Karolo ea Li-Peptide tse amanang le CRF le li-CRF lefifing la ho lemala (2014)

Brain Res. Sengoloa se ngotsoeng; e fumaneha ho PMC Feb 16, 2011.

Brain Res. La 16 Hlakubele 2010; 1314C: 3.

E phatlalalitsoe marang-rang Nov 11, 2009. Doi:  10.1016 / j.brainres.2009.11.008

PMCID: PMC2819562

NIHMSID: NIHMS164224

inahaneloang

Bokhoba ba lithethefatsi ke bokuli bo khutlang hape bo tšoaelitsoeng ke ho qobelloa ho batla le ho sebelisa lithethefatsi, nts'etsopele ea boikemelo, le ponahatso ea boemo bo bobe ba maikutlo ha setlhare se tlosoa. Ts'ebetso ea lits'ebetso tsa khatello ea kelello e anngoe e le karolo ea bohlokoa ea maikutlo a mabe a hlahisoang ke ts'ehetso e khannang ho batla lithethefatsi ka mekhoa e mebe e matlafatsang, e hlalosoang e le "lehlakore le lefifi" la bokhoba. Tlhahlobo ea tlhahlobo ea hona joale e mabapi le karolo ea corticotropin-releasing factor (CRF) le li-peptide tse amanang le CRF lehlakoreng le lefifi la ho lemalla. CRF ke mokena-lipakeng oa bohlokoa oa karabo ea li-hormonal, Autonomic le boitšoaro mabapi le khatello ea maikutlo. Ts'ebetso e behiloe boikarabelong ba CRF lits'ebetsong tsa extrahypothalamic ho amygdala e atolositsoeng, ho kenyelletsa le khubu ea bohareng ba amygdala, moalo o ka tlase oa "stria terminalis", le sebaka sa phetoho khetla ea li-nucleus accumbens, lehlakoreng le lefifi la ho lemalla. Urocortin / CRF2 lits'ebetso ha li hlahlojoe hanyane, empa liphetho li bontša karolo ea tsona ho neuroadaptation e amanang le tšebeliso e mpe ea lithethefatsi, ka linako tse ling e le khahlano le litlamorao tse hlahisoang ke CRF1 receptor. Bopaki bo susumetsang bo pheha khang ea hore tsamaiso ea khatello ea maikutlo ea CRF, ho kenyelletsa ts'ebetso ea eona ea hypothalamic-pituitary-adrenal axis, e bapala karolo ea bohlokoa ho kenyelletsa phetoho ho itšetleha le ho boloka ts'ebeliso ha e se e qaliloe. Ho utloisisa karolo ea lits'ebetso tsa CRF bokhobeng ha ho fane ka leseli ho neurobiology ea lehlakore le lefifi la bokhoba, empa hape ho fana ka sepheo sa lipalesa sa ho khetholla kotsi ea ho lemalla le ts'ebetso ea ho lemalla.

Moralo oa Khopolo: Bokhoba, khatello ea maikutlo le lehlakore le lefifi

Bokhoba ba lithethefatsi ke bokuli bo bocha bo sa foleng bo khethiloeng ke (i) ho qobelloa ho batla le ho sebelisa lithethefatsi, (iitahlehelo ea taolo ea phokotso ea tšebeliso ea lijo, le (iii) ho hlaha ha boemo bo bobe ba maikutlo (mohlala, dysphoria, ho tšoenyeha, ho se ts'oanelehe) ho bonts'ang lefu le khothalletsoang la ho tlohela ha ts'ebeliso ea ts'ebeliso ea lithethefatsi (e hlalositsoeng mona e le ts'episo) (Koob le Le Moal, 1997,Koob le Le Moal, 2008). Bokhoba ba tahi bo hlalositsoe e le bokuli bo fetohang bo nang le mekhahlelo e meraro—preoccupation / Ho lebella, binge / botaoa, 'me drainare / Ho ama hampe- eo ho itšunya-tšunya ho atisang ho hlaha hangata mathateng a qalang le ho qobelloa ho busa maemong a bolaeang. Ha motho a tloha ho tsubellellang ho ea bohlonong, phetoho e ba ho tloha ho matlafatsong e ntle ea ho khanna boitšoaro bo susumetsoang ho ea ho matlafatso e mpe ea ho khanna boitšoaro bo susumetsoang (Koob, 2004). Matlafatso ea tlhekefetso e ka hlalosoa e le ts'ebetso eo ho eona ho tlosoa hoa tšusumetso e nyarosang (mohlala, boemo bo bobe ba maikutlo ba ho tlohela lithethefatsi) ho eketsang monyetla oa karabelo (mohlala, tšebeliso ea lithethefatsi tse khothalletsoang). Mehato ena e meraro e nkuoe e le ho hokahana, e ba matla le ho feta, 'me qetellong e lebise ho boemo ba bophelo bo tsejoang ka hore ke bokhoba (Koob le Le Moal, 1997).

Tlhahlobo ea hajoale e shebisisa karolo ea corticotropin-releasing factor (CRF) ho se hlalositsoeng e le "lehlakore le lefifi" la potoloho ea bokhoba ba tahi (ke hore, drainare / Ho ama hampe Bohato ba potoloho ea lithethefatsi le likarolo tsa preoccupation / Boemo ba ho lebella). Lithethefatsi tse fapaneng li hlahisa mekhoa e fapaneng ea bokhoba ka ho hatisa likarolo tse fapaneng tsa potoloho ea bokhoba ba lithethefatsi, empa lithethefatsi tsohle tse lemalloang li bonts'a lintho tse tloaelehileng tse amanang le lehlakore le lefifi la bokhoba. Lintho tse tloaelehileng li kenyelletsa malaise e tebileng, dysphoria, le matšoenyeho nakong ea ho ikhula, sesosa sa ho itlosa bolutu se khethiloeng ke boemo bo tlase ba ho tšoenyeha / boemo ba dysphoric le ho ba le ts'oaetso e phahameng ea ho khutlela morao ha o le tlas'a khatello ea maikutlo e mpe. CRF e reretsoe ho bapala karolo ea bohlokoa litlamong tsa khatello ea maikutlo kapa khatello ea maikutlo ea ho khaotsa ho ts'oenyeha, ho tšoenyeha / khatello ea maikutlo joalo ka lithibelo tse iphetotseng tsa ts'ebetso, 'me ho khutlela mokhoeng oa ho sebelisa lithethefatsi nakong ea ts'ebeliso e mpe e bakiloeng ke khatello ea maikutlo.

Karolo ea CRF karolong e lefifi ea karolo ea potoloho ea bokhoba ba litekanyetso e reriloe ho mohanyetsi mohopolo oa mohanyetsi, o neng o atolositsoe libakeng tsa neurobiology tsa ts'ebeliso ea lithethefatsi ho tsoa ponong ea neurocircuitry. Ho entsoe mokhoa oa ho hlonepha mekhoa ea ts'ebetso ea boko ho hlalosetsa liphetoho tse phehellang tse khothatsang tse amanang le ts'ebeliso ea ts'ebeliso ea bokhoba ba tahi (Koob le Le Moal 2001,Koob le Le Moal 2008). Ka mofuta ona, bokhoba ba lithethefatsi bo hlalosoa e le mokhoa oa ho eketseha ha methapo ea boko / mekhoa e meng e tlisoang ke boemo bo seng botle ba maikutlo bo kentse letsoho ts'ebelisong e mpe ea lithethefatsi. Lits'ebetso tse amanang le litheko tsa ts'ebetso eo e leng karolo ea lithibelo tse tloaelehileng tsa homeostatic tsa mosebetsi oa moputso li sitoa ho khutla kahare ho sebaka se tloaelehileng sa homeostatic. Lits'ebetso tsena tse hanyetsanang li fetisoa ka hore li ka fetoloa ka mekhoa e 'meli: neuroadaptations ea kahare (liphetoho litseleng tsa moputso) le lipakeng tsa tsamaiso ea khatello ea methapo (ho hira mekhoa ea khatello ea kelello) (Koob le Bloom, 1988; Koob le Le Moal, 1997, 2008). Ho bokelloa ha methapo ea khatello ea kelello, eo CRF mohlomong e le eona karolo e hlahelletseng, e fana ka karolo e le 'ngoe ea ts'ebetso e mpe e khothalletsang ts'usumetso ea bokhoba ba tahi (Koob, 2008).

Corticotropin-Lokolla Factor

CRF ke polypeptide ea 41-amino acid e nang le karolo e kholo ho hokahanya karabelo ea khatello ea 'mele ka ho tsamaisana le li-hormone, likarabo le boitšoaro mabapi le khatello ea maikutlo. CRF (eo hape e bitsoang hormone ea corticotropin-e lokollang, leha lebitso la International Union of Pharmacology ke CRF) e ile ea tsebahala ka mekhoa ea khale ea tatellano ea peptide (Vale le al., 1981). Kamora nako, mefuta ea liphatlalatso tse tharo tsa CRF-urocortins 1, 2, le 3 (Ucn 1, Ucn 2, Ucn 3), e nang le Ucn 2 le Ucn3 le tsona li bitsoa peptide e amanang le khatello ea maikutlo le khatello ea khatello ea methapo - ka ho latellana — li ​​ne li bontšoa ka molemolo oa mehleng ena - mekhoa ea tlhaho. Li-agonists tsa CRF li ka fumaneha litlhapi (urotensin), lihoho (sauvagine), le liphoofolo tse anyesang (urocortin). Urocortin e ile ea rehoa lebitso la eona ka ho latellana ha eona le carp urotensin I (63%, "uro") le mammotlane CRF (45%, "cort"). Li-receptor tse peli tsa G-protein-coupled (CRF)1, CRF2) hore li-peptide tsa CRF / Ucn li tlama li kenya tšebetsong le li-affinities tse fapaneng li ile tsa khetholloa ka mokhoa o ts'oanang (Bale le Vale, 2004; Fekete le Zorrilla, 2007). Phuputso ea meriana le ea transgenic e bonts'a CRF ea boko le pituitary1 li-receptors li buisana le litlamorao tse ngata tse tšoanang le khatello ea tšebetso ea CRF (Heinrichs le Koob, 2004). Litlhahlobo tse fetileng tsa rona le ba bang li ithutile ka biology ea CRF system (Bale le Vale, 2004; Heinrichs le Koob, 2004).

CRF e na le ts'oaetso e pharalletseng bokong bohle empa haholo-holo lisele tsa mmele tsa lisele tse maemong a phahameng a hypothalamus, forebrain ea basal (haholo-holo amygdala e atolositsoeng), le tsamaiso ea kelello (Swanson et al., 1983). Tsamaiso e bohareng ea CRF e etsisa karabelo ea boitšoaro ho ts'ebetsong le khatello ea methapo, le tsamaiso ea bahanyetsi ba CRF receptor ka kakaretso e na le litlamorao tse khahlanong le khatello ea maikutlo (Heinrichs et al., 1994; Menzaghi et al., 1994; Spina et al., 2000; bakeng sa litlhahlobo, bona Dunn le Berridge, 1990; Koob et al., 1994, 2001; Sarnyai et al., 2001) (Lethathamo 1). Ho li-receptor tse peli tse kholo tsa CRF tse fumanoeng, CRF1 ts'ebetso ea receptor e amahanngoa le karabelo e eketsehileng ea karabelo (Koob le Heinrichs, 1999), le CRF2 ts'ebetso ea receptor e amahanngoa le ho fokotseha ha ho fepa le ho fokotsa ho arabela ha khatello ea maikutlo (Spina et al., 1996; Pelleymounter et al., 2000; empa bona Ho et al., 2001; Takahashi et al., 2001; Fekete le Zorrilla, 2007). Likokoana-hloko tse ngata tse kenang ka har'a mali le bokhopo bo ikhethileng, bo khethang CRF1 bahanyetsi ba li-receptor ba se ba nts'etsitsoe, empa ha ho CRF e nyane ea molek'hule2 lihanyetsi li se li hlahisitsoe (Zorrilla le Koob, 2007). Ka lebaka leo, mosebetsi o mongata o entsoe ho hlakisa karolo ea CRF1 li-receptors tsa ho lemalla le ts'ebetso e fokolang ho CRF2 receptor (bona ka tlase).

Lethathamo 1

Litlamorao tsa boitšoaro bo tsamaeang le li-peptide tsa CRF tse tsamaisoang haholo

Hormonal Stress Systems: Hypothalamic-Pituitary-Adrenal Axis

Karolo ea bohlokoa ea karabelo ea 'mele ho khatello ea maikutlo e amanang le bokhoba ba tahi ke hypislamic-pituitary adrenal (HPA) axis, tsamaiso e laoloang haholo ke CRF karolong ea bohlokoa ea hypothalamus (Setšoantšo sa 1). Mokokotlo oa HPA o entsoe ka likarolo tse tharo tse kholo: konokono ea "hypothalamus", "lobe" ea "pituitary gland" le gland ea "adrenal" bakeng sa tlhahlobo. Smith le Vale, 2006). Neurosecretory neurons karolong e arohaneng ea methapo ea methapo ea kutlo le ho lokolla CRF ka har'a methapo ea mali ea portal e kenang gland ea anterior. Tlamahano ea CRF ho CRF1 receptor ho pituitary corticotropes e etsa hore ho nkoe ha hormone ea adrenocorticotropic (ACTH) tsamaisong ea kemiso. ACTH ka lehlakoreng le leng e ntlafatsa tsoekere ea glucocorticoid le secretion ho tsoa adrenal cortex. Mokokotlo oa HPA o hlophisoa hantle ka ho fana ka likarabo tse mpe tse tsoang ho li-glucocorticoid tse potolohang tse sebetsang hantle ho li-glucocorticoid receptors libakeng tse peli tsa bohlokoa tsa kelello: nucleus ea methapo ea kutlo ea hypothalamus le hippocampus. Li-neurology tsa "hypophysiotropic" tsa "hemothricular nucleus" ea "hypothalamus" li ngotsoe ka likhakanyo tse ngata tse amanang, ho kenyeletsoa ho tsoa ho brainstem, li-nuclei tse ling tsa hypothalamic le likarolo tsa methapo ea methapo ea kutlo.

Setšoantšo sa 1

Setšoantšo se bonts'ang liketso tse 'maloa tsa CRF ho tsamaisa likarabo tsa khatello ea maikutlo' meleng. CRF e khanna mokokotlo oa "hypothalamic-pituitary adrenal axis" ka ho nka bohato ba ho lokolla li-hormone tsa adrenocorticotropic (ACTH) tsamaisong ea methapo ea lintho tsa tlhaho. CRF e sebetsa ...

Extrahypothalamic CRF Sistimi

CRF e boetse e teng kantle ho axis ea HPA ho laola likarabo tsa boits'oaro le boitšoaro ho bahatelli. Subntantial CRF-like immunoreacaction e teng ka neocortex, amygdala e atolositsoeng, medial septum, hypothalamus, thalamus, cerebellum, le autonomic midbrain le hindbrain nuclei, ho kenyelletsa le sebaka sa likarolo tse kenang ka hare (Charlton et al., 1987; Swanson et al., 1983). Tsamaiso ea projeke ea Ucn 1 e feta le CRF empa e na le thomello e fapaneng, e kenyelletsang pono, somatosensory, auditory, vestibular, motor, tegmental, parabrachial, pontine, Median raphe, le cerebellar nuclei (Zorrilla le Koob, 2005). CRF1 receptor e na le polelo e ngata, e pharalletseng bokong e fetang haholo ka ho ajoa ha CRF le Ucn 1.

CRF ea khetho e khethehileng2 agonists — mofuta oa li-urocortins tsa 2 XnUMX (Reyes et al., 2001) le Ucn 3 (Lewis et al., 2001) -Fiffer ho tloha Ucn 1 le CRF litlalehong tsa bona tsa neuropharmacological. Ucn 2 le Ucn 3 li bontša khethollo e phahameng ea tšebetso bakeng sa CRF2 receptor hape ba na le neanoanatomical karolelano e fapaneng le ea CRF le Ucn 1 (Setšoantšo sa 2). Ucn 2 le Ucn 3 ha li hantle haholo ho hypothalamic nuclei e hlalosang CRF2 receptor, ho kenyelletsa "nucleus ea" supraoptic, "neurococularular neurons" ea "patventricular nucleus" le "forebrain" ho kenyelletsa le "ventothedial hypothalamus", "septum" ea morao-rao, "nucleus ea" stria terminalis, le amygdala ea medial le cortical (Li et al., 2002). CRF2 (a) receptor isoform e fumaneha sebakeng sa neuronally libakeng tsa boko tse fapaneng le tsa CRF / Ucn 1 / CRF1 tsamaiso ea li-receptor, joalo ka khubung ea moea ea "hemothropic hypothalamic", "solaropic nucleus", "solaropic nucleus".

Setšoantšo sa 2

Schematic ea mammalian corticotropin-releasing factor (CRF) receptors (li-polygons tse khubelu), ligands tsa 'ona tsa tlhaho tse tlotsitsoeng (mahe a botala), le bahanyetsi ba li-receptor antagonists (mabala a maputsoa). Metsu e lefifi e bonts'a kamano ea "receptor". Li-ligand tse sehlopha se pharaletseng ...

Sebopeho sa Amygdala e Atolositsoeng: Khokahano ea CRF le Karolo e Lefifi ea Bokhoba

Lintlha tsa morao-rao tsa neuroanatomical le lipatlisiso tse ncha tse sebetsang li fane ka ts'ehetso ea maikutlo a hore methapo ea neuroanatomical bakeng sa litlamorao tse ngata tse amanang le lehlakore le lefifi la ts'ebeliso e ka kenyelletsa "potoloho e tloaelehileng ea neural" e etsang mokhatlo o ikemetseng kahara sebopeho sa basal, amygdala ”(Alheid le Heimer, 1988). Amygdala e atolositsoeng e bonts'a macrostosition e nang le likarolo tse 'maloa tsa bokapele ba basal: mokokotlo oa bethe ea stria terminalis, amygdala ea medial ea ka hare, le sebaka sa phetoho karolong e ka morao ea methapo ea methapo ea methapo (ke hore, khetla ea ka morao) (Johnston, 1923; Heimer le Alheid, 1991). Meetso ena e na le ho tšoana ho morphology, immunohistochemistry, le khokahanong (Alheid le Heimer, 1988), mme ba fumana khokahano e kopanetsoeng ho tsoa ho li-limbic cortices, hippocampus, basolateral amygdala, midbrain, le hypothalamus ea morao. Khokahano e sebetsang ho tsoa mohahong ona e kenyelletsa posterior medial (sublenticular) ventral pallidum, sebaka sa likarolo sa ventral, likhopolo tse fapaneng tsa ts'ebetso ea kelello, mme mohlomong e khahla haholo ho tloha sebakeng sa pono, ts'ebetso e ka nahanoang ho hypothalamus ea morao-rao (Heimer et al., 1991). Lintho tsa bohlokoa tsa amygdala tse atolositsoeng ha li kenyelle feela li-neurotransmitters tse amanang le litlamorao tse matlafatsang tsa lithethefatsi tsa tlhekefetso, joalo ka li-peptide tsa dopamine le li-opioid, empa le likarolo tse kholo tsa lits'ebetso tsa CRF tsa extrahypothalamic tse amanang le mekhoa e mebe ea ho matlafatsa (Koob le Le Moal, 2005; sheba ka tlase).

CRF, HPA Axis, le Bokhoba ba ho lemalla

Ho latela pono ea bokhoba, liphetoho tse tsoelang pele mokokotlong oa HPA li bonoa nakong ea phetoho ho tloha taolong e mpe ho ea ho tsamaiso e sa feleng ea lithethefatsi tsa tlhekefetso. Ts'ebetso e matla ea lithethefatsi tse ngata tsa tlhekefetso ho liphoofolo e qala ts'ebetso ea HPA mme pele e ka nolofalletsa tšebetso lipotolohong tse khothatsang tsa kelello le moputso oa lithethefatsi ka lebaka leo e nolofalletsa ho fumana boitšoaro bo batlang lithethefatsi (Piazza et al., 1993; Goeders, 1997; Piazza le Le Moal, 1997; Fahlke et al., 1996). E loketseng karolo ea CRF ka lehlakoreng le lefifi la ho lemalla, liphetoho tsena tse mpe li hlakoloa kapa li entsoe ka taolo e phetoa ea cocaine, opioids, nikotine le joala (Kreek le Koob, 1998; Rasmussen et al., 2000; Goeders, 2002; Koob le Kreek, 2007; Sharp le Matta, 1993; Semba et al., 2004). Karabelo ea atypical ho baetsi ba khatello ea maikutlo e entsoe ka sepheo sa ho kenya letsoho ho phehelleng le ho khutlela mokhoeng oa ho ts'epa opioid, 'me ka mor'a moo khopolo ena e fetiselitsoe lithethefatsing tse ling tsa tlhekefetso (Kreek le Koob, 1998).

Habohlokoa bakeng sa karolo ea CRF lehlakoreng le lefifi la ts'ebetso ea bokhoba, litekanyetso tse phahameng tsa ho potoloha ha li-glucocorticoids li ka fana ka maikutlo a ho koala li-axis tsa HPA empa li ka "sensitisa" lits'ebetso tsa CRF sebakeng se bohareng ba amygdala le basolateral amygdala tse tsejoang ho kenya letsoho ho likarabo tsa boits'oaro ho khatello ea maikutlo (Imaki et al., 1991; Makino et al., 1994; Swanson le Simmons, 1989; Schulkin et al., 1994; Shepard et al., 2000). Kahoo, le ha ts'ebetso ea selekane sa HPA e ka supa ts'ebeliso ea lithethefatsi tsa pele le binge / botaoa bohato ba ho lemalla, ts'ebetso e joalo le eona e ka lebisa ts'ebetsong e latelang ea lits'ebetso tsa khatello ea kelello tsa extrahypothalamic tse khethollang drainare / Ho ama hampe sethala (Kreek le Koob, 1998; Koob le Le Moal, 2005; Koob le Kreek, 2007).

Karolo ea CRF ho Mehlala ea liphoofolo

Tsamaiso e sa feleng ea lithethefatsi tse nang le ts'oaetso e ka fokotsang karabelo ea khatello ea maikutlo e kopantsoeng le CRF, ho kenyelletsa eseng feela axis ea HPA, empa le tsamaiso ea khatello ea kelello ea extrahypothalamic. Likarabo tse tloaelehileng ho lithethefatsi tsohle tsa tlhekefetso le joala li kenyelletsa, nakong ea ha motho a khaotsa ka matla, karabelo ea khatello ea maikutlo ea HPA e bonts'itsoeng maemong a phahameng a ACTH le corticosteroids le karabelo ea khatello ea kelello e sebetsang le khatello ea maikutlo ea amygdala CRF. Leha ho le joalo, ka makhetlo a poteletseng a bokhoba ba ho lemalla, karabelo ea HPA e sa sebetseng e etsahala empa ka karabelo ea ts'ebetso ea khatello ea maikutlo ea extrahypothalamic CRF (Koob le Kreek, 2007; Koob, 2008).

Ka vivo Microbalalization nakong ea ha motho a khaotsa ho ts'oaroa ka mora ho itlhomme kapa ho itaola ha lithethefatsi tsa tlhekefetso ho eketsa keketseho ea CRF ea kantle ho amygdala, karabelo e joalo ka khatello ea maikutlo (Merlo-Pich et al., 1995; Richter et al., 2000). Nakong ea ho khaotsa joala, lits'ebetso tsa CRF tsa extrahypothalamic li fetoha tse matlafatsang, 'me keketseho ea CRF ea kantle ho khubung ea khubu ea amygdala le bethe ea "stria terminalis" ea likhoto tse itšetlehileng ka eona (Merlo-Pich et al., 1995; Olive et al., 2002). CRF ea extracellular le eona e eketsehile kahare ho amygdala nakong ea ho khaotsa ho nicotine e sa foleng.George et al., 2007)) Ho tlohela ho itlopa joalaRichter le Weiss, 1999), le ho tlosoa pele ho tsoa ho li-opioid (Weiss et al., 2001) le cannabinoids (Rodriguez de Fonseca et al., 1997). Litaba tsa "tishu tsa" Amygdala CRF li ile tsa fokotsoa nakong ea ha a ne a tloheloa haholo ke ho pepeseha ha ethanol le ho itlhokofatsa ka ho itšireletsa ka koae (ka ho itšepa)Zorrilla et al., 2001; Funk et al., 2006; Koob, 2009).

Karabo e 'ngoe e tloaelehileng ea ho khaotsa ho matla le ho itima lijo ho lithethefatsi tsohle tse kholo tsa tlhekefetso ke ponahatso ea boemo bo bobe ba maikutlo, ho kenyelletsa le likarabo tse kang tsa ho tšoenyeha. Mefuta ea liphoofolo eo ho eona phapang e atisang ho fetoha hangata e arabisang feela ho buka le / kapa tse susumetsang tse khahlisang, tse kang lebala le bulehileng, tlhahlobo e matla ea ho itšireletsa, kapa tlhahlobo ea tšebelisano ea sechaba, kapa karabelo e sebetsang tšusumetsong e khathollang. joalo ka ha ho pataloa phuputso e entsoeng ka tšepe e entsoe ka motlakase, e bonts'itse karabo e kang ea ho tšoenyeha ka ho tlohela lithethefatsi tsohle tse kholo tsa tlhekefetso. Ho tlosoa ts'ebetsong e pheta-phetoang ea koae, joala, nicotine, cannabinoids le benzodiazepines ho hlahisa karabelo e kang ea bokuli ho feta maze, ho itšireletsa ka boits'ireletso, kapa tlhahlobo e sireletsang ea ts'ireletso, mme litlamorao tsena li khutlisoa ke tsamaiso ea bahanyetsi ba CRF (Sarnyai et al., 1995; Basso et al., 1999; Knapp et al., 2004; Overstreet et al., 2004; Tucci et al., 2003; George et al., 2007; Rodriguez de Fonseca et al., 1997; Skelton et al., 2007).

Ho feta moo, ts'ebetso ea moputso oa boko o fokotsehileng o amanang le ho tlosoa hoa lithethefatsi ke CRF1 receptor-itšetleha Likhahla tsa meputso nakong ea ha nicotine e tlosoa e koetsoe ke CRF1 antagonists (Bruijnzeel et al., 2007, 2009). U sebelisa mofuta oa boiketlo ba sebaka, CRF1 antagonist e boetse e thibetse nts'etsopele ea boemo bo fetohileng bo hlohlontšitsoeng ba ho susumetsoa ke ho tlosoa hoa opioid ho litloholo tse itšetlehileng ka opioid (Stinus et al., 2005). Boithuto bo nang le li-microinjections tsa bahanyetsi ba Noradrenergic le CRF li fane ka bopaki bakeng sa karolo ea karolo ea bohlokoa ea bethe ea stria terminalis (Delfs et al., 2000) le nucleus e bohareng ea amygdala (Heinrichs et al., 1995), ka ho fapana, sebakeng libaka tse nyarosang tse hlahisoang ke ho khaoha hoa opioid.

Bopaki ba bohlokoa bo tsoang laboratoring ea rona le ea ba bang bo bontšitse karolo ea bohlokoa bakeng sa CRF litlamorao tsa khothatso ea ethanol ho itšetleheng ka tsona. Nakong ea ho tlosoa ha ethanol, lits'ebetso tsa CRF tsa extrahypothalamic li fetoha tse matlafatsang, ka keketseho ea CRF ea kantle ho khubung ea khubu ea amygdala le bethe ea "stria terminalis" ho litoeba tse itšetlehileng ka eonaFunk et al., 2006; Merlo-Pich et al., 1995; Olive et al., 2002). Ts'isinyeho ea lits'ebetso tsa CRF ea boko e ts'elisoa hore e nyenyefatse boits'oaro bo ntlafalitsoeng joalo ka boits'oaro le taolo e ntlafalitsoeng ea ethanol e amanang le ho tlosoa hoa ethanol. Ho ts'ehetsa hypothesis ena, bahanyetsi ba CRF receptor ba hanyetsang, joalo ka CRBI ea HCR9-41 le D-Phe CRF12-41 (intracerebroventricular inj inj) fokotsa boitšoaro bo nkang khatello ea maikutlo joaloka ethanolBaldwin et al., 1991; bona ka holimo).

Ho pepesehela khafetsa khafetsa ea phepelo ea ethanol e sa foleng ho hlahisa keketseho e kholo ea ho kenella ha ethanol ho likhoto, ka bobeli nakong ea ho khaotsa ho matla le ho khaotsa ho tsitsitseng (libeke tsa 2 kapa ho feta ka mor'a ho tlohela ka sekhahla) (O'Dell et al., 2004; Rimondini et al., 2002). Tsamaiso ea Intracerebroventricular ea CRF1/ CRF2 mohanyetsi o thibetse keketseho e tlisoang ke ho itaola ha ethanol nakong ea ho ikhula ho matla (Valdez et al., 2004). Bohanyetsi ba CRF ha bo na phello ho boits'oaro ba ethanol ho liphoofolo tse ikemetseng (Valdez et al., 2004). Ha e kenngoa ka kotloloho mokokotlong oa bohareng ba amygdala, bahanyetsi ba CRF le bona ba fumane boitšoaro bo kang ba ho tšoenyeha bo hlahisoang ke ho tlosoa hoa ethanol (Rassnick et al., 1993) le tsamaiso ea ethanol ho likhoto tse ts'epahalang (Funk et al., 2006, 2007). Hape, ha ho na litlamorao tsa bahanyetsi ba CRF ba ileng ba bonoa mabapi le ho itaola ha ethanol ho liphoofolo tse ikemetseng. CRF1 bahanyetsi ba limolek'hule tse nyane ba ile ba fokotsa boits'oaro bo eketsehileng ba lithethefatsi tse amanang le phihlello e atileng ea ho itaola ka mokhoa oa "cocaine"Specio et al., 2008), nicotine (George et al., 2007), le heroin (Greenwell et al., 2009). Lintlha tsena li fana ka maikutlo a karolo ea bohlokoa bakeng sa CRF, haholo-holo ka har'a khubu ea amygdala, ho arolelanang taolo e eketsehang ea boits'oaro e amanang le ho its'epa.

Barekisi ba CRF ba kentse intracerebroventricularly kapa ka mokhoa o hlophisehileng ba boetse ba thiba likarabo tse kang tsa ho tšoenyeha joalo ka bahatelli ba hlokometsoeng nakong ea thobalano e sa khaotseng (Breese et al., 2005; Valdez et al., 2003) le taolo e phahameng ea ethanol e amanang le ts'ebetso ea nako e telele ea ho tlohela (Sabino et al, 2006; Funk et al., 2007; Richardson et al., 2008; Chu et al., 2007; Gilpin et al., 2008; Sommer et al., 2008; Gehlert et al., 2007). Liphetho tsena li fana ka maikutlo a hore ts'ebetso e setseng ea lits'ebetso tsa CRF e ntse e tsoela pele ho lahla lintho tse amanang le preoccupation / Ho lebella sethala. Ho ts'ehetsa ts'oaetso ena, liphoofolo ka bobeli tse tloheletsoeng ke "ethanol-" le "cocaine" li bonts'itse ts'oaetso ea CRF joalo ka amygdala e lateloang ke keketseho e tsoelang pele e fihlang maemong a phahameng a libeke tsa 6 kamora ho nts'oa (Zorrilla et al., 2001).

Kahoo, ts'ebetso ea CRF ea boko e na le karolo ea bohlokoa ho hatseng phetoho ho tloha ho e matla ho ea ho matlafatso e mpe e amanang le nts'etsopele ea likarolo tse susumetsang tsa ts'epahalo e bonts'itsoeng ts'ebetsong e eketsehileng ea lithethefatsi ka phihlello e atolositsoeng (bona Koob le Le Moal, 2008, bakeng sa tlhaiso-leseling e batsi ea moralo ona oa khopolo). Tlhahiso-leseling e tsoang liphatlalatsong tse bobebe, likarabo tse kang ho tšoenyeha, maemo a sebaka (moea o khelohileng sebaka), le phihlello e atolositsoeng ea tsamaiso ea lithethefatsi ka bongata li fetohile ho fana ka sebopeho sa neuropharmacological bakeng sa hypothesis e teng hona joale.

Urocortin le lekhoba la tahi

Palo e lekanyelitsoeng ea lipatlisiso e hlahlobile karolo ea lisebelisoa tsa urocortin tse ikemetseng ho li-receptor tsa CRF. Boithuto bo bongata bo fana ka maikutlo a hore lits'ebetso tsa urocortin li ka bapala karolo ea boits'oaro ba ethanol (Ryabinin le Weitemier, 2006). Metsoako ea litoeba le likhoto tse noang ethanol ka mokhoa o feteletseng li na le lisele tse hlahisang urocortin ka bokong ba Edinger-Westphal ha li bapisoa le mefuta e sa noeng haholo (Bachtell et al., 2002, 2003; Turek et al., 2005). Ho itlopa joala bo matla ho kenya ts'ebetsong lisele tsa urocortin bokong ba Edinger-Westphal (Ryabinin et al., 2003). Ucn 1 microinjection ka sebakeng sa projeke ea lisele tsa urocortin tse karolong ea Edinger-Westphal nucleus e kentse keketseho ea joala bo fokolang ba litoeba (Ryabinin et al., 2008). Matšoenyeho a lipopolysaccharide le ona a ile a eketsa ts'ebetso ea lisele tsa urocortin moleng oa Edinger-Westphal (Kozicz, 2003). Boithuto bo latelang bo bonts'itse hore li-stress tse ling le tsamaiso e matla ea li-psychostimulants li kenya lisele tsa urocortin sebakeng sa Edinger-Westphal, hona joale e rehelletsoe ka pIIIu, e fana ka maikutlo a hore lithethefatsi tse ngata tsa tlhekefetso le khatello ea maikutlo li ka kenya tšebetsong tsamaiso ea Ucn 1 sebakeng sena (Spangler et al., 2009). Leha ho le joalo, sensorization ea locomotor e bonoang ho litoeba ka tsamaiso e phetoang ea ethanol e ne e thibetsoe ke CRF1 antagonists eseng ho Ucn 1 kapa CRF2 Knice KniceMoruti et al., 2008). CRF2 Knice lithunya le tsona li ile tsa sitoa ho bonts'a ho fokotseha hoa ts'ebeliso ea ethanol ka bobeli ba 24 h li-botlolo tse peli tsa botlolo le lipallo tse fumanehang tse fokolang (Sharpe et al., 2005). Ka kakaretso, liphetho tsena li fana ka maikutlo a hore ts'ebetso ea Ucn 1 e tsoang pIIIu seterekeng sa Edinger-Westphal e hlahisoa ke tšebeliso e ngata ea ethanol. Leha ho le joalo, ketso ea eona e ka kopanngoa le CRF haholoanyane1 li-receptors ho feta CRF2 li-receptors.

Sebakeng sa ts'ebeliso ea matla ea ethanol e amanang le ts'ehetso ea ethanol, CRF e khethang haholo2 agonist, Ucn 3, ha e kenella intracerebroventricularly kapa ka kotloloho kahareng e bohareng ea amygdala, e bile le litlamorao tse ts'oanang le CRF1 antagonist ho fokotsa keketseho ea boits'oaro ba ethanol bo amanang le ho tlosoa ho matla ha likotlo tse itšetlehileng. Leha ho le joalo, ha ho na phello e bonoang litlamong tse sa tšepahaleng (Valdez et al., 2004; Funk le Koob, 2007). Ucn 3 e boetse e khetha ka nepo keketseho ea takatso ea ethanol e hlokometsoeng ho litoeba tsa C57BL / 6J nakong ea phihlello e fokolang ea ethanol (Sharpe le Phillips, 2009). Liphetho tsena li fana ka maikutlo a hore ts'ebetso ea Ucn 3 e ka thibela ho nooa ho tlasa tekano tlasa maemo a mmaloa mme e fana ka maikutlo mabapi le karolo ho CRF2 li-receptors tse khahlano le karolo ea CRF le Ucn 1 ka CRF1 li-receptors ho fetoleng phepelo ea ethanol ho liphoofolo tse its'epileng.

Ho tlohela-tšusumetso e matlafalitsoeng ea nako e telele litekong tsa hippocampal tse amanang le ho pepeseha ha k'hok'heine ea cocaine e phahameng e koetsoe ke bobeli ba CRF1 le CRF2 bahanyetsi ba receptor (Guan et al., 2009). Litlalehong tsa kelello tse tsoang ho septum ea morao-rao ka mor'a ho tsoa ka matla cocaine e sa foleng, phetoho ea CRF2 liketsahalo tsa receptor ho tloha inhibition ho tataisa li bonoe (Liu et al., 2005). Ho itšehla thajana ka nakoana ho tsoa ho ts'ebetso ea opioid e sa feleng ho koetsoe CRF2 Knice KnicePapaleo et al., 2008), athe litlamorao tse tlisoang ke ho tlosoa ke opioid, tse lekantsoeng ke ho hloea sebaka se itseng, li koetsoe CRF1 Knice KniceContarino le Papaleo, 2005). Ka kakaretso, liphetho tsena li fana ka maikutlo a hore nakong ea ho tlohela lithethefatsi tsa tlhekefetso, CRF2 Sistimi e ka kenella ho ts'ebetso ea methapo e fetisang ho itlhahisa ho itseng, ho khaotsa ho susumetsang le likarolo tsa liphetoho ho ithuteng. Lisaete tse amehang (mohlala, septum, amygdala, hippocampus), leha ho le joalo, li ntse li ikemiselitse ho ikemela.

Khatello ea Khatello ea Khatello ea Kelello

Boemo ba khatello ea maikutlo le khatello ea maikutlo haesale li amahanngoa le ho khutla hape le ho ba kotsing ea ho khutla hape (Koob le Kreek, 2007; Marlatt le Gordon, 1980). Bokhobeng ba joala ba motho, matšoao a mangata a ka tšoaetsoang ke maikutlo a seng monate a maikutlo a kang dysphoria, malaise, ho teneha le ho tšoenyeha, a tsoela pele nako e telele ka mor'a ho tlohela joala ka mokhoa o makatsang (Alling et al., 1982). Matšoao ana, ho khaotsa ho hang, hangata a etella pele ho khutlela morao (Hershon, 1977; Annis et al., 1998). Maikutlo a fosahetseng, ho kenyelletsoa le lintho tse bakang khalefo, pherekano, maswabi, ho tšoenyeha le letsoalo, ke ntho ea bohlokoa ea ho khutla hape (Zywiak et al., 1996) hape e ne e le eona ntho e ka pele-pele e ka khutlisetsang phepisong e kholo ea lekhetho la Marlatt (Lowman et al., 1996). Mathata a sithabetsang, khatello ea maikutlo, kapa khatello e amanang le ho khaola le eona e eketsa takatso ea lithethefatsi (Childress et al., 1994; Cooney et al., 1997; Sinha et al., 2000).

Karolo ea CRF ho khutlisetsong khatello ea maikutlo e bakang khatello ea maikutlo e latela mohlala oa liphetho tse batlang li bapisoa le karolo ea CRF liphellong tse ts'oanang le ho ts'oaroa ke matla le ho eketseha hoa ts'ebeliso ea lithethefatsi (litlhahlobo, bona Shaham le al., 2003; Lu et al., 2003). CRF e tsoakiloeng1/ CRF2 antagonists inj inj intracerebroventricularly le / kapa CRF1 bahanyetsi ba limolek'hule tse nyane ba thibetse ho khutlisetsoa hoa khatello ea kelello ea koae, opioid, joala le ts'ebetso ea ho tsuba ea nicotine (bona Liu le Weiss, 2002; Shaham le al., 2003; Lu et al., 2003; Le et al. 2000; Shaham et al. 1998; Gehlert et al., 2007; Bruijnzeel et al., 2009; Marinelli et al., 2007). Litlamorao tsena li 'nile tsa phetoa ka ente ea intracerebral ea CRF e tsoakiloeng1/ CRF2 antagonist kapa molek'hule-CRF e nyane1 antagonist ho "nucleus ea bedia" ea "stria terminalis", "median raphe", le sebaka sa ho arohana, empa eseng amygdala kapa nucleus Shaham le al., 2003; Lu et al., 2003), ho fana ka tlhahiso ea hore libaka tsa libaka tse fapaneng, joalo ka moeli oa "stria terminalis", "median raphe nucleus" le sebaka se arohaneng se ka bang bohlokoa bakeng sa ho khutlisetsoa ke khatello ea maikutlo, ho fapana le karolo ea CRF molemong oa ho eketseha hoa ts'ebeliso ea lithethefatsi -mamuso ao ho fihlela joale a seng a fumanehile sebakeng sa mantlha ho mantlha o bohareng ba amygdala (Funk et al., 2006). Hlokomela hore ho khutlisetsoa ka khatello ea maikutlo ho etsahala ntle le ts'usumetso e susumetsoang ea khatello ea kelello ea HPA (Erb et al., 1998; Le et al., 2000; Shaham le al., 1997).

Mohlala, lits'ebetso tsa CRF li boetse li supiloe sebakeng sa ho kenella ka mokokotlo, 'me khatello ea methapo ea methapo e ka lokolla CRF sebakeng se khubung ea ventral mme e na le karolo ea ho khutlisetsoa khatello ea maikutlo (Wang et al., 2005). Ts'usumetso ea ho ts'oara koae ea Footshock e koetsoe ke tsamaiso ea CRF2 receptor antagonist, and CRF agonists with solidant for the CRF binding protein siling the liphello tse hlahisitsoeng ke footshock, a fana ka maikutlo a ho nka karolo ha CRF ka bobeli2 li-receptors le protheine e tlamang ea CRF sebakeng se kenellang ka hare ho sepheo sa ho khutlisetsa khatello ea maikutlo (Wang et al., 2007). Liphetho tsena li lumellana le karolo ea CRF1 Sistimi ea amygdala e atolositsoeng ea khatello ea maikutlo e khutliselitsoeng ho eona (Shaham le al., 1998). Lisebelisoa tse ling tsa khatello ea kelello tse kenelletseng ho khutlisetsong e bakang khatello ea maikutlo mohlomong e amanang le litsamaiso tsa CRF tsa boko li kenyelletsa norepinephrine, orexin, vasopressin, le nociceptin (bona Shaham le al., 2003; Lu et al., 2003).

Ka hona, lits'ebetso tsa khatello ea kelello li ka ama bobeli drainare / Ho ama hampe mohato le preoccupation / Ho lebella sethala sa potoloho ea bokhoba ba lithethefatsi, le ha e le ka ho etsa likarolo tse fapaneng tsa moea oa maikutlo oa amygdala (karolo e bohareng ea amygdala) vs. mokokotlo oa bethe ea stria terminalis; Bona kaholimo) le dysreggement tse kenyang boemo bo bobe ba maikutlo ba ts'ebeliso ea lithethefatsi li ntse li tsoela pele nakong ea ts'oaetso e senang nako ea ho beha lenane la ho beha kotsing ea "ho lakatsa" ho khannoang ke ts'ebetso ea ts'ebeliso ea methapo ea methapo ea kutlo, cue-, le khatello ea khatello ea maikutlo.

CRF, lehlakore le lefifi, le bokhoba ba tsona: Sekhahla sa Khakanyo ea Khokahano ea Stress Systems le Tebelo

Lithethefatsi tsohle tse sebelisang tlhekefetso li kenella molatong oa HPA nakong ea ho inkela lithethefatsi khafetsa nakong ea ho tlosoa sethethefatsi ka ts'ebetso ea CRF maemong a pherese ea hypothalamus. Ha potoloho ea ts'ebeliso ea lithethefatsi le ho khaotsa e ntse e tsoela pele, karabelo ea axel ea HPA ea ts'oaroa, empa ho pepesetsoa ha kelello khafetsa ho li-glucorticoids tse ngata ho ka tsoela pele ho ba le litlamorao tse kholo ho lits'ebetso tsa khatello ea kelello tsa extrahypothalamic (Setšoantšo sa 3). Bopaki bo matla bo fana ka maikutlo a hore li-glucocorticoids li "nyenyefatsa" tsamaiso ea CRF ho amygdala (Imaki et al., 1991; Makino et al., 1994; Swanson le Simmons, 1989). Kahoo, karolo ea pele ea tlatsetso ea CRF lehlakoreng le lefifi ke ts'ebetso ea li-axis tsa HPA le li-glucocorticoids, tse hokahaneng qalong le karabelo e phahameng ho bocha le ho nolofalletsa moputso. Kamora nako, maikutlo a lits'ebetso tsa CRF ho amygdala e atileng a etsahala moo ba kenya letsoho ho karolo ea khatello ea phetoho ho tloha homeostasis ho ea ho pathophysiology e amanang le ts'ebeliso ea lithethefatsi. Karolo ena ea khatello ea maikutlo e ka bonts'a karolo ea karabelo ea mohanyetsi ts'ebetsong e fetelletseng ea lits'ebetso tsa moputso, e bitsoang anti-moputso (Koob le Le Moal, 2008).

Setšoantšo sa 3

Li-circuits tsa boko li phehelloa ho hloa mehatong e fapaneng ea potoloho ea ts'ebetso ea lithethefatsi ha ts'ebeliso ea ts'ebeliso ea lithethefatsi e tloha ho tse matla. Potoloho e ka holimo ka ho le letona e bua ka axislamic-pituitary-adrenal (HPA) axis eo (i) fepa ...

Ts'ebetso ea bohanyetsi, neuroadaptations e pakeng tsa sistimi e reretsoe ho kenyelletsa lits'ebetso tsa methapo ntle le tse kenyang liphetho tse ntle tsa lithethefatsi tsa tlhekefetso tse ngolisitsoeng kapa tse sa sebetsoang ka ts'ebetso e sa feleng ea sistimi ea moputso (Koob le Bloom, 1988). Neuroadaptation e pakeng tsa sistimi ke phetoho ea potoloho eo potoloho e ngoe e fapaneng (anti-moputso) e hlahisoang ke potoloho ea moputso ebile e na le liketso tse hanyetsanang, hape e fokotsa mosebetsi oa moputso. Ka hona, ho hira sistimi ea CRF nakong ea nts'etsopele ea ts'ebeliso ea litlhare tsohle tsa tlhekefetso ho ka ba le bohlokoa ba bohlokoa bo susumetsang. Ho eketsa pakeng tsa sistimi neuroadaptations e amanang le ho tlosoa ha ts'ebetso ea mohanyetsi oa-system e kenyelletsa ts'ebetso ea ts'ebetso ea dynorphin / κ-opioid, norepinephrine khatello ea kelello, tsamaiso ea extrahypothalamic vasopressin, mme mohlomong le tsamaiso ea orexin. Sistimi e thibelang khatello ea kelello, e kang neuropeptide Y le nociceptin, le eona e ka fokotsoa nakong ea nts'etsopele ea ts'epahalo, ka hona ea tlosa mochine oa ho khutlisa homeostasis (Koob le Le Moal, 2008). Ho kenyelletsa moo, ts'ebetso ea ts'ebetso ea khatello ea methapo ea kelello e ka se tlatsetse feela ho ts'ebetsong e mpe ea ts'usumetso e amanang le ho ila thipa haholo, empa hape e ka tlatsetsa ho tsofala, ho phehella ha dysphoria, le ho ba tsietsing ea khatello ea maikutlo nakong ea nako e telele ea ho itima lintho bathong. Liphetho tsena li fana ka maikutlo a hore tšusumetso ea ho tsoela pele ts'ebeliso ea lithethefatsi nakong ea ts'ehetso ha e kenyeletse feela phetoho mosebetsing oa li-neurotransmitters tse amanang le litlamorao tse matlafatsang tsa lithethefatsi tsa tlhekefetso nakong ea kholo ea kholo, joalo ka dopamine, li-peptide tsa opioid, serotonin, le γ- aminobutyric acid, empa le ho bokella lits'ebetso tsa khatello ea kelello le / kapa ho sitisoa ha lits'ebetso tsa khatello ea kelello (Koob, 2008; Koob le Le Moal, 2008).

Kahoo, ts'ebetso ea li-circuits tsa neural tse kenyelletsang CRF ka tloaelo e kenyelletsang karabelo tse nepahetseng ho khatello ea maikutlo e matla e tlatsetsa boemong bo sithabetsang ba maikutlo bo susumetsang tšusumetso e mpe ea temallo. The drainare / Ho ama hampe mohato o hlalositsoeng kaholimo o na le likarolo tsa bohlokoa tse susumetsang, tse kang ho se ts'oenyehe ho sa feleng, bohloko ba maikutlo, malaise, dysphoria, alexithymia, le tahlehelo ea meputso ea tlhaho, 'me e tsebahala ka liphoofolo ka ho eketseha ha meputso ea moputso nakong ea ho tlohela lithethefatsi tsohle tse kholo tsa tlhekefetso (Koob, 2008). Karolo ea bohlokoa ea lehlakore le lefifi la bokhoba ke mohopolo oa anti-moputso (ke hore, lits'ebetso tse behiloeng ho fokotsa moputso) (Koob le Le Moal, 1997,Koob le Le Moal, 2005,Koob le Le Moal, 2008). Ha ho ts'epa le ho nts'etsapele nts'etsopele, lits'ebetso tsa boko tse khahlano le moputso tse kang CRF li khothaletsoa ho hloa molemong oa ho hlahisa maemo a kang khatello ea maikutlo, 'me (Koob le Le Moal, 2001; Nestler, 2005; Aston-Jones et al., 1999).

Moralo o akaretsang oa khopolo nakong eohle ea tlhahlobo ena ke hore ho nka karolo ha konopo ea khatello ea kelello e kopantsoeng le CRF ho feta ho ikhutsa ha bonolo le homeostasis maemong a bokhoba ba taolo, empa haholoholo nts'etsopele ea allostasis. Allostasis e hlalosoa e le "botsitso ka phetoho" mme e fapane le homeostasis hobane phepelo pele, ho fapana le karabelo e mpe, mekhoa e hanoa hore e lebelletsoe (Sterling le Eyer, 1988). Le ha ho le joalo, bokhoni bona ba ho bokella lisebelisoa ka potlako le ho sebelisa mekhoa ea ho li fepa li lebisa boemong bo tšosang haeba litsamaiso li se na nako e lekaneng ea ho qala homeostasis. An naha e mameloang e ka hlalosoa e le boemo ba ho kheloha ho sa feleng ha tsamaiso ea taolo ho tsoa maemong a eona a tloaelehileng (homeostatic).

Lisebelisoa tsa khatello ea kelello li arabela ka potlako ho mathata a lebelletsoeng ho homeostasis empa li lieha ho lula kapa ho se koale hang ha o se o kopane (Koob, 1999). Kahoo, mochine oa 'mele o lumellang karabelo e potlakileng le e tsitsitseng ea phephetso ea tikoloho o fetoha mohloli oa thuto ea bophelo haeba nako e lekaneng kapa lisebelisoa li sa fumanehe ho koala karabelo. Bokhoba ba lithethefatsi, bo tšoanang le mafu a mang a sa foleng a 'mele a joalo ka khatello e phahameng ea mali, a mpefala ha nako e ntse e ea, a ba le tšusumetso e kholo ea tikoloho (mohlala, khatello ea maikutlo),' me e siea moelelo o setseng oa tlhaho o lumellang "ts'ebeliso e ncha" ea ts'oaetso hape kamora ho chechisetsoa ka morao ho botona le botšehali. Litšobotsi tsena tsa bokhoba ba lithethefatsi li lebisitse ho ho lekantsoeng ha bokhoba ba lithethefatsi e le taba ea ts'ebeliso e mpe ea homeostatic ea ts'ebetso ea maikutlo, empa joalo ka naha e tenang e nang le ts'ebetso ea CRF e le mofani oa bohlokoa. Boemo bona ba ho batla lithethefatsi bo hatelletseng bo emela motsoako oa ho phahama ho sa feleng ha lintlha tse behiloeng ke liphetoho tse ngata tse amanang le phetoho, ho kenyelletsa le ts'ebetso e fokotsehileng ea lisekete tsa meputso, tahlehelo ea taolo ea "cortex" e tlang pele ho ts'ebetso ea ts'ebetso ea ts'ebetso le ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'usumetso ea maikutlo le ts'ebetso ea boko ba CRF khatello ea maikutlo (Koob le Le Moal, 2008). Kamora nako, ho ntse ho totobala ka ho hlaka hore ho ba kotsing ea liphatsa tsa lefutso le hona ho ka bapala karolo karolong e lefifi ea mahlakore.

Mokhatlo o fumanoe pakeng tsa tagi ea maqhubu a li-single-nucleotide ea CRF1 mofuta oa mekhoa ea joala e nooang ho itlopa joala ho bacha le batho ba baholo ba itšebelisang joala.Treutlein et al., 2006). Phuputsong e ileng ea latela, bacha ba homozygous bakeng sa C allele ea R1876831 single-nucleotide polymorphism ba ile ba noella joala ho feta tekano mme ba ne ba e-na le litekanyetso tse phahameng tsa bophelo ba ho noella haholo mabapi le liketsahalo tse mpe tsa bophelo ho feta lithuto tse nkileng T-allele (Blomeyer et al., 2008). Phuputsong e latelang, homozygotes ea C allele ea rs1876831, hammoho le bakuli ba A allele of rs242938, ha ba pepesehetse khatello ea maikutlo, ba bontšitse ts'ebetso e kholo ea ho noha ho feta bajari ba ling tse ling (Schmid et al., 2009). Karolong e khethiloeng ea liphatsa tsa lefutso ea Marchigian-Sardinian, khetho e phahameng ea ethanol e amanang le polymorphism ea liphatsa tsa lefutso. crhr1 papatso le keketseho ea CRF1 letsoalo ho amygdala, le kutloelo-bohloko e eketsehileng ea khatello ea maikutlo le kutloelo-bohloko e eketsehileng ho CRF1 antagonist (Hansson et al., 2006). Likotong tse sa khetholloeng liphatsa tsa lefutso, ho pepesetsoa lits'ebetso tse ipheta-phetang tsa ho noella le ethanol, CRF1 mohanyetsi o thibetse ho ja ho eketsehileng ha ethanol ho amanang le ho koala nako e sa lekanyetsoang, phello e tsamaisanang le ho ngolisoa ha CRF1 mofuta le ho fokotseha hoa CRF2 liphatsa tsa lefutso ho amygdala (Sommer et al., 2008). Liphetho tsena ka kakaretso li fana ka monyetla o thabisang oa hore li-polymorphism tsa "single-nucleotide" bathong tsa motho li ka bolela tlokotsi ea li-syndromes tse ling tsa lino tse tahang tse amanang le lehlakore le lefifi.

lumela hore baa fokola

Litokisetso tsa buka ena e ngotsoeng ka letsoho li ile tsa tšehetsoa ke Institutes of Health ea lithuso ho DK26741 ho tsoa Setsing sa Naha mabapi le Lefu la Ts'oaetso ea Lefu la Ho Ts'oarela Lefu la Ts'oaetso ea Liphio le Setsi sa Pearson bakeng sa Patlisiso ea Tahi le Thibelo ea Tlatsetso. Sengoli se rata ho leboha Michael Arends ka thuso ea hae mabapi le ho lokisa le ho hlophisa buka ena e ngotsoeng ka letsoho.

Mongolo o botlaaseng ba leqephe

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