Li-receptors tsa CRF mobung oa accumcums o khethollang molekane oa bona ka lipatlisiso tsa majoe (2007)

Horm Behav. Sengoloa se ngotsoeng; e fumaneha ho PMC Dec 10, 2007.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

Horm Behav. Apr 2007; 51 (4): 508-515.

E phatlalalitsoe marang-rang Jan 27, 2007. Doi:  10.1016 / j.yhbeh.2007.01.006

PMCID: PMC2128037

NIHMSID: NIHMS22254

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

Sheba lihlooho tse ling ho PMC hore Qotsa sehlooho se hatisitsoeng.

Eya ho:

inahaneloang

Bopaki ba morao-rao bo bonts'a karolo ea corticotropin-releasing factor (CRF) taolong ea tlamahano ea maqhama a kopantsoeng le li-voes tsa prairie. Re kile ra bonts'a hore mefuta ea vole e monogamous le e seng monogamous e na le phapanyetsano e fapaneng haholo ea mofuta oa CRF receptor mofuta 1 (CRF)1) le mofuta oa CRF receptor 2 (CRF2) bokong, le CRF eo1 le CRF2 li-receptor densities ho li-nucleus accumbens (NAcc) li amana le mokhatlo o hlophisitsoeng oa sechaba. Li-monogamous prairie le li-voine tsa phaene li na le maemo a tlase haholo a mofuta oa CRF receptor 1 (CRF)1), le maemo a holimo haholo a mofuta 2 (CRF2) tlama, ho NAcc ho feta li-meadow tse se nang monogamous le li-voales tsa montane. Mona, re tlaleha hore li-microinjections tsa CRF ka kotloloho ho NAcc li potlakise kaho ea khetho ea molekane ho li-voes tsa banna tsa prairie. Li-injection tsa taolo ea CSF ho NAcc, le CRF ho caudate-putamen, ha lia ka tsa tsamaisa khetho ea molekane. Ka mokhoa o ts'oanang, liente tsa CRF ho li-NAcc tsa li-voles tsa meadow tse se nang monogamous le tsona ha lia ka tsa tsamaisa khetho ea molekane. Likopanong tsa prairie, ts'ebetso ena ea ts'ebetso ea CRF e ne e thibetsoe ke ente ea CRF1 kapa CRF2 bahanyetsi ba receptor ho NAcc. Litlamorao tsa Immunocytochemical bakeng sa CRF le Urocortin-1 (Ucn-1), ligands tse peli tsa endo native bakeng sa CRF1 kapa CRF2 li-receptors bokong, li senotse hore CRF, empa eseng Ucn-1, likhoele tsa immunoreactive li ne li le teng ho NAcc. Sena se ts'ehetsa maikutlo a hore ho lokolloa ha CRF ea lehae ho NAcc ho ka kenya tšebetsong CRF1 kapa CRF2 li-receptors tikolohong. Ha re kopanngoa hammoho, liphetho tsa rona li senola karolo e ncha ea litsamaiso tsa CRF tse sa sebetseng maemong a sechaba.

Keywords: li-nucleus accumbens, sehokelo, CRF1, CRF2, corticotropin-releasing factor, corticotrophin-releasing hormone, vole, neuropeptide receptors, joal bond, boitšoaro ba sechaba, monogamy, mefuta ea phapang

Ts'ebetso ea corticotropin-releasing factor (CRF) e kenella ho ts'ebetso ea methapo ea kutlo le khatello ea maikutlo, empa ha ho tsejoe haholo ka karolo ea eona boits'oarong ba sechaba. Liroto tsa Microtine li bonts'a mekhatlo e fapaneng ea sechaba mme ka hona li fana ka mokhoa o motle oa ho bapisa thutong ea neurobiology ea boitšoaro ba sechaba (Bacha le Wang, 2004). Prairie (Microtus ochrogaster) le li-voine tsa phaene (Microtus pinetorum) ba monogamous; balekane ba baholo ba theha litlamo tsa nako e telele tsa ho khetha ka bobeli tšimong le laboratoring (Getz, Carter, le Gavish, 1981; Salo, Shapiro, le Dewsbury, 1993). Ho fapana le hoo, sebaka se amanang haufi-ufi le (Microtus pennsylvanicus) le li-voes montane (Microtus montanus) a boitšoaro bo bobe ebile a le mongGruder-Adams le Getz, 1985; Shapiro le Dewsbury, 1990). Patlisiso e fetileng e senotse hore kabo ea boko ea li-receptor tsa neuropeptide bakeng sa oxytocin le vasopressin li bonahala li ikarabella bakeng sa liphapang tsa mefuta mokhatlong oa sechaba (Insel le Shapiro, 1992; Insel, Wang, le Ferris, 1994; Lim, Wang, Olazabal, Ren, Terwilliger, le Monyane, 2004b). Leha ho le joalo, bopaki ba morao-rao bo fana ka maikutlo a hore ts'ebetso e 'ngoe ea li-neuropeptide, CRF, le eona e bonahala e lekanya maqhama a kopantsoeng le li-voes tsa prairie (DeVries, Guptaa, Cardillo, Cho, le Carter, 2002).

Ho na le lithuto tse fokolang tse hlahlobang karolo ea lihormone tsa khatello ea maikutlo mekhoeng ea sechaba. Phuputso e 'ngoe e fumane hore taolo ea exorte corticosterone ho banna prairie voles e nolofalelitse ho theha maqhama a mabeli le mosali e motšo (DeVries, DeVries, Taymans, le Carter, 1996). Phuputso e ileng ea latela ea fumana hore CRF e laetsoe intracerebroventricularly (icv) e nolofalletsang khetho ea molekane litulong tsa banna ba rorisang, esita le ka litekanyetso tse tlase haholo tse neng li sa bonahale li ama ts'ebetso ea locomotor kapa boits'oaro bo kang bo tšoenyang (DeVries et al., 2002). Ntle le moo, khetho ea molekane e thibetsoe ke tsamaiso ea icv ea alpha-helical CRF e sa thibeleng li-receptor tsa CRF bokong (DeVries et al., 2002). Lintlha tsena li fana ka maikutlo a hore CRF e ka bapala karolo ea ho theha maqhama a mabeli ka mekhoa e ikemetseng e nang le matšoenyeho ka ho kenya letsoho lipakeng tsa li-receptor tsa bongoana tse sebetsang. Leha ho le joalo, CRF e kentsoeng icv e kanna ea sebetsa lipakeng tsa palo efe kapa efe ea libaka tsa boko ho tsamaisa khetho ea molekane, mme hajoale ha ho tsejoe hore na ke likarolo life tsa boko tse amehang ka kotloloho.

Kaha Sisteme ea CRF e kentse letsoho taolong ea sebopeho sa maqhama a mabeli, re boletse esale pele hore li-circuits tsa neural bakeng sa sistimi ena li tla fapana lipakeng tsa mefuta e nyarosang le e seng ea monogamous. Re bontšitse pejana hore, le ha kabo ea CRF mRNA le peptide e bonahala e bolokiloe haholo hara mefuta ea li-vole, kabo ea mefuta ea CRF receptor 1 le 2 (CRF1 le CRF2) li fapana haholo ka bokhabane bokong ka mefuta e mene e metle e bonts'a mekhatlo e fapaneng ea sechaba (Lim, Nair, le Bacha, 2005; Lim, Tsivkovskaia, Bai, Nyane le Ryabinin, 2006). Receptor binding e bonahala e lumellana le sebopeho se le seng sa bophelo sechabeng libakeng tse 'maloa tsa boko; le ha ho le joalo, ke li-nucleus accumbens (NAcc) tse arohaneng ka linako tsohle le mefuta e 'meli ea monogamous vole le mefuta e' meli e seng monogamous. Li-monogamous prairie le li-voine tsa phaene li na le maemo a tlase haholo a mofuta oa CRF receptor 1 (CRF) 1), le maemo a holimo haholo a mofuta 2 (CRF2) tlama, ho NAcc ho feta li-meadow tse se nang monogamous le li-voes tsa montane (Lim et al., 2005).

E ipapisitse le lithuto tsa rona tsa neuroanatomical tse bonts'ang phapang ea mefuta ea CRF1 le CRF2 Matšoenyeho a NAcc, re ananetse hore ketso ea CRF kahare ho NAcc, haholo, e ne e bohlokoa bakeng sa boits'oaro bo bobe ba sechaba ho li-voes tsa prairie. Taba ea mantlha, re ne re tseba hore na CRF e ka kena ka kotloloho ho NAcc e ka nolofalletsa moratuoa oa hae joang ka mor'a nako e khuts'oanyane ea ho ikopanya le moratuoa. Ka mor'a moo, re ile ra etsa tlhahlobo e tšoanang maqepheng ao e seng a monogamous. Ka mor'a moo, re ile ra qhekella CRF1 le CRF2 ho NAcc ho sebelisa bahanyetsi ba meriana ho tsebahatsa liphallelo tsa bona ho thehoeng ha balekane ba CRF. Qetellong, re bonts'a bopaki ba bohloka ba kalafo ea kalafo ea li-ligands tse peli tsa CRF1 le CRF2 li-receptors bokong, CRF- le Urocortin-1 (Ucn-1), ho NAcc ka li-voles tsa prairie. Liphetho tse tsoang liphuputsong tsena li bonts'a ka lekhetlo la pele hore CRF, e sebetsang ho NAcc e ka khothaletsa ho ikamahanya le sechaba le ho feta, hore CRF ka bobeli1 le CRF2 li-receptors li kentse letsoho ts'ebetsong ena.

METHODA

Lihlooho

Liphoofolo e ne e le batho ba baholo, ba botona le botšehali, meloko ea banna le basali (matsatsi a 70-100 ea lilemo) ho tsoa koloneng ea mosebetsi oa laboratori Univesithing ea Florida State eo pele e neng e nkiloe maetong a hapiloeng ke masimo a Illinois, USA. Li-voles tsa batho ba baholo ba nang le thobalano tsa batho ba baholo tse amanang le thobalano li ne li tsoa koloneng ea laboratori e fumanehang Univesithing ea Emory. Kamora ho khoesoa ka nako ea matsatsi a 21, lithuto li ile tsa beoa ka bobeli ba ngoanana kapa batho ba bong bo le bong le metsi mme purina ea mmutla oa Purina e ile ea fana ka lipapatso. Litsela tsohle li ne li bolokoa ka 14: lebone la 10: lebili le lefifi le nang le mocheso ho 20 ° C. Lintlha tse tsoang li-voles tsa 87 tsa banna ba kenyellelitsoeng li kenyelelitsoe litekong tsa pharmacology tsa CRF, hammoho le lipalo tse lekanang tsa li-voes tsa femu tsa basali tsa mofere-fere. Lintlha tse tsoang li-voles tsa mehend tsa banna tsa 10 le tsona li sebelisitsoe, hammoho le lipalo tse lekanang tsa li-voes tsa mehendi tsa basali tsa femform. Ho ile ha sebelisoa li-voes tsa prairie tse robeli lithutong tsa immunocytochemistry tsa CRF (n = 4 bakeng sa bong bo bong le bo bong).

Tataiso ea CRF ea khetho ea molekane

Li-voles tsa banna ba baholo ba banna (n = 31) li ne li ka etsoa ka mokhoa o kopaneng ho NAcc ba sebelisa mekhoa e seng molaong joalokaha ho hlalositsoe pele (Aragona, Liu, Curtis, Stephan, le Wang, 2003a; Liu le Wang, 2003). Lihlooho li ne li sa anngoe ka sodium pentobarbital (2.5 mg ka boima ba 'mele oa 40 gm), le 26 gauge bilateral guide cannulas (Plastics One, Roanoke, VA) e ikemiselitseng ho NAcc e kentsoe stereotaxically (Anterior 1.7 mm, Bilateral ± 1N Vral mm ho bregma). Liente tsa taolo (n = 4.0) li ne li reretsoe ho caudate-putamen (Anterior 6 mm, Bilateral ± 1.7 mm, Ventral −1 mm ho bregma). Kamora ho hlaphoheloa ha matsatsi a 2.5-3, lithuto li ile tsa amohela li-microinjections (5 nl ka lehlakoreng le leng) la CSF kapa lithethefatsi tse felisitsoeng ho CSF. Lisebelisoa li entsoe ka nale ea 200 gauge e atolositseng 33 mm ka tlase ho cannula ea tataiso sebakeng se fihletsoeng. Lenaka le ne le hokahane le sebakana sa Hamilton (Hamilton, Reno, NV) ka polyethylene-1 tubing, eo ka eona tharollo e ileng ea kenngoa butle ka pompo (MasterFlex L / S standard drive, Model 20-7016) ka lebelo la 21 nl / mets, ka lehlakoreng le leng. CRF ea motho / rat e fumanoe ho Sigma (St. Louis, MO).

Liphoofolo li ile tsa aroloa ka e 'ngoe ea lihlopha tse' ne: Taolo ea CSF (n = 7), 0.01 pg CRF ho NAcc (n = 9), 0.1 pg CRF ho NAcc (n = 15), le 0.1 pg CRF ho caudate-putamen (n = 6). Caudate-putamen (CP) ke karolo ea boko e tsoang feela ho NAcc hape e na le CRF2 li-receptors, ka hona li sebetsa joalo ka sebaka sa taolo ea anatomical bakeng sa litlamorao tsa CRF. Phoofolo e 'ngoe le e' ngoe e ne e fumana liente tse peli tsa 200 nl bophahamo ba eona pele e ne e le khutsufatso ea hora ea 6 le mosali ea neng a sa tsebe letho. Maqhubu a 0.01 pg CRF ho 200 nL ke 10 nM, ha khatello ea 0.1 pg CRF ho 200 nL ke 100 nM. Se baloang Ki bakeng sa CRF1 ke 11 nM, ha Ki e baliloe bakeng sa CRF2 ke 25 nM e amanang le 125I-sauvagine (Primus, Yevich, Baltazar, le Gallager, 1997). Cohabitation ea lihora tsa 6 ntle le ho ts'oaroa ka botsitso ha e khothalletse khetho ea molekane, joalo ka ha ho bonts'itsoe lithutong tse fetileng (Aragona et al., 2003a; Aragona, Liu, Yu, Curtis, Detwiler, Insel, le Wang, 2006). Hang ka mor'a ho lula hammoho, lithuto li ile tsa lekoa bakeng sa khetho ea molekane.

Teko ea moratuoa oa molekane e ne e le ho kenya e motona ka har'a lisebelisoa tse nang le likamore tsa 3 moo molekane oa mosali a kentsoeng terakeng e le 'ngoe, mme mosali e mong oa "osele" oa lilemo tse tšoanang le boiphihlelo ba bosodoma o ile a kenngoa ka mokotleng oa bobeli, joalo ka nakong e fetileng hlalositsoe (Carter, DeVries, le Getz, 1995). Mosali e mong le e mong oa khothaletso o ne a sebelisoa litekong tse peli tse arohaneng tsa khetho ea molekane, e le molekane hape e le moahi oa taba e ngoe, ka hona mosali e mong le e mong o bile le ponaletso e tšoanang ea sechaba le thobalano nakong ea hora ea 20 ea ho phomola. Bafetsi ba ile ba lumelloa ho solla ka bolokolohi lisebelisoa tsohle, 'me nako e sebelisitsoeng ho ikopanya le molekane le motho eo ba sa mo tsebeng e ile ea hlakoloa nakong ea tlhahlobo ea hora ea 3.

Ketsahalo ea locomotor e ile ea lekanngoa nakong ea tlhahlobo ea khetho ea molekane ho bona hore na litekanyetso tse khethiloeng tsa kalafo ea CRF li ama ts'ebetso e akaretsang ea tloaelo kapa boits'oaro bo ts'oenyehileng, joalo ka ha ho hlalositsoe pele (Hotta, Shibasaki, Arai, le Demura, 1999). Palo ea liphallo tsa likhopo ka lisebelisoa tse peli tsa thatohatsi ea molekane e ile ea hlahlojoa ka ho sebelisa li-sensor tsa infrared. Ho na le libalaka tse 'ne tsa infrared kahara mekotla e meraro ea lisebelisoa tseo motho a ratang ho li rata,' me maballo a mabeli a thunya kotopo e 'ngoe le e' ngoe e hokahanyang mabokose a mabeli. Palo eohle ea likotlo tsa lifoto e ile ea hlakisoa bakeng sa phoofolo ka 'ngoe nakong ea lihora tse tharo. Kamora tlhahlobo ea boits'oaro, lithuto li ile tsa etsoa sehlabelo mme libaka tsa ente tsa netefatsoa ho latela nalane.

Li-voles tsa banna ba baholo ba mehendi (n = 10) le tsona li ile tsa lekoa bakeng sa ho thusa nts'etsopele ea CRF ea khetho ea molekane. Liphoofolo li ne li ka kenngoa ka kotlolloho kahare ho NAcc joalo ka ha ho hlalositsoe kaholimo 'me ka nepo li fuoe se seng sa lihlopha tse peli: taolo ea CSF (n = 4), kapa CRF 0.1 pg (n = 6). Liteko tsa ho ratana le ho tloaelana le balekane li entsoe ka mokhoa o hlalositsoeng kaholimo bakeng sa li-voes tsa prairie. Mehlala e tona ea banna ba baholo e tsoang koloneng ea rona ka tloaelo ha e etse khetho ea balekane ha ba lula le mosali (Lim et al., 2004b).

CRF1- le CRF2-selective pharmacology le khetho ea molekane

Li-voes tsa adult prairie li ile tsa kenngoa ka bobeli ho NAcc joalo ka ha ho hlalositsoe kaholimo 'me ea aroloa ka e' ngoe ea lihlopha tse tharo: 0.1 pg CRF (n = 10), 0.1 pg CRF plus 10 pg CRF1 antagonist (CP-154,526) (n = 25), le 0.1 pg CRF le 10 pg CRF2 antagonist (anti-sauvagine-30) (n = 15). Anti-sauvagine-30 e fumanoe ho Sigma (St. Louis, MO), le CP-154,526 ho tsoa ho Michael Owens, Ph.D. (Yunivesithi ea Emory, Atlanta, GA). The mahloriso ea 10 pg CRF1 antagonist (CP-154,526) ho tharollo ea 200 nL ke 100 nM, ha khatello ea 10 pg CRF2 antagonist (anti-sauvagine-30) ho tharollo ea 200 nL ke 10 nM. Phoofolo e 'ngoe le e' ngoe e amohetse li-ente tsa 200 nl bophahamo ka kotloloho ho NAcc pele ho pherekano ea hora ea 6 e kopantsoeng le mosali e mocha. Hang ka mor'a ho ikopanya, lithuto li ile tsa lekoa bakeng sa khetho ea molekane joalokaha ho hlalositsoe ka holimo. Kamora tlhahlobo ea boits'oaro, lithuto li ile tsa etsoa sehlabelo mme libaka tsa ente tsa netefatsoa ho latela nalane. Liphoofolo tseo libaka tsa tsona tsa cannulation li kentsoeng kantle ho NAcc li ne li sa kengoe tlhahlobisong ea data ebile li sa hlahisoe ka palo eohle ea liphoofolo tse sebelisitsoeng.

Boitsebiso ba Lintlha

Lintlha tse tsoang tlhahlobong ea khetho ea molekane bakeng sa teko e 'ngoe le e' ngoe li ile tsa hlahlojoa ho sebelisoa 2 tsela ANOVA eo ho eona ho khothatsang (molekane kapa osele) le kalafo e neng e le mabaka. Ntle le moo, liteko tsa tlelase tsa Moithuti li ne li sebelisoa ho bapisa nako ho kopana le molekane le motho eo a sa mo tsebeng kahare ho sehlopha ka seng sa kalafo. Litokiso tsa Bonferroni bakeng sa boemo ba bohlokoa li entsoe bakeng sa teko e 'ngoe le e' ngoe bakeng sa ho fokotsa kotsi ea kotsi ea mofuta-I ka lebaka la papiso e ngata. Ba batona ba khethollotsoe ka ho etsa khetho ea molekane haeba ba qeta nako e fetang makhetlo a mabeli ba kopana le molekane ho feta osele.

Lintlha tse bokelitsoeng bakeng sa ts'ebetso ea locomotor li ile tsa hlakoloa ha palo ea likheo tsa borashe tse infrao bakeng sa phoofolo ka 'ngoe,' me ea lekanyetsoa kahare ho sehlopha ka seng sa kalafo. Liphetho li ile tsa hlahlojoa ho sebelisoa ANOVA e le 'ngoe ka kalafo joalo ka ntho e ikemetseng.

CRF le Urocortin-1 Immunohistochemistry

Li-voes tsa adult prairie li ne li sa anngoe haholo lipakeng tsa lihora tsa 10: 00 le 14: 00 e nang le isoflurane mme e entsoe ka saline e lateloang ke 2% paraformaldehyde ho 10 mM (pH 7.4) phosphate-buffered saline (PBS). Mehopolo e lahliloeng e ile ea romeloa bosiu bo le bong ka tharollo ea 2% paraformaldehyde / PBS mme ea lla hape ka 30% sucrose / PBS. Likarolo tse pharalletseng tsa onalm tse mashome a mararo a metso e mene li ne li siloa ka sekontiri ebe li sebetsoa bakeng sa immunohistochemistry ho latela liprotheine tse tloaelehileng (Ryabinin, Criado, Henriksen, Bloom, le Wilson, 1997; Weitemier, Tsivkovskaia, le Ryabinin, 2005) le liphetoho tsa lithane tse ntle haholo tse entsoeng litekong tsa pejana (Lim et al., 2006). Ka bokhutšoanyane, mosebetsi oa endoxidase oa peroxidase o ile oa emisoa ke ho kenella ka motsotso oa 15 ka motsotso oa 0.3% hydrogen peroxide. Bakeng sa antibody e khethehileng ea Urocortin-1, ho thibela ho entsoe ka ho kenngoa ka lihora tse hlano ka 2% Bovine Serum Albumin, 0.1% heparin, 0.01% Triton X-100 ho PBS. Bakeng sa antibody e khethehileng ea CRF, ho thibela ho entsoe ke ho kenngoa ka lihora tse hlano ka serum ea poli ea 4.5%, 0.3% Triton X-100 ho PBS. Li-antibodies tsa pele tsa mmutla tse hlokometseng Urocortin-1 (Sigma-Aldrich, St. Louis, MO) li sebelisitsoe ho insution 1: 5,000. Li-antibodies tsa mantlha tse lemohang CRF (Peninsula Laboratories, San Carlos, CA) li sebelisitsoe ho insulin 1: 15,000. Li-antibodies tsa anti-rabi tsa biotynylated (Vector Laboratory Inc., Burlingame, CA) li ile tsa sebelisoa ho fumana li-antibodies tsa mantlha. Ho sibolloa ha li-antibodies tsa bobeli ho entsoe ka Vectastain ABC kit (Vector), 'me nts'etsopele ea enzymatic e entsoe ka Metal Enhanced DAB kit (Pierce, Rockford, IL, USA). Boemo ba ho thibela pelehi ka matla bo ile ba hlahlojoa ke ho haelloa ke ts'ireletso ka botlalo libakeng tse sa tsejoeng ho hlahisa CRF kapa Urocortin-1. Futhermore, liteko tsa preborption tsa taolo ea li-antibodies tsena li kile tsa etsoa pele (Bachtell, Weitemier, Galvan-Rosas, Tsivkovskaia, Risinger, Phillips, Grahame, le Ryabinin, 2003).

Tlhahlobo ea setšoantšo sa Qualititative e ile ea etsoa ho sebelisoa sistimi e nang le microscope ea Olympus BX40 le videocamera e phahameng ea li-resolution (Olympus Qcolor3) e kenelletseng khomphutheng ea motho ea Macintosh e sebelisang OS-X. Litšoantšo tse tsoang karolong e le 'ngoe e lumellanang hantle le liphoofolo sebakeng se seng le se seng sa boko li ne li bokelloa ka mokhoa o ts'oanang oa khanya. Kaha ha ho lits'oants'o tsa immunopositive tse ileng tsa bonoa 'meleng ea lisele ho NAcc, palo ea li-neuron tse thibeloang ha e baloe ka bongata.

LIPOTSO

Tekanyetso ea litheko tsa li-receptor tsa CRF ho NAcc

Ho ne ho bontšitsoe pejana hore ho kenella ha icF ea CRF ho nolofalletsa ba ratoang ho ratoa ke baeti (DeVries et al., 2002). Ho ipapisitse le datha tsa rona tsa neuroanatomical tse bonts'ang phapang ea mefuta ea CRF1 le CRF2 ho NAcc, re fane ka maikutlo a hore NAcc ke sebaka sa ts'ebetso bakeng sa ho tataisa CRF ka khetho ea molekane. Boithuto ba pejana bo bontšitse hore tsamaiso ea li-icv e itšetlehileng ka litekanyetso ea CRF e ka nolofatsa khetho ea molekane ho li-voes tsa praemia tsa banna ka mor'a ho etsa likamano tse khuts'oanyane le mosali (DeVries et al., 2002). Ho ipapisitsoe le thuto ena, re qapile tekanyetso ea CRF ea liente tse amanang le site ho NAcc. Litekanyetso tseo re li sebelisitseng, 0.1 pg le 0.01 pg CRF e qhibilihile ho 200 nL isotonic solution (kapa 100 nM le 10 nM, ka ho latellana), li ne li le ka tlase ho litekanyetso tse tlase tsa li-icv tsa 0.1 ng le 1 ng CRF e qhibilihile ho 1 μL (kapa 210 nM le 2.1 μM, ka ho latellana) ((DeVries et al., 2002). Le ha CRF e bonts'itsoe ho tlama bakhethoa ho CRF1, e tlama le CRF2 ka tumellano e kholo (Ki e lekanang le 11 le 25, ka ho latellana) (Primus et al., 1997).

Tlhatlhobo ea data e akaretsang e sebelisitsoeng ka tsela ea 2 ANOVA e senotse phello e kholo ea phoofolo e hlasimollang (F (1,66) = 6.77, p <0.05), empa ha ho litlamorao kapa litšebelisano tse ling tse fumanoeng. Ho tseba hore na ke lihlopha life tseo ka khethollo li sebelisitseng nako ho ikopanya le balekane ho feta batho bao ba sa ba tsebeng, liteko tsa baithuti tsa t li ile tsa etsoa ka litokiso tsa Bonferroni tsa boleng ba p. Laola li-prairie voles tse nang le liente tse kopaneng tsa CSF ea maiketsetso ka har'a pole ea NAcc, kapa 0.1 pg CRF ho caudate-putamen, ha ea ka ea qeta nako e ngata haholo ho ikopanya le molekane ho feta phoofolo e susumetsang motho eo a sa mo tsebeng (p> 0.3, t-test ea Seithuti , Boemo ba Bonferroni bo behiloe ho p <0.01) (Setšoantšo sa 1A). Li-prairie voles tse entetsoeng ka leqhubu le tlase la CRF, 0.01 pg, e tloaetseng ho qeta nako e ngata ho ikopanya le molekane ho feta mojaki (p> 0.08, t-test ea Seithuti, boemo ba Bonferroni bo behiloeng ho p <0.01). Ka lehlakoreng le leng, li-prairie voles tse amohelang liente tse peli tsa leqhubu le phahameng la CRF, 10 pg ho NAcc septal pole, e sebelisitse nako e ngata ho ikopanya le molekane ho feta mojaki (p <0.1, t-test ea Seithuti, boemo ba Bonferroni ho p <0.01) (Setšoantšo sa 1A). Ntle le moo, le ha 6 feela ea liphoofolo tse laoloang tsa 13 e bonts'itse khetho ea molekane, e hlalosoang e le ho qeta nako e ngata hakana ho kopana le molekane ho bapisoa le motho eo a sa mo tsebeng, 12 ea liphoofolo tsa 15 e amohelang 0.1 pg ea CRF e bonts'itse molekane eo a mo ratang (Setšoantšo sa 1B). Liphoofolo tsa 3 tse sa kang tsa bontša khetho ea molekane li na le likhetho tse matla tsa osele, tse ka 'nang tsa baka ho haella ha phello e kholo ea kalafo kapa phello ea tšebelisano ho 2-way ANOVA. Ka hona, le ha infusions ea CRF ho NAcc e ne e eketsa nako ea ho hokahana le molekane oa motho eo a sa mo tsebeng, ha ea ka ea fella ka keketseho e akaretsang ea nako ea ho ikopanya le molekane.

Setšoantšo sa 1 

Li-injection tse nyane tsa CRF ho NAcc li thusa ho ratoa ke molekane ho li-voes tsa banna tsa praemia. (A) Laola liphoofolo tse fumaneng CSF ea maiketsetso ho NAcc, kapa 0.1 pg CRF ka har'a caudate-putamen (CP), ha e rate molekane ea fetang ...

Ka lebaka la mefuta e makatsang ea mefuta ea CRF1 le CRF2 Matšoenyeho a NAcc, re nahanne hore ketso ea CRF ka hare ho NAcc e tla thusa feela ho theha likhetho tsa balekane libakeng tsa thota, eseng libakeng tsa meoa tse sa nyalanang. Ka 'nete, mehloa e kenngoang le CSF, kapa tekanyetso e phahameng ea 0.1 pg CRF, ha ea ka ea qeta nako e ngata haholo ho ikopanya le molekane ho feta mojaki (p> 0.5, t-test ea Seithuti) (Setšoantšo sa 2).

Setšoantšo sa 2 

Li-injection tse nyane tsa CRF ho NAcc ha li khone ho tsamaisa khetho ea molekane ho li-voles tse se nang bo-monogamous male meave. Li-voles tsa meadow tsa batho ba baholo tse kenngoeng ka CSF ea maiketsetso, kapa 0.1 pg ea CRF ho NAcc, ha ea ka ea qeta nako e ngata e kopana le molekane ho feta ...

Ho ipapisitsoe le mefuta ea mefuta ea CRF1 le CRF2 phetiso ho NAcc, re qopile hore CRF ka bobeli1 le CRF2 e ka fetola boits'oaro ba khetho ea molekane, mohlomong ka mahlakore a fapaneng. Tlhatlhobo ea data e akaretsang e sebelisitsoeng ka tsela ea 2-ANOVA e senotse phello e kholo ea phoofolo e hlasimollang (F (1,94) = 7.52, p <0.05), empa ha ho litlamorao kapa litšebelisano tse ling tse fumanoeng. Li-prairie voles tse kentsoeng ka jareteng ea 0.1 pg ea CRF, hammoho le 10 pg e khethang CRF2 antagonist anti-sauvagine-30, ha a ka a qeta nako e ngata le molekane kapa motho eo a sa mo tsebeng (p> 0.3, t-test ea Seithuti, boemo ba Bonferroni bo behiloeng ho p <0.016) (Setšoantšo sa 3A). Ho khahlisang ke hore li-prairie voles li kenella ka kotara ea 0.1 pg ea CRF, hammoho le 10 pg e khethang CRF1 mohanyetsi CP-154,526-1, hape e bonts'itse thibelo ea khetho ea molekane (p> 0.5, t-teko ea Seithuti, boemo ba Bonferroni bo behiloeng ho p <0.016) (Setšoantšo sa 3A). Laola li-prairie voles tse entetsoeng ka 0.1 pg CRF ho NAcc li ile tsa lekoa ka nako e le ngoe, 'me tsa fumanoa li pheta liphetho tsa mantlha tsa ho nolofatsa khetho ea molekane (p <0.01, t-test ea Seithuti, boemo ba Bonferroni bo behiloeng ho p <0.016) (Setšoantšo sa 3A). Ntle le moo, ha 8 kantle ho maqhubu a 10 CRF a hloahloa a bontšitse khetho ea molekane, ke 11 feela ea liphoofolo tsa 25 tse amohelang CRF1 antagonist, le 6 ho tsoa ho liphoofolo tsa 15 tse amohelang CRF2 antagonist, o bontšitse thato ea molekane (Setšoantšo sa 3B). Liphetho tsa rona li bontša hore ts'ebetso ea CRF ka bobeli1 le CRF2 li-receptors tsa NAcc lia hlokahala bakeng sa ho thusa ho khothaletsoa ke CRF bakeng sa khetho ea molekane ho li-voes tsa prairie.

Setšoantšo sa 3 

Ka bobeli CRF1 le CRF2 li-receptor ho NAcc lia hlokahala bakeng sa tlhahiso ea khetho ea balekane ba CRF e nolofalitsoeng libakeng tsa thota. (A) Liphoofolo tse entetsoeng ka 0.1 pg CRF ho NAcc li qetile nako e ngata li ikopanya le molekane ho feta mojaki (p <0.01, Student's ...

Ketsahalo ea locomotor e ne e sa fapana haholo lipakeng tsa lihlopha tsa kalafo (F (1,80) = 1.37, p> 0.05, ANOVA ea tsela e le 'ngoe), leha ts'ebetso ea locomotor e ne e le tlase liphoofolong tse amohelang CRF ho NAcc. Liphetho li bontšoa ho Lethathamo 1. Karolo ea nalane ea nalane ea boemeli e bonts'a sebaka sa cannulation sa NAcc se bonts'itsoe Setšoantšo sa 4.

Setšoantšo sa 4 

Netefatso ea nalane ea ho bea cannula. (a) Receptor autoradiogram ka lehlakoreng le letšehali e bontša sebaka sa CRF2 ka prairie vole NAcc. (b) Photographicenta e emelang karolo ea bongoana e nang le litšila e bonts'ang ho ts'oaroa ha cannula ho emisa kahare ...
Lethathamo 1 

Ketsahalo ea locomotor e emeloang ke palo e felletseng ea likhahla tsa infrared borokho kapa liphaphatha tse kenngoang kahara goroko, tse ka hare ho sehlopha ka seng sa kalafo. Ha ho na phapang e kholo lipakeng tsa lihlopha tsa kalafo (F = 1.37, p> 0.05, tsela e le 'ngoe ea ANOVA).

Ts'ireletso ea CRF- le Ucn-1 ho NAcc

Ho bonts'a lifoto tsa li-photomicrographs tseo ho tsona ho nang le CRF receptor ligands tse teng ho NAcc, re entse CRF- le Urocortin-1 (Ucn-1) immunoreacuction ho li-voes tsa batho ba baholo ba prairie. Likarolo tsa boko tse emelang ts'ebetso bakeng sa immunocytochemistry ea CRF li bonts'oa Setšoantšo sa 5. Likhoele tse sebetsanang le CRF tse sa sebetseng li ile tsa bonoa ho NAcc ka bobeli ba bong bo se nang liphapang tse totobetseng tsa ho ajoa kapa letsoalo la likhoele (Setšoantšo sa 5b). Likhoele tsa ucn-1 li ne li sa bonoe ho NAcc ka li-voes tsa basali kapa tsa basali tsa basali (Setšoantšo sa 5c). Ka hona, ho ka etsahala hore CRF ke e 'ngoe ea li-ligands tsa endo native tse ka kopanyang CRF1 le CRF2 receptors in the vole NAcc ho tsamaisa khetho ea molekane. Ho joalo, CRF e bontšitsoe hore e tlama CRF ka bobeli1 le CRF2, e nang le tumellano e phahameng ea makhetlo a mabeli ho isa ho a leshome bakeng sa CRF1 (Primus et al., 1997). Leha ho le joalo, re ke ke ra hlakola monyetla oa hore li-ligands tse ling tsa morao-rao joalo ka Urocortin-2 kapa Urocortin-3 le tsona li ka kenya letsoho taolong ea neural ea sebopeho sa maqhama a mabeli.

Setšoantšo sa 5 

Ts'ireletso ea CRF le Ucn-1 libakeng tsa prairie voles. (a) Rat atlas schematic e bonts'a sebaka sa ntlafatso ea 10x ea NAcc (bona sethala) (Paxinos le Watson, 1998). (b) Karolo ea viri ea Prairie e bonts'a likhoele tsa CRF-immunoreactive ho NAcc (bona metsu). (c) Prairie ...

TŠOHLOA

Lithutong tse fetileng, re bonts'itse phapang ea mefuta ea CRF1- le CRF2 polelo e amanang le mokhatlo o hlophisitsoeng oa sechaba ho mefuta e mene e metle. Li-praefe tsa monogamous le li-voine tsa phaene li ne li le maemong a holimo ho CRF2 ho NAcc, le maemo a tlase a CRF1 ho NAcc, bapisoa le mefuta e se nang monogamous meadow le montane vole (Lim et al., 2005). Re ipapisitse le litaba tsena, re fumaneng kholo ea hore ketso ea CRF ka hara NAcc e ne e le bohlokoa boits'oarong ba boitšoaro bo botle ba sechaba sechabeng sa libaka tsa thorisoe. Thutong e teng hona joale, re bonts'a lekhetlo la pele hore li-ente tsa CRF ka kotloloho ho NAcc li sebetse khetho ea molekane ho li-voes tsa banna tsa praemia. Tlhahlobo ea ANOVA ea mekhoa e 'meli e hlokometse phello ea mantlha ea phoofolo ea tšusumetso, ke hore, nako e eketsehileng e sebelisitsoe ho hokahana le molekane ho feta motho ea sa mo tsebeng, empa ha ho na phello e ka sehloohong ea kalafo kapa tšebelisano e fumanoeng. Likhetho tse matla tsa osele ho liphoofolo tsa 3 tsa sehlopha sa 0.1 pg CRF NAcc li fokolitse phapang, ho thibela ho bona phello ea tšebelisano. Leha ho le joalo, papiso e arohaneng ea nako e sebelisoang le litemana tsa molekane e mong e senotse likhetho tsa bohlokoa bakeng sa molekane ho sehlopha sa 0.1 pg CRF NAcc. Phello ena e ile ea phetoa thutong ea bohanyetsi, e paka hore o bile le tšusumetso e matla. Phetoho ena ea likhethong tsa balekane e ne e sa amanngoe le keketseho e kholo ea lipalo nakong e sebelisitsoeng le molekane kapa ho fokotseha ha nako e sebelisitsoeng le motho eo u sa mo tsebeng, empa ho bile joalo ka lebaka la khetho e eketsehang ka kakaretso bakeng sa molekane ea amanang le mojaki. Ka lehlakoreng le leng, CRF ha e na tšusumetso ho khetho ea molekane ho li-voles tse se nang monogamous meadow. Ntle le moo, re bonts'a hore ts'ebetso ena ea ho thusa e fetoloa ke ketso ea CRF ho CRF ka bobeli1 le CRF2 li-receptors. Qetellong, re bonts'a bopaki ba Photomicrograph ba hore likhoele tsa CRF tse sa sebetseng li fumaneha kahara lebitso la Vole NAcc, li bonts'a hore CRF e ka ba e 'ngoe ea li-ligands tse emelang CRF.1 le CRF2 li-receptors ho NAcc nakong ea kaho ea khetho ea molekane. Ha e nkuoa hammoho, lintlha tsena li bonts'a karolo e ncha ea litsamaiso tsa CRF li sebetsang ka hara NAcc ka boits'oaro ba sechaba.

Lintlha tsa rona tse bonts'ang hore CRF ho NAcc e nolofalletsa boikhethelo ba molekane e ts'ehetsa maikutlo a rona a mantlha a hore lits'ebetso tsa CRF tse amehang li kenelletse ho kopanngoeng ha maqhama a mabeli ho li-voes tsa prairie. Re bile le hypothes e eketsehileng ea CRF eo2 li-receptor, ka ho khetheha, li ne li nyatsuoa ka ho teba ha ho fanoa ka bongata ba CRF2 Li-receptors mefuteng e 'meli ea monogamous vole empa eseng mefuta e' meli e se nang monogamous vole (Lim et al., 2005). Liphetho tse tsoang tlhahlobisong ea lipalesa tsa mehend li tšehetsa tšibollo ena, hobane ts'oaetso ea CRF ha e na tšusumetso ho khetho ea molekane ho mofuta o se nang CRF hantle2 li-receptors ho NAcc. Ntle le moo, re fumane hore tšebelisano-mmoho ea CRF2-selective antagonist e thibela likhetho tsa molekane ho li-voiri tsa prairie. Lintlha tsena li senola karolo e ka bang bohlokoa ho CRF2 li-receptors ka li-bond tsa maqhama a mabeli.

Le ha ho le joalo, re fumane hape hore tšebelisano-mmoho ea CRF1-hanyetsi oa mohanyetsi ea thibetsoeng ho khetha khetho ea molekane ho li-voiri tsa prairie. Sephetho sena se ile sa makatsa le ho feta, ka lebaka la CRF eo1 li-receptors li hlahisoa ho NAcc ka mefuta e seng ea monogamous le ea monogamous. Ha li nkuoa hammoho, li hlakisa bohlokoa ba ka bobeli receptor subtypes bakeng sa polelo ea khetho ea molekane, mme o supa monyetla oa hore ho khetholoha ha "receptor" ke taba e rarahaneng e ka thusang molemong oa ho phenyekolla ho eketsehileng. Ho a khonahala hore ho ka ba le tšubuhlellano lipakeng tsa li-subtypes tse peli tsa NAcc nakong ea boitlamo ba maqhama, mme ho ka ba ho khahlisang ho tsoela pele ho hlahloba liketsahalo tsa cellular tsa CRF1- le CRF2-Ko fokotsa methapo ea kutlo kapa ho bona hore na CRF1 le CRF2 li-receptor li ka ba tsa sebetsa li-neuron tse tšoanang. Hape hoa etsahala hore li-agents tse ling tse kang proteni e tlamang ea CRF, e ka sebetsang e le sebaka sa polokelo bakeng sa CRF ea mahae, e ka ameha (Jahn, Eckart, Brauns, Tezval, le Spiess, 2002).

Tekanyetso ea CRF e sebetsang ea li-ente tse ikhethang tsa setsi ho NAcc tse thusitseng khetho ea molekane ha ea fella ka phello e matla ea kalafo ea lithethefatsi mosebetsing oa locomotor, o hlalosoang e le boitšoaro bo joalo ka letsoalo. DeVries le Carter (2002) o fumane litekanyetso tse sebetsang tsa CRF icv bakeng sa khetho ea molekane ho 0.1 le 1.0 ng (210 nM le 2.1 respectiveM, ka tatellano), mme ha a ka a bona phapang mesebetsing ea locomotor lipakeng tsa lihlopha tsa kalafo (DeVries et al., 2002). Methapo ea bona e ne e le kholo ho isa ho 1000, 'me e ne e le habeli habeli ho feta makhetlo a mabeli ho feta tekanyetso eo re e sebelisitseng site-directly ho NAcc (10,000 nM le 10 nM). Thutong ea rona, leha re sa ka ra bona phapang e kholo liketsahalong tsa kalafo, empa ho ne ho e-na le mokhoa o fokolang oa ho tšela linepe tse 'maloa liphoofolong tse fumanang CRF e le' ngoe ho NAcc. Leha ho ka etsahala hore CRF e ka hlahisa litholoana tse poteletseng mabapi le boits'oaro bo kang ho tšoenyeha, ka hona e ka ama sebopeho sa khetho ea balekane, re lumela hore mabaka a hlakileng ke a fokotsehileng a ho palama sehlopheng sa CRF feela ke phello ea keketseho ea eketseha khetho ea molekane, ke hore, nako e sebelisitsoeng kahare ho kharebe ea molekane oa hau. Sena se ts'ehetsa maikutlo a hore CRF e kanna ea ba le pale e 'ngoe, e arohaneng ea ho laola boitšoaro ba sechaba, mohlomong e sa ikemisetseng litlamorao tsa HPA mabapi le matšoenyeho.

Re boetse re bonts'a bopaki ba Photomicrograph ba CRF-immunoreactivity ho NAcc sebakeng se ts'oanang le sa CRF2 li-receptors in monogamous prairie voles. Sena se fana ka maikutlo a hore CRF e ka ba e 'ngoe ea li-ligands tsa mofuta oa khale tse sebetsang ho CRF1 le CRF2 li-receptors ho NAcc. Le ha CRF e bonts'itsoe ho tlama bakhethoa ho CRF1, e tlama le CRF2 ka tumellano e kholo (Primus et al., 1997). Ditlhare tsa ucn-1-immunoreactive ha lia ka tsa bonoa ho NAcc, empa li ile tsa bonoa libakeng tse ling tsa boko tse joalo ka konopo ea Edinger-Westphal (Lim et al., 2006). Ha rea ​​khona ho etsa limmapa tsa Urocortin-2 kapa likere tsa Urocortin-3 bokong ba vole ka lebaka la ho haelloa ke ts'oaetso e khethehileng; leha ho le joalo, e tla ba ho khahlisang ho tseba hore na li-ligands tsena tse ka bang teng, le tsona li tlama CRF2 li-receptors tse nang le kamano e phahameng, le tsona li teng ho NAcc hammoho le CRF2 li-receptors.

Bokapele ba sefahleho, haholo-holo NAcc, bo 'nile ba tsebahatsoa khafetsa e le sebaka sa bohlokoa sa boko bakeng sa ho theha maqhama a kopantsoeng le li-voes tsa prairie. Ka lebaka la karolo ea NAcc tseleng ea moputso oa mesolimbic dopamine, ho nahanoa hore moputso oa tlhaho le mekhoa ea ho matlafatsa tlasa sebopeho sa maqhama a mabotho, hoo molekane a kopantsoeng le khetho e khethiloeng (Aragona et al., 2003a; Lim, Murphy, le Monyane, 2004a). Re kile ra bonts'a pele ka litlatsetso tsa meriana le liphatsa tsa lefutso hore li-receptor tsa "ventral" tsa "vasopressin" V1a lia hlokahala bakeng sa ho thehwa ha setlamo sa monna le ha se hlahisoa ka ho fetelletseng ka mefuta e seng ea monogamous vole (Lim et al., 2004b; Lim le lenyane, 2004). Li-receptor tsa Oxetocin ho NAcc li hlokahala bakeng sa khetho ea molekane ho li-voes tsa basali tsa prairie (Bacha, Lim, Gingrich, le Insel, 2001). Accumbal dopamine D1 le li-receptor tsa D2 le tsona li bontšitsoe ho fetolela mokhoa oa ho khetha le ho hlokomela molekane ho banna le basali, mme ha e le hantle dopamine e buisana le oxytocin nakong ea ts'ebetso ena ea boits'oaro (Aragona et al., 2003a; Aragona et al., 2006; Aragona, Liu, Yu, Damron, Perlman, le Wang, 2003b; Liu le Wang, 2003). Ka hona, ts'ebetso ea li-receptor ea CRF e kanna ea kenya letsoho potolohong e kholo e fetohang ho NAcc ho hlahisa boitšoaro bona bo rarahaneng ba sechaba. Tumellanong le khopolo ena, ho na le bopaki ba hore li-receptor tsa CRF ho NAcc li ka fetolela tokiso ea dopamine ho striatum (Lu, Liu, Huang, le Zhang, 2003), le bopaki ba pele ba morao-rao bo bonts'ang hore ts'ebetso ea li-receptor tsa Nacc CRF e ka susumetsa khatello ea methapo bakeng sa matlafatso ea tlhaho (Berridge, Pecine le Schulkin, 2004). Phuputso e 'ngoe e bontšitse CRF2 li-receptors tikolohong ea ventral tegmental, e romellang monahano oa dopaminergic ho NAcc, e ka susumetsa tšebeliso ea nako e telele, sehokelo sa mmele sa thuto ea boits'oaro le mokhatlo oa moputso (Ungless, Singh, Crowder, Yaka, Ron, le Bonci, 2003). Hobane khetho ea molekane e entsoe e le mofuta oa thuto ea tlhaho ea moputso, li-receptors tsa CRF ho NAcc li ka bapala karolo e ts'oanang ea ho theha bokhoni ba synaptic nakong ea sebopeho sa maqhama a kopanetsoeng lipapatsong tsa tumellano.

Ho theha maqhama a kopantsoeng ka tlhaho ke ts'ebetso e rarahaneng ea kelello e hlokang ho kopanngoa ha linaha tse ngata tsa kantle le tse ka hare. Ho theha bonto ea maqhama ho hlaha ho tsoa lits'ebetsong tsa mekhoa e mengata ea boits'oaro ho kenyelletsa tlhokomeliso ea sechaba, mokhoa le tšusumetso ea sechaba, mme li kenyelletsa ho ithuta le ho hopola. Oxetocin le vasopressin li ameha ka botlalo ho ts'ebetsong ea neural ea mehopolo ea sechaba le ho theha mohopolo oa sechaba (Bielsky, Hu, Szegda, Westphal, le Young, 2004; Ferguson, Monyane, Hearn, Matzuk, Insel, le Winslow, 2000). Dopamine e kanna ea ameha maemong a phahameng a susumetsang a tšebelisano-mmoho le molekane oa motho, le matlafatso a hlokahalang ho theha khetho ea molekane. CRF e ka fana ka mochine oo ka oona khatello ea kelello e ka hare e fetolang khetho ea molekane. Ho supa matšoao a CRF ho ka thusa liphetoho tsa nako e telele ho polasetiki ea neural nakong ea kaho ea maqhama a mabeli. Tsamaiso e 'ngoe le e' ngoe ea methapo ea kutlo e bapala karolo e fapaneng empa ea bohlokoa ho boits'oaro bo rarahaneng ba ho tlamahana, le ho thijoa ha sistimi e le 'ngoe ho ka sitisa sebopeho sa maqhama a mabeli.

Karolo ea CRF taolong ea boitšoaro ba sechaba e ithutile hanyane, leha lithuto tse ngata tse amanang le CRF li le maemong a khatello le boits'oaro. Ho na le bopaki bo matla ba hore CRF2 mesebetsi ea ts'ebetso ea li-receptor ho fokotsa ho tšoenyeha le boits'oaro-bo joalo ka boits'oaro ho litoeba (Bale, Contarino, Smith, Chan, Khauta, Sawchenko, Koob, Vale, le Lee, 2000; Bale le Vale, 2003). Boitšoaro ba sechaba, khatello ea maikutlo le matšoenyeho li tsamaisana haholo, haholo-holo boits'oarong bo kenyelletsang ts'ehetso ea sechaba kapa ho sebetsana le ho khetholoha sechabeng. Li-voiri tsa Prairie tse entseng marang-rang a mabeli li bonts'a maemo a phahameng a corticosterone nakong ea karohano ea sechaba le molekane, mme ho kopana hape le molekane ho khutlisetsa maemo ana morao ho motheo (Carter, DeVries, Taymans, Roberts, Williams le Getz, 1997). Mananeo a tlotlo ea banna a ntseng a sesa ka mokhoa o qobelloang, khatello ea kelello, a bonts'a ts'ebetso ea ho theha maqhama a mabeli ka mor'a kopano e khuts'oane le molekane (DeVries et al., 1996). Kamora nako, banna ba babeli ba nang le bonngoe ba arotsoeng ke balekane ba bona ba bontša maano a ho sebetsana le bona ka teko e qobelloang ho feta balekane ba bona ba arohaneng, 'me liphetoho tse joalo tsa boits'oaro li tsamaea le keketseho ea CRF mRNA ho NAcc (Bosch, Nair, Neumann, le Bacha, 2005).

Lintlha tsena li fana ka maikutlo a hore boitšoaro ba sechaba le khatello ea maikutlo bo na le kamano ea boiphetetso, ho feta moo, limolek'hule tse ts'oanang tse kentsoeng khatello ea maikutlo le matšoenyeho le tsona li bapala karolo ea bohlokoa boits'oarong ba sechaba. Ebile, ho na le bopaki ba hore "social" neuropeptides vasopressin le oxytocin e ka fetolela khatello ea maikutlo le boitšoaro ba ho tšoenyeha (Bielsky et al., 2004; Landgraf, Gerstberger, Montkowski, Probst, Wotjak, Holsboer, le Engelmann, 1995; Liebsch, Wotjak, Landgraf, le Engelmann, 1996; Mantella, Vollmer, Li, le Amico, 2003; Ring, Malberg, Potestio, Ping, Boikess, Luo, Schechter, Rizzo, Rahman, le Rosenzweig-Lipson, 2006; Windle, Shanks, Lightman, le Ingram, 1997). Kahoo, limolek'hule tse ts'oanang tse fetolang boemo ba khatello ea kelello bo ka kenya letsoho taolong ea boits'oaro bo kopanetsoeng joalo ka sebopeho sa maqhama a mabeli, le hore limolek'hule le lipotoloho tse hlahisitsoeng molemong oa boitšoaro bo le bong li ka laola tse ling ka matla.

lumela hore baa fokola

Univesithing ea Emory, re rata ho leboha Dr. Michael J. Owens ka mosa ka ho re fa setsi sa CP-154,526. Hape re ka rata ho leboha Lorra Miller le Meera Modi ka thuso ea bona mabapi le liteko tsa mehend vole. Qetellong re rata ho leboha Drs. A. Courtney DeVries Univesithing ea Ohio State le C. Sue Carter Univesithing ea Illinois, Chicago ka mosebetsi oa bona oa bo-pula-maliboho CRF libakeng tsa tumello le mangolo a lengolo la Dr. DeVries mabapi le liteko tsa meriana.

Ts'ehetso ea lithuso: Patlisiso ena e tšehelitsoe ke lithuso tsa NIH MH65050 ho MML, AA13738 ho AER, MH58616 ho ZXW, MH64692 ho LJY, le NSF STC IBN-9876754 le Jerkes Center Grant RR00165.

Mongolo o botlaaseng ba leqephe

Boitlhotlhollo ba Mohoeletsi: Ena ke faele ea PDF ea mongolo o ngotsoeng ka letsoho o sa amoheloang o amoheletsoeng bakeng sa ho hatisoa. Joaloka tšebeletso ho bareki ba rona re fana ka phetolelo ena ea pele ea mongolo o ngotsoeng ka letsoho. Mongolo o ngotsoeng ka letsoho o tla ba le ho kopitsa, ho kenya lihlopha le ho hlahloba bopaki bo hlahang pele o hatisoa ka mokhoa oa oona oa ho qetela. Ka kopo hlokomela hore nakong ea mekhoa ea tlhahiso ea lihlahisoa e ka fumanoa e ka amang litaba, le litsebiso tsohle tsa molao tse sebetsang koranteng e amanang le eona.

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