Ubongo woyesedwa umadya: Maulendo okondweretsa ndi kukhumba mu kunenepa kwambiri ndi matenda okudya (2010)

Kent C. Berridge, Chao-Yi Ho, Jocelyn M. Richardndipo Alexandra G. DiFeliceantonio

Zomwe timadya, nthawi ndi zingati, zonse zimakhudzidwa ndi njira zopindulitsa za ubongo zomwe zimapangitsa 'kukonda' ndi 'kufuna' chakudya. Monga chiwonetsero, kutayika kwa madera a mphotho kungapangitse kukula kwa kunenepa kwambiri ndi matenda ovutika. Pano ife tikuyesa njira za ubongo zomwe zimadziwika kuti zimakonda 'kukonda' ndi 'kufuna' chakudya, ndi kuyesa momwe zimagwirizanirana ndi njira zowonetsera njala ndi zosowa, zokhudzana ndi matenda. 'Kuwoneka' njira zimaphatikizapo maulendo a hedonic omwe amagwirizanitsa zigawo zowonongeka za cubic-millimeter mu ziwalo zam'mbuyo zam'mimba monga nucleus accumbens ndi ventral pallidum (kumene opioid / endocannabinoid / orexin zizindikiro zingakulitse zosangalatsa). 'Kufuna' njirazi zimaphatikizapo makina akuluakulu a opioid mu nucleus accumbens, striatum, ndi amygdala yomwe imadutsa pamtunda wa hedonic, komanso masolimbic dopamine machitidwe, ndi zizindikiro zamakono zomwe zimagwirizana ndi machitidwe awo. Timaganizira njira zomwe ubongo uwu umaperekera maulendo angapite nawo ku kunenepa kwambiri kapena kuvutika kwa zakudya.

Kulephera kwa mphoto chifukwa

Choyamba, n'zotheka kuti mbali zina za mphotho mphoto zimayenda molakwika chifukwa chodyera kapena matenda enaake. Zakudya zikhoza kukhala "zokonda" kwambiri kapena zochepa pokhapokha mwa mphotho yopanda ntchito. Mwachitsanzo, kutsegula kwa opioid kapena endocannabinoid hedonic hotspots mu nucleus accumbens ndi palralum ventral yomwe ili pansipa ingapangitse kuti 'kukonda' kuchitidwa pofuna kukondweretsa zosangalatsa mwa anthu ena. Kuwongolera mochulukitsa za 'kukhumba' magawo kungapangitse zotsatira za hedonic ya zakudya, kupanga munthu onse 'monga' ndi 'kufuna' chakudya kuposa anthu ena, ndipo amathandizira kudya kwambiri ndi kunenepa kwambiri (Berridge, 2009; Davis et al., 2009). Mofananamo, mawonekedwe osokoneza bongo amatha kuchepetsa 'kukonda' ndi matenda odwala matenda a anorexia.Kaye et al., 2009).

Ngakhale osasangalatsa malingaliro, mwayi wina wosokoneza mphotho ndi wakuti 'kufuna' kudya kungawoneke, ngati kulimbikitsidwa kumachokera ku hedonic 'kukonda' (Finlayson et al., 2007; Mela, 2006). Kusiyanitsa kwa 'kufuna' kuchokera 'kukonda' muzovuta zina ndizowoneka chifukwa ubongo umawoneka kuti ukupanga 'kufuna' ndi 'kukonda' kudzera njira zopatukana, monga tafotokozera pansipa. Zotsatira za chakudya chokoma mtima zikhoza kupangitsa kuti 'kufuna' ndi kugwiritsidwa ntchito mopitirira muyeso ngakhale kuti sizingatengeke mwachindunji, mwina kudzera mwa hyper-reactivity mu mesocorticolimbic dopamine-glutamate njira zothandizira (kapena CRF kapena ma opioid circuits zomwe zingayambitse njirazi). Zikatero, kupenya, kununkhiza, kapena kulingalira bwino kwa chakudya kungayambe kukakamiza kudya, ngakhale kuti munthuyo sapeza chowonadi chenichenicho kuposa chokondweretsa pamapeto pake. Zonsezi zakhala zotchulidwa pa nthawi ina. Mmodzi wa iwo amayenera kulingalira chifukwa mayankho osiyanasiyana angagwiritsidwe ntchito ku matenda osiyanasiyana kapena mitundu yambiri ya kunenepa kwambiri.

Osasokoneza mopepuka mphoto ntchito monga zotsatira

Gawo lachiwiri la zowonjezera ndiloti mphotho za ubongo sizingakhale chifukwa choyambitsa kudya, komabe zimayamba kugwira ntchito mopanda ntchito monga zosavuta, zomwe zimapangitsa kuti azikhala ndi zakudya zambiri, kudya kosafunikira kapena kulemera kwa thupi. Zikatero, machitidwe a ubongo 'okonda' ndi 'kufuna' angayese kuyendetsa bwino, koma amawoneka kuti ndi osalongosoka mu maphunziro a ubongo, kotero kuti akhoza kukhala wofiira wofiira kwa ofufuza. Komabe, ngakhale kusokoneza ntchito zopatsa mphotho kungapereke mawindo a chithandizo chamankhwala omwe akukonzekera kukonza khalidwe la kudya mwa gawo poyendetsa mphoto ntchito mmbuyo mwayomweyo.

Kukhazikika kwabwino mu ubongo mphotho

Chachitatu, n'zotheka kuti nthawi zambiri ubongo umapindula kachitidwe kachitidwe kawirikawiri mu kunenepa kwambiri kapena matenda odwala, osasintha ngakhale kachiwiri. Zikatero, zomwe zimayambitsa vuto la kudya zikanatha kukhala kunja kwa ubongo ntchito. Inde, mphotho ya ubongo ikhoza kugwira ntchito ngati zothandizira kuti potsirizira pake zithandiza pokhapokha kudya zakudya zina ngakhale popanda chithandizo.

Kupanga 'kufuna' popanda 'kukonda'

Chiwonetsero chodabwitsa kwambiri cha kulimbitsa mtima monga chosiyana chimachokera ku milandu imene 'kufuna' kwasinthidwa kokha ndekha, popanda kukweza hedonic 'kukonda' mphotho yomweyo. Kupeza kwathu koyamba kwa 'kufuna' -kusa-'kufuna 'kunabwera zaka makumi awiri zapitazo kuchokera ku kafukufuku wokhudza kudya komwe kunayambitsidwa ndi magetsi a lateral hypothalamus mu makoswe, inagwirizanirana ndi Elliot Valenstein (Berridge ndi Valenstein, 1991). Kugwiritsa ntchito makina a electrode mumtundu wa laterpot hypothalamus kumayambitsa makoswe kuti azidya mwamphamvu (Valenstein et al., 1970), ndipo ma electrodes amenewa amachititsa maulendo a ubongo omwe amapezeka ndi masolimbic dopamine kumasulidwa (Hernandez et al., 2008). Kutsitsimutsa komweku kumagwiritsidwa ntchito ndi nyama monga mphotho, ndipo kutsegulira kwa electrode kwadodometsedwa kuti zipangitse kudya mwa kuwonjezetsa zotsatira za hedonic za chakudya. Kodi makoswe okondweretsa kwenikweni akufuna 'kudya' chifukwa chakuti 'ankakonda' zakudya zambiri? Mwina chodabwitsa poyamba, yankho lake linakhala 'ayi': Kutsegulira kwa electrode yopanda mphamvu kunalepheretsanso kukondweretsa 'kulakalaka' kwa sucrose (monga lip licking, yofotokozedwa mwatsatanetsatane), ngakhale kuti makoswe amadya kawiri zakudya zambiri monga zachizolowezi (Berridge ndi Valenstein, 1991)(Zizindikiro 2 & 3.) M'malo moonjezera 'kukonda', electrode imangowonjezera 'kusokoneza' zochita (monga mapapu) kuti azipaka kukoma, monga ngati, china chilichonse, sucrose inakhala yosasangalatsa. Izi ndi zotsutsana zotsatila za 'kufuna' kuchokera pa 'kukhumba' zimasonyeza kufunikira kozindikiritsa magawo ena a neural omwe ali nawo. Tidzalongosola motsatira machitidwe a ubongo okhudzana ndi 'chakudya' ndi 'kukonda' chakudya, ndikuwone momwe machitidwewa akugwirizanirana ndi machitidwe ena oyendetsa.

 

Chithunzi 2

'Kufuna' zowonjezera zimayambitsidwa ndi hypothalamic stimulation kapena dopamine kukwera

 

Chithunzi 3

'Kuwonda' kwa kukoma sikumapitsidwanso ndi hypothalamic electrodes kapena dopamine kukwera

Zosokonezeka za anorectic zotsatira za dopamine (ndi zotsatira zoopsa za dopamine blockade)?

Komabe, pamakhalabe zovuta zogwirizana ndi maganizo athu kuti dopamine amatsutsana ndi "kufuna" chakudya, ndipo izi ziyenera kuvomerezedwa. Chomwe chimakhala chovuta kumvetsa ndicho chakuti mankhwala oletsa antiyytics omwe amachititsa kuti D2 receptors iwonjezere zakudya zamatenda ndi kuwonjezera kulemera kwa thupi (Cope et al., 2005; Stefanidis et al., 2009). Komabe, kufotokoza kwa izi kungabwere kuchokera ku blockade ndi antipsychotics yemweyo ya serotonin 1A ndi 2C receptors, ndi histamine H1 receptor, yomwe ingagwirizanitse bwino ndi kulemera kwoposa D2 occupancy (Matsui-Sakata et al., 2005).

Mwina chinthu chovuta kwambiri ndi chakuti dopamine imakhala ndi zovuta komanso zosiyana kuponderezana chilakolako chofuna kudya, monga momwe amachitira mankhwala osokoneza bongo odziwika bwino. Osachepera, systemic amphetamine ndi zokopa zokhudzana ndi chilengedwe zomwe zimalimbikitsa dopamine ndi norepinephrine moletsa kudetsa chilakolako ndi kudya. Komabe, zotsatira zina za amphetamine zimatha kukhala ndi zotsatira za kutuluka kwa norepinephrine, komwe kuli ndi njala yambiri yomwe imalepheretsa hypothalamus, mwina pogwiritsa ntchito alpha-1 -adrenoreceptors (mosiyana ndi zotsatira zoopsa za alpha-2 receptors) (Adan et al., 2008; Wellman et al., 1993). Komanso, n'kofunika kuzindikira kuti dopamine yokha ingakhale ndi zotsatira zosiyana pa kudya muzipangidwe zosiyana za ubongo, komanso pazinthu zosiyana ngakhale mu dongosolo limodzi (Cannon et al., 2004; Kuo, 2003). Mwachitsanzo, dopamine imakhala ndi zotsatira zosawerengeka m'maganizo a hypothalamic arcuate, mwina mwa kuchepetsa mphutsi Y (Kuo, 2003), komanso kuchuluka kwa dopamine kungakhale ndi zotsatira zosawerengeka komanso mkati mwa nucleus accumbens ndi neostriatum, ngakhale kuti m'munsi mwa dopamine kukwera kumene kumathandiza kudya ndi "kufuna" chakudya (Cannon et al., 2004; Evans ndi Vaccarino, 1986; Inoue et al., 1997; Pal ndi Thombre, 1993; Wise et al., 1989). Pomaliza, nkofunikanso kuzindikira kuti mphamvu za dopamine zolimbikitsana nthawi zambiri zimayesedwa kuti zikhale zokopa chifukwa cha mphotho - kulola kuti chiwerengerocho chiyambe 'kufuna' mphotho yomwe imatsogolera, m'malo mowonjezera kukula kwa chakudya ndi chakudya (Pecina et al., 2006; Smith et al., 2007; Wolterink et al., 1993; Wyvell ndi Berridge, 2000; Wyvell ndi Berridge, 2001). Dopaminergic cue-yomwe imayambitsa 'kufuna' ingapangitse munthu kugonjetsedwa ndi chiyeso chodya, ndipo pamene chakudya chatangoyamba (mwachitsanzo, opioid) njira za ubongo zingawononge kukula kwa ufa kuchokera pamenepo. Kawirikawiri, udindo wa dopamine umawongolera sikuti umangokhala pamwamba kapena pansi, koma zimakhala zosiyanasiyana mosiyana ndi ubongo komanso m'maganizo osiyanasiyana.

Nucleus accumbens hotspot

Chombo choyamba chopeza chinapezeka mkati mwa nucleus accumbens, komwe chimagwiritsira ntchito zizindikiro za opioid ndi endocannabinoid kuti zikhale zozizwitsa 'zokonda' (Chithunzi 4 & 5). Malo otetezekawa amakhala m'magulu a chigwirizano cha pakati pa nucleus accumbens: makamaka, mu chiwindi cha mamitamitamita a minofu mu rostrodorsal quadrant ya chigoba chamkati. M'malo otchedwa hedonic hotspot, 'kukonda' kukoma kumawonjezeredwa ndi microinjection ya mankhwala omwe amatsanzira opioid yodalirika kapena endocannabinoid zamagetsi. Izi zimaphatikizapo maganizo a ofufuza ambiri omwe amakhulupirira kuti cholojekiti cha opioid kapena cannabinoid receptor chowunikira chimachititsa chilakolako china mwa kuwonjezera 'kukonda' chifukwa cha kuyanjana kwa chakudya (Baldo ndi Kelley, 2007; Barbano ndi Cador, 2007; Bodnar et al., 2005; Cooper, 2004; Dallman, 2003; Higgs et al., 2003; Jarrett et al., 2005; Kelley et al., 2002; Kirkham ndi Williams, 2001; Kirkham, 2005; Le Magnen et al., 1980; Levine ndi Billington, 2004; Panksepp, 1986; Sharkey ndi Pittman, 2005; Zhang ndi Kelley, 2000). Zotsatira zathu zinkatsatira malingaliro awo a hedonic ndipo, ponena za magawo ena a ubongo, athandizira kufotokozera malo a ubongo omwe ali ndi udindo wopititsa patsogolo masewera. Kafukufuku wotsogoleredwa ndi Susana Peciña mu labototori yathu poyamba adapeza malo osungirako mankhwala omwe amapezeka mumtundu wambiri, pogwiritsa ntchito microinjections ya mankhwala opioid agonist (DAMGO; [D-Ala², N-MePhe⁴, Gly-ol] -enkephalin). DAMGO yatsala pang'ono kugwiritsa ntchito mtundu wa opioid receptor, ndipo mu hotspot izi zikuwoneka mokwanira kuti zikhale zosangalatsa zojambulajambula ndi ubongo pa zokoma (Pecina, 2008; Peciña ndi Berridge, 2005; Peciña et al., 2006; Smith et al., 2010). Kupitirira kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri kawiri, 'Kusokoneza' zochita kwa quinine sikudapitsidwenso, koma kunayesedwa ndi kuyambitsa opioid mkati ndi kuzungulira malo ozungulira. Momwemo zokondweretsa zokoma zimakula, ndipo kusakondwa kwachisoni kumachepetsedwa panthawi yomweyo, ndi kukondweretsedwa kwa matenda a hedonic hotspot.

Matenda osokoneza bongo, mankhwala a ubongo ofanana ndi matenda a tetrahydrocannabinol a chipatala, ali ndi malo awo omwe amachititsa kuti atsegule ndi opioid hotspot. Kafukufuku wolembedwa ndi Stephen Mahler ndi Kyle Smith mu labata yathu anapeza kuti anandamide, omwe amagwira ntchito mu ubongo mwa kulimbikitsa mtundu wa CB1 wa receptor, amatha kugwira ntchito mofanana ndi mankhwala opioid kuti awononge chisangalalo cha sucrose kukoma (Mahler et al., 2007; Smith et al., 2010). Mankhwala a Anandamide microinjections m'kati mwawo amawongolera mobwerezabwereza chiwerengero cha zabwino 'zokonda' nkhope zomwe zimayambitsa kulawa zomwe zimapangidwa kuchokera ku makoswe, monga momwe zinakhalira opioid, pomwe kuyambiranso kwakukulu kwa kulawa kowawa sikudapitsidwenso. Chinthu chimodzi chodabwitsa chimene chingapangitse kulumikizana ndi zowonjezerazi ndi "shell hotspot" ndizoti zizindikiro za opioid ndi endocannabinoid zingagwirizane kapena kugwirizana. Anandamide akuti agwiritse ntchito mbali imodzi ngati njira yotsitsimutsa anthu, yomwe imatha kumasulidwa ndi khungu lopangidwa ndi khungu la chigoba kuti liziyandama kumalo osungirako mankhwala a presynaptic axon ndi kulimbikitsa mapulogalamu a CB1, ndipo mwinamwake kumasula kumasulidwa kwa opioid musanayambe (Cota et al., 2006; Kirkham, 2008; Piomelli, 2003). Mofananamo, zizindikiro za opioid zimayambitsa ndondomeko yothamanga ya post-synaptic mu chipolopolo imatha kulandira kumasulidwa kwa endocannabinoid. Kafukufuku wamtsogolo angathe kufufuza ngati chizindikiro cha endocannabinoid ndi opioid chikugwirizana ndi njira zogwirira ntchito zogwirira ntchito.

Nyanja yaikulu ya opioid ya 'kufuna' mu nucleus accumbens

Kuonjezera kukulitsa 'kukonda', microinjections ya DAMGO kapena anandamide mu accumcums hotspot yomweyo komanso nthawi yomweyo ndikulimbikitsa 'kufuna' kudya, kusonyeza kuwonjezeka kwa kudya. Koma mbali zina zoyandikana za nucleus accumbens zimangokhala 'kufuna' pokhapokha zitayikidwa ndi opioids, popanda kuwonjezera 'kukonda' (Chithunzi 5). Izi zikutanthauza kuti pamene opioid neurotransmission mu cubic-millimeter hotspot ali ndi mwayi wapadera wokweza 'kukonda' (poyerekezera ndi, kunena kuti, dopamine neurotransmission), kutsegula kwa opioid kunja kwa malo otere si hedonic, ndipo kumangotanthauza 'kufuna' popanda 'kukonda' '(nthawizina ngakhale kuchepetsa' kukonda '). Mwachitsanzo, opioid hedonic hotspot imakhala ndi 10% chabe ya nucleus accumbens, komanso ngakhale 30% ya chipolopolo chake chamkati. Komabe DAMGO microinjections m'kati mwa 100% ya chipolopolo chamkati mwachulukidwe chinawonjezereka 'kufuna', kuposa kukayikira kuchuluka kwa chakudya chodya. DAMGO imalimbikitsa 'kufuna' mogwira mtima ngakhale pa 'coldspot' yowonjezera yomwe microinjections zomwezo zimatsitsa 'kukonda' pansi pazinthu zachibadwa (Peciña ndi Berridge, 2005). Kufufuza kwa Hedonic kumangogwiritsidwa ntchito pokhapokha ngati mphutsi zimakhala zovuta kwambiri, komanso zimagwiritsidwa ntchito ndi opioid ndi chizindikiro cha endocannabinoid (Peciña ndi Berridge, 2005). Kufalitsa njira zambiri za 'kufuna' zimagwirizana ndi zofukufuku zapitazo zomwe opioids zimalimbikitsa chakudya 'chofuna' mukati yonse yonse yosungunuka komanso ngakhale kunja kwa nyumba zomwe zimaphatikizapo amygdala ndi neostriatum (Cooper ndi Higgs, 1994; Kelley, 2004; Kelley et al., 2005a; Levine ndi Billington, 2004; Amatsenga ndi Oyera, 2002). Malo ambiri a opioid sangakhale hedonic.

Kodi neostriatum ikugwira nawo ntchito 'kufuna' kapena 'kukonda'?

The ventral striatum (nucleus accumbens) imatchuka chifukwa cha zolimbikitsa, koma posachedwa dorsal striatum (neostriatum) yakhala ikukhudzidwa ndi zokondweretsa komanso mphotho (kuphatikizapo ntchito yodziwika bwino yomwe imatuluka).Balleine et al., 2007; Palmiter, 2007; Schultz ndi Dickinson, 2000; Volkow et al., 2002; Wanzeru, 2009). Mwachitsanzo, dopamine neurons yomwe imayambitsa neostriatum mu nyenyezi zimapereka mphoto zotsatilapo ndi zolakwika zowonongeka (madzi osadziwitsidwa mphoto) mofananamo ndi dopamine neurons yomwe imayambira ku nucleus accumbens (Schultz ndi Dickinson, 2000). Dopamine ya munthu yotulutsidwa mu dorsal striatum imaphatikizapo chilakolako chomwe chimapangidwa ndi kuyang'ana chakudya kapena mankhwala (mu maphunziro ena, ogwirizana kwambiri kusiyana ndi ventral striatum) (Volkow et al., 2002; Volkow et al., 2008; Wang et al., 2004a). Neostriatal dopamine imafunika kuti apange khalidwe loyenera la kudya, monga kudya chakudya kumabwezeretsedwanso ku mbewa zakupha zaphaka za dopamine m'malo mwa kusintha kwa dopamine mu neostriatum (Palmiter, 2007; Szczypka et al., 2001).

Mofananamo, mu kukopa kwa opioid ya neostriatum ikhoza kuyambitsa kudya, mwina mu gawo lotulukira (Zhang ndi Kelley, 2000). Powonjezera zotsatirazi, tapeza posachedwa kuti madera ena a neostriatum amathanso kulumikizana ndi chakudya chomwe chimalimbikitsidwa ndi opioid, kuphatikiza magawo ena akutali a neostriatum. Makamaka, zomwe tawonetsa zikuwonetsa kuti kukondoweza kwa opioid kwa dorsomedial quadrant ya neostriatum kumathandizira kudya zakudya zokoma (DiFeliceantonio ndi Berridge, zomwe zimawonedwa). Pakafukufuku waposachedwa woyendetsa ndege, tawona kuti makoswe amadya chokoleti chopitilira kawiri (maswiti a M&M atalandira ma microinjection a DAMGO mu dorsomedial striatum kuposa momwe amayang'anira ma microinjection oyendetsa galimoto. Chifukwa chake zotsatira zathu zimagwirizana ndi lingaliro loti ngakhale magawo owoneka bwino kwambiri a neostriatum atha kutenga nawo mbali pakupanga chilimbikitso chodya mphotho ya chakudya (Balleine et al., 2007; Palmiter, 2007; Schultz ndi Dickinson, 2000; Volkow et al., 2002; Wanzeru, 2009).

Kodi orexin hedonic hotspot mu ventral pallidum?

Kodi palinso mankhwala enaake omwe amachititsa kuti azikonda? Wovomerezeka mmodzi ndi orexin, woganiza kuti akukhudzana ndi njala ndi mphotho mumzinda wa lateral hypothalamic (Aston-Jones et al., 2009; Harris et al., 2005). Mankhwala a Orexin neurons kuchokera ku hypothalamus mpaka pa ventral pallidum, makamaka m'dera lawo lotchedwa posterior lomwe lili ndi opioid hedonic hotspot (Baldo et al., 2003). Ventral pallidum neurons motero amalandira orexin mwachindunji, ndipo motero amafotokoza receptors kwa orexin (Nixon ndi Smale, 2007).

Zotsatira za kafukufuku waposachedwapa mu labu yathu zikuwonetsa kuti orexin mu palralum ventral ingapangitse 'kukonda' mphoto zabwino (Ho ndi Berridge, 2009). Chao-Yi Ho wapeza kuti microinjections ya orexin-A yomwe ili pamalo otsika monga opioid hedonic hotspot ya palralum yamalimba imapangitsa chiwerengero cha 'kukonda' zomwe zimachita kuti sucrose kukoma. Orexin microinjections mu ventral pallidum amalephera kuonjezera zoipa zosokoneza zomwe zimachitika ku quinine, zomwe zimasonyeza kuti zabwino zokhazokha zokhutira zokondweretsa zinawonjezeka osati zonse zokoma -Ho ndi Berridge, 2009). Ngakhale kufufuza kwina kuli kofunika, zotsatirazi zoyambirira zimasonyeza njira imene njala imatha kuyipiritsira zakudya zabwino kwambiri, mwinamwake kupyolera mu orexin hypothalamus-to-ventral-pallidum link.

Umboni womaliza wakuti ventral pallidum amakhudzidwa ndi mphamvu ya hedonic ya 'zokondweretsa' zowawa ndikuti kuwombera mazenera m'makalata otchedwa posterior hedonic hotspot 'okonda' okoma, amchere komanso zakudya zina (Aldridge et al., 1993; Aldridge ndi Berridge, 2010; Beaver et al., 2006; Calder et al., 2007; Tindell et al., 2004; Tindell et al., 2005; Tindell et al., 2006). Neurons mu hotspot ya ventral pallidum moto mofulumira pamene makoswe amadya pellet shuga, kapena ngakhale kukumana ndi zotsatira za mphotho, monga kuyeza ndi makina osindikizira opangidwa ma electrodes (Tindell et al., 2004; Tindell et al., 2005). Kuthamanga kwa sucrose-kumayambitsa neuroni kumawonekera mwachindunji hedonic 'kukonda' kwa kukoma (Aldridge ndi Berridge, 2010). Mwachitsanzo, ventral pallidal neurons moto pamene mankhwala a sucrose alowetsamo pakamwa koma neurons yomweyi sidzawombera njira ya NaCl yomwe imakhala yapamwamba katatu kuposa madzi amchere komanso osasangalatsa kumwa. Komabe, ventral pallidum hotspot neurons mwadzidzidzi imayaka moto kwa kukoma kwa madzi a m'nyanja zitatu. Ngati chikhalidwe cha mchere chimakhudzidwa ndi makoswe (Tindell et al., 2006; Tindell et al., 2009) pogwiritsa ntchito furosemide ndi deoxycorticosterone ngati mankhwala kuti azitsanzira zizindikiro zowonongeka zowonongeka za angiotensin ndi aldosterone (Krause ndi Sakai, 2007), ndi kuonjezera zomwe zikuwoneka ngati 'mukukonda' za kukoma kwa mchere kwambiri (Berridge ndi Schulkin, 1989; Tindell et al., 2006). Momwemonso neurons mu code ventral pallidum amasangalala zosangalatsa m'njira yomwe imakhudzidwa ndi zosowa za thupi za nthawiyo. Kuwona kuti mazembera a hedonic ali mu malo amodzi omwe amachititsa kuti opioid ayambe kukonzekera kuti ayambe kukonda kwambiri kukoma kwake amasonyeza kuti kuwombera kwawo kungakhale mbali ya njira yomwe imapangitsa kuti chisangalalo chisangalatse pakumverera kwa kukoma (Aldridge ndi Berridge, 2010).

Chinthu chimodzi chomwe palralum ya ventral ikhoza kukweza 'kufuna' popanda 'kukonda' ikuwoneka pambuyo poletsa kusokoneza GABA neurons mu ventral pallidum, (Smith ndi Berridge, 2005). Kyle Smith adayambitsa kachilombo ka GABA, bicuculline, yomwe imatulutsa ma neurons kuchokera ku tonic GABAergic kukakamizidwa, mwinamwake kuwathandiza kuti magetsi asokonezedwe mofananako ndi electrode yokha. Zotsatira za m'maganizo za ventral pallidal depolarization zinali zofanana ndi zomwe zowonjezera mphamvu zamagetsi zowonongeka. Kudya chakudya kunabwerekanso koma panalibe kuwonjezeka konse pochita momwe amafunira kuti ayambe kuyamwa (mosiyana ndi zovuta za opioid ndi DAMGO microinjections pa webusaitiyi, yomwe yowonjezera 'kufuna' ndi 'kukonda' palimodzi) (Smith ndi Berridge, 2005).

Mgwirizano wa chigawo cha nucleus accumbens ndi palralum hotspots

Sikuti nkhono zonse zimagwiritsidwa ntchito ndipo palralum imakhala ndi malo otentha omwe amachititsa kuti 'azikonda,' koma zigawo ziwirizi zimagwirira ntchito limodzi kuti zithe kugwiritsidwa ntchito kuti zikhale zokopa.Smith ndi Berridge, 2007). Pogwira ntchito mu labayi yathu, Kyle Smith anapeza kuti microinjections ya opioid agonist m'kati mwa hotspot inkayang'aniridwa kutali ndi Fos kufotokozera kwinakwake, posonyeza kuti malo alionse amawatumizira ena kuti azikonda 'hedonic'. Kuonjezera apo, opioid blocked ndi naloxone mu hotspot akhoza kuthetsa 'kukonda' opangidwa ndi DAMGO microinjection mumalo ena, kusonyeza kuti mogwirizana mogwirizana ankafunika. Zochitika zoterezi zimasonyeza kuti mapuloteni awiriwa amalumikizana mozungulira mu dera limodzi lokonda, ndipo dera lonse likufunika kukweza zotsatira za hedonic. Komabe, kugwilitsila nchito pokhapokha kungachititse kuonjezera 'kufuna' ndi kudya zakudya mosasamala kanthu kowonjezera pallidal kutenga nawo mbali (ndipo mosasamala kanthu kuti 'kukonda' kumagwiritsidwa ntchito panthawi yomweyo) (Smith ndi Berridge, 2007).

Chakudya ngati maginito olimbikitsa pa nthawi ya njala

Njira imodzi ndi kukweza 'kufuna' chakudya mwachindunji panthaŵi ya njala, ndipo mwinamwake kukweza chidwi chimenecho mwa anthu ovuta kwambiri. Kwa anthu, kulimbikitsidwa kwakukulu kwa chakudya cha mchere kwawerengedwa m'maphunziro ena ndi kayendetsedwe ka maso kamodzi kothamanga kwambiri kapena kwa nthawi yayitali kapena kawirikawiri pakuwona zakudya, kapena ndi zofanana. Mwachitsanzo, anthu okhwima amadziwongolera kuti aziwoneka bwino kuposa chakudya choposa anthu ochepa kwambiri, makamaka akakhala ndi njala (Nijs et al., 2009). Lipoti linanso limasonyeza kuti njala imapangitsa kuti chakudya chikhale cholimbikitsana ndi anthu olemera komanso olemera kwambiri, monga momwe kuwonetseredwa ndi kuwonjezereka kwa nthawi yaitali, koma kuti anthu ena amatha kukhala ndi mphamvu zowonjezera zowonjezera zowonjezera chakudya ngakhale atangodya kumene (Castellanos et al., 2009). Kulimbitsa mtima kwakukulu kwa mafano a zakudya kungakhalenso wofanana ndi lingaliro lachikhalidwe lochokera ku psychology la anthu limene kunenepa kwambiri kumaphatikizapo kuwonjezera kwina kapena kuchitapo kanthu kuti zikhale zolimbikitsa (Nisbett ndi Kanouse, 1969; Schachter, 1968).

Opioid alliesthesia panthawi ya njala?

Chimodzimodzinso, hedonic 'kukonda' chakudya chimakula panthawi ya njala. Kukonzekera kwa opioid kosasokonezeka mu malo otchedwa hedonic hotspots ndi mtsogoleri wamkulu kuti apange chakudya kuti azikhala bwino pa nthawi ya njala. Ngati kukoma kwa chakudya pakakhala njala kunachotsa kutuluka kwa opioid kosasunthika pofuna kukweza m'matope a opioid, chakudya chingadye bwino kusiyana ndi chitetezo. Aliyense yemwe anali ndi mawonekedwe okhwima a njira iyi ya hedonic angapeze chakudya kuti alawe bwino kwambiri. Pachifukwachi, timaganiza kuti chilengedwe cha mtundu wa opioid chimachokera ku chilengedwe cha enkephalin. Endogenous B-endorphin ndizowonjezereka bwino kwambiri m'malo ovomerezeka ndi opioid kusiyana ndi enkephalin, ndipo B-endorphin neurons akuti apangidwe kuchokera ku hypothalamus kupita ku ziwalo zina zamagetsi (Bloom et al., 1978; Zangen ndi Shalev, 2003), koma endorphins sangakhalepo mu chipolopolo chamkati mokwanira kuti akwaniritse ntchitoyi (SJ Watson, kuyankhulana kwaumwini, 2009). Choncho, enkephalins, m'malo mwa B-endorphin, ndi omwe amapezeka kwambiri mu-opioid signal mu nucleus accumbens shell. Enkephalin imachokera ku chiwerengero chachikulu cha neuroni mkati mwa chipolopolo (anthu omwe amafotokoza enkephalin mRNA pamodzi ndi D2 receptors ndi GABA mRNA), komanso kuchokera ku maonekedwe a neurons ochokera ku ventral pallidum ndi zomangamanga zomwe zimaperekanso GABA ndi chizindikiro cha enkephalin.

Chochititsa chidwi cha hypothalamic-thalamic-chimagwiritsira ntchito dera la ubongo pofuna kulimbitsa zizindikiro za enkephalin mu nucleus accumbens shell mu njala za caloric zomwe Ann Kelley ndi anzake ankanena (Kelley et al., 2005a). Kelley et al. analimbikitsa kuti ma orexin neurons m'ntchito yophatikiza hypothalamus kuyambitsa glutamate neurons m'kati mwa thalamic. Komanso, thalamic paraventricular neurons polojekiti ya nucleus accumbens shell kumene amagwiritsira ntchito zizindikiro za glutamate kuti azisangalala ndi ma interneurons akuluakulu a acetylcholine. Kelley ndi anzake ankanena kuti potsirizira pake acetylcholine neurons mu kaphatikizana kake makamaka amachititse pafupi pafupi enkephalin neurons. Mitsempha yotulutsa enkephalin iyenera kukhala yochuluka kwambiri yomwe imaphatikizapo mkati mwa chigoba chokhala ndi makilogalamu makumi asanu ndi awiri (1,2 millimeter hedonic shell shell). (Chodabwitsa, minda ya acetylcholine neurons yayitali pafupifupi 1 mm m'mimba mwake). Momwemo njala ikhoza kuyambitsa chizindikiro cha opioid chokhazikika mkati mwa nucleus accumbens hotspot kuti liwathandize 'kukonda' ndi 'kufuna' chakudya chokoma.

Kodi njira zothandizira matenda a allyesthesia?

Njira ina yopezera chakudya kuti ikhale yabwino pa nthawi ya njala ndi ntchito yotsegulira anthu m'kati mwachisawawa chimodzimodzi. Umboni umasonyeza kuti matenda a endocannabinoids angathenso kulandira njala. Mwachitsanzo, Kirkham ndi anzake adanena kuti 24-hr mofulumirira makoswe imabweretsa mafinocannabinoids, anandamide ndi 2-arachidonoyl, glycerol mu ziwalo zomangira thupi kuphatikizapo nucleus accumbens (Kirkham et al., 2002). Kukumana ndi matenda a nthendayi kumapangitsa kuti hedonic 'azikonda' chakudya (Kirkham, 2008; Kirkham, 2005). Izi zingachititse kuti 'zisangalatse' makamaka ngati zizindikiro za endocannabinoid zikhoza kufika pa hotspot imodzimodziyo pakati pa nucleus accumbens, kumene anandamide microinjections amadziwika kuti imakondweretsa 'kukonda'Mahler et al., 2007). Ndizodabwitsa kuti mafinocannabinoids amathandizanso mesolimbic dopamine pogwiritsa ntchito ventral tegmental m'dera ndi malo ena, omwe angapangitse kuti thupi likhale lofunika kwambiri la zakudya zosasangalatsa popanda hedonic 'kukonda' (Cota et al., 2006; Kirkham, 2005).

Kodi njira zolimbana ndi mankhwala ophera mafuta a alliesthesia?

Zina mwazochitika zimaphatikizapo orexin kachiwiri, koma kuchita mwachindunji kuposa kupyolera mwachonderera thalamic loop kuti athandize hotspot neurons (Kelley et al., 2005a). Neuroni yowunikira kwambiri yowonjezera imapezeka mu lateral hypothalamus, kumene apatsidwa kuti athetse mphotho ya chakudya, mankhwala, chiwerewere, ndi zina zotero (Aston-Jones et al., 2009; Harris et al., 2005; Harris ndi Aston-Jones, 2006; Muschamp et al., 2007) [ma orexin owonjezera kapena hypocretin neurons amapezekanso m'maganizo ena a hypothalamic, omwe m'malo mwake amatha kukambirana mofulumira komanso mosamala (Berridge et al., 2009; Espana et al., 2001)].

Ma orexin neurons okhudzana ndi mphoto mu lateral hypothalamus amavomerezedwa pogwiritsa ntchito zizindikiro za neuropeptide-Y (NPY) pa njala (Berthoud ndi Morrison, 2008; Gao ndi Horvath, 2007). Ena orexin neurons polojekiti palralum ndi nucleus accumbens (Baldo et al., 2003; Borgland et al., 2009; Korotkova et al., 2003; Peyron et al., 1998; Zheng et al., 2007). Monga tafotokozera pamwambapa, tangopeza kumene kuti orexin microinjections mu palralum hotspot yachilendo amatha kukondweretsa 'kukonda'Ho ndi Berridge, 2009). Mwachindunji, ndiye kuti orexin activation pa njala ingathandize kwambiri kuwonetsa hedonic ndi kuyambitsa neurons mu hedonic hotspots, monga posterior ventral pallidum. Momwemo orexin ikhoza kugwira ntchito mofanana ndi hedonic hotspot monga mu zizindikiro za opioid zomwe zimachitika mu ventral pallidum (ndipo mwachidziwikire mu nucleus accumbens). Kuwonjezera pamenepo, orexin ikhoza kuyambitsa 'kufuna' zonse kudzera m'mabwalo oterewa ndi majekesero kuti masolimbic dopamine neurons mu ventral tegmentum.

Njira za Leptin za allyeshesia?

Mosiyana ndi zimenezo, satiety imateteza 'kukonda' ndi 'kufuna' chakudya ngakhale ngati kuli kovuta kuthetsa mphotho ya chakudya (Berridge, 1991; Cabanac, 1979; Cabanac ndi Lafrance, 1990; Kringelbach et al., 2003; O'Doherty et al., 2001; Small et al., 2001). Njira imodzi yokha yopangira mankhwala osokoneza bongo panthawi ya satiety ndi leptin, yotsekedwa ku maselo othupi mu thupi. Leptin imagwiritsa ntchito ma neuroni mumtundu wochuluka, nthenda zina za hypothalamic komanso mu ubongo, kuphatikizapo ventral tegmentum momwe zimatha kuyendetsa masolimbic dopamine maulendo ndi chakudya chosowa (Choi et al., 2010; Figlewicz ndi Benoit, 2009; Friedman ndi Halaas, 1998; Fulton et al., 2006; Grill, 2010; Hommel et al., 2006; Leinninger et al., 2009; Robertson et al., 2008). Leptin ikhoza kuchititsa kuti alliesthesia 'ikhale' yokonda 'kuponderezana mwa kulimbikitsa hypothalamic arcuate POMC / MAP neurons kuti athandize MCR4 receptors pa mapiritsi a paraventricular, kapena kupondereza an arcuate NPY-AGrP neurons kuti ateteze orexin neurons mu lateral hypothalamus, motero kuchepetsa opioid kapena orexin kukakamiza malo otchedwa hedonic hotspots mu ventral pallidum kapena nucleus accumbens.

Kwa anthu, Farooqi ndi O Rahilly ndi anzake adalengeza zotsatira zosangalatsa zomwe zimapangitsa kuti ntchito ya leptin isagwiritsidwe ntchito poletsa 'kufuna' kapena 'kukonda' mwa mtundu wina wa majini olemera kwambiri: anthu obadwa ali ndi leptin, omwe amakhala ngati ana nthawi zonse funani chakudya ndipo posakhalitsa mukhale ochepa (Farooqi et al., 2007; Farooqi ndi O'Rahilly, 2009). Ngati palibe leptin anthuwa amachulukitsa ziwerengero zofanana ndi zakudya zomwe zimagwirizana kwambiri ndi nucleus accumbens activation ndi zakudya zomwe zimayesedwa ndi fMRI. Mosiyana ndi anthu ambiri, iwo adasinthidwa kuti asadye chakudya chokwanira, posonyeza kuti kulimbika kwa chilakolako cha 'limbic' ndi 'kufuna' ntchito ngakhale panthawi yopuma. Farooqi ndi anzake amagwiritsanso ntchito kuti kupereka mankhwala oyenera a leptin kwa anthuwa amachititsa kuti caloric satiety ayambe kuthetsa mphamvu yogwiritsira ntchito zakudya, kotero kuti kukonda kwake kumagwirizanitsa ndi nucleus accumbens activation pokhapokha atakhala ndi njala, ndipo sakhalanso ndi chakudya pambuyo pa chakudya . Zofufuza zoterezi zikuwoneka ngati zikugwirizana ndi lingaliro lakuti leptin (kuyanjana ndi zizindikiro zina za njala / satiety) amatha kugwiritsa ntchito zizindikiro zogwiritsira ntchito chakudya kuti zisawononge 'kukonda' ndi 'kufuna' zakudya (Farooqi et al., 2007).

Mu makoswe, leptin administration mu ventral tegmental m'deralo ikhoza kuthetsa kuwombera mitengo ya mesolimbic dopamine neurons, mofanana ndi kuchepetsa 'kufuna', ndi kulepheretsa kudya zakudya zokoma (Hommel et al., 2006). Leptin ndi insulini onse awonetsedwanso m'dera la ventral tegmental kuti asatengere makhalidwe odyera komanso zakudya zomwe zimawathandiza kuti asamangidwe mofanana ndi ma DAMGO microinjection (Figlewicz et al., 2007; Figlewicz ndi Benoit, 2009). Zochita za insulin zomwe zimachitika m'dera la ventral zikuoneka kuti zikuphatikizapo kukwera kwa dopamine transporter (DAT) mu dopamine neurons ndi kuchepetsa kuperewera kwa synaptic m'magazi a dopamine mu nucleus accumbens (Choi et al., 2010; Figlewicz et al., 2007; Figlewicz ndi Benoit, 2009). Komabe, ziyenera kuzindikiranso kuti pali zochepa zochepa zokhudzana ndi lingaliro lakuti leptin imatsitsa chakudya "chofuna" ndi "kukonda". Zodabwitsa kuti, mwachitsanzo, pafupifupi zosiyana ndi zotsatira zafotokozedwa mu mbewa zosavomerezeka za leptin (ob / ob), mu leptin ija imawonekera kuti iwononge congenitally low levels of accumbens dopamine (Fulton et al., 2006; Myers et al., 2009). Chigawo ichi cha puzzles chilipo kuti chifotokozedwe.

Papepalali limaperekedwera kukumbukira Ann E. Kelley (mtsogoleri wa chidziwitso cha chakudya) komanso Steven J. Cooper (mtsogoleri wa psychopharmacology ya mphotho ya chakudya). Ogwira ntchito za asayansi odziwikawa adayambitsa magawo ambiri a nkhaniyi, ndipo imfa zawo zaposachedwa zinali zopweteka zomvetsa chisoni kumunda. Tikuthokoza Ryan Selleck kuti asinthe Zizindikiro 1, , 2,2ndipo And3.3. Zotsatira zomwe zafotokozedwa apa zikuchokera ku ntchito zothandizidwa ndi zopereka za DA015188 ndi MH63649 zochokera ku NIH.

Chodzikanira cha Wosindikiza: Imeneyi ndi fayilo ya PDF ya zolembedwa zosavomerezeka zomwe zavomerezedwa kuti zifalitsidwe. Monga ntchito kwa makasitomala athu ife tikupereka malemba oyambirira a zolembedwazo. Mipukutuyi idzayambanso kujambula, kufotokozera, ndi kubwereza umboni umene umapezekapo musanatulutsidwe mawonekedwe ake omalizira. Chonde dziwani kuti panthawi yopanga zolakwika zingapezeke zomwe zingakhudze zomwe zili, komanso zotsutsana ndi malamulo zomwe zimagwiritsidwa ntchito pa magaziniyo.

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