O le vaega faʻasalalau o le thalamus e maua mai i taui masani ma fualaau faʻatauāina: faʻamatalaga lata mai o se matafaioi taua mo le orexin / hypocretin faailoilo i totonu o lenei kuluma i totonu o amioga faʻatau fualaau (2014)

Front Behav Neurosci. 2014; 8: 117.

Lomia i luga o le initaneti 2014 Apr 3. Tui:  10.3389 / fnbeh.2014.00117

PMCID: PMC3982054

O lenei tusiga ua taua e isi tusiga i le PMC.

Alu i le:

lē faʻatino

O se lu'itau tele mo le manuia o togafitiga o vaisu o fualaau faasaina o le umi e mafai ona toe fa'afo'i ma le tele o faiga ua a'afia i le fa'amalosia e toe fa'aaoga fualaau fa'asaina i le taimi o le fa'amama. Talu ai nei, o le orexin / hypocretin (Orx / Hcrt) system ua faʻaalia e faia se sao i amioga suʻesuʻe fualaau. O le Orx / Hcrt system e faʻatonutonu ai le tele o faʻagasologa o le physiological, e aofia ai le fafagaina, metabolism malosi, ma le faʻaosofia. Ua fa'aalia fo'i le fa'afaigaluegaina e fualaau fa'asaina. Orx / Hcrt neurons o loʻo tele lava i totonu o le hypothalamus pito i tua o loʻo faʻaogaina i le paraventricular nucleus o le thalamus (PVT), o se itulagi ua faʻamaonia o se "auala-ala" e faʻatautaia faʻamatalaga ona faʻaogaina lea o le taui mesolimbic ma le faʻalavelave faʻalavelave faʻafuaseʻi. . E ui lava e le o manatu o se vaega o le "vaisu o fualaau faasaina", o faʻamaoniga lata mai o loʻo faʻaalia ai o le PVT o loʻo aʻafia i le faʻaogaina o galuega tau taui i le lautele ma le faʻatonuina o fualaau faʻapitoa. O faʻamaoniga o loʻo faʻaalia ai se matafaioi mo le Orx / Hcrt transmission i le PVT i le faʻaogaina o galuega taui i le lautele ma le faʻatonuina o vailaʻau faʻapitoa. O le tasi manatu e faapea o le mulimulitaia o fualaau faasaina, o le Orx/Hcrt system e maua ai se sao taua i le soalaupuleina o aafiaga o fualaau faasaina. vs. taui masani. O le iloiloga o loʻo i ai nei o loʻo talanoaina ai suʻesuʻega lata mai o loʻo fautua mai ai le faʻaogaina o le PVT e ala i vailaʻau faʻaleagaina, aemaise lava Orx / Hcrt-PVT neurotransmission.

uputatala: paraventricular nucleus o le talamus, orexin / hypocretin, vaisu o fualaau faasaina, amioga suʻesuʻe fualaau faasaina, taui masani

faʻatomuaga

O vaisu o fualaau ose ose ma'i faifai pea e toe fa'afo'i mai e fa'aalia e ala i le sa'ilia pea o fualaau fa'asaina ma le inuina o fualaau (O'Brien ma McLellan, 1996; Leshner, 1997; O'Brien et al., 1998; McLellan et al., 2000). O le faʻamalamalamaina o le neurobiological mechanisms o loʻo faʻavaeina le natura faifai pea o vaisu ma le faʻamaoniaina o togafitiga faʻafomaʻi mo le puipuia o le toe faʻafoʻi ua tulaʻi mai o se mataupu tutotonu i suʻesuʻega o vaisu.

E tele suʻesuʻega na taumafai e faʻamalamalamaina le neuronal substrates e faʻatonutonu ai uiga faʻamalosi o amioga o vaisu. O vaega o faiʻai ua faʻamaonia e aʻafia i le toe faʻafoʻi (saili fualaau) -e pei o amioga e aofia ai le medial prefrontal cortex, basolateral amygdala, totonugalemu o le amygdala, moega o le stria terminalis, hippocampus, nucleus accumbens, ma dorsal striatum (Everitt). et al., 2001; McFarland ma Kalivas, 2001; Cardinal et al., 2002; Goldstein ma Volkow, 2002; Ito et al., 2002; Va'ai, 2002; Kalivas ma Volkow, 2005; Weiss, 2005; Belin ma Everitt, 2008; Steketee ma Kalivas, 2011). Talu ai nei, o faʻamaoniga faʻaalia na faʻaalia e mafai foi ona aofia ai le talamus i le neurocircuitry o vaisu. O le mea moni, e manatu o se fesoʻotaʻiga taua tele i le va o le ventral striatopallidum ma le dorsal striatum ma e mafai ona saofagā i le atinaʻeina o amioga faʻamalosi e suʻe fualaau (Pierce ma Vanderschuren, 2010).

I totonu o le nuclei o le thalamus, o le paraventricular nucleus o le thalamus (PVT) o loʻo i ai se tulaga taua o le neuroanatomical ma o lea e aʻafia ai fausaga na aʻafia i amioga suʻesuʻe fualaau (Moga et al., 1995; Bubser ma Deutch, 1998; Van der Werf et al., 2002). O le taua tele mo lenei iloiloga o le hypothalamic orexin / hypocretin (Orx / Hcrt) innervation o le PVT. Orx / Hcrt peptides o loʻo maua i filo o loʻo i totonu o itulagi uma o lenei thalamic nucleus, ae o loʻo maua le fiber density i le ogatotonu lata ane ma le intralaminar thalamic nuclei (Kirouac et al., 2005). E ui lava o faʻamaoniga faʻamalosi e faʻaalia ai se matafaioi mo Orx / Hcrt i le faʻaosoina ma le tausia o le tulaga fafagu (de Lecea, 2012), o isi faʻamaoniga e lagolagoina ai se matafaioi taua ma faʻapitoa i le faʻatinoina o taui lautele ma le faʻaaogaina o fualaau faasaina aemaise lava (mo le iloiloga, vaʻai Mahler et al., 2012).

O se iloiloga taua pe a faʻatatau i le faʻagasologa lautele o taui o le mea lea e faʻaeseese ai le faʻailoga neural e fesoʻotaʻi ma le "masani" amioga manaʻo. vs. amio fa'atonu. O se tasi o mea e mafai ona fai o le neuronal circuits e faʻatalanoaina le pulea o le suʻeina o fualaau faasaina ma le tagofia o fualaau oona o mea masani faʻaosofia neuronal substrates e sili atu ona malosi le faʻaaogaina e fualaau faasaina ma e le faʻapitoa mo faʻagasologa o vaisu. O le faʻamalosia o le neuronal activation lea e "masani" e pulea ai le tali atu mo taui masani e mafai ona fatuina ai ni tulaga faʻaosofia fou poʻo le toe faʻafeiloaʻi faʻailoga e masani ona pulea ai tali mo taui masani i amioga faʻasaina (Kelley ma Berridge, 2002). O le faʻamoemoe o lenei iloiloga o le aoteleina lea o suʻesuʻega lata mai o loʻo fautua mai ai le faʻaogaina o le PVT e ala i vailaʻau o le faʻaleagaina, faʻapitoa Orx / Hcrt-PVT transmission, e avea o se faiga fou neurotransmission i le etiology o le sailia o fualaau faʻamalosi.

O le PVT

O le PVT o loʻo taoto faʻatasi ma le pito i tua o le ventricle lona tolu. O le PVT o se vaega o le dorsal midline thalamic nuclei ma e iai sona sao taua i galuega e fesoʻotaʻi ma le faʻaosofia, gauai, ma le faʻalauiloaina (Bentivoglio et al., 1991; Groenewegen ma Berendse, 1994; Van der Werf et al., 2002). E ui lava o le ogatotonu ma le intralaminar thalamic nuclei na muamua faʻamoemoe e auai i le faʻagasologa o mea e le faʻaituau faʻailoga (Berendse ma Groenewegen, 1991), ua iloa nei o tagata taʻitoʻatasi o nei nuclei o loʻo faʻaogaina vaega eseese o le cortex ma le striatum (Groenewegen ma Berendse, 1994; Van der Werf et al., 2002; Smith et al., 2004).

O suʻesuʻega Neuroanatomical ua faʻaalia ai e maua e le PVT faʻamatalaga mai vaega faiʻai e fesoʻotaʻi ma le faʻamalosi ma le faʻaogaina o le tino (Cornwall ma Phillipson, 1988b; Chen ma Su, 1990; Ruggiero et al., 1998; Krout ma Loewy, 2000; Krout et al., 2002; Hsu ma Tau, 2009). E le gata i lea, o le PVT, e ala i ana fuafuaga i le pito i luma o le cortex ma le nucleus accumbens (Berendse ma Groenewegen, 1990; Su ma Bentivoglio, 1990; Brog et al., 1993; Freedman ma Cassell, 1994; Moga et al., 1995; Bubser ma Deutch, 1998; Otake ma Nakamura, 1998; Parsons et al., 2007; Li ma Kirouac, 2008; Vertes ma Hoover, 2008; Hsu ma Tau, 2009), tuʻuina lenei fausaga thalamic i se tulaga tulaga ese e aʻafia ai cortico-striatal masini e aofia i taui ma faʻaosofia (Pennartz et al., 1994; Cardinal et al., 2002; Walker et al., 2003).

E maua e le PVT mea fa'aoga tetele ma manino mai le tele o vaega o le hypothalamus, e aofia ai le suprachiasmatic, arcuate, dorsomedial, ma ventromedial nuclei, ma preoptic ma lateral hypothalamic area (Cornwall ma Phillipson, 1988a; Chen ma Su, 1990; Novak et al., 2000a; Peng ma Bentivoglio, 2004; Kirouac et al., 2005, 2006; Otake, 2005; Hsu ma Tau, 2009), fausaga taua mo le faʻaalia o amioga faʻaosofia (Swanson, 2000). O le mea e ofo ai, o le PVT o le faʻamoemoe o Orx / Hcrt hypothalamic neurons (Kirouac et al., 2005) ma ua faʻaalia e galue o se fesoʻotaʻiga i le va o le hypothalamus ma cortical-striatal projections e manaʻomia mo le tuʻufaʻatasia o le paleni o le malosi, faʻaosofia, ma taui o meaʻai (eg, Kelley et al., 2005).

O faʻataʻitaʻiga na suʻesuʻeina le faʻamalosia o le neuronal o le PVT ua faʻaalia pea o lenei faiʻai e faʻaaogaina i taimi o le faʻaosofia poʻo le atuatuvale (Peng et al., 1995; Bhatnagar ma Dallman, 1998; Novak ma Nunez, 1998; Bubser ma Deutch, 1999; Novak et al., 2000b; Otake et al., 2002). O le PVT ua aʻafia foi i le faʻatonutonuina o meaʻai ma le hypothalamic-pituitary-adrenal activity i le tali atu i le faʻalavelave masani, taumafa taumafa, ma le paleni malosi (Bhatnagar ma Dallman, 1998, 1999; Jaferi et al., 2003). E ui lava e leʻi aofia muamua i le neurocircuitry o mea ua fai ma vaisu, o faʻamaoniga lata mai e aʻafia ai le PVT i le faʻaogaina o amioga faʻasaina. O le mea moni, o le PVT o loʻo faʻatinoina i vaega o faiʻai o loʻo aʻafia i le puleaina o amioga suʻesuʻe fualaau, e pei o le nucleus accumbens, amygdala, moega o le stria terminalis, ma le pito i luma o le cortex (Moga et al., 1995; Bubser ma Deutch, 1998; Van der Werf et al., 2002). O le mea taua, o suʻesuʻega muamua na faʻaalia ai le faʻagaoioia o le PVT i le taimi o le suʻeina o le ethanol (Dayas et al., 2008; Hamlin et al., 2009), ma faʻamatalaga lata mai ua faʻaalia ai le malosi ma le filifilia o le PVT i le taimi o le sailiga o cocaine e le tupu i le taimi o taui masani (faʻataʻitaʻiga, o se faʻamalosia masani masani) saili (Martin-Fardon et al., 2013). Faatasi ai ma le tele o galuega tauave o loʻo taʻua i luga, o lenei iloiloga o loʻo talanoaina ai le auai o le PVT i vailaʻau- vs. amioga masani saili taui (o le pulea o fualaau faasaina). O lenei iloiloga o loʻo faʻaogaina ai le faaupuga "faʻamalosia masani" poʻo le "taui masani" e faʻamalamalamaina ai se tulaga e le o ni fualaau (e masani lava o se vaifofo suamalie suamalie) o le a avea ma faʻatusatusaga faʻatonutonu mo le vailaʻau.

Ole Orx/Hcrt system

Orx/Hcrt peptides, orexin A ma le B (Orx-A ma Orx-B), e taʻua foi o hypocretins (Hcrt-1 ma Hcrt-2), o neuropeptides ia e faʻaalia i neu o le dorsal tuberal hypothalamic nuclei: lateral hypothalamus, perifornical nucleus , ma le dorsomedial hypothalamus (de Lecea et al., 1998; Sakurai et al., 1998b). Orx-A/Hcrt-1 ma Orx-B/Hcrt-2 o oloa ia o se polypeptide muamua muamua e tasi, prepro-orexin, e ala i le faiga masani proteolytic (de Lecea et al., 1998). O nei peptides e faʻasoa faʻasologa tutusa ma o le ligands mo tali e lua: Hcrt-r1 ma Hcrt-r2. O le Hcrt-r1 e fusifusia Orx-A ma le 20-30 nM affinity ae e sili atu le maualalo o le sootaga (10- i le 1000-fold lalo) mo Orx-B, ae o le Hcrt-r2 e fusifusia uma peptides e tutusa tutusa (i le 40 nM laina; Sakurai et al., 1998a; Ammoun et al., 2003; Scammell ma Winrow, 2011). O le tele o suʻesuʻega ua fautua mai o Orx / Hcrt faʻafeiloaʻi e faʻapipiʻi i G-proteins. Ae ui i lea, o le G-coupling o nei faʻafeiloaʻi e mamao mai le manino ae faʻavae i luga o le tele o suʻesuʻega o le Hcrt-r1 ma le Hcrt-r2 atonu e faʻaluaina Gi / o, Gs ma le Gq aiga G-porotini (Gotter et al., 2012; Kukkonen, 2013).

Orx / Hcrt neurons maua mea faʻaoga mai le tele o vaega o faiʻai ma poloketi i le faiʻai atoa, ma faʻafefea ai le tele o neuronal circuitries (Peyron et al., 1998; Aso et al., 1999; Nambu et al., 1999). E mafai ona maua fa'amauina Orx / Hcrt i le cerebral cortex, olfactory bulb, hippocampus, amygdala, basal forebrain, hypothalamus, tuberomammillary nucleus, PVT, arcuate nucleus o le hypothalamus, ma le fai'ai (Peyron et al., 1998; Aso et al., 1999; Nambu et al., 1999). Orx / Hcrt neurons maua faʻataʻitaʻiga mai le medial prefrontal cortex, nucleus accumbens shell, amygdala, bed nucleus o le stria terminalis, arcuate nucleus o le hypothalamus, ma preoptic area (Sakurai et al., 2005). E tusa ai ma le Hcrt-rs, ua faʻaalia le faʻatapulaʻaina o tufatufaga o le Hcrt-r1 ma le Hcrt-r2 mRNAs, ma le eseesega o galuega i le va o le Hcrt-r1 ma le Hcrt-r2 (Trivedi et al., 1998; Lu et al., 2000; Marcus et al., 2001; mo iloiloga, tagai Aston-Jones et al., 2010), fa'atulagaina o matafaioi fa'aletino eseese mo ta'iala ta'itasi talisu'e.

Ona o ana fesoʻotaʻiga, o le Orx / Hcrt system o loʻo aʻafia i le tele o galuega faʻaletino. O le Orx / Hcrt system e matua'i a'afia i le fa'atonutonuina o le fafagaina, fa'aoso, moe / ala, le fa'alavelave fa'alavelave, malosi homeostasis, ma le taui (mo le iloiloga, va'ai Tsujino ma Sakurai, 2013). Aemaise lava le taua mo lenei iloiloga, o faʻamaoniga e lagolagoina se matafaioi taua ma faʻapitoa mo le Orx / Hcrt system i vaisu fualaau (mo le iloiloga, vaʻai Mahler et al., 2012), aemaise lava Orx / Hcrt neurons o loʻo i totonu o le hypothalamus pito i tua (Harris et al., 2005). Aemaise lava, o nei neu e faʻaogaina i le PVT, nucleus accumbens shell, ventral pallidum, ventral tegmental area, ogatotonu tutotonu o le amygdala, ma le moega o le stria terminalis (Peyron et al., 1998; Baldo et al., 2003; Winsky-Sommerer et al., 2004). Muamua na aafia i le faatonutonuina o le fafagaina o amioga (Sakurai et al., 1998a; Edwards et al., 1999; Haynes et al., 2000, 2002), o nei neurons o loʻo i ai se matafaioi faʻapitoa i galuega tau taui, faʻatasi ai ma se sao faapitoa i amioga faʻasaina (Harris et al., 2005).

Ole faiga ole Orx/Hcrt e fa'atatau ile a'afiaga ole amio ole fa'a'au'auna fa'asua

Orx / Hcrt ua lipotia mai e faʻaleleia ai le faʻamalosia o aʻafiaga o faʻamalosi e faʻatatau i le maua o fualaau faasaina, faʻateleina le faʻaosofia e suʻe le vailaʻau, ma faʻateleina le faʻamalosia o gaioiga o fualaau faʻaleagaina.

O le mea moni, o le intra-ventral tegmental area microinjection o Orx-A e maua ai se faafouga o le morphine-induced conditioned place preferred (CPP), ae o le puleaina o le Hcrt-r1 antagonist. N-(2-methyl-6-benzoxazolyl)-N'-1,5-n-aphthyridin-4-yl urea (SB334867) faʻaitiitia le faʻaalia o le CPP faʻaosoina o le morphine (Harris et al., 2005). E ogatasi ma le matafaioi a Orx / Hcrt i le faʻaaliga o le CPP, pe a tui faʻapitoa, o le Hcrt-r1 antagonists SB334867 ma le 5-bromo-N-[(2S,5S) -1-(3-fluoro-2-methoxybenzoyl) -5-methylpiperidin-2-yl]methyl-pyridin-2-amine (GSK1059865) faʻaitiitia le faʻaalia o le cocaine- ma le amphetamine-induced CPP (Gozzi et al., 2011; Hutcheson et al., 2011; Sartor ma Aston-Jones, 2012), fautua mai se tulaga iloga mo Hcrt-r1 i le tauia o aʻafiaga o cocaine ma amphetamine. O le mea e malie ai, o le auai o le Hcrt-r2 na faʻamatalaina talu ai nei i nisi o aʻafiaga o amioga a le ethanol. Puipuia o le Hcrt-r2 faʻaaoga (2,4-dibromo-phenyl)-3-([4S,5S]-2,2-dimethyl-4-phenyl-[1,3]dioxan-5-yl)-urea (JNJ-10397049) na lipotia mai e faʻaitiitia ai le mauaina, faʻamatalaga, ma le toe faʻaleleia o le CPP faʻaosoina ethanol (Shoblock et al ., 2011), o loʻo fautua mai ai o le Hcrt-r2 atonu o loʻo aʻafia tele i le tauia o le ethanol.

Orx / Hcrt ua faʻamatalaina foi e faia se sao i le psychostimulant-induced locomotor sensitization. SB334867 tui i totonu poʻo totonu o le ventral tegmental area na poloka ai le mauaina o le cocaine sensitization, faʻafefeteina le malosi o galu faʻaosofia e faʻaosoina e cocaine i dopaminergic neurons o le ventral tegmental area (Borgland et al., 2006), ma poloka le faʻaalia o le amphetamine sensitization (Quarta et al., 2010). Ae le gata i lea o le faʻalogoina o le amphetamine ma le faʻaalia o kenera e fesoʻotaʻi ma palasitisi i le vaega o le ventral tegmental pe a uma le amphetamine masani (Winrow et al., 2010).

Ua lipotia mai foi le Orx/Hcrt e auai i le faatonutonuina o le faaosofia e ave fualaau faasaina. Pe a tui i totonu o le ventral tegmental area, Orx-A / Hcrt-1 faʻateleina le vaʻaia mo le cocaine le pulea e le tagata lava ia i luga o se faasologa o le faʻatulagaina o le faʻamalosia (España et al., 2011). O le faʻaleagaina o le Hcrt-r1 ma le SB334867 e faʻaitiitia ai le faʻaosofia e pulea e le tagata lava ia cocaine ma faʻaitiitia ai le faʻaleleia atili o le dopaminergic signaling i totonu o le nucleus accumbens pe a tui i totonu o le ventral tegmental area (España et al., 2010). E le gata i lea, o le poloka o Hcrt-r1 e faʻaitiitia ai le nicotine (Hollander et al., 2008) ma heroin (Smith ma Aston-Jones, 2012) pulea e le tagata lava ia, ma o le Hcrt-r1 poʻo le Hcrt-r2 antagonism e faʻaitiitia ai le faʻaogaina o le ethanol, e aunoa ma le faʻalavelaveina o le sucrose self-administration (Lawrence et al., 2006; Shoblock et al., 2011; Brown et al., 2013). Ma le mea mulimuli, o suʻesuʻega talu ai nei ua faʻaalia ai o le tetee a le Hcrt-r2 e faʻaitiitia ai le faʻamalosia o le heroin self-administration (Schmeichel et al., 2013).

O le Orx/Hcrt e iai sona sao taua i le su'eina o fualaau faasaina e mafua mai i le popole po'o le fa'atupuina o le siosiomaga. Intracerebroventricular (ICV) tui ole Orx-A/Hcrt-1 faʻatuputeleina le intracranial self-stimulation (ICSS) thresholds ma toe faʻafoʻi le cocaine ma le nicotine saili (Boutrel et al., 2005; Plaza-Zabala et al., 2010). E le gata i lea, o le poloka o le Hcrt-r1 e taofia ai le toe faʻaleleia o le cocaine, ethanol, ma le heroin suʻesuʻe (Boutrel et al., 2005; Lawrence et al., 2006; Richards et al., 2008; Smith et al., 2010; Jupp et al., 2011b; Smith ma Aston-Jones, 2012; Matini-Fardon ma Weiss, 2014a,b).

O le Orx/Hcrt system ua fa'aalia fo'i e iai sona sao i le fa'amavaeina o vaila'au. SB334867 e faʻaitiitia ai faʻailoga o le nicotine ma le morphine (Sharf et al., 2008; Plaza-Zabala et al., 2012), ma Orx / Hcrt neurons o loʻo faʻagaoioia pe a maeʻa le puleaina o le nicotine ma le taimi o le nicotine (Pasumarthi et al., 2006; Plaza-Zabala et al., 2012) ma le morphine (Georgescu et al., 2003) faaui i tua. O nisi suʻesuʻega o loʻo fautua mai ai le i ai o se fesoʻotaʻiga i le va o le toto Orx / Hcrt maualuga ma faʻamaoniga o le alu ese mai le ava malosi i tagata (Bayerlein et al., 2011; von der Goltz et al., 2011), lagolagoina le manatu o le Orx / Hcrt system e taua tele mo suiga o amioga e fesoʻotaʻi ma le faʻalagolago i fualaau faʻasaina ma le faʻateʻaina i manu ma tagata.

O se vaega tutotonu mo Orx / Hcrt neurons i le hypothalamus pito i tua i vaisu o loʻo i ai (Harris et al., 2005). Orx / Hcrt neurons i le hypothalamus pito i tua e faʻaaogaina e ala i mea faʻamalosi e fesoʻotaʻi ma cocaine, ethanol, morphine, ma meaʻai (Harris et al., 2005; Dayas et al., 2008; Matini-Fardon et al., 2010; Jupp et al., 2011b), ma Orx / Hcrt microinjection i le hypothalamus pito i tua e faʻateleina ai le faʻaaogaina o le ethanol (Schneider et al., 2007). O le faʻamatalaga o le CPP faʻaosoina e meaʻai, morphine, ma cocaine e fesoʻotaʻi ma le faʻagaoioia o le lateral hypothalamus Orx / Hcrt neurons (Harris et al., 2005). O le mea e malie ai, o le cocaine-induced CPP na fesoʻotaʻi ma le faʻaitiitia o le Orx / Hcrt mRNA faʻamatalaga i le hypothalamus pito i tua, e taʻu mai ai se ituaiga o faʻamatalaga taui e mulimuli mai i le malosi o le neuronal activation na aʻafia e cocaine (Zhou et al., 2008).

Amio ma faʻamaoniga faʻamaonia e faʻaalia ai se matafaioi mo le Orx / Hcrt faʻailoga i le neurobehavioral ma le faʻaosofia o aʻafiaga o le ethanol ma isi vailaʻau o le faʻaleagaina (Borgland et al., 2006; Bonci ma Borgland, 2009; Thompson ma Borgland, 2011). O le mea taua, Orx / Hcrt o hypothalamic neuropeptides lea na lipotia muamua e faʻatonutonu le fafagaina (Sakurai et al., 1998a). O le poloka o le Hcrt-r1 e le SB334867 e faʻaitiitia ai meaʻai (Haynes et al., 2000; Rodgers et al., 2001; Ishii et al., 2005), ma o le Orx / Hcrt system e foliga mai o loʻo faʻafaigaluegaina i le faʻatonutonuina o le faʻaogaina o meaʻai sili ona suamalie (Nair et al., 2008; Borgland et al., 2009; Choi et al., 2010).

E ui o le Orx / Hcrt system e lauiloa e faʻatonutonu (natura) galuega taui, o suʻesuʻega o loʻo taʻua i luga o loʻo faʻaalia ai o le Orx / Hcrt system e iai foi sona sao taua i le neurobehavioral ma le faʻaosofia o aʻafiaga o fualaau faʻaleagaina. O suʻesuʻega talu ai nei na faʻaalia ai o le Orx / Hcrt system, o le mea moni, e sili atu le malosi o le faʻaaogaina o fualaau faʻasaina nai lo le faʻamalosia o fualaau faʻasaina. Mo se faʻataʻitaʻiga, Hcrt-r1 poʻo le Hcrt-r2 poloka e sili atu ona aoga i le faʻaitiitia o le faʻaogaina o le ethanol nai lo le sucrose intake (Shoblock et al., 2011; Jupp et al., 2011a; Brown et al., 2013). E le gata i lea, o le faʻaaogaina o se faʻataʻitaʻiga toe faʻaleleia o manu o le toe faʻafoʻi, lea e faʻaosofia ai le cocaine, ethanol, ma faʻamalosi masani e faʻaalia ai tulaga tutusa o le toe faʻaleleia, togafitiga faʻafomaʻi o le Hcrt-r1 filifili toe faʻafoʻiina le toe faʻaleleia e faʻaosoina e se cocaine-poʻo le ethanol-stimulus. e leai ni aʻafiaga i luga o le faʻamalosi tutusa e faʻatulagaina i se faʻamalosia masani (Martin-Fardon ma Weiss, 2009, 2014a,b; Matini-Fardon et al., 2010).

O le PVT e saofagā i amioga su'esu'e fualaau

O le PVT ua faʻatulagaina e avea ma faʻasalalauga autu e faʻaogaina ai le Orx / Hcrt-coded reward-related communication i le va o le hypothalamus pito i tua ma le ventral ma dorsal striatum (Kelley et al., 2005). O lenei neurocircuitry hypothalamic-thalamic-striatal atonu na tupu aʻe e faʻaumiumi ai tulaga faʻaosofia totonugalemu ma faʻalauteleina le fafagaina i tua atu o le faʻataunuʻuina o manaʻoga vave, ma faʻatupuina ai le malosi faʻaagaga mo le le lava o meaʻai i le lumanaʻi (Kelley et al., 2005). O loʻo faʻapea o le faʻaaogaina faʻaleagaina o lenei faiga e ala i vailaʻau o le faʻaleagaina e mafai ona "faʻafefeteina" lana galuega agai i le tele o amioga faʻatonuina fualaau faasaina, lea e ono faʻamatalaina ai le faʻateleina o le lagona o le Orx / Hcrt system i le faʻalavelave faʻalavelave i amioga suʻesuʻe vailaʻau e ese mai le amio. faasino i taui masani.

O le tele o fa'amaoniga e lagolagoina ai le auai o le PVT i le toe fa'afo'isia o amioga su'esu'e vaila'au fa'apitoa e fa'aosoina e fa'aoso fa'atatau ile maua ole vaila'au lava ia. Mo se faʻataʻitaʻiga, o le toe faʻaleleia o le suʻeina o le ava malosi e fesoʻotaʻi ma le faʻafaigaluegaina o le PVT (Wedzony et al., 2003; Dayas et al., 2008; Perry ma McNally, 2013). E le gata i lea, o le le toe faʻaaogaina o le PVT e taofia ai le toe faʻaleleia o le suʻeina o le ethanol (Hamlin et al., 2009; Marchant et al., 2010), le toe fa'auluina o le cocaine (James et al., 2010), fa'alogoina o cocaine (Young and Deutch, 1998), ma le faʻaalia o le cocaine-induced CPP (Browning et al., 2014). E le gata i lea, o PVT neurons e faʻagaoioia e ala i le toe faʻaalia i cocaine-paiga (Brown et al., 1992; Franklin ma Druhan, 2000), methamphetamine-paiga (Rhodes et al., 2005), ma ethanol-paiga (Wedzony et al., 2003; Dayas et al., 2008) faʻaupuga faʻapitoa, ae o le faʻaalia i le sucrose-related stimulus e le faʻaosoina ai le PVT activation (Wedzony et al., 2003).

I le faaopoopo atu i le tele o suʻesuʻega na faʻaalia ai se sao o le PVT i vaega eseese o vaisu o fualaau faasaina, o le sao faʻapitoa a Orx / Hcrt faʻailoga i totonu o lenei thalamic nucleus ua tosina mai talu ai nei le tele o le gauai. O le PVT o loʻo faʻafefeteina e le Orx / Hcrt fibers (Kirouac et al., 2005; Parsons et al., 2006) ma o se puna tele o le glutamatergic afferents i le nucleus accumbens, le moega o le stria terminalis, le ogatotonu o le amygdala, ma le medial prefrontal cortex (Parsons et al., 2007; Li ma Kirouac, 2008; Vertes ma Hoover, 2008; Hsu ma Tau, 2009). O nei vaega fai'ai o se vaega o le neurocircuitry o vaisu. O suʻesuʻega muamua na faʻaalia ai o le polokaina o Hcrt-r1 faʻafeiloaʻi i le PVT e leʻi maua ai se faʻaitiitia o le toe faʻaleleia o le suʻeina o cocaine (James et al., 2011) o loʻo fautua mai o le faʻafefe o le Hcrt-r2 i totonu o lenei faiʻai e mafai ona sili atu le lelei i le polokaina o vailaʻau o aʻafiaga faʻaleagaina. I le maliliega ma nei manatu, o isi suʻesuʻega ua faʻaalia ai le microinjection o le Hcrt-r2 antagonist (2).S)-1-(3,4-dihydro-6,7-dimethoxy-2(1H) -isoquinolinyl) -3,3-dimethyl-2- [(4-pyridinylmethyl) amino] -1-butanone hydrochloride (TCSOX229) ae le o le SB334867 i totonu o le PVT na matua faʻaitiitia ai le faʻaalia o le naloxone-induced conditioned place aversion (CPA; Li; et al., 2011), e fa'ailoa mai ai se matafaioi fa'apitoa mo le PVT Hcrt-r2 i le fa'atalanoaina o le ave'ese o le morphine. E le gata i lea, o le nicotine mataʻutia na faʻateleina le faʻaaliga Fos i Orx / Hcrt neurons e faʻaalia mai le hypothalamus pito i tua i le PVT (Pasumarthi ma Fadel, 2008), fautuaina le auai o lenei auala i le faaosofia o le nicotine. O se matafaioi mo Orx / Hcrt faʻataʻitaʻiga mai le hypothalamus pito i luga i le PVT i le suʻega ethanol e lagolagoina e suʻesuʻega na faʻaalia ai o faʻamatalaga faʻasalalauga e fesoʻotaʻi ma le ava e faʻagaoioia ai nei neu (Dayas et al., 2008). Aemaise lava, sili atu Fos-positive hypothalamic Orx / Hcrt neurons na matauina i isumu na faʻaalia i faʻalavelave faʻapitoa na fesoʻotaʻi muamua ma le maua o le ethanol. vs. o isumu na faʻaalia i faʻamaʻi tutusa na faʻapipiʻiina muamua ma le leai o se taui, ma o le ethanol-related stimuli na faʻateleina ai le numera o le Fos-positive PVT neurons e vavalalata vavalalata ma Orx / Hcrt fibers (Dayas et al., 2008).

O le mea taua, ua lipotia mai le PVT e auai i le tulafono faatonutonu o le fafagaina. Mo se faʻataʻitaʻiga, manuʻa o le PVT (Bhatnagar ma Dallman, 1999) poʻo le faʻasaina o PVT neurons ma le GABAA tagata tetee muscimol (Stratford ma Wirtshafter, 2013) na faʻaalia e faʻateleina le fafagaina. E faʻapea foʻi, o le electrolytic lesion o le PVT na faʻaosoina ai le faʻaitiitia o le maualuga o le gaogao ma le toto corticosterone maualuga e masani ona gaosia e le faʻamoemoe e maua mai meaʻai (Nakahara et al., 2004). Na'o ni nai fa'ata'ita'iga o le sao o lenei thalamic nucleus i le fa'atonutonuina o taumafa o lo'o ta'ua iinei, ma o le talanoaina atili o lenei mataupu e sili atu nai lo le lautele o le iloiloga nei. O vaega o lo'o mulimuli mai o lo'o talanoaina ai su'esu'ega talu ai nei mai lenei falesu'esu'e o lo'o fa'amatalaina ai le a'afiaga patino o le PVT (ma le Orx/Hcrt transmission) i le su'eina o vaila'au. vs. amioga masani faaosofia agai i se faʻamalosia masani.

O le PVT e ese'ese le su'eina e cocaine vs. taui faanatura: fa'amaopoopo ma le su'ega cocaine

O isi faʻamaoniga mai lenei fale suʻesuʻe (Martin-Fardon et al., 2013) ua faʻaalia se mamanu faʻapitoa o le faʻafaigaluegaina o le PVT e ala i faʻamalosi e fesoʻotaʻi ma cocaine vs. fa'aoso fa'atutu fa'atasi ma se fa'amalosi fa'amalie masani, susu fa'amalieina suamalie (SCM). O le fa'amoemoe o lenei su'esu'ega o le fa'avaeina lea o le faiga fa'afaigaluegaina o le PVT fa'aosoina e ala i le tu'uina atu o se fa'ailoga fa'ailoga (S).D) faʻapipiʻiina i cocaine poʻo le SCM e faʻaaoga ai se manu faʻataʻitaʻiga o loʻo faʻamatalaina muamua (faʻataʻitaʻiga, Baptista et al., 2004; Matini-Fardon et al., 2007, 2009). I se faapuupuuga, na aʻoaʻoina tamaʻi iole Wistar e faʻafesoʻotaʻi le SD faʻatasi ai ma le maua o cocaine poʻo SCM (S+) vs. saline poʻo le leai o se taui (S-). I le maeʻa ai o le faʻaumatia o le cocaine- ma le SCM-faʻamalosia le tali atu, na tuʻuina atu i ai le S.+ poʻo le S- toatasi. Tuuina atu o le cocaine S+ poʻo le SCM S+ (ae le o le S-) ina ua mae'a fa'aoso fa'aoso fa'atupuina tulaga tutusa o le toe fa'aleleia e pei ona fa'amatalaina i su'esu'ega muamua (Baptista et al., 2004; Matini-Fardon et al., 2007, 2009). O le faiʻai na faʻaigoaina mo Fos i le PVT, ma o le Fos-positive neurons na faitauina pe a uma le cocaine S.+ poʻo le SCM S+ faʻamatalaga ma faʻatusatusa i faitauga na maua ina ua maeʻa S- fa'aaliga. Tuuina atu o le cocaine S+ ae le o le saline S- fa'agaoioia c-fos. I se eseesega, o le tuʻuina atu o le SCM S+ ma le leai o se taui S- maua ai neural fa'agaioiga tutusa. O se faʻasologa faʻasologa i le va o le toe faʻaleleia o tali ma le numera o Fos-positive cell i le PVT na faʻaalia ai se fesoʻotaʻiga taua i le vaega cocaine ae le o le SCM vaega (Martin-Fardon et al., 2013). O nei faʻamatalaga o loʻo fautua mai ai o le PVT e faʻapitoa ona faʻafaigaluegaina i le taimi o le toe faʻaleleia o le cocaine e suʻe ae le o le SCM saili, faʻaopoopoina le lagolagoina o le manatu o lenei thalamic structure o loʻo aʻafia i le vailaʻau o vaisu.

Orx/Hcrt i le pvt fa'atalanoa amioga su'esu'e cocaine i isumu

O le fesoʻotaʻiga taua i le vaega o le cocaine ae le o le SCM vaega o loʻo fautua malosi mai ai o le cocaine e faʻaosoina le dysregulation o le neurotransmission i le PVT. O le faʻamoemoe o le isi suʻesuʻega o le suʻesuʻeina lea o le matafaioi patino a le PVT Orx / Hcrt transmission i le suʻeina o koko. vs. amio fa'aosofia aga'i i le su'ega SCM. Na aʻoaʻoina tamaʻitaʻi Wistar e pulea e le tagata lava ia cocaine puʻupuʻu (ShA; 2 h / aso), cocaine umi (LgA; 6 h / aso; ie, se manu faʻataʻitaʻiga o le faʻalagolago i le koko), poʻo le SCM (30 min / aso) mo le aofaʻi o aso e 21 ona faʻataʻitaʻiina lea o aʻoaʻoga faʻaumatia i aso uma mo le 14 aso. O le aso na sosoʻo ai, na maua ai e isumu le intra-PVT microinjections o Orx-A / Hcrt-1 (0, 0.25, 0.5, 1, ma le 2 μg) ona tuʻu lea i totonu o potu faigaluega i lalo o tulaga faʻaumatia mo le 2 h. Orx-A/Hcrt-1 toe fa'afo'i le ShA ma le LgA cocaine su'e ma le SCM su'e ae fa'atasi ai ma fa'amatalaga tu'ufa'atasiga-tali. O aʻafiaga o le Orx-A / Hcrt-1-faʻaosoina le toe faʻaleleia i luga o cocaine o loʻo sailia i le vaega o le ShA na faʻaalia i se faʻaogaina o le fua o le U-foliga, faʻatasi ai ma le maualalo o tui ae le o maualuga maualuga e faʻaalia ai le toe faʻaleleia (Matzeu et al., 2013). I se faʻatusatusaga, Orx-A / Hcrt-1 faʻaosoina le toe faʻaleleia i le vaega SCM i maualuga ae le maualalo doses. O se suiga agavale i le Orx-A / Hcrt-1 dose-effect function na matauina mo le toe faʻaleleia o le ShA cocaine saili pe a faʻatusatusa i le SCM saili. E le gata i lea, o le Orx-A / Hcrt-1-induced reinstatement i le LgA group na maua ai se suiga agavale i luga o le gaioiga-tali faʻatusatusa i le vaega SCM ma se suiga agai i luga faʻatusatusa i le vaega o le ShA. O nei suʻesuʻega o loʻo fautua mai ai o se talaʻaga o le faʻalagolago i le koko e taʻitaʻia ai suiga o le neuroadaptive i le maualuga o le PVT, e mafua ai le "faʻaalia" o le LH-PVT-Orx / Hcrt transmission, e atagia mai i le faʻalauteleina o le lagona (ie, o se suiga i le agavale) ma faʻateleina tali amio. (ie, o se suiga agai i luga) i aʻafiaga o Orx-A / Hcrt-1, faʻateleina le faʻaogaina o Orx / Hcrt-PVT i amioga suʻesuʻe cocaine ma le aʻafiaga patino o le PVT i le neurocircuitry e fesoʻotaʻi ma le sailiga o cocaine. O le iloaina o le Orx / Hcrt e auai i le faʻatonutonuina o le tele o faʻagasologa o le physiological, e mafai e se tasi ona finau e faapea o le faʻaogaina o le Orx / Hcrt i totonu o le PVT e mafai ona maua ai ni aʻafiaga e le faʻapitoa. Talu ai nei, na lipotia mai ai o le intra-PVT pulega o Orx-A i doses 1.5- i le 4.5-fold maualuga atu nai lo le maualuga fua o loʻo faʻaaogaina iinei na matua faʻateleina ai le faʻamaisa ma le teuga, lea e ono faʻalavelave ai (ie, faʻaitiitia) le tali atu a le tagata (Li et. al., 2010). Ae ui i lea, i le suʻesuʻega nei, na toe faʻaleleia e le pulega a Orx-A (faʻateleina) amio suʻesuʻe taui; o le mea lea, i luga o le fua o fualaau ua filifilia, e le tatau ona faia e Orx-A soʻo se suiga e le faʻapitoa i amioga "faʻalagona" e mafai ona faʻamatalaina mo gaioiga eseese-tali o loʻo gaosia i vaega eseese.

iʻuga

O se malamalamaga sili atu i le neurotransmission o loʻo faʻavaeina amioga faʻamalosi e fesoʻotaʻi ma vaisu o le a maua ai se auala sili atu ona taulaʻi ma aoga e faʻavae ma faʻaumiumi ai fualaau faasaina ma le ava malosi. O faʻamatalaga mai lenei fale suʻesuʻe ma tusitusiga o loʻo faʻaalia ai o le Orx / Hcrt-PVT o loʻo i ai se sao taua i amioga e faʻaosofia e faʻamalosi e faʻatatau i fualaau faasaina. vs. taui masani ma o le talafaasolopito o le faʻalagolago i cocaine e suia ai le lagona o le PVT i le Orx-A priming effect. O loʻo faʻaalia ai o vailaʻau o le faʻaleagaina i le lautele e le faʻatonutonuina le neurotransmission i le PVT ma o le faʻaaogaina o fualaau faʻasaina poʻo le ava malosi, o le Orx / Hcrt system e maua ai se sao faʻapitoa i le faʻatalanoaina o vailaʻau o le sauaina saili. vs. saili taui masani. O mea o loʻo totoe e faʻamalamalamaina o neuromechanisms i tua atu o lenei aʻafiaga o le Orx / Hcrt-PVT transmission. O le tasi manatu o le talaʻaga o le faʻaaogaina o fualaau faʻasaina ua faʻaosoina ai le le faʻatonutonuina o le lateral hypothalamus-Orx/Hcrt-PVT neurotransmission, e atagia mai i se suiga i le Orx/Hcrt receptor expression i le PVT poʻo se suiga ole Orx/Hcrt production i le lateral hypothalamus lea i totonu. O le suiga e atagia mai i se faʻamaopoopoina i le va o le faʻagaioiina o le PVT ma le amio suʻesuʻe cocaine. O se tala'aga o le pulea e le tagata lava ia fualaau faasaina e mafai foi ona faaosofia ai le neuroadaptations (fa'ata'ita'iga, faʻaleleia le malosi o le synaptic) i le PVT lea e faʻalavelaveina ai lana galuega "masani" agai i le tele o amioga faʻatonuina fualaau.

Mafaufau i le taua o le toe faʻaleleia o le puipuiga i tagata taʻitoʻatasi, e taua le faʻamautinoa pe o aʻafiaga o mea faigaluega faʻafomaʻi (faʻataʻitaʻiga, Hcrt-r antagonists) suia i tagata taʻitoʻatasi, e pei ona faʻamatalaina muamua mo metabotropic glutamate receptors (Aujla et al., 2008; Hao et al., 2010; Sidhpura et al., 2010; Kufahl et al., 2011) ma le faiga o le nociceptin (eg, Economidou et al., 2008; Matini-Fardon et al., 2010; Aujla et al., 2013) ma pe o fa'atalanoaina e le PVT ia a'afiaga. O tusitusiga ma faʻamaumauga na gaosia e la matou fale suʻesuʻe e lagolagoina malosi se masini e leʻi iloa muamua, e taʻua o le dysregulation o le Orx / Hcrt-PVT transmission, i le mafuaʻaga o le faʻalagolago i vailaʻau, lea e mafai ona fesoasoani e iloa ai ni faʻataʻitaʻiga togafitiga mo vaisu.

Feteenaʻiga o tului

Fai mai tusitala o le suʻesuʻega sa faia i le leai o soʻo se fefaʻatauaʻiga faʻapisinisi pe tau tupe e mafai ona avea o se feteenaʻiga e ono aʻafia ai.

tautinoga

Ole numera lea ole lomiga 25036 mai le Scripps Research Institute. O lenei suʻesuʻega na lagolagoina e le NIH/NIDA foaʻi DA033344 (Remi Martin-Fardon). E faafetaia e tusitala ia M. Arends mo le fesoasoani i le sauniaina o tusitusiga.

mau faasino

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