ne bo ikemiselitse ho sebelisa boemo ba α ba α0.05.

Results

Quanifying ea MOR e tlamang ho pholletsa le striatum

Boithuto ba pejana bo supile li-MOR ka har'a khetla ea dorsomedial NAc e le bohlokoa bakeng sa hedonics e ntle (ke hore, "hedonic hotspot"), mme ho phatlalalitsoe hore sena se ka amahanngoa le letsoalo le phahameng la MORs sebakeng sena (Pecina le Berridge, 2000; Smith le Berridge, 2007). Phuputsong ea rona e fetileng, re hlokometse (qualitatively) hore li-prairie voles li bonts'a letso le phahameng la li-MORs ka har'a khetla ea dorsomedial NAc (Resendez et al., 2012, Fig. 6), mme hona ho bonahala le pampiring e sa tsoa hatisoa ke sehlopha se seng (Burkett et al., 2011, bona Feie. 4). Thutong e teng hona joale, re fana ka quanifying ea pele ea letsoalo la MOR ho theosa le maemo a basali ba basali ba rorisang (Feie. 1A-D) le ho bonts'a hore letsoalo la MOR le fapana ka libaka (F(3,19) = 4.70, p = 0.02). Ka ho khetheha, libakeng tse haufi le "striatum", MOR e tlamang ka har'a khetla ea dorsomedial NAc e phahame haholo ho feta khetla ea "ventc"p = 0.05; Feie. 1E). MOR e tlamang kahare ea motheo oa NAc le eona e ne e phahame haholo ho feta khetla ea "ventc"p = 0.01; Feie. 1E). Matšoenyeho a tlamang a MOR a ne a sa fapana haholo pakeng tsa libaka tse ling tsa striatum. Le ha li-MOR ka hare ho dorsal striatum li ne li se holimo haholo ho feta li-ventral striatum tse pampiring ena, ho bohlokoa ho hlokomela hore sena e kanna ea ba sephetho sa phapang ho pharalatso ea patch / matrix hobane letsoele la MOR le phahame haholo lipakeng (kapa li-striosomes) le tlase. ka har'a matrix (Graybiel le Chesselet, 1984; Johnston et al., 1990; Gerfen, 1992).

Setšoantšo sa 1. 

MOR tlamahane ka har'a striatum. A, Left, setšoantšo se emelang sa MOR e tlamang letsoalo ka har'a rostral striatum. B, Ka ho le letona, setšoantšo sa Moemeli oa setlamo sa MOR ka har'a caudal striatum. Ka lehlakoreng le letona la setšoantšo ka seng, re supa libaka tse sekasekiloeng ho fumana letsoalo le tlamang la MOR. C, Setšoantšo se kopaneng sa khetla ea rostral ea li-voes tsa basali tsa basali. D, Khetla ea caudal. E, Ho rostral striatum, ho tlama ha MOR ho ne ho phahame haholo mokokotlong oa NAc le dorsomedial NAc ha ho bapisoa le khetla ea ventral NAc (n = 5). F, MOR binding e ne e phahame libakeng tsohle seterekeng sa rostral ha se bapisoa le caudal striatum (n = 5). G, H, Ho ne ho se na phapang ho MOR e tlamang botsitso pakeng tsa prairie le maqhubu a mehend ho (G) rostral kapa (H) libaka tse kholo tsa "striatum"n = 5). *p ≤ 0.05. **p ≤ 0.005.

MORI e tlamang e ne e boetse e fapana ka linako tse ling tsa "grostal-caudal gradient". Likarolong tsohle tsa striatum, letsoalo le kopanyang le ne le phahame haholo libakeng tse rostral ha le bapisoa le likarolo tsa caudal: dorsal striatum (t(4) = 4.69, p = 0.009), mantlha ea NAc (t(4) = 3.41, p = 0.03), khetla ea dorsomedial NAc (t(4) = 3.77, p = 0.02), le khetla ea ventc NAc (t(4) = 3.48, p = 0.03) (Feie. 1F). Ka bobeli, tlhaiso-leseling ena e bonts'a hore, kahare ho striatum, MOR e tlamang letsoalo e phahame haholo libakeng tsa sebaka se phahameng. Ntle le moo, ka har'a khetla ea NAc, letsoalo le kopanyang la MOR le phahame haholo kahara sebaka sa rostral dorsomedial (Feie. 1C,D).

Ho tseba hore na ho na le phapang lipakeng tsa mofuta o kopanyang oa MOR pakeng tsa mefuta e nyarosang le e sa amaneng le likhomo, re ile ra bapisa letsoalo le kopanyang lipakeng tsa basali ba basali ba melumo ea maoatle le li-voales tsa mehend e tšehali, mofuta o sa hlasimoloheng oa mofuta oa vole (Beery le Zucker, 2010). Papiso ena e entsoe hobane lithuto tsa pejana li bonts'itse likamano lipakeng tsa mekhoa e tlamellang li-receptor le mekhatlo ea boiketlo ea mofuta oa liphoofolo tse ntle.Insel le Shapiro, 1992; Insel et al., 1994; Wang et al., 1997; Young le al., 1997, 1999; Lim le lenyane, 2004; Aragona et al., 2006; Barrett et al., 2013). Hoa tšoana le ka holimo, ho kopanya ha MOR ho ne ho lekantsoe ho dorsal striatum, mokokotlo oa NAc, khetla ea dorsomedial NAc, le khetla ea ventral NAc. E lumellana le lithuto tse fetileng (Insel le Shapiro, 1992), ho ne ho se na phapang ea mefuta ea ho ikamahanya pakeng tsa libaka leha e le life tsa rostral striatum (F(2,32) = 0.41, p = 0.53; Feie. 1G). Ka har'a "caudal striatum", ANOVA ea ho kopanya MOR e ne e le bohlokoa (F(2,32) = 4.12, p = 0.05), empa post hoc Teko ha e a ka ea senola liphapang tse ikhethang lipakeng tsa sebaka leha e le sefe sa striatum (Feie. 1H).

Sebopeho se kopaneng sa li-receptor tsena ho pholletsa le mefuta e metle e fana ka maikutlo a hore li-MOR ka har'a striatum ha li nke karolo e tobileng mokhatlong o ikhethileng oa sechaba empa ho bonahala o bapala karolo e akaretsang ts'ebetsong ea meputso ea tlhaho. E lumellana le sena, ka har'a NAc ea mefuta e meng, letsoalo le phahameng la MOR le ka bonoa ka leqhobong la dorsomedial NAc ea lere (Herkenham et al., 1984) le ho tlama MOR kahare ho khetla ea motho ea NAc ho boetse ho tlalehiloe ho phahame haholo (Voorn et al., 1996), hape e fana ka tlhahiso ea hore li-MOR tsa libaka tse ikhethang li ka sebetsa e le chelete e tloaelehileng ea moputso. Ho etsa tlhahlobo ea hore na li-MOR ke tsa bohlokoa bakeng sa moputso oa sechaba, ka hona, ho bohlokoa bakeng sa tlamahano ea sechaba, re ile ra etsa tlhahlobo e felletseng ea li-MORs nakong eohle ea karolo eo li e phethang ho phetha karolo ea bona ea maqhama a kopaneng.

Li-MOR le sebopeho sa khetho ea molekane

Dorsal striatum

Haufinyane ho bontšitsoe hore blockade of MORs in dorsal striatum with 1 μg CTAP e thibetse ho theoa ha likhetho tsa molekane ho li-voes tsa basali tsa prairie (Burkett et al., 2011). Ka hona, re qalile ka ho pheta tlhahiso ena. Joalokaha ho hlalositsoe pele (Burkett et al., 2011), laola basali ba fumaneng aCSF ba bonts'a likhetho tsa molekane oa bohlokoa (t(10) = 2.895, p = 0.02; Feie. 2A). Ntle le moo, re boetse re pheta thuto ena ka ho bonts'a blockade ea MORs ka har'a dorsal striatum ka CTAP e thibelang ho ratwa ha balekane (Burkett et al., 2011), leha karabo ea rona ea lethal dose e ne e fapana. Ka ho khetheha, ha re a pheta-pheta ho fumana hore blockade ea MORs ka har'a dorsal striatum e nang le 1 μg CTAP e thibela sebopeho sa khetho ea molekane (t(8) = 3.34, p = 0.01; Feie. 2A). Leha ho le joalo, tekanyetso e phahameng ea CTAP (3 μg) e sebelisitsoeng thutong ea hona joale e thibetse sebopeho sa khetho ea molekane (t(5) = 0.72, p = 0.50; Feie. 2A). Blockade ea li-MORs dorsal striatum ha ea ka ea ama nako eohle ea ho ikopanya (F(2,26) = 2.38, p = 0.114; Feie. 2C) kapa palo ea nako e sebelisitsoeng kamoreng e ngoe le e ngoe (F(2,72) = 9.41, p = 0.97; Feie. 2B) nakong ea tlhahlobo ea khetho ea molekane. Kahoo, ha re fumana kakaretso ea li-MORs ka har'a dorsal striatum inhibits sebopeho sa khetho ea molekane e lumellana le se phatlalalitsoeng tlalehong e fetileng (Burkett et al., 2011), mme phapano ea tekanyetso e sebetsang e kanna ea ba litholoana tsa phapang e nyane kamora ho beoa hoa probe (Feie. 5), haholo ha ho fuoa phapang lipuisanong tsa patch / matrix (Graybiel, 1990; Gerfen, 1992) (Feie. 2A, inset), kapa ho lula ho khonahala hore ho be le phapang e nyane lipakeng tsa lithuto tse tsoang likoloneng tse peli tse fapaneng.

Setšoantšo sa 2. 

Li-MOR ka har'a dorsal striatum laola li-bond tsa marang-rang ka thibelo ea ho tlolelana. A, Ente ea aCSF kapa tekanyetso e tlase ea CTAP ho dorsal striatum ha e ea ka ea thibela ho ratwa ha molekane, athe liente tsa tekanyetso e phahameng ea CTAP sebakeng sena li felisitse khetho ea molekane. Setšoantšo, setsi sa ente se soeufalitsoe ka bohlooho (ka letsohong le letšehali) le ho tlangoa ha MOR ka har'a dorsal striatum (ka ho le letona). B-D, MOR blockade ha e ame (B) nako ea likhomo kapa (C) nako eohle ea puisano (ke hore, nako e sebelisitsoeng ho ikopanya le molekane + eo u sa mo tsebeng) nakong ea tlhahlobo ea khetho ea molekane. Leha ho le joalo, blockade ea MORs ka tekanyetso e phahameng ea CTAP e fokotse (D) palo e felletseng ea linako tsa ho holofatsa nakong ea ho hlonepha (n = 6-10). *p ≤ 0.05.

Setšoantšo sa 5. 

Litšoantšo tsa setšoantšo sa litšoantšo tse emelang libaka tsa ente ea aCSF, 1 μg CTAP, kapa 3 μg CTAP ka har'a dorsal striatum, mantlha ea NAc, khetla ea dorsomedial NAc, kapa khetla ea ventral NAc.

Habohlokoa, thibelo ea li-MORs dorsal striatum e fokotsehile haholo palo e felletseng ea linako tsa ho tlolelana nakong ea bolulo (F(2,26) = 3.58, p = 0.04; Feie. 2D) ntle le ho ama boemo ba litšebelisano tse kopanetsoeng sechabeng nakong ea bolulo (F(2,120) = 0.97, p = 0.40; Lethathamo 2). Post hoc Liteko li senotse hore lithuto tse amohetseng tekanyo e phahameng ea CTAP ho dorsal striatum li nyane haholo ho feta lithuto tse laoloang (p = 0.05; Feie. 2D). Habohlokoa, taolo ea MOR mabapi le boits'oaro ba botle ba tlotliso e lumellana le thuto e fetileng (Burkett et al., 2011); 'me hobane ho ratoa ho bohlokoa molemong oa khetho ea balekane, datha tsena li fana ka maikutlo a hore tsamaiso ea lethal dose ea CTAP ho dorsal striatum e fumanehang ho ruruha ke mokhoa oo ho etsa moratuoa oa khethollo ho senyehileng. Ho fokotseha hona ha boiketsetso ha ho kopane le ho fokotseha ka kakaretso hoa ts'ebetso ea makoloi kaha ho koaloa ha MORA ka har'a dorsal striatum ho ne ho sena tšusumetso mosebetsing oa pherekano nakong ea sebaka sa bolulo (F(2,120) = 1.37, p = 0.27; Lethathamo 3).

Tafole 2. 

Boitšoaro bo kopanetsoeng nakong ea ho kopanyaa

Tafole 3. 

Ts'ebetso ea mokhoa oa ho hlopha mahlo nakong ea ho hlophisa lintho ka ho kopanyaa

Mantlha ea NAc

Ka mor'a moo re ile ra leka karolo e ka etsahalang bakeng sa li-MOR ka hare ho NAc konokono molemong oa khetho ea balekane (Feie. 5). Blockade of MORs kahara NAc konokono le e nang le tlase (t(5) = 3.07, p = 0.03) kapa phahameng (t(5) = 3.07, p = 0.03) lethal dose ea CTAP ha ea ka ea thibela sebopeho sa khetho ea molekane (Feie. 3A). Hape ha ho na phello e akaretsang ka nako e sebelisitsoeng ka kamoreng e ngoe le e ngoe (F(2,57) = 0.03, p = 0.97; Feie. 3B) kapa nako eohle ea ho ikopanya (F(2,21) = 0.18, p = 0.88; Feie. 3C) nakong ea tlhahlobo ea khetho ea molekane. Nakong ea ho phathisana, ho ne ho boetse ho se na litlamorao ho boits'oaro bo kopanetsoeng (F(2,108) = 0.06, p = 0.94; Lethathamo 2) kapa ts'ebetso ea locmotor (F(2,108) = 0.87, p = 0.43; Lethathamo 3). ANOVA ka kakaretso e bontsitse mokhoa oa ho fokotseha hoa boits'oaro ba mathoasong (F(2,21) = 3.00, p = 0.07; Feie. 3D), mme ho hloka bohlokoa ho ka ba teng ka lebaka la phapang e phahameng ea boits'oaro ba mating lithutong tse tšoaroang ka tekanyetso e tlase ea CTAP (1 μg). A t Teko ka hona e ile ea etsoa ho bapisa ka kotloloho frequency ea mating pakeng tsa lithuto tsa taolo le lithuto tse tšoaroang ka 1 kapa 3 μg CTAP. Ha ho na phapang lipakeng tsa palo ea likamano tsa botona le botšehali lipakeng tsa basali ba taolo le ba tšoaroang ka 1 μg CTAP (t(15) = 0.22, p = 0.83), empa ho bile le phapang e kholo lipakeng tsa basali ba taolo le ba tšoaroang ka 3 μg CTAP (t(14) 2.94, p = 0.01). Ho lumellana le tlhahlobo ea lipalo-palo e sebelisitsoeng ho lihlopha tse ling kaofela tsa kalafo (le tse sebelisoang ho bapisa lihlopha tse fetang tse peli), tlhaiso-leseling ka kakaretso e tlalehiloe e le mokhoa, empa ho bohlokoa ho hlokomela hore phello ea MOR blockade kahare ho NAc ea mantlha e bonahala e na le litlamorao tse fapaneng boits'oarong ba ho tsofala le ho etsa khetho ea molekane.

Setšoantšo sa 3. 

Li-MOR tse ka hare ho motheo oa NAc ha li na karolo ea bohlokoa ho thehoeng ha balekane ba ratang. AHa ho na ente kapa liente tsa ente ea CTAP e tlase kapa e phahameng e nang le tšusumetso ea sekhahla sa molekane ea khethiloeng. Setšoantšo, setsi sa ente se soeufalitsoe ka bohlooho (ho le letšehali) le ho tlama MOR kahare ho NAc konopo (ka ho le letona) B-D, MOR blockade ka hare ho NAc ha e na phello ho (B) nako ea likhomo kapa (C) kakaretso ea nako ea ho ikopanya (ke hore, nako e sebelisitsoeng ho ikopanya le molekane + eo u sa mo tsebeng) nakong ea tlhahlobo ea khetho ea molekane, leha ho ne ho e-na le mokhoa oa (D) ho fokotseha ha palo ea lihloba tsa matingn = 5 kapa 6). *p ≤ 0.05 (tloaelo). #p = 0.07 (tloaelo).

Ho sitoa ha MOR blockade kahare ho motheo oa NAc ho ama haholo likhetho tsa molekane ho lumellana le lithuto tsa nakong e fetileng tse sa bontsheng karolo ea mantlha ea NAc boits'ebetsong bona (Aragona et al., 2006; Aragona le Wang, 2007; Resendez et al., 2012). Leha ho le joalo, ha tšekamelo ea ho fokotseha ha mathe e nahanoa mabapi le ho fokotseha ho hoholo hoa dorsal striatum le ho haelloa ke phello ea ho tsofala ho khetla ea NAc (bona ka tlase), datha ea hona joale e lumellana le maikutlo a hore striatum ke e hokahane ka tsela e kenang ka hare ho "sorsolateral spiraling system" e tla etsa hore motheo oa NAc e be sebaka sa phetoho pakeng tsa khetla ea NAc le dorsal striatum (Haber et al., 2000; Haber, 2003; Everitt le Robbins, 2005; Vanderschuren le Everitt, 2005). Ka hona, li-MOR tikolohong ena li ka ba le litlamorao tse pakeng tsa ho ts'oaroa ho sa lekanang ho ama boitšoaro ba khetho ea molekane. Litlamorao tse bohareng tsa pharmacological kahare ho mantlha ea NAc ka boits'oaro ba khetho ea molekane e lumellana le maikutlo a hore mekhoa ea ts'ebetso ea striatum e sebetsa ka tsela e kholo, le litlamorao tse bohareng tsa boitšoaro ba moputso oa sechaba li ka fumanoa libakeng tsa phetoho, joalo ka motheo oa NAc.

NAc khetla

Liphuputso tse fetileng li bontšitse hore khetla ea NAc ke sebaka se nang le mathata a mangata (Kemoto, 2007; Britt le McGehee, 2008; Resendez et al., 2012; Watabe-Uchida et al., 2012), haholoholo mabapi le ts'ebetso (Pecina le Berridge, 2005; Smith le al., 2010; Lammel et al., 2011; Britt et al., 2012; Richard et al., 2013). Mohlala, khetla ea rostral dorsomedial NAc e fetolela hedonics e ntle, athe khetla ea "ventc" ea NEc ha e (Pecina le Berridge, 2005; Mahler et al., 2007; Faure et al., 2010; Smith le al., 2010). Libaka tsena li boetse li ikhethile ka tsela e fapaneng; li fapane haholo MOR binding, le khetla ea dorsomedial NAc e nang le matla a maholohali ha a bapisoa le khetla ea ventral NAc (Burkett et al., 2011, bona Feie. 1). Ka hona, re ile ra hla ra leka ho bona hore na ke li-MOR tse ka har'a subregions tsena tse laolang likhetho tsa molekane ka mokhoa o fapaneng (Feie. 5).

Re qalile ho pheta lipatlisiso tsa morao-rao (Burkett et al., 2011) ka ho bonts'a blockade ea MORs kahare ho khetla ea "ventc NAc ka" (t(8) = 3.62, p = 0.007) kapa phahameng (t(7) = 3.31, p = 0.03) tekanyo ea CTAP ha e a ka ea susumetsa sebopeho sa khetho ea molekane (Feie. 4A). Leha ho le joalo, ho fapana le khetla ea "ventc" ea NAc, blockade ea MORs ka har'a khetla ea rostral dorsomedial NAc e nang le e tlase (t(7) = 0.80, p = 0.45) kapa phahameng (t(4) = 0.46, p = 0.67) tekanyo ea CTAP e felisitsoeng mabapi le ho ratwa ha molekaneFeie. 4A). Phello ena ha ea bakoa ke litlamorao tsa lithethefatsi ho boits'oaro bo tloaelehileng sechabeng kapa ts'ebetsong ea locomotor hobane blockade ea MORs sebakeng leha e le sefe sa khetla ea NAc ha ea ka ea ama boitšoaro bo kopanetsoeng (F(4,180) = 0.81, p = 0.53; Lethathamo 2) kapa ts'ebetso ea ho ferekanya nakong ea ho phomola (F(4,180) = 0.90, p = 0.48; Lethathamo 3). Nakong ea tlhahlobo ea khetho ea balekane, ho ne ho se na phapang e felletseng ka nako e sebelisitsoeng ka phapusing e ngoe le e ngoe lipakeng tsa lihlopha tsa kalafo (F(4,105) = 0.17, p = 0.96; Feie. 4B) kapa nako eohle ea ho ikopanya (F(4,40) = 2.23, p = 0.08; Feie. 4C). Mmoho, lintlha tsena li bonts'a hore, kahara NAc, MOR taolo ea sebopeho sa likamano tsa molekane e ikhethile ho khetla ea dorsomedial NAc, setereke se nang le MORs (Feie. 1), hape, ho bohlokoa ka ho fetisisa, e kileng ea hlahisoa ke li-hedonics tse ntle (Pecina le Berridge, 2005).

Setšoantšo sa 4. 

Li-MOR ka hare ho dorsomedial, empa eseng li-ventral, khetla ea NAc e bohlokoa bakeng sa kaho ea khetho ea molekane. A, Ente e ikhethileng ea Site ka bobeli le ka tekanyetso e tlase le e phahameng ea CTAP ka har'a dorsomedial NAc shell inhibited preference organised, athe liente tsa e ka ba mofuta oa CTAP li ne li sena ts'ebetso khetla ea "ventc" ea ventc. Ho kenella, Setsi sa ente khetla ea dorsomedial Nac ('mala o lefifi) kapa khetla ea "ventc" (leseli le bohlooho) (le letšehali) le ho tlama ha MOR ka har'a khetla ea NAc (ka ho le letona). B-D, MOR blockade e nang le tekanyetso ea CTAP ka har'a khetla ea NAc ha ea ka ea ama (B) nako ea likhomo, (C) nako eohle ea ho ikopanya (ke hore, nako e sebelisitsoeng ho ikopanya le molekane + eo u sa mo tsebeng), kapa (Dpalo ea likhahla tse tlohelang batho ba bangn = 4-9). *p ≤ 0.05. **p ≤ 0.005.

Ho fapana le dorsal striatum, thibelo ea litheko tsa molekane ea kopantseng mofuteng oa dorsomedial NAc e ne e sa amanngoe le ho fokotseha ha botsitso joalo ka taolo ea tekanyetso e tlase kapa e phahameng ea CTAP ka hara khetla ea dorsomedial NAc e fetotse palo yohle ea likamano tsa mating (F(4,38) = 1.14, p = 0.35; Feie. 4D) nakong ea ho phomola. Ntle le moo, hobane ts'itiso ena ea khetho ea molekane (ka MOR blockade ka sebopeho sa dorsomedial NAc) ha e sebetse ka molawana oa boitšoaro ba mating empa e le sephetho sa ho ts'oaroa, lintlha tsena li fana ka maikutlo a hore MORs ka har'a dorsomedial NAc shell e laole sebopeho sa khetho ea molekane. ka mekhoa e fapaneng ea kelello ho feta e fumanehang ka har'a dorsal striatum e amang ka kotlolloho boits'oaro ba ho tsofala, ho ka etsahala, li-hedonics tse ntle tse amanang le ho tlolelana.

Puisano

Sebopeho sa khetho ea li-Partner ke mohlala o matla oa moputso oa sechaba, 'me thuto ea hona joale e har'a tse ngata tse bonts'ang hore moputso oa boko o tataisoa ke oa bohlokoa bakeng sa boitšoaro bona (Wang et al., 1999; Gingrich et al., 2000; Aragona et al., 2003; Liu le Wang, 2003; Lim le lenyane, 2004; Curtis le Wang, 2005a, b; Aragona et al., 2006; Aragona le Wang, 2007; Lim et al., 2007; Burkett et al., 2011; Moahi et al., 2011; Keebaugh le Monyane, 2011; Liu et al., 2011). Thona joale thuto ke ea pele ho bonts'a hore ho khetheha ha tikoloho ho li-MORs ka har'a ts'ebetso ea maqhama a kopantsoeng ke litholoana tsa mekhoa e fapaneng e amanang le moputso oa sechaba.

Re qalile ho pheta lipatlisiso tsa morao-rao (Burkett et al., 2011) ka ho bonts'a hore sebopeho sa khetho ea molekane se hloka ts'ebetso ea li-MOR kahare ho dorsal striatum, e leng sebaka sa boko seo MORs e arolelanang likarabo tse susumetsang tsa boitšoaro (DiFeliceantonio et al., 2012). Aka mehla, re atolosa tsebo ena ea hajoale ka ho fana ka bopaki ba pele ba hore li-opioid tsa mehleng ea NAc le tsona li bohlokoa bakeng sa tlhahiso ea khetho ea balekane; ka kotloloho, ts'ebetso ea li-MORs kahare ho khetla ea NAc e kentsoeng ho li-hedonics tse ntle e hlokahala bakeng sa ho thehoa ha bonto. Habohlokoa, lintlha tsena li fana ka bopaki ba pele ba hore patch ena e teteaneng ea li-MORs ka har'a khetla ea dorsomedial NAc ha e arolelane feela li-hedonics tse ntle tse amanang le moputso oa lijo (Pecina le Berridge, 2000; Smith le Berridge, 2007) empa e ka bapala karolo e akaretsang ts'ebetsong ea neural ea meputso e meng ea tlhaho, ho kenyelletsa le moputso oa sechaba. Mmoho, datha ea rona e bonts'a mekhoa e 'meli e tšoanang e ka bapisoang le e' ngoe moo MOR e laolang sebopeho sa khetho ea molekane: e ngoe eo MORs ka har'a dorsal striatum e laolang ts'usumetso ea ho etsa boits'oaro ba ho ts'ehetsa tloaelo ea bonto le ea bobeli eo MORs ho dorsomedial NAc shell e laolang ts'ebetso e ntle ea hedonic eo ke litholoana tsa liketso tse thabisang sechabeng, tse kang ho ruruha.

Ho susumetsa, dorsal striatum, le moratuoa oa khetho ea

Sebopeho sa lithahasello tsa balekane ho li-voiri tsa prairie se nolofalletsoa ke ho tlolelana (Williams et al., 1992), 'me thuto ea hona joale e bontša hore methapo ea methapo e tsamaisang mokhoa ona, joalo ka ts'ebetso ea opioid ea ka hare ho dorsal striatum, e kena-kenana le ts'ebetso ea ho qala ea ho qala. Le ha ho le joalo feela tlhahlobo ea opioid ea tlotliso ea tlholeho e tlisoang ke tlhompho ea lihlahisoa tsa tlotlo ea basali.Burkett et al., 2011) ka hona ha e utloisisoe hantle, datha tse tsoang ho mefuta e meng li kentse ts'ebetso ena ka kotloloho molemong oa ho emisa (Coolen et al., 2004; Parra-Gamez et al., 2009; Komisaruk et al., 2010) le sebopeho sa likhetho tsa tikoloho e amanang le ho ruruha (Coria-Avila et al., 2008). Nakong ea botšehali, li-opioid tsa mofuta oa tsoelo-pele li lokolloa libakeng tsa bokong tsa moputso (Szechtman et al., 1981), 'me ho lokolloa ha li-peptide tsena ho bohlokoa bakeng sa ho hlahisa likarabo tse susumetsoang ka thobalano ha blockipheral blockade of MORs in rats e eketsa nako ea phomolo ea ho tsofala hape e fokotsa leqhubu la linako tsa ho hlaseloa hangata ((Ismail et al., 2009). Aka tloaelo, polelo ea enkephalin, ligo ea endo native bakeng sa MORs (Simantov et al., 1977), keketseho ea dorsal striatum ea likhoto tsa basali nakong ea proestrous (Roman et al., 2006): nako ea potoloho ea bohlokoa bo makatsang moo ho bang le llizing ea lisele le methapo ea progesterone e etsang hore motho a tsebe ho tsitsa, ho lekola thobalano le tšusumetso (Smith le al., 1975; Becker, 2009). Ka bobeli, liphetho tsena li fana ka maikutlo a hore ts'ebetso ea li-MOR ka hare ho dorsal striatum e tataisa likarolo tsa susumetso tsa boitšoaro ba thobalano.

I, bopaki ba morao-rao bo tsoang lipatlisisong tsa moputso oa lijo bo beha ka kotloloho li-MOR kahare ho dorsal striatum ka boits'oaro bo susumetsangr (DiFeliceantonio et al., 2012). Ka ho khetheha, enkephalin e lokolloa ka dorsal striatum nakong ea ts'ebeliso ea lijo, 'me tokollo ena e tsamaisana hantle le lebelo leo ts'ebeliso ea lijo e qalang ka lona. (DiFeliceantonio et al., 2012), ho bonts'a hore ts'ebetso ea li-MORs tikolohong ena ho bohlokoa bakeng sa ho matlafatsa karabelo ea takatso ho khothatsong e khotsofatsang (Richard et al., 2013). Ka hona, ho thibeloa ha li-receptor tsena ha ho le teng ka har'a tšusumetso e matla haholo sechabeng, joalo ka motho ea ka kopanyang molekane, ho ka fokotsa tšusumetso ea ho batla moputso (ke hore, ho tlolelana). Le ha ho sa khonehe ho lekanya sepheo sa ts'ebetso ea ho tsofala mofuteng oa hona joale, Lordosis ka mosali ho hlokahala bakeng sa ho phethela katleho ea phepo e ntle, ka hona ha ho na monyetla oa hore dorsal striatal MOR blockade e fokotse mating ka phokotso ea tsamaiso ea thobalano (Becker, 2009). Leha ho le joalo, liphuputso tse ling li hlokahala ho senya karolo e tobileng ea bo-'mali ba botona ba botšehali ho boits'oaro ba basali.

Ho khahlisang, ts'ebetso ea dorsal striatum e boetse e nahanoa hore e laola likarolo tse susumetsang tsa khetho ea molekane ho batho ha sebaka sena se kenngoa ts'ebetsong molemong oa likamano tsa lerato, empa ts'ebetso ena ha e tsamaellane le boemo bo botle ba hedonic bo susumetsoang ke molekane. (Aron et al., 2005). Ka mokhoa o ts'oanang, enkephalin e hlahisitsoeng kahare ea dorsal striatum nakong ea ts'ebeliso ea lijo ha e amane le likarabo tsa hedonic ts'usumetso ena. (DiFeliceantonio et al., 2012). Kahoo, ts'ebetso ea li-MOR ka hare ho dorsal striatum ho bonahala e ikhethile likarolo tsa susumetso tsa ho batla moputso. Ka kakaretso, datha tsena li fana ka maikutlo a hore li-MOR tse ka hare ho dorsal striatum li ka ba bohlokoa ho theho ea khetho ka ho hlahisa likarabo tsa boitšoaro tse susumetsoang sechabeng, tse kang ho ruruha, le litlamorao tse tlisoang ke ho hola, joalo ka ho etsa khetho ea molekane.

Li-hedonics tse ntle, khetla ea rostral dorsomedial NAc, le sebopeho sa khetho ea molekane

MORs ka har'a khetla ea dorsomedial NAc e kentse letsoho ho li-hedonics tse ntle (Berridge le Kringelbach, 2008) tHat e bohlokoa maemong a qalang a popeho (Panksepp et al., 1980; Resendez le Aragona, 2013). Nakong ea boiketlo ba batho ba phetseng hantle, banna le basali ba rorisang basali ba kenella lipakeng tsa litšebelisano tse monate tsa bophelo bo botle, joalo ka boits'oaro ba ho etsa lipatlisiso, ho tlolelana le ho tsikinyeha (Carter le Getz, 1993). Litšebelisano tsena li bohlokoa molemong oa ho theha tlamo (Williams et al., 1992), le datha ho tsoa thutong ea hona joale e bonts'a hore blockade ea MORs ka hara khetla ea doromedial NAc ha e ea ka ea kena-kenana le ho ikopanya le batho le ho nyalana (ke hore, boits'oaro bo kopanetsoeng bo amanang le moputso oa sechaba). Ho fapana le moo, ho tlosoa hoa lets'oao le hlakileng la hedonic kamora ho emisoa ke ho thibela MORs ka har'a khetla ea dorsomedial NAc ho senya moputso oa sechaba mme ho kena-kenana le qeto e khothatsang ea sechaba. (Aragona le Wang, 2009; Resendez le Aragona, 2013). Lintlha tsena li tsamaisana le thuto ea pejana ea moputso oa sechaba o bonts'itseng hore ts'ebetso ea li-MOR ka har'a khetla ea NAc, mme mohlomong ho supa lebitso la hedonic, ho bohlokoa ho tataisa boits'oaro bo susumetsoang ke sechaba. (Trezza et al., 2011).

Karolo ea li-hedonics kamanong ea sechaba e tšehetsoa ka matla ke lingoliloeng tsa batho, mme likamano tsa setsoalle le molekane ea tlohelang lenyalo li hlalositsoe e le ntho e khahlisang (Fisher et al., 2006). Litšebelisano tsa kahare le molekane kapa ho shebella lifoto tsa maikutlo a lerato a susumetsang mofets'ePanksepp et al., 2002; Fisher et al., 2006). Ka bobeli, tlhaiso-leseling ena e fana ka maikutlo a hore li-circuits tsa moputso oa bophelo bo botle ba 'mele ho pholletsa le mefuta ea liphoofolo tse anyesang li ameha ho thehoeng se ikhethileng. Sena se bua le ho iphetola ha karolo ea tšusumetso e ntle khokahanong; mme ka ho re potoloho e tšoanang ea neural e ka kopanya thabo, mosebetsi oa rona o na le moelelo oa "chelete e tloaelehileng ea neural" e bohlokoa bakeng sa tšusumetso e akaretsang, ho kenyeletsoa boits'oaro bo kopanetsoeng sechabeng (Cabanac, 2002; Burgdorf le Panksepp, 2006).

Ho sebetsa ka mokhoa o ts'oanang le oa ho hlasimolla libopeho tsa moratuoa

Ho sebetsa ka kelellong bokong ho kenyelletsa tšebelisano lipakeng tsa likarolo tse ts'oanang tsa tšebetso ea methapo e amanang le likarolo tsa kelello, koloi le maoto a maqhubu (Flaherty le Greybiel, 1994; Haber, 2003; Kreitzer le Berke, 2011). Mabapi le sebopeho sa khokahanyo, ho se kopane pakeng tsa boits'oaro bo khothalletsoang, joalo ka mathe, le tšebeliso e ntle ea hedonic ea boitšoaro bo joalo e ka nka khato ea ho fokotsa moputso oa ka moso oa bophelo ba morao-rao, joalo ka ho kopana le molekane ea hloahloa nakong ea tlhahlobo ea khetho ea molekane. (Resendez le Aragona, 2013). Ho khahlisang, lipehelo le liphetho ka har'a striatum li hlophisitsoe ka mokhoa oa topographical, spiral (Haber et al., 2000; Belin et al., 2009) e ka ikarabellang bakeng sa liphapang tsa tikoloho ho MOR taolo ea sebopeho sa maqhama a mabeli kahare ho striatum. Ka ho khetheha, blockade of MORs in the dorsal striatum e ka fokotsa tšusumetso ea ho hlahisa likarabo tse nepahetseng tsa koloi ho sephetho se ikhethileng sa sechaba (ke hore, ho fokotseha ha mathe), athe ba leng khubung ea dorsomedial NAc ba bonahala ba laola likhakanyo tse ntle tsa hedonic tsa khothatso e tšoanang ea sechaba. Kahoo, ts'ebelisano pakeng tsa lits'ebetso tse fapaneng tsa neural tse fapaneng ka ho fapana tse tsamaisang moelelo oa boitšoaro bo amanang le moputso oa sechaba ke oa bohlokoa molemong oa ho ikamahanya le maemo.

Qetellong, lipakeng tsa li-voogamous prairie voles (Getz et al., 1981), khetho ea molekane e tla fella ka tsoalo e atlehileng ke ea bohlokoa haholo (Curtis, 2010; Resendez et al., 2012), mme thuto ea hona joale e bonts'a hore ts'ebetso e nepahetseng ea MOR libakeng tse ikhethileng tsa striatum e bile teng ho nolofatsa ho etsa liqeto tsa boiketlo ba sechaba (Resendez le Aragona, 2013). Ka har'a striatum, li-MOR tse ka hare ho dorsal le subralions li sebetsa ka tsela e ts'oanang ho loants'oa mating le litlamorao tse nyarosang tsa ho tlolelana. Hammoho, tlhaiso-leseling e teng hona joale le datha tse tsoang lipatlisisong tsa moputso oa lijo li bonts'a hore li-MOR ka har'a striatum ha li nke karolo e itseng mofuteng o mong oa moputso (Berridge le Kringelbach, 2013) empa ho e-na le hoo e sebetse joalo ka chelete e akaretsang ea neural ho susumetsa likarabo tsa boitšoaro bo khotsofatsang / bo lumellanang, ho kenyelletsa le sebopeho sa setlamo se ikhethileng.

Mongolo o botlaaseng ba leqephe

  • E amohetse August 28, 2012.
  • Tlhahlobo e amohetse April 16, 2013.
  • E amohetse April 16, 2013.

  • Mosebetsi ona o tšehelitsoe ke National Science Foundation Grant 0953106 ho BJA le Rackham Merit Fsoci ho SLR Re leboha Yan Liu ka thuso ka opioid receptor autoradiography, Kirsten Porter-Stransky bakeng sa tlhahlobo ea lipalopalo, li-Piper Keyes bakeng sa ts'ebetso ea boko, le Zouxin Wang monehelo o fanoang ka seatla se bulehileng oa li-voales voles.

  • Bangoli ha ba phatlalatse lithahasello tsa lichelete.

  • Litaba li lokela ho lebisoa ho Brandon J. Aragona kapa Shanna L. Resendez, Lefapha la Psychology, Univesithi ea Michigan, Ann Arbor, MI 48109, [imeile e sirelelitsoe] or [imeile e sirelelitsoe]

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