Ts'ebetso ea khatello ea kelello ea amygdala le lithethefatsi (2009)

Resin ea Boko. 2009 October 13; 1293: 61-75. Pu10.1016 / j.brainres.2009.03.038

inahaneloang

Ho hasoa ha methapo ea maikutlo ea boko e thusang ho hlasimolla le khatello ea maikutlo ke karolo ea bohlokoa ea pathophysiology ea bokhoba ba lithethefatsi. Bokhoba ba lithethefatsi ke bokuli bo khutlang hape bo tšoaelitsoeng ke ho qobelloa ho batla le ho sebelisa lithethefatsi le nts'etsopele ea ho ts'epahalla le ho bonts'a boemo bo bobe ba maikutlo ha setlhare se tlosoa. Ts'ebetso ea lits'ebetso tsa khatello ea kelello e khothalletsoa ho ba karolo ea bohlokoa ea maikutlo a mabe a hlahisoang ke ts'ehetso e khannang ho batla lithethefatsi ka mekhoa e mebe ea ho matlafatsa. Sepheo sa tlhahlobo ea hona joale ke karolo ea likarolo tse peli tsa bohlokoa tsa ts'ebetso ea ts'ebetso ea khatello ea kelello ho nts'etsopele ea kholo. Khatiso e behiloe ho liketso tsa neuropharmacological tsa corticotropin-releasing factor (CRF) le norepinephrine lits'ebetsong tsa extrahypothalamic ho amygdala e atolositsoeng, ho kenyelletsa le karolo e bohareng ea "amygdala" bokella. Bopaki bo qholotsang bo tiisa hore lits'ebetso tsena tsa khatello ea kelello, tse sa tsotelleng haholo-holo karolo ea ho itšepa le ho lemalla, li bapala karolo ea bohlokoa ho kenyelletsa phetoho ho itšetleha le ho boloka ts'ehetso hang hoba e qalisoe. Ho utloisisa karolo ea khatello ea khatello ea kelello le lits'ebetso tse khahlanong le khatello ea maikutlo ha ho fane feela ka leseli la "neurobiology" la "lehlakore le lefifi" la ho lemalla empa ho boetse ho fana ka leseli ka mokhatlo le ts'ebetso ea mantlha ea maikutlo a kelello a tataisang boitšoaro bo susumetsang.

Keywords: Tlatsetso, Neurobiology, khatello ea maikutlo, Corticotropin-releasing factor, Norepinephrine, amygdala e atolositsoeng

1. Moralo oa likhopolo: bokhoba ba khatello, khatello ea maikutlo, ho tlosoa ha sepheo le tšusumetso e mpe

Ho lemalla lithethefatsi ke bokuli bo sa feleng bo tšoaelitsoeng ke ho qobelloa ho batla le ho nka lithethefatsi le tahlehelo ea taolo ho fokotsa ts'ebeliso. Ntlha ea boraro ea mantlha e kenyellelitsoeng ke ba bang mme e bohlokoa haholo ho tlhahlobo ea hona joale ke ho hlaha ha boemo bo sa thabiseng ba maikutlo (mohlala, dysphoria, matšoenyeho, ho hloka botsitso) ha phihlello ea lithethefatsi e thibetsoe (e hlalositsoeng mona joalo ka ho its'epaha) (Koob le Le Moal, 1997, 2008). lemalla ntho e e sebelisoa ka mokhoa o tšoanang kopanong ea hona joale le polelo Ho Itlhahisa ka Litaba (hajoale e hlalositsoe ke Buka ea ho hlahloba le ea Statistical ea Mathata a kelello, Khatiso ea 4th; Mokhatlo oa Mahlale oa Amerika, 1994), empa "ho itšetleha" ka "d" ea boemo bo tlase ho tla sebelisoa ho hlalosa ponahalo ea ho tlosoa ha lefu la ts'ebetso ha lithethefatsi tse sa feleng li emisoa (Koob le Le Moal, 2006). Ka linako tse ling empa tšebeliso e fokolang ea lithethefatsi e na le 'nang bakeng sa tlhekefetso kapa ho ba le ts'oaetso ho fapana le ho hlaha hoa boemo bo sa foleng ba ts'ebeliso ea lithethefatsi.

Khatello ea Kelello e ka hlalosoa e le karabelo ea litlhoko (hangata tse se nang letsoalo) holim'a 'mele (Selye, 1936) eo nalaneng e kileng ea hlalosoa ke liphetoho tse fapaneng tsa 'mele tse kenyelletsang ts'ebetso ea mokokotlo oa hypothalamic-pituitary-adrenal (HPA). Ts'ebetso ena e tšoauoa ka tokollo ea li-adrenal steroid tse bakiloeng ke tokollo ea li-hormone tsa adrenocorticotropic (ACTH) ho pituitary. Ho lokolloa ha li-hormone tsa adrenocorticotropic ho laoloa, ke tokollo ea hypothalamic corticotropin-releasing factor (CRF) tsamaisong ea "portitu" ea semelo sa bohareng. Tlhaloso ea khatello ea maikutlo e tsamaellanang haholo le lipontšo tsa eona tse ngata ka sebopeho ke phetoho efe kapa efe lits'ebetsong tsa kelello tsa homeostatic (Burchfield, 1979). Kaho ea khatello ea maikutlo hamorao e hokahantsoe le ho aha ho tsosa takatso mme ka hona e ka emela ts'ebetso e fetelletseng ea ts'oaetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea 'mele ea' mele kapa ea maikutlo.Hennessy le Levine, 1979; Pfaff, 2006).

Bokhoba ba lithethefatsi bo hlalositsoe e le bokuli bo kenyelletsang likarolo tsa ho nkeha maikutlo le ho qobelloa (Feie. 1). Ho se tsitsisehe a ka hlalosoa e le motho ea kenang ts'usumetso e potlakileng, e sa reroang ho susumetso ea kahare le kantle ntle le ho sheba litlamorao tse mpe tsa karabelo ena ho motho ka mong kapa ho ba bang. Ho qobelloa e ka hlalosoa e le mamello ha u arabela leha u tobana le litlamorao tse mpe kapa mamello maemong a karabelo e fosahetseng maemong a khetho. Lintho tsena ka bobeli li bonts'a tšusumetso e eketsehileng ea ho batla lithethefatsi 'me li na le bonnete ba sefahleho le matšoao a Phokotso ea Lithethefatsi joalokaha ho hlalositsoe ke American Psychiatric Association.

Feie. 1

Sekema bakeng sa tsoelo-pele ea ts'ebeliso ea lino tse tahang ka nako e telele, e bonts'a phetoho ea ts'ebetso ea ts'ebetso ea ts'usumetso. Ho tloha qalong, ho matlafatsa, litlamorao tse ntle tsa lithethefatsi, ts'ebetso ea bokhoba e tsoela pele ha nako e ntse e tsoela pele ho bolokoa ...

Ho fokotsa mekhahlelo ea ho nkeha maikutlo le ho qobella ho hlahisa tloaelo ea ho lemalla lintho tse ngata e nang le mekhahlelo e meraro.preoccupation / Ho lebella, ho itlopa joala / botahoa, 'me drainare / Ho ama hampe- eo hangata ho susumetsoa ke matla ho qalang le ho qobelloa ho hoholo maemong a ho bolaa. 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).

Mehopolo ea tlhahlobo ena ke hore karolo ea bohlokoa ea ts'ebetso ea bokhoba ba ts'ebetso e kenyelletsa ts'ebetso e matla ea lits'ebetso tsa khatello kelellong e sebetsanang empa e ikemetse ka lits'ebetso tsa khatello ea li-hormone. Lisebelisoa tse joalo tsa khatello ea kelello li fetisoa ka ho eketsehileng hore li fumanehe sebakeng sa potoloho ea methapo e bohareng ea amygdala le ho hlahisa boemo bo bobe ba maikutlo bo fetoha tšusumetso e matla ea ho batla lithethefatsi e amanang le ts'ebeliso e qobelloang. Tsepamiso ea pampiri ena e tla ba karolo ea CRF le norepinephrine ho tšebeliso ea lithethefatsi e le karolo ea mantlha ea sistimi e rarahaneng e bolokang maikutlo homeostasis.

2. Sistimi ea khatello ea maikutlo ea Hormonal: hypothalamic-pituitary-adrenal axis

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 ntšoa ha ACTH tsamaisong ea kemiso. Adrenocorticotropic hormone ka lehlakoreng le leng e tsosa synthesis ea glucocorticoid le secretion ho tsoa ho 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 boko: konokono ea potoloho le hippocampus. Li-neurology tsa "hypophysiotropic" tsa "moth" ea "hypothalamus" li hlalositsoe 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.

3. Sistimi ea khatello ea kelello: corticotropin-releasing factor le norepinephrine

Corticotropin-releasing factor ke 41 amino acid polypeptide e laolang karabelo ea lihormone, kutloelo-bohloko le boitšoaro mabapi le khatello ea maikutlo. Ho sibolloa ha li-peptide tse ling tse nang le sebopeho sa Homology, haholo-holo lelapa la urocortin (urocortins 1, 2, le 3), o khothalelitse likarolo tse akaretsang tsa li-neurotransmitter bakeng sa lits'ebetso tsa CRF maemong a boitšoaro le a ho ikarabela ho khatello ea maikutlo (Bale le Vale, 2004; Hauger et al., 2003). Immunantiac CR-like immunoreactivity e teng ka neocortex, amygdala e atolositsoeng, medial septum, hypothalamus, thalamus, cerebellum, le autonomic midbrain le hindbrain nuclei (Charlton et al., 1987; Swanson et al., 1983). Ho ajoa ha projeke ea urocortin 1 e phethelletse le CRF empa e na le kabo 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 urocortin 1.

CRF ea khetho e khethehileng2 agonists-- mofuta oa 2 urocortin urocortin 2 (Reyes et al., 2001) le urocortin 3 (Lewis et al., 2001-Differ ho tsoa ho urocortin 1 le CRF litlalehong tsa bona tsa neuropharmacological. Urocortins 2 le 3 li bonts'a khethollo e phahameng ea ts'ebetso bakeng sa CRF2 li-receptor hape li na le neanoanatomical karolelano e fapaneng le ea CRF le urocortin 1. Urocortins 2 le 3 haholo ha e le hantle li-hypothalamic nuclei tse 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 methapo ea kutlo libakeng tsa boko tse fapaneng le tsa CRF / urocortin 1 / CRF1 tsamaiso ea li-receptor, joalo ka khubung ea moea ea "hemothropic hypothalamic", "solaropic nucleus", "solaropic nucleus".

Norepinephrine e tlama ho malapa a mararo a ikhethileng a li-receptors, α1, α2, le β-adrenergic, eo e 'ngoe le e' ngoe ea eona e nang le li-subtypes tse tharo tse amohelang (Rohrer le Kobilka, 1998). The α1 lelapa la receptor le na le α1a, α1b, le α1d. Mong le e mong subtype o kenya phospholipase C mme o hokahanngoa le inositol phosphate sistimi ea bobeli ea len messengerosa ka G-protein Gq. Oa sebetsang hantle oa α1 antagonist e sebelisoang ho etsa lipatlisiso tsa ts'ebeliso ea lithethefatsi ke prazosin. The α2 lelapa le na le α2a, α2b, le α2c. Mong le e mong subtype inhibits adenylate cyclase ka coupling ho inhibitory G-protein Gi. Tse peli tse α2 lithethefatsi tse atisang ho sebelisoa ha ho etsoa lipatlisiso tsa lithethefatsi ke thetse2 agonist clonidine le α2 yohimbine antagonist Lelapa la β-adrenergic receptor le na le β1, β2, le β3. Mong le e mong subtype activates adenylate cyclase ka coupling ho G-protheine Gs. Ke lithethefatsi tse fokolang tsa β-adrenergic tse sibolotsoeng lipatlisisong tsa ts'ebeliso ea lithethefatsi, ntle le β-adrenergic antagonist propranolol, mohlomong ka lebaka la bioavailability e mpe ea boko.

Mohlomong e tsotehang le ho feta ke tšebelisano e phatlalalitsoeng ea methapo ea methapo ea CRF le li-system tsa norepinephrine tsa methapo. E hlalosoa e le sistimi ea ho fepa pele maemong a mangata a makhopho le letsoalo la basal, CRF e kenya tšebetsong norepinephrine, le norepinephrine le eona e etsa tšebetso CRF (Koob, 1999). Bopaki bo bongata ba pharmacologic, physiologic, le anatomic bo tšehetsa karolo ea bohlokoa bakeng sa tšebelisano-hloko ea CRF-norepinephrine seterekeng sa locus coeruleus ho arabela li khatello tsa khatello (Valentino et al., 1991, 1993; Van Bockstaele et al., 1998). Leha ho le joalo, norepinephrine e boetse e susumetsa ho lokolloa ha CRF ka har'a kutu ea methapo ea hypothalamus (Alonso et al., 1986), mookotaba oa bethe ea stria terminalis, le khubu ea bohareng ba amygdala. Litsamaiso tse joalo tsa phepelo li ile tsa etsoa hore li be le bohlokoa bo sebetsang ba ho bokella setho bakeng sa phephetso ea tikoloho, empa mochine o joalo o ka hlaseleha habonolo ho lefu la kelello (Koob, 1999).

4. Amygdala e atolositsoeng: sebopeho sa khatello ea kelello le bokhoba ba tahi

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 tsa tšusumetso ea ho lemalla lithethefatsi e ka kenyelletsa "potoloho e tloaelehileng ea" "neural" e thehang mokhatlo o ikhethileng kahare ho basel, "Alheid le Heimer, 1988). Amygdala e atolositsoeng e emela sebopeho se nang le likarolo tse ngata tsa sebopeho sa motheo sa bokapele: mokokotlo oa bethe ea stria terminalis, amygdala e bohareng ea moea, le sebaka sa phetoho karolong e ka morao ea methapo ea methapo ea methapo (ke hore, khetla la 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 le Alheid, 1991). Lintho tsa bohlokoa tsa amygdala tse atolositsoeng ha li kenyeletse feela li-neurotransmitters tse amanang le litlamorao tse matlafatsang tsa lithethefatsi tsa tlhekefetso, empa le likarolo tse kholo tsa methapo ea khatello ea kelello e amanang le ts'ebetso e mpe ea ts'ehetso (Koob le Le Moal, 2005).

5. Bopaki ba pharmacological bakeng sa karolo ea CRF le norepinephrine maemong a mabe a maikutlo a amanang le ho tlosoa hoa lithethefatsi

Karabelo e tloaelehileng ho tloheng ho matla le ho ithiba ho tloha lithethefatsing tsohle tse kholo tsa tlhekefetso ke ponahatso ea likarabo tse kang tsa ho tšoenyeha kapa tse kang tse khelohang. Mefuta ea liphoofolo e senoletse likarabo tse kang tsa ho tšoenyeha ka litlhare tsohle tse kholo tsa tlhekefetso nakong ea ha motho a khaotsa haholo (Feie. 2). Phapang e itšetlehileng hangata ke karabelo ea maikutlo moqoqong oa nova kapa / kapa oa maikutlo a makatsang, joalo ka lebala le bulehileng kapa karabo e phahameng, kapa karabelo e matla e khothalletsang, e kang ho patela projeke ea motlakase e nang le motlakase. Ho khaotsa ho busoa khafetsa k'hok'heine ho hlahisa karabo e kang ea bokuli maemong a phahameng a tlatsetso le teko ea ho patela, tseo ka bobeli li khutlisoang ke tsamaiso ea bahanyetsi ba CRF (Sarnyai et al., 1995; Basso et al., 1999). Ho khaotsa ho reroa ha opioid ka mokhoa o reriloeng ho boetse ho hlahisa litlamorao tse joalo ka (Schulteis et al., 1998; Harris le Aston-Jones, 1993). Ho khaotsa ho tsoang li-opioids ka mokhoa o reriloeng le hona ho hlahisa mefuta e mengoa (Stinus et al., 1990). Mona, ho fapana le khetho ea sebaka, maemo a litoeba a pepesitsoeng tikolohong e itseng ha a ntse a tlosoa li-opioid nako e teletsana, a sebelisa nako e nyane tikolohong e hulang chelete e ngata ha a hlahisa khetho pakeng tsa tikoloho eo le tikoloho e sa lefelloeng. Tsamaiso ea tsamaiso ea CRF1 receptor antagonist le tsamaiso e etsoang ka kotloloho ea intracerebral ea CRF ea peptide1/ CRF2 antagonist e boetse e fokotse mekhoa e khothalletsang sebaka ea ho khaotsa ho ikhula (opioid)Stinus et al., 2005; Heinrichs et al., 1995). Li-antagonists tsa ts'ebetso tse sebetsang (ke hore, β1 antagonist le α2 agonist) e thibetse ho ts'oaroa ha moea ka mokhoa oa ho tlohela "Delfs et al., 2000).

Feie. 2

Litlamorao tsa mohanyetsi oa CRF ho ethanol, nikotine, cocaine le ho khaotsa ho susumetsoa ke opioid. (A) Kameho ea tsamaiso ea methapo ea kutlo ea CRF peptide antagonist α-helical CRF9-41 likotong tse lekiloeng moahong o moholo o kopaneng ...

Ho tlosoa ha Ethanol ho hlahisa boitšoaro bo kang ba ho tšoenyeha bo khutlisoang ke tsamaiso ea intracerebroventricular ea CRF1/ CRF2 bahanyetsi ba peptidergic (Baldwin et al., 1991), Ts'ebetso ea botsitso ea CRF ea peptidergic1/ CRF2 antagonist ho amygdala (Rassnick et al., 1993), le li-injection tsa systemic tsa CRF e nyane ea molek'hule1 antagonists (Knapp et al., 2004; Overstreet et al., 2004; Funk et al., 2007). Barekisi ba CRF ba kentse intracerebroventricularly kapa ka mokhoa o hlophisehileng ba boetse ba thiba likarabo tse kang tsa ho tšoenyeha tse kang tsa khatello tse bonoang nakong ea ho itšunya-tšunya ho nako ho sa feleng ka ethanol (Breese et al., 2005; Valdez et al., 2003). Ho khaotsa ho noka ho tloha ho nicotine ho hlahisa likarabo tse kang tsa ho tšoenyeha tse khutliselitsoeng ke bahanyetsi ba CRF (Tucci et al., 2003; George et al., 2007). Litlamorao tsena tsa bahanyetsi ba CRF li fumanehile sebakeng se bohareng ba amygdala (Rassnick et al., 1993).

6. Bopaki ba Neurochemical bakeng sa karolo ea CRF le norepinephrine litlamong tse susumetsang tsa ho tlosoa ke lithethefatsi tse mpe

Tsamaiso e sa feleng ea lithethefatsi tsa tlhekefetso ekaba ka ho itaola kapa ho itaola ka ntle ho CRF ho tsoa ho amygdala e atolositsoeng ke Ka vivo microsalysis (Feie. 3). Ho fihlella ka mokhoa o ts'oanang oa ho itaola ka mokhoa o ikemetseng oa koae bakeng sa 12 h ho ekelitse CRF ea li-extracellular CRF ka dialysates tsa khubu ea khubu ea amygdala (Richter le Weiss, 1999). Ho tlosoa hoa opioid ho bakiloeng kamora ho kenella ho sa feleng ha morphine pellet ho likhoto ho eketsehile ka kantle ho CRF karolong e bohareng ea amygdala (Weiss et al., 2001). Tsamaiso ea nicotine e hlobaetsang le ho tlosoa hoa nicotine e sa feleng e phahamisetseng CRF extrahypothalamically ho basb forebrain (Matta et al., 1997). Ho se sebetse hantle ha mofuta oa CRF joalo ka ha ho kile ha bonoa litšoantšong tsa batho ba baholo tse pepesetsoang nicotine nakong ea bocha ebile ho hokahantsoe le phenotype e kang ea ho tšoenyeha (Slawecki et al., 2005). CRF ea extracellular e bontšitsoe hore e eketseha ka har'a khubu ea bohareng ba amygdala nakong ea ho khaola nicotine e sa foleng e tsamaisoang ka minipump (George et al., 2007). Nakong ea ho tlosoa ha ethanol, lits'ebetso tsa CRF tsa extrahypothalamic li fetoha tse matlafatsang, 'me ho na le keketseho ea CRF ea kahare ho khubung ea khubu ea amygdala le bethe ea "stria terminalis" ea likhoto tse itšetlehileng nakong ea ho tlohela ka matla (2-12 h) (Funk et al., 2006; Merlo-Pich et al., 1995; Olive et al., 2002). Ho itlhahisa ho tlositsoeng ponts'o ea nako e telele ea "cannabinoid" ho boetse ho eketsehile CRF karolong e bohareng ea amygdala (Rodriguez de Fonseca et al., 1997). Liphetho tsena ka kakaretso li bonts'a lithethefatsi tsohle tse kholo tsa tlhekefetso li hlahisa keketseho e kholo ea maemo a tsoang kantle ho CRF a lekantsoeng ke Ka vivo microdialysis nakong ea ho khaotsa ho matla ka mor'a ts'ebetso ea lithethefatsi tse sa foleng.

Feie. 3

(A) Litlamorao tsa ho tlosoa hoa ethanol ho ts'ireletso ea mmele ea CRF-CRF-L-IR) ho amygdala e khethiloeng ke microdialysis. Dialysate e ile ea bokelloa ka makhetlo a mane a 2 h makhetlo a neng a fetoloa khafetsa ka linako tse sa tsitsang tsa 2 h. Linako tse nne tsa mehlala e ne e tsamaisana ...

Norepinephrine ke khale a rerile hore e butsoe nakong ea ho tlohela lithethefatsi tsa tlhekefetso. Opioids e fokotse ho thunya ha methapo ea methapo ea kutlo ea kemiso ho "oradrenergic neurons" ho latela locus coeruleus, 'me coeruleus e ile ea kenngoa nakong ea ha ho ne ho etsoa opioid (Nestler et al., 1994). Litlamorao tse sa feleng tsa opioid tsamaisong ea locus coeruleus noradrenergic li bontšitsoe lethathamong le pharalletseng la lithuto ho kenyelletsa ho eketseha ha tsela ea cyclic adenosine monophosphate (cAMP) ea ho saena le polelo e eketsehang ea tyrosine hydroxylase (Nestler et al., 1994). Boithuto ba morao-rao bo bonts'a hore mabaka a neurotrophic (mohlala, neurotrophic factor le neurotrophin-3 e tsoang ho li-neurons tse seng tsa Noradrenergic) e ka ba tsa bohlokoa bakeng sa li-neuroadaptations tsa molek'hule tse tsamaeang tseleng ea locus coeruleus noradrenergic (Akbarian et al., 2001, 2002). Bopaki bo boholo bo boetse bo fana ka maikutlo a hore ho liphoofolo le ho batho, lits'ebetso tse bohareng ba "noradrenergic" li kenelletse nakong ea ha ho tlosoa ka matla ethanol mme ho ka ba le bohlokoa bo susumetsang. Ho itlopa joala ho batho ho amana le ts'ebetso ea ts'ebetso ea noradrenergic ho mokelikeli oa cerebrospinal (Borg et al., 1981, 1985; Fujimoto et al., 1983). Boitšoaro bo sa feleng ba ho itlhompha (ho kenella ha 23 h) ho matlafalitse ho lokolloa ha norepinephrine sebakeng sa "patothricular nucleus" ea hypothalamus (Sharp le Matta, 1993; Fu et al., 2001) le Amygdala (Fu et al., 2003). Leha ho le joalo, nakong ea morao-rao ea tokiso ea 23 h phihlello ea nicotine, maemo a norepinephrine a ne a se a sa phahamisoe amygdala, a fana ka maikutlo a ho hlaka / ho mamella joalo-joalo (Fu et al., 2003).

7. Bopaki ba pharmacological ba karolo ea CRF le norepinephrine ho khothaletso e matla ea ho batla lithethefatsi ho ho tlohela

Bokhoni ba li-agents tsa neuropharmacological ho thibela litlamorao tse kang tsa ho tšoenyeha le maikutlo a ts'oanang a ho tlosoa hoa lithethefatsi bo ka bolela esale pele litlamorao tsa ts'usumetso ea basebeletsi bana lipapatsong tsa liphoofolo tsa phihlello e atileng ea lithethefatsi. Mefuta ea liphoofolo e fihlelletsoeng nako e telele e kenyelletsa ho pepesehela liphoofolo lipakeng tsa ho ikoetlisetsa lithethefatsi kahare (cocaine, 6 h; heroin, 12 h; nicotine, 23 h) le tlhahiso ea mouoane (14 h on / 12 h off) bakeng sa ethanol. Liphoofolo li se li lekoa ka linako tse fapaneng hore li itokolle, ho tloha 2-6 h bakeng sa ethanol ho isa matsatsing a nang le nicotine. Bohanyetsi ba CRF ba ile ba thibela khetho ea lithethefatsi tse amanang le ts'ebeliso e eketsehileng ea ho ikakhela ka setotsoana khoebong ea koae (Specio et al., 2008), nicotine (George et al., 2007), le heroin (Greenwell et al., 2009a). Bohanyetsi ba CRF bo boetse bo thibetse ho ipusa ho eketsehang ha ethanol ho likhoto tse itšetlehileng (Funk et al., 2007) (Lethathamo 1, Feie. 4).

Lethathamo 1

Karolo ea CRF ho itšetleha
Feie. 4

Litholoana tsa CRF e nyane ea molek'hule1 bahanyetsi ba li-receptor ba khahlanong le lithethefatsi ho itaola ho litoeba (A) Phello ea CRF e nyane ea molek'hule1 receptor antagonist MPZP mabapi le ts'ebetso ea ho itaola ea joala (g / kg) literekeng tse ts'epahalang le tse sa ts'epahaleng. Teko e ne e le ...

Bopaki ba libaka tse ikhethileng bokong bo tsamaisang liketso tsena tsa bohanyetsi ba CRF bo thehiloe khubung ea bohareng ba amygdala. Liente tsa bahanyetsi ba CRF ba kentseng ka kotloloho mokokotlong oa amygdala li thibetse likotsi tse tlisoang ke ho tlosoa hoa opioid (Heinrichs et al., 1995) le ho thibela litlamorao tse kang tsa ho rengoa hoa ethanol (Rassnick et al., 1993). Intracerebroventricular tsamaiso ea CRF1/ CRF2 mohanyetsi D-Phe CRF12-41 e thibetse keketseho e bakiloeng ke ts'ebetso ea ho itlhompha ka nako ea boits'oaro bo matla le ho itšila nako e telele (Valdez et al., 2004; Rimondini et al., 2002). Ha e kenngoa ka kotloloho khokahanong e bohareng ea amygdala, litekanyetso tse tlase tsa D-Phe CRF12-41 self ethanol self-management in ratsFunk et al., 2006). CRF2 agonist, urocortin 3, e kentsoeng ka har'a khubu ea "amygdala" e boetse e thibetse boits'ireletso ho ethanol ho likhoto tse itšetlehileng ka ethanol (Funk et al., 2007), ho fana ka tlhahiso ea CRF ea boiphetetso1/ CRF2 ketso e khubung e bohareng ea amygdala e kenyang letsoho lipakeng tsa lino tse tahang tse ntšitsoeng ka thipa ho rat (Bale le Vale, 2004).

Lintlha tsena li fana ka maikutlo a karolo ea bohlokoa bakeng sa CRF, haholo-holo kahare-hare ho amygdala, ho arolelanang tsamaiso e eketsehang ea boits'oaro e amanang le ts'ehetso mme e fana ka maikutlo a hore CRF ka bokapele ba basal le eona e ka ba le karolo ea bohlokoa ntlafatsong ea litlamorao tse tlatselletsang tse susumetsang. e khannang takatso e matla ea lithethefatsi e amanang le cocaine, heroin, le ts'ehetso ea nicotine.

Ts'ehetso e boetse e na le karolo ea lits'ebetso tsa norepinephrine ho tsamaiso ea ethanol le ho tsamaiso e eketsehang ea taolo e amanang le ho its'epa. Bopaki ba bohlokoa bo ts'ehetsa tšebelisano lipakeng tsa methapo ea methapo e bohareng norepinephrine le ho matlafatsa matla le ethanol. Letotong la lithuto tsa pele, Amit le basebetsi-'moho ba bonts'itse hore ts'ebeliso ea ethanol ea boithaopo e fokotsehile ka litšitiso tse khethiloeng ka bobeli tsa pharmacological le neurotoxin tse ikhethang tsa mosebetsi oa noradrenergic (Amit et al., 1977; Brown le Amit, 1977). Tsamaiso ea li-inhibitors tsa dopamine tsa β-hydroxylase tse khethiloeng li hlahisitse khatello e kholo ea tšebeliso ea joala lijaneng tsa pele tse neng li rata joala (Amit et al., 1977). Tsamaiso e bohareng ea neurotoxin 6-hydroxydopamine ho litekanyetso tse felisang haholo norepinephrine neurons le tsona li thibetse tšebeliso ea ethanol ho likhoto (Brown le Amit, 1977; Mason et al., 1979). Intragastric boits'oaro ba ethanol le bona bo ne bo thibetsoe ke thibelo ea dopamine β-hydroxylase (Davis et al., 1979). Mokhethoa oa ho fokotseha hoa norepinephrine ka har'a meroalo ea methapo e phahameng ea CanNUMXBL / 57J e fokotse tšebeliso ea ethanol (Ventura et al., 2006). Litoeba tse nang le "knockout of brain norepinephrine" tse fanoang ka tlhahiso ea dopamine β-hydroxylase, li na le mofuta o fokotsehileng oa ethanol (Weinshenker et al., 2000).

Ho lithuto tsa morao-rao, α1 norazrenergic receptor antagonist prazosin e thibile tšebeliso e eketsehileng ea lithethefatsi tse amanang le ts'ehetso ea ethanol (Walker et al., 2008), keketseho e atolositsoeng ea koae (Wee et al., 2008), le phihlello e kholo ea li-opioid (Greenwell et al., 2009b) (Lethathamo 2, Feie. 5). Kahoo, data e fetolang e fana ka maikutlo a hore tšitiso ea ts'ebetso ea noradrenergic e thibela ts'ebetso ea ethanol, hore methapo ea methapo ea kutlo ea Noradrenergic e matlafatsoa nakong ea ho khaotsa lithethefatsi, le hore litsebi tsa ts'ebetso ea Noradrenergic li ka thibela ts'ebetso e eketsehileng ea lithethefatsi e amanang le ho tlosoa ka matla.

Lethathamo 2

Karolo ea norepinephrine ho itšetleha
Feie. 5

Liphello tsa α1 adrenergic receptor antagonist prazosin mabapi le taolo ea lithethefatsi ho likhoto tse itšetlehileng ka eona. (A) Karabo (± SEM) likarabo tsa ethanol nakong ea linako tsa 30 metsotso ho liphoofolo tse its'epahalletseng le ethanol tse latelang 0.0 le 1.5 ...

8. Cellular sebakeng se bohareng ba "amygdala" bakeng sa tšusumetso ea ts'ebelisano ea CRF le norepinephrine ho itšetleha

Lithuto tsa cellular tse sebelisang mekhoa ea electrophysiological li bonts'itse ts'ebetso ea γ-aminobutyric acid (GABA) kahare ho amygdala e atolositsoeng e ka bonts'a maikutlo a mabe a maikutlo a bohlokoa a susumetsang bakeng sa ts'ebeliso ea lithethefatsi ho ts'ebelisong (Koob, 2008). CRF ka boeona e ntlafatsa GABAA inhibitory postsynaptic potentials (IPSCs) ho lirekoto tsa seleng ea mantlha ea amygdala le bethe ea "stria terminalis" litokisetsong tsa methapo ea boko, mme phello ena e thibetsoe ke CRF1 antagonists mme e koetsoe ho CRF1 Knice KniceNie et al., 2004; Kash le Winder, 2006). Amygdala, CRF e fumaneha sebakeng se kahara karolo ea methapo ea methapo ea methapo ea kutlo (GABAergic neurons) karolong e ka tlas'a bethe ea "stria terminalis" le "kati" ea "amygdala" tse fapaneng le tseo colocalize enkephalin (Letsatsi le al., 1999).

Bakeng sa norepinephrine, bopaki bo fana ka ts'ebetso e ts'oanang mohubeng oa bethe ea stria terminalis eo ho eona lirekoto tsa selulo ka botlalo ho tloha litokisetsong tsa slice li bonts'itseng hore norepinephrine e ntlafalitse methapo ea methapo ea kutlo ea "GABAergic". Phello ea noradrenergic e ne e bonahala e le teng ka α1 receptor (Dumont le Williams, 2004). Haeba datha e tsoang mokokotlong oa "amygdala" le "nucleus" ea "stria terminalis" e kopantsoe, lintlha tse itseng li tla bonahala: CRF le norepinephrine li eketsa ts'ebetso ea GABAergic, liketso tse maemong a seleng tse tsamaellanang le litlamorao tsa boits'oaro tse hlalositsoeng kaholimo ka neuropharmacological lithuto.

Hobane lithethefatsi tsa GABAergic hangata ke li-anxiolytics tse matla, taba ea hore li-neurotransmitters tse tsosang takatso li ka hlahisa tšebetsong ea methapo ea kutlo ea "Gabaergic" le "neurotransmitters" li ka sithabetsa phetiso ea GABAergic sebakeng sa boko se tsejoang ho ameha ka boits'oaro bo amanang le khatello ea maikutlo. Leha ho le joalo, ts'ebetso ea GABAergic ea lehae kahare ho khubung e bohareng ea amygdala e kanna ea susumetsa karabelo ea methapo ea methapo ea kutlo ea inhibitory ea methapo ea methapo ea methapo e laolang tlhaiso-leseling ka methati ea tikoloho ea amygdaloidal (ke hore, ka disinhibition ea methapo e bohareng ea amygdala) ho eketsa thibelo libakeng tse tlase tse parolang karabelo ea boitšoaro (Feie. 6).

Feie. 6

Neurocircuitry mokokotlong o bohareng ba amygdala amanang le CRF le norepinephrine ho tlosoa ka khothalletso. CRF ha e sebelisetsoe feela ho khanna li-interneurons tsa GABAergic tse tsamaisang methapo ea maikutlo le methapo ea kutlo, empa hape le ho otloloha ka kotloloho. ...

Liphetoho ho li-neurotransmission tsamaisong ea khatello ea kelello ka nts'etsopele ea ho its'etleha li ka bonts'a sensitization ea GABAergic neuron ho liketso tsa khatello ea kelello / lits'ebetso tsa anti-khatello ea maikutlo. Ho lokolloa ha GABA ho tlisoang ke ethanol karolong e bohareng ea amygdala ho eketsehile le ho feta liphoofolong tse its'epileng, tse bonts'itsoeng ka bobeli ka elektrophysiological le Ka vivo mehato ea microsalysis (Roberto et al., 2004). Kholiso ea ethanol e kenyellelitsoeng ho GABAergic IPSCs e koetsoe ke CRF1 antagonists (Nie et al., 2004; Roberto et al., 2004) mme ha ea ka ea bonoa ho CRF1 Knice KniceNie et al., 2004). Kahoo, liphetoho tse sa feleng tse bakang ts'ebetso ea methapo ea kutlo ea li-neuronal tsa li-interneurons tsa GABA karolong e bohareng ea amygdala li ka hokahanngoa le boemo ba cellular le liketso tsa CRF tse bonts'ang sephetho sa boitšoaro mefuteng ea liphoofolo ea ho itlopa joala.

Ho fanoa ka hore boholo ba li-neuron tse bohareng ba li-amygdala ke GABAergic (Letsatsi le Cassell, 1993), mochine o arolelanang liphofu tse ka tlase tsa noka e amanang le linaha tsa maikutlo o ka supa li-neurons tse thibelang nako le nako kapa tse amanang le phepelo ea methapo ea kutlo kapa li-inhibitory tsa projene tsa neurons ho li-brainstem kapa libakeng tse tlase (mohlala, bethe ea boko ba stria terminalis). Kahoo, karolo e bohareng ea amygdala e kanna ea hlalosoa e le "heke" e laolang phallo ea tlhahisoleseling lipotolohong tsa intra-amygdaloidal. Ho feta moo, ho hlophisoa hantle ha GABAergic inhibitory system karolong e bohareng ea amygdala e ka ba ntho ea bohlokoa bakeng sa ho laola li-neuron tsa lehae le tse hlahisoang ho ea tlase mochesong oa li-nuclei (Feie. 6).

9. Sistimi ea khatello ea kelello le bokhoba ba tahi

Bokhoba ba lithethefatsi, bo tšoanang le mafu a mang a bophelo bo sa feleng le kelello bo joalo ka khatello e phahameng ea mali, bo mpefala ha nako e ntse e ea, bo tlas'a tšusumetso e kholo ea tikoloho (mohlala, khatello ea ka ntle), 'me bo siea mohlala o setseng oa tumellano o lumellang "tšebeliso e mpe" ea maikutlo hape le lilemo kamora ho khaotsoa le ho ila thipa. Litšobotsi tsena tsa bokhoba ba lithethefatsi li lebisitse ho ho lekantsoeng ha bokhoba ba lithethefatsi e le taba feela ea taolo ea homeostatic ea ts'ebetso ea maikutlo, empa joalo ka karohano e matla le homeostasis ea lits'ebetso tsena li bitsoa allostasis (Koob le Le Moal, 2001; Koob le Le Moal, 2008). Motsoako o hlalositsoeng mona ke hore bokhoba ba lithethefatsi bo emeloa ke mokhoa oa ho phomola o laolang tlhaho le phoofolo. Allostasis e hlalosoa e le botsitso ka ho fetoha le ntlha e fetotsoeng (Sterling le Eyer, 1988) hape e kenyelletsa mochine o fetisang phepelo ho fapana le mekhoa e mebe ea ho fana ka maikutlo a homeostasis. Sisteme e fanang ka phepo e na le melemo e mengata bakeng sa ho fihlela litlhoko tsa tikoloho. Mohlala, ho homeostasis, ha tlhoko e eketsehang e hlahisa letšoao, ho fana ka maikutlo a fosahetseng ho ka lokisa tlhokahalo, empa nako e hlokahalang e ka ba telele le lisebelisoa li kanna tsa se fumanehe. Ho hlahlojoa khafetsa ha tlhoko le phetoho e tsoelang pele ea litekanyetso tsohle ho fihlela liteisheneng tse ncha ho kenyelletsoa hore li etsahale ka allostasis. Bokhoni bona ba ho bokella lisebelisoa ka potlako le ho sebelisa mekhoa ea ho iphelisa e ka lebisa ho linaha tse tšabehang haeba lits'ebetso li se na nako e lekaneng ea ho theha 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).

Motsoako o hlalositsoeng mona ke hore lits'ebetso tsa khatello ea kelello li arabela ka potlako ho mathata a lebelletsoeng ho homeostasis (ho sebelisa lithethefatsi tse ngata haholo) empa li lieha ho lula kapa ho se koaloe hang ha li 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. Tšebelisano lipakeng tsa CRF le norepinephrine bokong ba methapo ea kelello le basal, ka menehelo e tsoang lits'ebetsong tse ling tsa khatello ea kelello, e ka lebisa maemong a sa feleng a maikutlo a kang a amanang le bokhoba (Koob le Le Moal, 2001).

Litaba tse joalo tse mpe tsa maikutlo li kenella haholo nakong ea ho tlohela lithethefatsi tse mpe tsa tlhekefetso empa hape li "khothatsoa" maemong a mabeli a amanang le ho khutlela morao ho batla lithethefatsi. Sebaka sa pele ke ho aha lintho tse thibeloang nako eohle. Matšoao a mangata a khethiloeng ke linaha tse sithabetsang tsa maikutlo a ntse a tsoela pele nako e telele kamora hore a khaotse ho lithethefatsi tsa tlhekefetso. Ho tlohela ts'ebeliso ea lino tse tahang, mohlala, ho hlahile haholo bathong, moo ho tenehang, tsitsipano le matšoenyeho ho tlalehiloeng ho phehella ho tloha libekeng tsa 5 kamora ho tlohela ho fihlela ho fihlela likhoeli tsa 9 (Roelofs, 1985; Alling et al., 1982). Matšoao ana, ho tlohela ka mor'a ho ba boiqapelo, a tloaetse ho amana le tlhaho le ho putlama hangata mme a etella pele ho khutlela morao (Hershon, 1977; Annis et al., 1998). Lethathamo le ka pele la ho khutla hape le ama hampe (Zywiak et al., 1996; Lowman et al., 1996). Thutong ea bobeli ea bakuli tekong ea bongaka ea beke ea 12 e ts'ehetsoeng joala mme e sa kopane le maemo afe kapa afe a amanang le lefu la maikutlo la DSM-IV, kamano le ho khutla hape le boemo bo bobe bo amanang le bobe bo ne bo le matla haholo (Mason et al., 1994). Mosebetsi oa liphoofolo o bonts'itse hore pele ho ts'epa ho theola tlase ho theola "ts'epo ea ho ts'epahalla" hoo liphoofolo tse neng li itšepa pele li neng li tšepisitsoe hape li bonts'ang matšoao a matla a ho tlohela mmele ho feta lihlopha tse amohelang joala lekgetlo la peleBranchey et al., 1971; Baker le Cannon, 1979; Becker le Hale, 1989; Becker, 1994). Nalane ea ho itšetleha ka likhoto tsa Wistar tsa banna e ka hlahisa kholo ea nako e telele taolong ea ethanol kamora ho ikhula ho matla le ho tlosoa setulong (Roberts le al., 2000; Rimondini et al., 2002, 2008; Sommer et al., 2008). Keketseho ea boits'oaro e boetse e tsamaisana le karabelo e eketsehang ea boits'oaro ho khatello ea maikutlo le karabelo e eketsehang ho bahanyetsi ba lits'ebetso tsa CRF tsa boko (Valdez et al., 2003, 2004; Gehlert et al., 2007; Sommer et al., 2008).

Sebaka sa bobeli ke maikutlo a eketsehang a ho khutlisetsa mekhoa ea ho batla lithethefatsi e bontšitsoeng ho khutlisetsoa ka kelellong. Likhatello tse fapaneng, bathong le liphoofolong, li tla khutlisetsa ho batla lithethefatsi. Ho liphoofolo, hangata ho batla lithethefatsi hoa tima ka ho pepesetsoa khafetsa tikolohong e batlang lithethefatsi ntle le lithethefatsi le maemong a ts'ebetso ho pepesehela karabelo ea mofani ntle le lithethefatsi. Khatello ea khatello ea maikutlo, joalo ka footshock, khatello ea maikutlo sechabeng, kapa khatello ea meriana (mohlala, yohimbine) e khutlisa boitšoaro bo batlang lithethefatsi. Potoloho e khutšoane ea ho khutlisa khatello ea maikutlo e bakiloeng ke khatello e kholo e tsamaellanang le ho khaotsa ho matla ho susumetsang ho hlalositsoeng ka holimo (Shaham le al., 2003). Nalane ea ho ts'epa e eketsa ts'ebetso e tlisoang ke khatello ea maikutlo (Liu le Weiss, 2002).

Liphephetso tse phetoang (mohlala, tšebeliso e feteletseng ea lithethefatsi tsa tlhekefetso) li lebisa boitekong ba kelello ka liphetoho tsa lisele, tsa cellular le tsa neurocircuit ho boloka botsitso empa ka litšenyehelo. Bakeng sa sebopeho sa bokhoba ba lithethefatsi se hlakisitsoeng mona, ho kheloha masala ho tsoa ho melao e tloaelehileng ea maikutlo a kelello (ke hore naha e mameloang) e khothatsoa ke liphetoho tse ngata tse amanang le methapo ea kutlo, ho kenyelletsa mosebetsi o fokotsehileng oa mekotla ea meputso, tahlehelo ea taolo e phahameng, ho tsamaisa mekhatlo ea khothatso le karabelo e ntle ea tsamaiso ea khatello ea kelello e hlalositsoeng ka holimo. Lits'ebetso tsa khatello ea kelello tse senyehileng li eketsoa ka matla ho kenya letsoho ho tlatselletsong ha ho batla lithethefatsi le ho ts'oara lithethefatsi le ho khutlela bothateng ba ho batla lithethefatsi le ho ts'oara lithethefatsi tse tsejoang ka hore ke tšebeliso ea lithethefatsi (Koob, 2009).

10. Kakaretso le liqeto

Ho itšunya-tšunya ho lithethefatsi tsohle tse kholo tsa tlhekefetso ho eketsa meputso, likarabo tse kang ho tšoenyeha, le CRF ho amygdala, e 'ngoe le e' ngoe e nang le bohlokoa bo susumetsang. Ts'ebeliso e matla ea lithethefatsi e amanang le ho ts'ehetsoa ha e anngoe feela ke ho lahleheloa ke ts'ebetso ea lits'ebetso tsa moputso empa hape le ho hira lits'ebetso tsa khatello ea kelello tse kang CRF le norepinephrine ho amygdala e atolositsoeng. Mekhoa ea brain arousal / khatello ea maikutlo ho amygdala e atolositsoeng e kanna ea ba karolo ea maikutlo a maikutlo a mabe a tsamaisang ts'ebeliso ea lithethefatsi tsa tlhekefetso mme a ka feta ka likarolo tse mpe tsa maikutlo tse ling tsa psychopathologies tse ling.

lumela hore baa fokola

Ena ke nomoro ea phatlalatso 19930 e tsoang ho TheHTMLps Research Institute. Patlisiso e tšehelitsoe ke Setsi sa Pearson sa Alcoholism le Tlatsetso ea Tlatsetso le Litsi tsa Sechaba tsa lithuso tsa bophelo bo botle AA06420 le AA08459 ho tsoa Setsing sa Naha sa Ts'ebeliso e Mpe ea Joala le Tahi, DA04043 le DA04398 ho tsoa Setsing sa Naha sa Ts'ebeliso e Mpe ea Lithethefatsi, le DK26741 ho tsoa Setsing sa Naha sa Lefu la Ts'oaetso. Le Mafu a Ts'oaetso le a Liphio. Sengoli se rata ho leboha Mike Arends ka thuso ea hae mabapi le ho hlophisoa ha letsoho.

References

  • Akbarian S, Bates B, Liu RJ, Skirboll SL, Pejchal T, Coppola V, Sun LD, Fan G, Kucera J, Wilson MA, Tessarollo L, Kosofsky BE, Taylor JR, Bothwell M, Nestler EJ, Aghajanian GK, Jaenisch R .Nurotrophin-3 modulates Noradrenergic neuron function le ho tloheloa ke opiate. Mol Psychiatry. 2001;6: 593-604. [E fetotsoe]
  • Akbarian S, Rios M, Liu RJ, Gold SJ, Fong HF, Zeiler S, Coppola V, Tessarollo L, Jones KR, Nestler EJ, Aghajanian GK, Jaenisch R. Boreleli bo hlahisitsoeng ke neurotrophic bo hlokahala bakeng sa polasetiki e hlahisitsoeng ke "opadateate" ea noradrenergic. methapo. J Neurosci. 2002;22: 4153-4162. [E fetotsoe]
  • Alheid GF, Heimer L. Liphetoho tse ncha ho mokhatlo oa basal forebrain tsa bohlokoa bo ikhethileng bakeng sa mathata a amanang le neuropsychiatric: likarolo tsa striatopallidal, amygdaloid, le corticopetal tsa substantia innominata. Khopolo-taba. 1988;27: 1-39. [E fetotsoe]
  • Alling C, Balldin J, Bokstrom K, Gottfries CG, Karlsson I, Langstrom G. Lithuto mabapi le nako ea ho hlaphoheloa ha morao ka mor'a ts'ebeliso e mpe ea ethanol: thuto ea sefapano ea matšoao a biochemical le psychiatric. Phallo ea Psychiatr Scand. 1982;66: 384-397. [E fetotsoe]
  • Alonso G, Szafarczyk A, Balmefrezol M, Assenmacher I. Bopaki ba Immunocytochemical bakeng sa taolo e susumetsang ke "ventral noradrenergic bundle" ea "parrestellular neurons" ea "patortricular nucleus" e hlahisang li-corticotropin tse lokollang lihormone le vasopressin ka likhoto. Resin ea Boko. 1986;397: 297-307. [E fetotsoe]
  • Mokhatlo oa Maiketsetso oa Amerika. Buka ea ho hlahloba le ea Statistical ea Mathata a kelello. 4th. Mochine oa khatello ea kelello oa Amerika; Washington DC: 1994.
  • Amit Z, brown ZW, Levitan DE, Ogren SO. Noradrenergic mediation ea thepa e matlafatsang ea ethanol: I. Khatello ea tšebeliso ea ethanol litsing tsa laboratori tse latelang thibelo ea dopamine-beta-hydroxylase. Arch Int Pharmacodynam Ther. 1977;230: 65-75.
  • Annis HM, Sklar SM, Moser AE. Bong bo amanang le ho khutlisetsa maemo a tlokotsi, ho sebetsana ka katleho le sephetho har'a ba lemaletseng joala. Ho lemalla Behav. 1998;23: 127-131. [E fetotsoe]
  • Baker TB, Cannon DS. Monyetla oa ho tlosoa hoa ethanol ka ho its'etleha pele. Psychopharmacology. 1979;60: 105-110. [E fetotsoe]
  • Baldwin HA, Rassnick S, Rivier J, Koob GF, Britton KT. Mohanyetsi oa CRF o khutlisetsa karabo "ea ho tšoenyeha" ho tlosoa ha ethanol ka hara rat. Psychopharmacology. 1991;103: 227-232. [E fetotsoe]
  • Bale TL, Vale WW. Li-CRF le li-receptors tsa CRF: karolo ea boikarabello ba khatello ea maikutlo le boits'oaro bo bong. Annu Rev Pharmacol Toxicol. 2004;44: 525-557. [E fetotsoe]
  • Basso AM, Spina M, Rivier J, Vale W, Koob GF. Corticotropin-releasing factor antagonist e bonts'a phello e "ts'oenyehileng joalo" ts'ebetsong ea ho patela e ts'ireletso empa eseng molekong o phahameng le o mong o latelang koae ea cocaine e sa foleng. Psychopharmacology. 1999;145: 21-30. [E fetotsoe]
  • Becker HC. Kamano e ntle lipakeng tsa palo ea likhechana tsa pele tsa ho khaotsa ethanol le ho teba ha lithahasello tsa kamoso tse latelang tsa ho khaotsa. Psychopharmacology. 1994;116: 26-32. [E fetotsoe]
  • Becker HC, Hale RL. Ho hlohlelletsa mofuta oa locomotor oa tšusumetso ho litoeba tsa C57BL / 6 kamora tsamaiso ea RO15-4513. Psychopharmacology. 1989;99: 333-336. [E fetotsoe]
  • Borg S, Kvande H, Sedvall G. Central norepinephrine metabolism nakong ea tahi e nang le tahi ho lithethefatsi le baithaopi ba phetseng hantle. Saense. 1981;213: 1135-1137. [E fetotsoe]
  • Borg S, Czamecka A, Kvande H, Mossberg D, Sedvall G. Maemo a boemo ba bophelo le ho tsepamisa maikutlo ha MOPEG ho mokelikeli oa mokokotlo oa bakuli ba joala ba banna nakong ea ho ikhula. Alcohol Clinic Exp Res. 1985;9: 103-108. [E fetotsoe]
  • Branchey M, Rauscher G, Kissin B. Liphetoho karabong ea joala kamora ho thehwa hoa ts'ehetso ea 'mele. Psychopharmacologia. 1971;22: 314-322. [E fetotsoe]
  • Breese GR, Overstreet DH, Knapp DJ, Navarro M. Ho tlosoa hangata ha ethanol ho matlafatsa khatello ea maikutlo e kang boits'oaro: ho thibela ke CRF1- le bahanyetsi ba benzodiazepine-receptor le 5-HT1a-receptor agonist. Neuropsychopharmacology. 2005;30: 1662-1669. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Brown ZW, Amit Z. Litlamorao tsa ho ikhetholla ha catecholamine ka 6-hydroxydopamine ka khetho ea ethanol ho likhoto. Neurosci Lett. 1977;5: 333-336. [E fetotsoe]
  • Burchfield S. Karabelo ea khatello ea maikutlo: pono e ncha. Psychosom Med. 1979;41: 661-672. [E fetotsoe]
  • Charlton BG, Ferrier IN, Perry RH. Ho tsamaisoa ha corticotropin-releasing factor-like immunoreacaction bokong ba motho. Neuropeptides. 1987;10: 329-334. [E fetotsoe]
  • Davis WM, Werner TE, Smith SG. Ho matlafatsa le infusionsastric infusions ea ethanol: thibelo ea FLA 57. Pharmacol Biochem Behav. 1979;11: 545-548. [E fetotsoe]
  • Letsatsi HE, Curran EJ, Watson SJ, Jr, Akil H. Distinct methapo ea methapo ea kutlo karolong e bohareng ea "amygdala" le "bed" ea "stria": bopaki ba ts'ebetso ea bona e khethiloeng ke interleukin-1β J Comp Neurol. 1999;413: 113-128. [E fetotsoe]
  • Delfs JM, Zhu Y, Druhan JP, Aston-Jones G. Noradrenaline e setulong sa methapo ea methapo e bohlokoa bakeng sa boiphetetso bo etsang hore motho a khahloe ke moea. Tlhaho. 2000;403: 430-434. [E fetotsoe]
  • Dumont EC, Williams JT. Noradrenaline e baka GABAA inhibition of bed nucleus of the stria terminalis neurons e kenella sebakeng sa moea oa mokokotlo oa ventral. J Neurosci. 2004;24: 8198-8204. [E fetotsoe]
  • Fu Y, Matta SG, Brower VG, Sharp BM. Secoretion ea Norepinephrine ho hypothalamic paraventricular nucleus ea likhoto nakong ea phihlello e sa lekanyetsoang ea nicotine e ikemetseng: thuto ea vivo micodialysis. J Neurosci. 2001;21: 8979-8989. [E fetotsoe]
  • Fu Y, Matta SG, Kane VB, Sharp BM. Ho lokolloa ha Norepinephrine ho amygdala ea likhoto nakong ea boits'oaro bo sa feleng ba nicotine: an Ka vivo ho ithuta ka microdialysis. Neuropharmacology. 2003;45: 514-523. [E fetotsoe]
  • Fujimoto A, Nagao T, Ebara T, Sato M, Otsuki S. Cerebrospinal fluid fluid monoamine metabolites nakong ea ho khaotsa joala le ho hlaphoheloa. Biol Psychiatry. 1983;18: 1141-1152. [E fetotsoe]
  • Funk CK, O'Dell LE, Crawford EF, Koob GF. Corticotropin-releasing factor in the main nucleus of amygdala mediates ntlafatso ea boitšoaro ea ethanol maemong a khaotsoeng, likhoto tse itšetlehileng ka ethanol. J Neurosci. 2006;26: 11324-11332. [E fetotsoe]
  • Funk CK, Zorrilla EP, Lee MJ, Rice KC, Koob GF. Corticotropin-releasing factor 1 antagonists khetha ka tsela e itseng e fokotsa ho itaola ha ethanol ho likhoto tse itšetlehileng ka ethanol. Biol Psychiatry. 2007;61: 78-86. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Gehlert DR, Cippitelli A, Thorsell A, Le AD, Hips mosa PA, Hamdouchi C, Lu J, Hembre EJ, Cramer J, Pina M, McKinzie D, Morin M, Ciccocioppo R, Heilig M. 3- (4-Chloro-2 -morpholin-4-yl-thiazol-5-yl) -8- (1-ethylpropyl) -2,6-dimethyl-imidazo [1,2-b] pyridazine: "bongo-penetrant", "corticantant" e fumanehang ka molomo, e fumanehang hape e na le corticon. katleho ho mehlala ea liphoofolo tsa joala. J Neurosci. 2007;27: 2718-2726. [E fetotsoe]
  • George O, Ghozland S, Azar MR, Cottone P, Zorrilla EP, Parsons LH, O'Dell LE, Richardson HN, Koob GF. CRF-CRF1 ts'ebetso ea ts'ebeliso ea methapo e hokahanya keketseho ea ho nts'etsopele ea ho nicotine ho likhoto tse itšetlehileng ka nicotine. Proc Natl Acad, Science US A. 2007;104: 17198-17203. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Greenwell TN, Funk CK, Cottone P, Richardson HN, Chen SA, Rice K, Lee MJ, Zorrilla EP, Koob GF. Corticotropin-releasing factor-1 receptor antagonists e fokotsa ho itaola ha heroin ka nako e telele, empa eseng litheolelo tsa nako e khuts'oanyane. Ho lemalla Moferefere. 2009a;14: 130-143. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Greenwell TN, Walker BM, Cottone P, Zorrilla EP, Koob GF. Prazosin ea í1 adrenergic receptor antagonist e fokotsa boikemelo ba heroin ka litekong ka phihlello e atolositsoeng ea tsamaiso ea heroin. Pharmacol Biochem Behav. 2009b;91: 295-302. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Harris GC, bahanyetsi ba Aston-Jones G. β-Adrenergic ba hlahisa matšoenyeho a ho tlosa litšebelisong tsa likhoto tse itšetlehileng ka koae le morphine. Psychopharmacology. 1993;113: 131-136. [E fetotsoe]
  • Hauger RL, Grigoriadis DE, Dallman MF, Plotsky PM, Vale WW, Dautzenberg FM. International Union of Pharmacology: XXXVI. Boemo ba hona joale ba nomenclature ea li-receptors tsa corticotropin-releasing factor le ligands tsa bona. Pharmacol Rev. 2003;55: 21-26. [E fetotsoe]
  • Heilig M, Koob GF. Karolo ea bohlokoa bakeng sa ho lopolla bokhoba ba corticotropin. Trends Neurosci. 2007;30: 399-406. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Heimer L, Alheid G. piecing hammoho puzzle of basal forebrain anatomy. Ka: Napier TC, Kalivas PW, Hanin I, bahlophisi. Tlhaselo ea Basal: Ho Utloisisa Mosebetsi. Tsoelo-pele ho Bongaka ba Tlhahlobo le Biology. Moq. 295. Plenum Press; New York: 1991. maq. 1-42.
  • Heinrichs SC, Menzaghi F, Schulteis G, Koob GF, Stinus L. Tlhatlhobo ea sesosa sa corticotropin ho lokolleng hoa amygdala e fumana litlamorao tse bohloko tsa ho tlosoa ha morphine. Behav Pharmacol. 1995;6: 74-80. [E fetotsoe]
  • Hennessy JW, Levine S. Khatello ea maikutlo, tsamaiso ea boroko le lefu la pituitary-adrenal: hypothesis ea psychoendocrine. Ka: Sprague JM, Epstein AN, bahlophisi. Tsoelo-pele ho Psychobiology le Psychology Psychology. 8th. Press Press; New York: 1979. maq. 133-178.
  • Hershon HI. Matšoao a ho khaotsa joala le tloaelo ea ho noha. J Sekolo sa joala. 1977;38: 953-971. [E fetotsoe]
  • Johnston JB. Likeletso tse ling hape thutong ea ho iphetola ha limela. J Comp Neurol. 1923;35: 337-481.
  • Kash TL, Winder DG. Neuropeptide Y le c orticotropin-releasing factor bi-mwelekeo o tsamaisang phetisetso ea li-inhibitory synaptic mokokotlong oa bethe ea stria terminalis. Neuropharmacology. 2006;51: 1013-1022. [E fetotsoe]
  • Knapp DJ, Overstreet DH, Moy SS, Breese GR. SB242084, flumazenil, le CRA1000 thibela ethanol e tlosang matšoenyeho lithutong. Joala. 2004;32: 101-111. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Koob GF. Corticotropin-releasing factor, norepinephrine le khatello ea maikutlo. Biol Psychiatry. 1999;46: 1167-1180. [E fetotsoe]
  • Koob GF. Pono e khothalletsoang ka hohle-hohle: litlamorao ho psychopathology. Ka: Bevins RA, Bardo MT, bahlophisi. Lintlha Tseo U li Tsotelletsang Thutong ea Tsamaiso ea Lithethefatsi. Nebraska Symposium on Motivation. Moq. 50. Univesithi ea Nebraska Press; Lincoln NE: 2004. maq. 1-18.
  • Koob GF. Karolo ea litsamaiso tsa khatello ea kelello bokhobeng. Neuron. 2008;59: 11-34. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Koob GF. Li-substrates tsa Neurobiological bakeng sa lehlakore le lefifi la ho qobella ho lemalla. Neuropharmacology. 2009;56(Suppl 1): 18-31. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Koob GF, Le Moal M. Tlhekefetso ea lithethefatsi: dysregulation ea hedonic homeostatic. Saense. 1997;278: 52-58. [E fetotsoe]
  • Koob GF, Le Moal M. Bokhoba ba lithethefatsi, khatello ea moputso le allostasis. Neuropsychopharmacology. 2001;24: 97-129. [E fetotsoe]
  • Koob GF, Le Moal M. Plasticity ea moputso oa neurocircuitry le 'lehlakore le lefifi' la bokhoba ba lithethefatsi. Nat Neurosci. 2005;8: 1442-1444. [E fetotsoe]
  • Koob GF, Le Moal M. Neurobiology ea Tlatsetso. Press Press; London: 2006.
  • Koob GF, Le Moal M. Tlatsetso le ts'ebetso ea boikoetliso ba kelello. Annu Rev Psychol. 2008;59: 29-53. [E fetotsoe]
  • Lewis K, Li C, Perrin MH, Blount A, Kunitake K, Donaldson C, Vaughan J, Reyes TM, Gulyas J, Fischer W, Bilezikjian L, Rivier J, Sawchenko PE, Vale WW. Khethollo ea urocortin III, setho se eketsehileng sa lelapa la corticotropin-releasing factor (CRF) le nang le kamano e phahameng bakeng sa CRF2 receptor. Proc Natl Acad Sci US 2001;98: 7570-7575. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Li C, Vaughan J, Sawchenko PE, Vale WW. Urocortin III-immunoreactiveakanyo ea kelello bokong ba ratoa ka ho fetellana ka libaka tsa mofuta oa 2 corticotrophin-releasing factor receptor expression. J Neurosci. 2002;22: 991-1001. [E fetotsoe]
  • Liu X, Weiss F. Tlatsetso ea khatello ea maikutlo le lithahasello tsa lithethefatsi mabapi le ho khutlisetsoa hoa takatso ea ethanol: ho eketsoa ke nalane ea ho ts'epa le karolo ea ts'ebetso e ts'oanang ea ts'ebetso ea corticotropin-e lokollang le mekhoa ea opioid. J Neurosci. 2002;22: 7856-7861. [E fetotsoe]
  • Lowman C, Allen J, Stout RL. Ho pheta-pheta le katoloso ea lekhetho la Marlatt la likotsi tse khutlang hape: kakaretso ea lits'ebetso le liphetho. Sehlopha sa Lipatlisiso se Khutlang. Mathata. 1996;91(Suppl): S51-S71. [E fetotsoe]
  • Mason ST, Corcoran ME, Fibiger HC. Manonyeletso a Noradrenaline le ethanol ho rat. Neurosci Lett. 1979;12: 137-142. [E fetotsoe]
  • Mason BJ, Ritvo EC, Morgan RO, Salvato FR, Goldberg G, Welch B, Mantero-Atienza E. Patlisiso e laoloang habeli, e laoloang ke placebo ho lekola katleho le polokeho ea nalmefene HCl ea molomo bakeng sa ts'ebeliso ea joala. Alcohol Clinic Exp Res. 1994;18: 1162-1167. [E fetotsoe]
  • Matta SG, Valentine JD, Sharp BM. Ts'ebetso ea Nicotinic ea li-neurons tsa CRH libakeng tsa bongoaneng tsa extrahypothalamic tsa boko ba rat. Endocrine. 1997;7: 245-253. [E fetotsoe]
  • Merlo-Pich E, Lorang M, Yeganeh M, Rodriguez de Fonseca F, Raber J, Koob GF, Weiss F. Keketseho ea maemo a kantle ho corticotropin-a ho lokolla a lekanang le a amanang le ts'ireletso nakong ea amygdala ea litoeba tse tsohileng nakong ea khatello ea khatello le ho tlosoa ha ethanol joalo ka ha ho lekantsoe ka microdialysis. J Neurosci. 1995;15: 5439-5447. [E fetotsoe]
  • Nestler EJ, Alreja M, Aghajanian GK. Mehato ea limolek'hule le tsa cellular tsa ketso ea opiate: lithuto ho rat locus coeruleus. Brain Res Bull. 1994;35: 521-528. [E fetotsoe]
  • Nie Z, Schweitzer P, Roberts AJ, Madamba SG, Moore SD, Siggins GR. Ethanol e ntse e fetisa phetisetso ea GABAergic bohareng ba amygdala ka CRF1 li-receptors. Saense. 2004;303: 1512-1514. [E fetotsoe]
  • Olive MF, Koenig HN, Nannini MA, Hodge CW. Maemo a phahamisitsoeng a extracellular CRF mokokotlong oa bethe ea stria terminalis nakong ea ho tlosoa ha ethanol le phokotso ka ho kenella ha ethanol nakong e tlang. Pharmacol Biochem Behav. 2002;72: 213-220. [E fetotsoe]
  • Overstreet DH, Knapp DJ, Breese GR. Ho feto-fetoha ha mekhoa e mengata ea ho ts'oaroa ha ethanol e tlisoang ke CRF le CRF1 li-receptors. Pharmacol Biochem Behav. 2004;77: 405-413. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Pfaff D. Khopolo ea Brain Arousal le Tlhahisoleseling: Mechanisms ea Neural and genetic. Harvard University Press; Cambridge MA: 2006.
  • Rassnick S, Heinrichs SC, Britton KT, Koob GF. Microinjection ea corticotropin-releasing factor antagonist ho "nucleus" e bohareng ea amygdala e khutlisa litlamorao tse ts'oanang le ethanol. Resin ea Boko. 1993;605: 25-32. [E fetotsoe]
  • Reyes TM, Lewis K, Perrin MH, Kunitake KS, Vaughan J, Arias CA, Hogenech JB, Gulyas J, Rivier J, Vale WW, Sawchenko PE. Urocortin II: setho sa lelapa la neuropeptide la corticotropin-releasing factor (CRF) le khethiloeng ka khetho ea mofuta oa li-receptors tsa 2 CRF. Proc Natl Acad Sci US 2001;98: 2843-2848. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Richardson HN, Zhao Y, Fekete EM, Funk CK, Wirsching P, Janda KD, Zorrilla EP, Koob GF. MPZP: mofuta o monyane oa molek'hule o bitsoang corticotropin-releasing factor mofuta oa 1 receptor (CRF)1) mohanyetsi. Pharmacol Biochem Behav. 2008;88: 497-510. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Richter RM, Weiss F. Ka vivo Ho lokolloa ha CRF ho rat amygdala ho eketsoa nakong ea ha ho khaotsa koae ho litheko. Synapse. 1999;32: 254-261. [E fetotsoe]
  • Rimondini R, Arlinde C, Sommer W, Heilig M. Keketseho e sa feleng ea tšebeliso ea boithaopo ea ethanol le molaoana o hatisitsoeng bokong ba rat ka mor'a ho pepesetsoa joala nako le nako. FASEB J. 2002;16: 27-35. [E fetotsoe]
  • Rimondini R, Sommer WH, Dall'Olio R, Heilig M. Ho mamella joala ka nako e telele ho latela nalane ea ho itšetleha. Ho lemalla Moferefere. 2008;13: 26-30. [E fetotsoe]
  • Roberto M, Madamba SG, Stouffer DG, Parsons LH, Siggins GR. Ho eketsoa ha GABA ka har'a amygdala e bohareng ea likhoto tse itšetlehileng ka ethanol. J Neurosci. 2004;24: 10159-10166. [E fetotsoe]
  • Roberts AJ, Heyser CJ, Cole M, Griffin P, Koob GF. Ho nwa haholo hoa ethanol ka mora nalane ea ho its'epa: mohlala oa liphoofolo oa allostasis. Neuropsychopharmacology. 2000;22: 581-594. [E fetotsoe]
  • Rodriguez de Fonseca F, Carrera MRA, Navarro M, Koob GF, Weiss F. Ts'ebetso ea corticotropin-e lokollang sesosa tsamaisong ea limbic nakong ea ho khaotsa cannabinoid. Saense. 1997;276: 2050-2054. [E fetotsoe]
  • Roelofs SM. Hyperventilation, ho tšoenyeha, ho lakatsa joala: sesosa sa ho khaotsa joala. Joala. 1985;2: 501-505. [E fetotsoe]
  • Rohrer DK, Kobilka BK. Lintlha tse tsoang ho vivo modation ea adrenergic receptor gene. Annu Rev Pharmacol Toxicol. 1998;38: 351-373. [E fetotsoe]
  • Sarnyai Z, Biro E, Gardi J, Vecsernyes M, Julesz J, Telegdy G. Brain corticotropin-releading factor Mediates beha boitšoaro bo kang "ho tšoenyeha" bo susumetsoang ke ho khaotsa koae ka litoeba. Resin ea Boko. 1995;675: 89-97. [E fetotsoe]
  • Schulteis G, Stinus L, Risbrough VB, Koob GF. Clonidine e thibela ho hapa empa e se polelo ea ho tlosoa ha opiate maemong a litoeba. Neuropsychopharmacology. 1998;19: 406-416. [E fetotsoe]
  • Selye H. A lefu le hlahisoang ke li-nocuous agents tse fapaneng. Tlhaho. 1936;138: 32.
  • Shaham Y, Shalev U, Lu L, de Wit H, Stewart J. Mohlala oa ho khutlisetsa lithethefatsi morao: nalane, mokhoa le liphetho tse kholo. Psychopharmacology. 2003;168: 3-20. [E fetotsoe]
  • Sharp BM, Matta SG. Ho tseba ka Ka vivo Microbalalization ea nicotine e khothalletsang norepinephrine secretion ho tsoa ho hypothalamic paraventricular nucleus ea litoeba tse tsamaeang ka bolokolohi: tekanyo-kholo le ho hloka matla. Endocrinology. 1993;133: 11-19. [E fetotsoe]
  • Slawecki CJ, Thorsell AK, Khoury AE, Mathe AA, Ehlers CL. Ho eketseha ha ts'oaetso ea CRF joalo ka NPY le litšoelesa tse kang tsa NPY litekong tsa batho ba baholo ho pepesetsoa nicotine nakong ea bocha: kamano e amanang le ho tšoenyeha joalo ka boits'oaro bo joalo. Neuropeptides. 2005;39: 369-377. [E fetotsoe]
  • Smith SM, Vale WW. Karolo ea li-axis tsa hypothalamic-pituitary-adrenal ho likarabo tsa neuroendocrine ho khatello ea maikutlo. Dialogues Clin Neurosci. 2006;8: 383-395. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Sommer WH, Rimondini R, Hansson AC, Hips mosa PA, Gehlert DR, Barr CS, Heilig MA. Phallo ea takatso ea tahi ea boithaopo, maikutlo a boitšoaro ho imeloa kelellong, le amygdala crhr1 polelo e latelang nalane ea nalane ea ts'epo. Biol Psychiatry. 2008;63: 139-145. [E fetotsoe]
  • Specio SE, Wee S, O'Dell LE, Boutrel B, Zorrilla EP, Koob GF. CRF1 bahanyetsi ba li-receptor ba kenyelletsa ho ikarola ho eketsehileng ha koae ho likhoto. Psychopharmacology. 2008;196: 473-482. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Sterling P, Eyer J. Allostasis: paradigm e ncha ea ho hlalosa methapo ea kutlo. Ka: Fisher S, Lebaka la J, bahlophisi. Handbook of Life Khatello ea kelello, Kelello le Bophelo. John Wiley; Chichester: 1988. maq. 629-649.
  • Stinus L, Le Moal M, Koob GF. Li-bokellane tsa nyutlelie le li-amygdala ke li-substrates tse ka khonehang bakeng sa litla-morao tsa tšusumetso ea ho ts'oaroa ha opiate. Khopolo-taba. 1990;37: 767-773. [E fetotsoe]
  • Stinus L, Cador M, Zorrilla EP, Koob GF. Buprenorphine le mohanyetsi oa CRF1 o thibela ho fumana litheko tsa maemo a tlisoang ke ho hlobola ha opiate a hohelang. Neuropsychopharmacology. 2005;30: 90-98. [E fetotsoe]
  • Letsatsi N, Cassell MD. Li-neurons tsa "GABAergic" tse kahare ho rat e atolositsoeng ea rat. J Comp Neurol. 1993;330: 381-404. [E fetotsoe]
  • Swanson LW, Sawchenko PE, Rivier J, Vale W. Mokhatlo oa "corticotropin-releasing factor immunoreactive cell" le lisele tse tsoang bokong ba rat: thuto ea immunohistochemical. Neuroendocrinology. 1983;36: 165-186. [E fetotsoe]
  • Tucci S, Cheeta S, Seth P, File SE. Corticotropin e tlosang mohanyetsi oa factor, α-helical CRF9-41, e khutlisa boemo bo ts'oaroang ke nicotine, empa eseng e sa laoloang, matšoenyeho. Psychopharmacology. 2003;167: 251-256. [E fetotsoe]
  • Valdez GR, Zorrilla EP, Roberts AJ, Koob GF. Ho ts'oaroa ha corticotropin-releasing factor ho hlahisa karabelo e ntlafalitsoeng ea khatello ea maikutlo e bonoang nakong ea ho itšunya-tšunya ha ethanol. Joala. 2003;29: 55-60. [E fetotsoe]
  • Valdez GR, Sabino V, Koob GF. Keketseho e ts'oanang ea boits'oaro bo ts'oanang le boits'oaro ba ethanol ho litsi tse itšetlehileng: ho khutlisoa ka ts'ebetso ea corticotropin-releading factor-2 receptor activation. Alcohol Clinic Exp Res. 2004;28: 865-872. [E fetotsoe]
  • Valentino RJ, Page ME, Curtis AL. Ts'ebetso ea "neuradrenergic locus coeruleus neurons" ka khatello ea hemodynamic e bakoa ke tokollo ea lehae ea tlhahiso ea corticotropin. Resin ea Boko. 1991;555: 25-34. [E fetotsoe]
  • Valentino RJ, Foote SL, Page ME. The locus coeruleus e le sebaka sa ho hokahanya corticotropin-releasing factor le mediadrenergic ea likarabo tsa khatello ea maikutlo. Ka: Tache Y, Rivier C, bahlophisi. Corticotropin-Lokolla Factor le Cytokines: Karolo Karabong ea Khatello ea Khatello. Liphatlalatso tsa New York Academy of Science. Moq. 697. New York Academy of Science; New York: 1993. maq. 173-188.
  • Van Bockstaele EJ, Colago EE, Valentino RJ. Amygdaloid corticotropin-releasing factor liteishene tsa locus coeruleus dendrites: katlase bakeng sa ho hokahana ha maoto le maikutlo le boikoetliso ba karabelo ea khatello. J Neuroendocrinol. 1998;10: 743-757. [E fetotsoe]
  • Ventura R, De Carolis D, Alcaro A, Puglisi-Allegra S. Ethanol ts'ebeliso le moputso li itšetlehile ka norepinephrine ho cortex ea pele. Neuroreport. 2006;17: 1813-1817. [E fetotsoe]
  • Walker BM, Rasmussen DD, Raskind MA, Koob GF. α1-Noradrenergic receptor antagonism e thibela litheko tse tlisoang ke ho arabela ha ethanol. Joala. 2008;42: 91-97. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Wee S, CD ea Mandyam, Lekic DM, Koob GF. α1Karolo ea sistimi ea Noradrenergic le ho eketsa tšusumetso ea ho jella koae ka likhoto tse nang le phihlello ea nako e telele. Eur Neuropsychopharmacol. 2008;18: 303-311. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Weinshenker D, Rust NC, Miller NS, Palmiter RD. Boitšoaro bo amanang le Ethanol ba litoeba tse haelloang ke norepinephrine. J Neurosci. 2000;20: 3157-3164. [E fetotsoe]
  • Weiss F, Ciccocioppo R, Parsons LH, Katner S, Liu X, Zorrilla EP, Valdez GR, Ben-Shahar O, Angeletti S, Richter RR. Motheo oa Biology oa Kokoana-hloko ea Cocaine. Liphatlalatso tsa New York Academy of Science. Moq. 937. New York Academy of Science; New York: 2001. Boitšoaro bo matla ba ho batla lithethefatsi le ho khutlela morao: neuroadaptation, khatello ea maikutlo le maemo; maq. 1-26.
  • Zorrilla EP, Koob GF. Buka ea Matšoenyeho le Brain. Mekhoa ea Mahlale a ho Behavioral and Neural Science. Moq. 15. Saense ea Elsevier; New York: 2005. Karolo ea li-urocortins 1, 2 le 3 bokong; maq. 179-203.
  • Zywiak WH, Khokahano GJ, Maisto SA, Westerberg VS. Khutlisa lipatlisiso le Mabaka a Potso ea ho Noa: tlhahlobo ea lintlha tsa ho khutla ha lekhetho la Marlatt. Mathata. 1996;91(Suppl): S121-S130. [E fetotsoe]