Ndemanga: Ndemanga iyi inapangidwa ndi mutu wa NIDA, Nora Volkow, ndi gulu lake. Zimakayikira kuti mankhwala osokoneza bongo komanso makhalidwe oipa amakhala ndi njira zofananamo kapena zowonongeka. Izi zimakhala zomveka chifukwa chizoloŵezi cha mankhwala osokoneza bongo chikuphwanyidwa ndi oyang'anira dera la neural kuti agwirizane, kugonana, ndi kudya. Popeza kugonana kumatulutsa dopamine mobwerezabwereza monga kudya zakudya zomwe mumazikonda, ndipo wogwiritsa ntchito zolaula angathe kusunga dopamine kwa maola ambiri, ndizowononga kuti kusokoneza bongo sikungakhaleko.
Behav Neurosci yapamwamba. 2011 Oct 21.
Volkow ND, Wang GJ, Fowler JS, Tomasi D, R. Baler
gwero
National Institute on Abuse, 6001 Executive Boulevard 6001, Room 5274, Bethesda, MD, 20892, USA, [imelo ndiotetezedwa].
Kudalirika
Zizolowezi zonse zoledzeretsa ndi kunenepa kwambiri zimatha kufotokozedwa ngati vuto lomwe limakhala lofunika kwambiri kwa mtundu umodzi wa mphotho (mankhwala ndi chakudya, mwachitsanzo) zimakhala zosavomerezeka mopitirira malire, komanso kwa ena. Chitsanzochi chikugwirizana ndi kuti mankhwala ndi chakudya chimakhala ndi mphamvu zowonjezera zomwe mwina zimalimbikitsidwa ndi kuwonjezeka kwa dopamine mu limbic system-yomwe, nthawi zina kapena mwa anthu omwe ali pachiwopsezo, imatha kupondereza njira zowongolera zaubongo. Kufanana kotereku kwachititsa chidwi kwambiri kumvetsetsa zofooka zomwe zimagwirizanitsa komanso zovuta zowonongeka pakati pa kuledzera ndi kunenepa kwambiri. Tsopano, ubongo ukuganiza zowonjezera wayamba kufotokoza zomwe zimachitika pakati pazirombo ziwirizi ndi kufotokozera maulendo ena a ubongo ophwanyidwa omwe ma dysfunction angathe kufotokozera zolakwika zokhudzana ndi makhalidwe m'mabuku aumunthu. TZotsatira zake zimasonyeza kuti onse omwe ali ovuta kwambiri komanso osokoneza bongo ali ndi vuto la dopaminergic njira zomwe zimayendera njira zothandizana ndi nthenda zomwe zimagwirizanitsidwa osati zokhudzana ndi mphotho zowonjezera komanso zolimbikitsana, komanso ndi chikhalidwe (kukumbukira / kuphunzira) , ndi kuzindikira zamkati. Pano, timagwirizanitsa zotsatira zomwe zimachokera ku positron emission tomography zomwe zimatithandiza kuzindikira kuti ntchito ya dopamine imakhala yotayirira kwambiri komanso kuti munthu amenepa kwambiri, ndikupatsanso chitsanzo chothandizira kupeza njira zothandizira mankhwala omwe angapindulitse zonsezi.
1 Background
2 Udindo wa Dopamine mu Mphoto Yambiri kwa Mankhwala Osokoneza Bongo ndi Zakudya
3 Kujambula DA pakuyankha kwa mankhwala osokoneza bongo komanso kufotokoza zida zolimbitsa thupi
4 Mphamvu ya Kulephera Kuletsa Kutetezedwa
5 Kuphatikizidwa kwa Makonzedwe Otsitsimula
6 Kuphatikizidwa kwa Zokambirana zapakati
7 The Circuitry of Aversion
8 Mankhwala Osokoneza Matenda ndi Mphoto ya Chakudya: Njira Yopangidwira Yogwira Ntchito
1 Background
Dopamine (DA) amaonedwa kuti ndiwopindulitsa ku zotsatira zopindulitsa za madalitso achilengedwe ndi mankhwala. Komabe, udindo wawo kuwonongeka ndi makhalidwe okhwima omwe ali oledzeretsa ndi kunenepa kwambiri sikudziwika bwino. Maphunziro a PET athandiza kwambiri pofotokoza udindo wa ubongo wa DA m'zoledzeretsa (kuphatikizapo gawo lake mu mphotho ya mankhwala) ndi kunenepa kwambiri. Inde, mankhwala osokoneza bongo (kuphatikizapo mowa) amawonongedwa ndi anthu kapena amadzipangira okha ndi nyama za laboratory chifukwa zimakhala zopindulitsa, zomwe zimagwirizanitsa kudzera mwazomwe zimapangidwanso ndi DA mu njira ya masolimbic (Wochenjera 2009). HKomabe, ngati akugwiritsa ntchito mankhwala ozunguza bongo, kafukufuku akuwonetsa kuti matendawa sakhudza dera la mphotho la DA koma ndi njira zina za DA zomwe zimakhudzidwa ndi kusintha kwa zikhalidwe, zizolowezi, ndi ntchito zoyendetsera ntchito (kuletsa kulamulira, kuthandizira, komanso chisankho -kupanga), komanso kuti kuchepa kwa DA kungaphatikizepo kuwonjezereka kwa kusokonezeka maganizo ndi kusokonezeka kwa chidziwitso cha kumvetsera komwe kumakhudzana ndi kuledzera. Kafukufuku wamakono ndi zachipatala awonetsanso zina zokhudzana ndi matenda a ubongo (ndi mauropaptides) omwe amachititsa maudindo ofunika mu mankhwala ndi mankhwala osokoneza bongo (ie, matenda ophera tizilombo toyambitsa matenda, opioids) ndipo amathandizidwa kwambiri ndi kusintha kwa mankhwala omwe amatsatira mobwerezabwereza mankhwala osokoneza bongo (ie, glutamate, opioids, GABA, corticotropin-release factor). Katundu wa glutamatergic ndi wotchuka kwambiri pankhaniyi chifukwa umagwirizanitsa zosokoneza zomwe zimakhalapo kwa nthawi yaitali komanso kuvutika maganizo kwa nthawi yaitali zomwe zakhala zikuwonetsedwa mu zinyama za mankhwala osokoneza bongo (Thomas et al. 2008). Maphunziro okhudzana ndi machitidwe enawa angapezeke kwina kulikonse (Kalivas 2009; Koob 1992).
Popeza mankhwala osokoneza bongo amachititsa kuti pakhale mphotho yomweyo yomwe imapatsa mphoto chakudya, sizingatheke kuti, kawirikawiri, kafukufuku wopanga ubongo wathandizira lingaliro lakuti kuwonongeka kwa madongosolo a DA-modulated kumakhudzidwanso ku matenda, kukhumudwitsa khalidwe labwino. Chakudya, monga mankhwala osokoneza bongo, chimalimbikitsa DA yomwe imatulutsa mchere ndipo imapangitsa anthu kukhala ndi makhalidwe omwe ali oyenera kuti adye ndi kudya chakudya, kupereka umboni wothandizidwa ndi DA osati chakudya chokha komanso komanso zosowa za hedonic. Mitengo ya chakudya (ie, caloric zofunikira) ndi kuchepa kwa chiletso choletsedwa kuwonetsetsa kudya mopitirira malire (Avena et al. 2008; Volkow et al. 2008a).
Pano, timakumbukira zofufuza kuchokera ku zojambula zamaganizo zomwe zimagwiritsidwa ntchito makamaka pazomwe zikugwedezeka m'madera oyendetsa ubongo omwe amasokonezeka ndi kunenepa kwambiri komanso kuledzera. Ndikoyenera kukumbukira, komabe, kuti kayendedwe ka makhalidwe odyetsa zakudya ndi ovuta kwambiri kusiyana ndi kayendedwe ka kudya mankhwala. Ambiri amatsatiridwa ndi zotsatira zopindulitsa za mankhwala osokoneza bongo pamene poyamba sanagwiritsidwe ntchito ndi zotsatira zake zokhazokha zokhazokha (zizindikiro za hedonic) komanso ndi zowonongeka ndi zikuluzikulu zomwe zimawona kuti zakudya zofunika m'thupi zimakhala zofunika kuti pakhale (homeostatic factors). Chochititsa chidwi, pali umboni wochuluka wosonyeza kuti zinthu zotchedwa homeostatic (mwachitsanzo, insulini, leptin, ghrelin) zimapatsa chakudya chokwanira mwa kuwonjezeka kapena kuchepetsa mphamvu ya ubongo m'madera ozungulira kuti akhale chakudya (Volkow et al. 2011a).
2 Udindo wa Dopamine mu Mphoto Yambiri kwa Mankhwala Osokoneza Bongo ndi Zakudya
Kaya mwachindunji kapena mwachindunji, mankhwala osokoneza bongo amasonyeza kuti ali ndi mphamvu zowonjezera DA mu nucleus accumbens (NAc) kudzera m'magwiridwe osiyana ndi majekeshoni osiyanasiyana (Nestler 2004) (Chith. 1). Diso la DAlimbic DA [madera a DA mu dera lotchedwa ventral tegmental area (VTA) yomwe ikuyendera mu NAC] ikuwoneka kuti ndi yofunika kwambiri kwa mphotho ya mankhwala (Wochenjera 2009). Komabe, monga momwe tafotokozera m'munsimu, njira zina za DA [mesostriatal (DA maselo omwe amagwiritsira ntchito digra akulowera ku dorsal striatum) ndi mesocortical (DA maselo a VTA akulowera kutsogolo) amathandizanso kuwononga mankhwala osokoneza bongo (Wochenjera 2009). Zonsezi, zikuwoneka kuti zotsatira zowonjezera komanso zoyipa za mankhwala zimayendetsedwa ndi chipangizo cha DA chotsitsa, chomwe chimapangitsa DA kukula ndi kupitirira. Mosiyana ndi zimenezi, kugwa pansi kwa ntchito yayikulu yomwe imachitika moledzeretsa kumagwirizana ndi kusintha kwa khungu la DA cell ndi kuwombera madera ochepa koma otsika kwambiri (Grace 2000; Wanat et al. 2009). Izi zimaphatikizapo malonjezano a D1 (D1R), omwe ndi ochepa kwambiri a DA omwe amachititsa kuti AMP iwonetseke bwino, monga momwe zimakhalira ndi mankhwala ozunguza bongo komanso momwe zimakhalira, chifukwa izi zimagwirizana ndi zigawo za DA zofunikira. kuti amuthandize D1R. Mosiyana ndi zimenezi, D2Rs, zomwe zimalepheretsa kuti AMP iwonetsedwe, imalimbikitsidwa ndi DA komanso mphamvu ya DA. Dziwani kuti, chifukwa cha kusowa kwa ma radiotracers omwe amapanga zithunzi za DA za D1, D3, D4, ndi D5 mitundu, maphunziro ambiri pa zotsatira za kugwiritsira ntchito mankhwala osokoneza bongo ndi chizolowezi mu ubongo waumunthu akuyang'ana pa D2Rs.
Chith. 1 Mankhwala osokoneza bongo amachititsa mphoto ndi maulendo a ancillary kudzera mu njira zosiyanasiyana, komabe onse amachititsa zotsatira zofanana ndi zomwe zimachitika mu VTA ndi NAc. Momwemonso, zolimbikitsa zimapangitsa kuti AC acalal DA, pomwe opiates amachita zimenezi pochepetsa mawu oletsa kugwiritsira ntchito GABAergic interneurons pa DA kuzindikiritsa zonse mu VTA kapena apo NAC. Ngakhale njira zina zowonongeka sizowonekera bwino, pali umboni wosonyeza kuti chikonga chingayambitse VTA DA mwachindunji kupyolera mu nicotinic acetylcholine receptor (nAChR) pa neuroni ndi mwachindunji kupyolera mwa kukweza kwa mapulogalamu ake pamapeto a mitsempha ya glutamatergic yomwe ilibe maselo a DA. Mowa amaoneka kuti amaletsa kumapeto kwa GABAergic mu VTA, zomwe zimapangitsa kuti ma DA neononi asawonongeke mu VTA. Zina mwa zina zoterozi, kudzera mwa kuyambitsidwa kwa CB1 receptors pa matenda a glutamatergic ndi GABAergic m'mitsempha ya NAc, ndipo NAC imadzipangira okhaokha. Phencyclidine (PCP) ikhoza kuchitapo kanthu poletsa zizindikiro za NMDA zowonongeka ku NAC. Kuonjezera apo, pali umboni wina wotsimikizira kuti chikonga ndi mowa zingagwirizanenso ndi njira zowonongeka za opioid komanso njira zosagwiritsidwa ntchito. PPT / LDT, peduncular pontine tegmentum / pambuyo pake. Wosindikizidwa ndi chilolezo Nestler (2005)
Kwa anthu, kafukufuku wa PET wasonyeza kuti mankhwala ambiri (stimulants (Drevets et al. 2001; Volkow et al. 1999b), nicotine (Brody et al. 2009), mowa (Boileau et al. 2003), ndi chamba (Bossong et al. 2009)] kuwonjezera DA mu dorsal ndi ventral striatum (kumene NAc ilipo). Maphunzirowa amagwiritsa ntchito ma radiotracers angapo, monga [11C] raclopride, yomwe imamangiriza D2R koma pamene izi sizikumanga DA wodalirika (osagwira ntchito), yomwe pansi pazimene zimayambirapo zimakhala zofanana ndi 85-90% ya D2R yopweteka (Abi-Dargham et al. 1998). Motero, kuyerekeza kwa [11C] kumanga raclopride pambuyo pa placebo ndipo pambuyo pothandizira mankhwala kungatithandize kuthandizira kuchepa kwa D2R kupezeka chifukwa cha mankhwala (kapena zovuta zina zomwe zingawonjezere DA). Izi zimachepa mu [11C] kumanga raclopride kumaphatikizapo kukula kwa DA (Breier et al. 1997). Maphunzirowa asonyeza kuti DA yomwe imapangidwanso ndi mankhwala osokoneza bongo imawonjezereka kwambiri poyerekezera ndi kukula kwa chidziwitso chodziwika bwino kapena "chokwera" [onani ndemanga (Volkow et al. 2009a)] (Chith. 2).
Chith. 2 Zotsatira za intravenous methylphenidate (MP) mu chigwirizano cha raclopride ndi mgwirizano pakati pa kuwonjezereka kwa DA kumene kunayambitsidwa ndi MP mu statum ndi kudzidzimva kwa "mkulu". Kusinthidwa kuchokera ku Volkow et al. (1999b)
Maphunziro a PET awonetsanso mgwirizano wowonekera komanso wowongoka pakati pa mankhwala a pharmacokinetic (mwachitsanzo, msangamsanga umene umalowa nawo ndi kuchoka mu ubongo) ndi zotsatira zake zowonjezera. Mwachindunji, mankhwala osokoneza bongo amafika pachimake mu ubongo kwambiri "mkulu" (Volkow et al. 2009a). Mwachitsanzo, chifukwa cha cocaine yomwe imafika mu ubongo (yomwe imafufuzidwa kupyolera mu PET), pamene cocaine inalowa mu ubongo mofulumira (utsi wa fodya kapena iv), inachititsa kuti "mwamphamvu" kwambiri kuposa pamene inalowa pang'onopang'ono. (Volkow et al. 2000). Izi zimagwirizana ndi maphunziro odziwika bwino omwe amasonyeza mgwirizano womwewo pakati pa mankhwala osokoneza bongo ndi mankhwala ake (Balster and Schuster) 1973). IneT ndizomveka kuganiza kuti DA yowopsya komanso yayikulu yowonjezera chifukwa cha mankhwala osokoneza bongo angayesedwe kuwonjezeka kwa DA ndikuthamanga komwe kumabwera chifukwa cha kuwombera kwa DA komwe kumagwirizanitsidwa, mu ubongo, ndi kukonzanso za chidziwitso cha mphotho ndi chidziwitso (Schultz 2010). Dokotala wotere wochulukitsidwa ndi mankhwala owonjezera mankhwalawa ku NAC angafunikire kuledzera, koma kuti iwo amapezeka ndi anthu osagwiritsidwa ntchito mosagwiritsidwa ntchito, amasonyeza kuti sangakwanitse kufotokozera kugwiritsira ntchito mankhwala osokoneza bongo komanso kugwiritsira ntchito mankhwala osokoneza bongo.
Panopo pali umboni wosonyeza kuti mayankho a dopaminergic ndi ofanana ndi chakudya chokwanira komanso kuti njirazi zimathandizira kwambiri kudya ndi kunenepa kwambiri. Zimadziwika kuti zakudya zina, makamaka omwe ali ndi shuga ndi mafuta, zimapindula kwambiri (Lenoir et al. 2007). Zakudya zapamwamba za kalori zingalimbikitse kudya-kudyetsa (kudyetsa kusagwirizana ndi zosowa zofunikira) ndi kuyambitsa mgwirizano wophunzira pakati pa zokopa ndi mphotho. Malinga ndi chisinthiko, malo omwe ali ndi zakudya zokometsetsa amagwiritsidwa ntchito popindulitsa m'mapangidwe kumene chakudya sichinali chosowa kapena / kapena chosakhulupirika, chifukwa chinachititsa kuti chakudya chidye pamene chikupezeka, kuwapatsa mphamvu kusungidwa mu thupi (monga mafuta) kuti agwiritsidwe ntchito mtsogolo . Mwamwayi, m'madera ngati athu, kumene chakudya chimakhala chokwanira komanso chopezekapo nthawi zonse, kusintha kumeneku kwakhala kolakwa.
Mapepala angapo a mitsempha, kuphatikizapo DA, mavitamini, opioids, serotonin, komanso mahomoni ndi mapuloteni omwe amaphatikizapo mankhwala a homeostatic zakudya monga insulini, orexin, leptin, ndi ghrelin, akhala akukhudzidwa ndi zotsatirapo za chakudya (Atkinson) 2008; Cason et al. 2010; Cota et al. 2006). Mwa izi, DA wakhala akufufuzidwa bwino kwambiri ndipo ndi yabwino kwambiri. Kufufuza kwa makoswe kwasonyeza kuti, poyambira pa chakudya choyamba, kuwombera kwa DA neurons mu VTA kumawonjezeka ndi kuwonjezeka kwa DA kumasulidwa ku NAc (Norgren et al. 2006). Mofananamo, ali ndi thanzi labwinobwino, anthu olemera kwambiri, kudya kwabwino kumasonyezedwa kuti atulutse DA m'ndondomeko yofanana ndi momwe chakudya chimakhalira (Small et al. 2003) (Chith. 3). Komabe, monga momwe tawonera m'maphunziro ndi ogwiritsira ntchito mankhwala osokoneza bongo, kuwonjezeka kwa chakudya kumabweretsa kuwonjezeka kwa DA yekhayo sangathe kufotokoza kusiyana kwa kudya kwabwino ndi kumwa mowa mwauchidakwa chifukwa izi zimachitika kwa anthu abwino omwe sadya kwambiri. Momwemo, monga momwe zilili ndi chizolowezi choledzeretsa, kugwiritsidwa ntchito pansi pa nthaka kumakhala kotanganidwa ndi kusowa kwa kayendedwe ka chakudya.
Chith. 3 Dopamine kumasulidwa chifukwa chodyetsa. Gawo la Coronal kuchokera ku mapu a T of reduction significative in [11C] malungo a raclopride omwe amamanga (BP) pambuyo pakudyetsa. Mtengo wazitsulo umayimira mawerengedwe owonetsera. (Wosindikizidwa ndi chilolezo Small et al. 2003)
3 Kujambula DA pakuyankha kwa mankhwala osokoneza bongo komanso kufotokoza zida zolimbitsa thupi
Udindo wa DA pakulimbikitsana ndi wovuta kwambiri kuposa kungolembera pa mphotho pachisudzo (hedonic pleasure); Mwachitsanzo, zovuta zomwe zimapangitsa kuti DA iwonjezeke komanso ikuluikulu imayambanso kuyambitsa mayankho komanso kuwalimbikitsa (Owesson-White et al. 2009). Izi ndizofunikira chifukwa, kupyolera mu ndondomeko ya chikhalidwe, zosakhudzana ndi ndale zomwe zimagwirizana ndi reinforcer (kaya zachibadwa kapena mankhwala olimbitsa thupi) amatha kudziwonjezera okha ku DA mu striatum (kuphatikizapo NAc) poyembekeza mphotho, motero chilimbikitso champhamvu chofuna mankhwala (Owesson-White et al. 2009). Komabe, kusokoneza mphotho ndi njira zomwe zimagwiritsira ntchito mankhwala osokoneza bongo zimakhala zovuta kuposa kudya zakudya chifukwa cha mankhwala osokoneza bongo, pogwiritsa ntchito mankhwala osokoneza bongo, chifukwa cha mankhwala osokoneza bongo, kutulutsa mankhwala a DA (ie, nicotine) kapena kuonjezera kutuluka kwa DA (ie, amphetamine).
Maphunziro a ubongo omwe amawayerekezera ndi DA akuwonjezeka chifukwa cha mankhwala osokoneza bongo a methylphenidate (MP) kapena amphetamine (AMPH) pakati pa nkhani za cocaine zomwe zimagwiritsidwa ntchito molamulidwa ndi maulamuliro zinawonetsa kuti chiwerengero cha MP kapena AMPH-induced DA chikuwonjezeka mu striatum (50% ndi 80% mwa anthu ogwira ntchito mozunza anzawo) ndi kuchepetsa kudzidzimva kwazomwe zotsatira za mankhwalawa zokhudzana ndi mankhwala osagwiritsira ntchito mankhwala osokoneza bongo (Martinez et al. 2007; Volkow et al. 1997) (Chith. 4). Izi zidadabwitsa chifukwa MP ndi AMPH ali ndi mankhwala ofanana ndi mankhwala a cocaine ndi methamphetamine, motero, komanso ogwiritsa ntchito mankhwala osokoneza bongo sangathe kusiyanitsa pakati pawo pamene akugwiritsidwa ntchito moyenera. Popeza kuti kuchepetsa kuchepa kwa mankhwala opatsirana pogwiritsa ntchito mankhwala osokoneza bongo kunkawoneka ngati owononga mankhwala a cocaine anali atachotsedwa kapena ayi, izi zikutanthauza kuti kuchoka sikokusokoneza (Volkow et al. 2011b). Izi ndi zotsatira zokhudzana nazo (Volkow et al. 2009a) zimagwirizana ndi lingaliro lakuti yankho la hedonic limakhala losavomerezeka kwa anthu osokoneza bongo, komanso kulimbikitsa lingaliro lakuti mankhwala opatsirana kwambiri a DA omwe amachititsa mankhwalawa mu NAC sangathe kufotokozera mwa iwo okha chiwopsezo chowonjezeka chowadya.
Chith. 4 DA amasinthidwa ndi iv MP iv muzitsulo komanso muzochita zokhudzana ndi cocaine. Zithunzi zojambulidwa zochititsa chidwi za BPND (BPND) za [11C] raclopride mu nkhani zokhala ndi mankhwala a cocaine (n = 19) ndi ma controls (n = 24) omwe amayesedwa pambuyo pa placebo ndi pambuyo pa iv MP. Kupezeka kwa D2R (BPND) mu caudate, putamen, ndi ventral striatum pambuyo pa placebo (buluu) ndi pambuyo Pulezidenti (wofiira) mu maulamuliro komanso m'mayendedwe a cocaine. MP imachepetsanso D2R ku maulamuliro koma osati muzogwiritsira ntchito mankhwala osokoneza bongo. Zindikirani kuti olakwira a cocaine amasonyeza onse akuchepetsedwa kupezeka kwa D2R yoyamba (measurement placebo) ndipo amachepetsedwa ku DA atapatsidwa iv MP (kuyesedwa monga kuchepa kwa kupezeka kwa D2R kuchokera payambira). Ngakhale wina angakayikire momwe kupezeka kwa D2R kochepa kosavuta kuwonetsa kuchepa kwa MP, kumakhala kovuta kuti awonetseke kuti mankhwalawa amachititsa kuchepetsa kupezeka kwa D2R pamene akupezeka ndi mankhwala a cocaine amasonyeza kuti zotsatira zake zowonongeka wa MP pa [11C] kumangidwa kwa raclopride kukuwonetseratu kutuluka kwa DA. Wosindikizidwa ndi chilolezo (Volkow et al. 1997; Wang et al. 2010)
Yankho la VTA DA neurons lopindulitsa kusintha kosintha ndi kubwereza mobwerezabwereza.
Ngakhale kuti maselo a DA akuwotcha pamayambiriro a mphotho yamaphunziro, kubwereza kwa DA kumabwereza kuti asokoneze mphotho pamoto komanso m'malo mwa moto pamene akuwombera zomwe zimapereka mphotho (Schultz et al. 1997). Izi zikutheka kuti azigwira ntchito ya DA pakuphunzira ndi kusunga. Inde, kugwiritsira ntchito mankhwala osokoneza bongo chifukwa cha mankhwala osokoneza bongo kumatha kumayambitsa matenda opatsirana pogwiritsa ntchito maulendo oyenerera omwe amakhudzana ndi chizoloŵezi cha chizoloŵezi ndi khalidwe lachikhalidwe. Tkusintha kwakukulu kumayendetsedwa kwambiri ndi kusintha kwa D1R ndi kusintha kwa synaptic mu NMDA zokhala ndi glutamate ndi AMPA receptors (Luscher ndi Malenka 2011; Zweifel et al. 2009). Kugwiritsa ntchito maulendowa n'kofunika kwambiri chifukwa cha zotsatira za matenda chifukwa zotsatira zotsatiridwazi zimathandiza kufotokoza chilakolako chachikulu cha mankhwala (chilakolako) ndi kugwiritsira ntchito molakwika komwe kumachitika pamene nkhani zowonongeka zimagwiritsidwa ntchito pazinthu zowononga mankhwala. Lingaliro limeneli likugwirizana ndi zozizwitsa zokha (Volkow et al. 2006b; Wong et al. 2006) zomwe zimasonyeza kuti mphamvu ya cocaine yomwe imagwirizanitsidwa nayo ikuyambitsa kukwera kwa DA mu dorsal striatum ndipo imayambitsa kuwonjezereka kwa chidziwitso chokhudzidwa ndi chilakolako cha odwala cocaine (Fig. 5). Kuchokera pamene storum striatum imathandiza kwambiri pophunzira chizolowezi (Belin et al. 2009; Yin et al. 2004), mgwirizanowu ukhoza kuwonetsa kulimbitsa zizoloŵezi monga chizoloŵezi choledzera chimakula. Izi zikuwonetsa kuti kusokonezeka kwakukulu kwauchidakwa kungagwirizane ndi mayankho omwe ali ndi DA omwe amachititsa kukhala ndi zizoloŵezi zomwe zimayambitsa chilakolako chachikulu ndi mankhwala osokoneza bongo. Chochititsa chidwi n'chakuti pogwiritsa ntchito mosamala mankhwala omwe ali ndi cocaine, DA ikuwonjezeka chifukwa cha zizindikiro zooneka ngati zazikulu kwambiri kuposa zomwe zimapangidwa ndi mankhwala osokoneza bongo omwe amawunikira m'magulu awiri (Volkow et al. 2011b, 2006b), kuwonetsa kuti mayankho ogwirizana angayendetsere chizindikiro cha DA chomwe chili ndi zifukwa zogwiritsira ntchito mankhwala ngakhale pamene zotsatira zake za mankhwala zikuwoneka kuchepetsedwa. Choncho, ngakhale mankhwala osokoneza bongo angayambe kulandira mphotho mwa kudutsa kwa DA mu ventral striatum, mobwerezabwereza ntchito, ndipo monga chizoloŵezi chimawonekera, zikuwoneka kuti akusintha kuchokera ku mankhwala kupita ku chikhalidwe chokhazikika. Malingana ndi kafukufuku m'matumba a laboratori, malingaliro a glutamatergic kuchokera ku prefrontal cortex ndi amygdala kupita ku VTA / SN ndi NAc amalumikizana ndi mayankho awa (Kalivas 2009). Momwemonso, kungonena za mphotho kungakhale mphotho yomwe imalimbikitsa khalidwe lofunikira kwa mankhwala (kapena chakudya).
Chith. 5 Kusintha kwa DA kumapangidwira ndi zikhalidwe zomwe zimakhala zovuta kwambiri. Zithunzi zojambulidwa zogwiritsidwa ntchito (BPND) zokhudzana ndi [11C] raclopride m'nkhani za mankhwala a cocaine (n = 17) omwe amayesedwa pamene akuwonera kanema kosalekeza (masewero achilengedwe) komanso pamene akuwonera kanema ya cocaine (nkhani zopatsa cocaine). Kupezeka kwa D2R (BPND) mu caudate, putamen, ndi ventral striatum kwa kanema koti (blue) ndi video ya cocaine-cues (yofiira). Mankhwala a cocaine adachepetsanso D2R muzinthu zowonjezera. c Mgwirizano pakati pa kusintha kwa D2R (kukuwonetseratu kuwonjezeka kwa DA) komanso kudzipangitsa kudzikonda kwanu kwa cocaine chifukwa cha kanema wa cocaine. Kusinthidwa kuchokera ku ref. (Volkow et al. 2006b)
IChochititsa chidwi, mtundu uwu wa "kusintha" wamtunduwu wawonetsedwanso kwa anthu olimbikitsa zachilengedwe, zomwe zingachititse kuti kuwonjezereka kwa DA kukhale kofanana komanso kochepa pang'ono, kuchokera ku ventral kupita ku zigawo zina zazing'ono za statum panthawi yosinthika kuchokera ku buku lachidziwitso lomwe liri lovomerezeka Zopindulitsa pazinthu zogwirizana zomwe zikulosera. Kusintha kumeneku kumaperekedwa kupyolera mu chizindikiro cha DA, chomwe chikuwoneka ngati chikhomo cha "zolakwika zowonetsera mphotho" (Schultz 2010). Zowonjezereka zowonjezereka kwa madontho a DA ochokera m'madera omwe akugwiritsidwa ntchito pokonza zinthu zowonongeka, homeostatic (hypothalamus), mphotho (NAc), mafilimu (amygdala ndi hippocampus), ndi ma multimodal (orbitofrontal cortex for salience attribution) , yesetsani ntchito yawo poyankha mphoto komanso zolembapo (Geisler ndi Wise 2008). Makamaka, ziwonetsero za amygdala ndi orbitofrontal cortex (OFC) kwa DA neurons ndi NAc zimakhudzidwa ndi mayankho a chakudya (Petrovich 2010). Zoonadi, kafukufuku adawonetsa kuti pamene nkhani zopanda amuna ndizosafunika kwambiri zimapemphedwa kuti zilepheretsa chilakolako chawo cha chakudya - pamene zidawoneka ndi zakudya zowonjezera chakudya, ziwonetsetsa kuchepa kwa maselo amygdala ndi OFC (komanso hippocampus), insula ndi striatum, ndi kuti kuchepa kwa OFC kunagwirizanitsidwa ndi kuchepetsa chakudya chofuna kudya (Wang et al. 2009). Chotsutsana chomwecho cha ntchito yamagetsi ku OFC (komanso ku NAc) chawonetsedwa mwa owononga a cocaine pamene anafunsidwa kuti ateteze chilakolako chawo chokhudzana ndi mankhwala osokoneza bongo poyang'ana mankhwala a cocaine (Volkow et al. 2009b).
Komabe, kutuluka kwa zilakolako zoterezi, zomwe zimadyanso chakudya mwa anthu abwino omwe samadya kwambiri, sizingakhale zopweteka kwambiri ngati sizikuphatikizana ndi kuchepa kwa ubongo kuti zitha kulepheretsa makhalidwe oipa.
4 Mphamvu ya Kulephera Kuletsa Kutetezedwa
Kukhala ndi mphamvu zowonongera mayankho oyenerera kudzapangitsa munthu kuti asakhale ndi makhalidwe olakwika, monga kumwa mankhwala osokoneza bongo kapena kudya mopitirira malire, komanso kuonjezera chiopsezo chake (kapena kunenepa kwambiri) (Volkow ndi Fowler) 2000; Volkow et al. 2008a).
Kafukufuku wa PET adapeza kuchepa kwakukulu kwa kupezeka kwa D2R mu ndondomeko yazovuta zomwe zikupitirira kwa miyezi ingapo pambuyo pa kuchotsedwa kwadzidzidzi [zowonongedwa (Volkow et al. 2009a)]. Mofananamo, kufufuza kwapadera m'makina a rodent ndi osakhala anthu akuwonetsa kuti kuwonetsa mobwerezabwereza mankhwala kumagwirizanitsidwa ndi kuchepetsa m'magulu a D2R (Nader et al. 2006; Thanos et al. 2007; Volkow et al. 2001). Mu striatum, D2Rs imayimilira kusindikiza mu njira yopanda njira yowonongeka imene imayendetsa zigawo za prefrontal; ndipo kugwidwa kwake kwasonyezedwa kuti kuwonjezere mphamvu ku zotsatira za mankhwala osokoneza bongo (Ferguson et al. 2011). Kwa anthu omwe amamwa mankhwala osokoneza bongo, kuchepetsa D2R kumaphatikizapo ntchito yochepa ya zigawo za prefrontal zomwe zimatsimikiziridwa ndi kuchepa kwa kagwiritsidwe kake ka shuga (mu chigawo cha ubongo) ku OFC, kalembedwe ka gyrus (ACC), ndi dorsolateral prefrontal cortex (DLPFC) ) (Volkow et al. 2001, 1993, 2007) (Chith. 6). Monga OFC, ACC, ndi DLPFC zimaphatikizapo kulumikizidwa mwamphamvu, malamulo oletsa kuteteza / kutengeka maganizo, komanso kupanga chisankho, motsatira, awonetseratu kuti malamulo awo olakwika ndi D2R-mediated DA omwe akuwonekera pazinthu zovuta kwambiri akhoza kulimbikitsa kufunika kokhala ndi mankhwala osokoneza bongo m'makhalidwe awo komanso kutaya mphamvu zowonjezera mankhwala (Volkow ndi Fowler) 2000). Kuonjezera apo, chifukwa chosowa mu OFC ndi ACC zimakhala ndi zizoloŵezi zovuta kuchita (Fineberg et al. 2009), Kufooka kwa DA kwa madera amenewa kumapangitsa kuti munthu adye mankhwala osokoneza bongo (Goldstein ndi Volkow) 2002). Zoonadi, mu amtundu wa methamphetamine, D2R yochepa kwambiri inkaphatikizidwa ndi kukhudzidwa (Lee et al. 2009), komanso ananeneratu kuti kukakamizidwa kwa cocaine kumakoswe (Everitt et al. 2008). Chochitika chosiyana, chomwe chiwopsezo choyamba cha mankhwala osokoneza bongo osokoneza bongo m'dera la prefrontal, ndi momwe kugwiritsira ntchito mankhwala mobwerezabwereza kumachepetsa kuchepa kwa D2R, ndi kotheka. Zoonadi, phunziro lomwe linapangidwa ndi anthu omwe, ngakhale kuti anali ndi chiopsezo chachikulu chauchidakwa (mbiri yabwino ya banja lauchidakwa) sanali zidakwa, anapeza kupezeka kwapadera kuposa D2R yomwe inkagwirizanitsidwa ndi maselo ovomerezeka a OFC, ACC, ndi DLPFC (Volkow et al. 2006a). Izi zikuwonetsa kuti, pa nkhaniyi pangozi yauchidakwa, ntchito yoyenera yogwirira ntchito inali yolumikizidwa ndi kuwonetsa chizindikiro cha D2R, chomwe chidawatchinjiriza kuledzera.
Chith. 6 Zolumikizano pakati pa kupezeka kwa D2R ndikupezeka ndi kagayidwe kake m'madera a prefrontal brain. zithunzi za Axial ubongo zowononga komanso zakumwa za mankhwala a cocaine chifukwa cha zithunzi zoyambirira za kupezeka kwa D2R mu striatum (zomwe zinapezedwa ndi [11C] raclopride) komanso ubongo wa shuga m'magazi a OFC (umapezeka ndi [18FDG). b Mgwirizano pakati pa D2R yopweteka ndi kagayidwe ka metabolism mu OFC mu maphunziro a cocaine-addicted ndi methamphetamine-osokonezeka. Wosindikizidwa kuchokera ku Volkow et al. (2009a) Copyright (2009), ndi chilolezo kuchokera kwa Elsevier
Momwemo, umboni wa kuwonongeka kwa maulendo oyendetsa ndege umapezekanso pakati pa anthu ovuta kwambiri. Maphunziro awiri ovomerezeka ndi opaleshoni apereka umboni wa kuchepa kwa chizindikiro cha D2R chogwidwa, chomwe, monga tafotokozera pamwamba, chikugwirizana ndi mphoto (NAc) komanso ndi kukhazikitsidwa kwa zizolowezi (dorsal striatum) mu obesity (Geiger et al. 2009; Wang et al. 2001). Chofunika kwambiri, kuchepa kwa kupezeka kwa D2R kwachitsulo kwagwirizanitsidwa ndi kudya chakudya chokwanira mu makoswe olemera (Johnson ndi Kenny 2010) komanso ndi kuchepa kwachitetezo chaching'ono mu OFC ndi ACC mwa anthu ovuta kwambiri (Volkow et al. 2008b) (Chith. 7a-c). Popeza kuti ntchitoyi inalepheretsedwa mu OFC ndi ACC ikukakamizika [onani ndemanga (Fineberg et al. 2009)], izi zikhoza kukhala mbali ya momwe D2R yosautsika yowonetsera imathandizira hyperphagia (Davis et al. 2009). Kuonjezerapo, popeza kuti kuchepa kwa D2R kuwonetsetsanso kowonjezera kuchepetsa kukhudzidwa kwa mphoto zina zachilengedwe, kuchepa kwa anthu olemera kungathandizenso kudya (Geiger et al. 2008).
Chith. 7 Hyperphagia ikhoza kuchitika chifukwa choyendetsa galimoto kuti ipereke mphoto yochepa ya mphoto (yochitidwa kupyolera mu dopamine yoyendetsedwa ndi corticostriatal circuits) kuphatikizapo kuwonjezeka kowonjezereka kovuta (chakudya cha hedonic chomwe chimagwiritsidwa ntchito pang'onopang'ono kupyolera mu khungu losakanikirana). Zithunzi zojambulidwa za kupezeka kwa DA D2 receptor (D2R) pakuwongolera (n = 10) komanso pamitu yolemetsa kwambiri (n = 10). b Zotsatira za (Statistical Parametric Mapping) SPM yodziwitsa madera aubongo momwe D2R imalumikizidwa ndi kagayidwe ka shuga, izi zimaphatikizapo medial OFC, ACC, ndi dorsolateral PFC (dera lomwe silikuwonetsedwa). c Kutsetsereka pakati pa striatal D2R ndi zochitika zama metabolic mu ACC m'maphunziro onenepa kwambiri. d Zithunzi zojambulidwa zitatu za SPM zowonetsa madera omwe ali ndi metabolism yayikulu kwambiri kuposa maphunziro owonda (P <0.003, yopanda tanthauzo). e Zotsatira zamitundu yosiyanasiyana ya SPM zowonetsedwa mu ndege yam'mbali yokhala ndi chithunzi chapamwamba kwambiri cha somatosensory homunculus. Zotsatira (z mtengo) zimaperekedwa pogwiritsa ntchito utawaleza pomwe pamakhala ofiira> achikaso> obiriwira. Poyerekeza ndi maphunziro owonda, maphunziro onenepa kwambiri anali ndi kagayidwe kake koyambira kambiri m'malo omwe pakamwa, milomo, ndi lilime zimaimiridwa ndipo zimakhudzidwa ndikukonza chakudya. Kusinthidwa, ndi chilolezo, kuchokera ku Volkow et al. (2008a) (a-c) ndi Wang et al. (2002) (d, e)
Mfundo imeneyi imagwirizana ndi umboni wosonyeza kuti kuchepa kwa ntchito ya DA kuchepa mu VTA kumabweretsa kuwonjezeka kwakukulu kwa zakudya zopangira mafuta (Stoeckel et al. 2008). Mofananamo, poyerekeza ndi anthu olemera kwambiri, anthu oposa onse omwe anali ndi zithunzi za chakudya chapamwamba (zowonongeka) anawonetsa kuwonjezereka kwa neural m'madera omwe ali gawo la mphoto ndi maulendo othandiza (NAC, dorsal striatum, OFC , ACC, amygdala, hippocampus, ndi insula) (Killgore ndi Yurgelun-Todd 2005). Mosiyana ndi izi, kuyendetsa bwino thupi, kuyendetsa kwa ACC ndi OFC (zigawo zomwe zimagwira ntchito molimbika polojekitiyo ku NAC) pakuwonetsa chakudya chapamwamba chokhala ndi kalori kunapezeka kuti sizinagwirizane ndi thupi lawo (BMI). Stice et al. 2008b). Izi zikusonyeza kugwirizana kwakukulu pakati pa kuchuluka kwa chakudya chomwe chikudyetsedwa (chikuwonetsedwa ndi gawo mu BMI) ndi kuyanjanitsa kwa madera kumadera okwera-calories chakudya (chikuwonetsedwa mu kuchitidwa kwa OFC ndi ACC) mwa anthu olemera, omwe ataya kunenepa kwambiri.
Chodabwitsa n'chakuti, anthu olemera kwambiri amawonetsa zochepa zowonjezera madera a mphotho kuchokera ku chakudya choyenera (chomwe chimatchedwa kuti chakudya chowonongetsa chakudya) kuposa anthu odzichepetsa, pamene iwo akuwonetseratu kuwonjezereka kwa madera ozungulira omwe amawathandiza kuti asamangogwiritsa ntchito (Stice et al. 2008b). Mfundo yomalizayi inafanana ndi madera omwe maphunziro apitalo adalongosola ntchito yowonjezereka mu mayesero ovuta kwambiri omwe ayesedwa pazowonjezera (osakakamiza) (Wang et al. 2002) (Chith. 7d, e). Ntchito yowonjezereka ya madera omwe amachititsa kuti zikhale zovuta zitha kupangitsa kuti anthu ambiri azidya zakudya zina zowonjezera, koma kuchepetsa kuyamwa kwa malingaliro a dopaminergic chifukwa chodya choyenera chingayambitse kupambanitsa ngati njira yowonjezeretsera zofooka za D2R-mediated signaling (Stice et al. 2008a). Kuyankha kwakachepetsedwa kwa mphotho yomwe ikuyendetsedwa ndi chakudya kumabuku owonjezera ndi kukumbukira kuwonjezeka kwawonjezeka kwa DA komwe kunayambitsidwa ndi mankhwala osokoneza bongo omwe ali osokonezeka poyerekeza ndi maphunziro omwe sali ovuta.
Khoti la prefrontal cortex (PFC) limagwira ntchito yofunikira kwambiri, kuphatikizapo kuletsa mphamvu (Miller ndi Cohen) 2001). Njirazi zimayendetsedwa ndi D1R ndi D2R (mwinamwake D4R) ndipo motero, kuchepa kwa ntchito ya PFC, m'kuledzeretsa ndi kunenepa kwambiri, kungapangitse kuti anthu asamavutike komanso azikakamizidwa. Kupezeka kwapansi kwachibadwa kwa D2R mu statum ya anthu olemera kwambiri, omwe agwirizanitsidwa ndi ntchito zochepetsedwa ku PFC ndi ACC (Volkow et al. 2008b) ndizomwe zimapangitsa kuti azilephera kudya chakudya. Zoonadi, kugwirizana pakati pa BMI ndi D2R yomwe imabweretsera chiwonetsero imakhala yovuta kwambiri (Wang et al. 2001) komanso mopitirira muyeso (Haltia et al. 2007a) anthu amachirikiza ichi. Kumvetsetsa bwino njira zomwe zimapangitsa kuti PFC iwonongeke kwambiri (kapena kuledzeretsa) kungathandize kuti pakhale njira zothandizira, kapena kuti zitsitsimutso, zowonongeka mwatsatanetsatane m'madera odziwika bwino. Mwachitsanzo, kuchepetsa kubwezeretsa, chomwe ndi chizoloŵezi chokhazikitsa mphotho monga ntchito ya kuchedwa kwa nthawi ya kubwezeretsa, ndi chimodzi mwa ntchito zofufuzidwa kwambiri zomwe zimafufuzidwa pazomwe zimakhudzana ndi kukhudzidwa ndi kukhudzidwa. Kuwonetsa kuchepetsa kwafufuzidwa kwakukulu kwambiri mwa ogwiritsira ntchito mankhwala osokoneza bongo omwe amasonyeza kukonda kwambiri zapang'ono-koma-mwamsanga pa mphoto zazikulu-koma-kuchedwa (Bickel et al. 2007). Komabe, kafukufuku wowerengeka omwe anachitidwa ndi anthu okhwima kwambiri awonanso umboni wa zofuna zapamwamba, mwamsanga, ngakhale mwayi wochulukitsidwa wa mavuto aakulu omwe adzakhalepo m'tsogolo (Brogan et al. 2010; Weller et al. 2008). Ndipo posachedwapa, kafukufuku wina anapeza mgwirizano wabwino pakati pa BMI ndi kuwonetserana kwapadera, komwe phindu la m'tsogolomu silidzapindulitsidwe phindu labwino (Ikeda et al. 2010). Chochititsa chidwi, kuchepetsa kuchepetsa kuwoneka kumadalira ntchito ya ventral striatum (Gregorios-Pippas et al. 2009) komanso za PFC, kuphatikizapo ofalitsa OFC (Bjork et al. 2009), ndipo amamvetsera DA manipulations (Pine et al. 2010). Mwachindunji, kulimbitsa chizindikiro cha DA (ndi mankhwala a L DOPA) kunachulukitsa kukhudzidwa ndi kuchotsa kwa nthawi.
5 Kuphatikizidwa kwa Makonzedwe Otsitsimula
Chizindikiro cha Dopaminergic chimapangitsanso chidwi. Zizolowezi za makhalidwe monga mphamvu, kulimbikira, ndi kuyesetsa kuyesetsa mwakhama kuti akwaniritse zolinga, zonse zimagwirizana ndi kusintha kwa DA pogwiritsa ntchito zigawo zingapo, kuphatikizapo NAc, ACC, OFC, DLPFC, amygdala, dorsal striatum, ndi ventral pallidum (Salamone et al. 2007). Kuonongeka kwa DA kukuphatikizidwa ndi kulimbikitsidwa kuti atenge mankhwala osokoneza bongo, chifukwa chake anthu osokoneza bongo amayamba kuchita zinthu zoopsa kuti apeze mankhwala osokoneza bongo, ngakhale atakhala ndi zotsatira zoyipa komanso zoipa (Volkow ndi Li 2005). Chifukwa kutenga mankhwala osokoneza bongo ndiko kumayendetsa galimoto yoyambitsa mankhwala osokoneza bongo (Volkow et al. 2003), zizoloŵezi zowonongeka zimadzutsidwa ndikulimbikitsidwa ndi ndondomeko yopezera mankhwalawa koma amayamba kutengeka komanso osasamala akamagwira ntchito zosagwirizana ndi mankhwala. Kusintha kumeneku kwaphunziridwa poyerekezera zochitika za ubongo zomwe zimachitika poyang'anizana ndi zizindikiro zomwe zikuchitika popanda zifukwa zoterezi. Mosiyana ndi kuchepa kwa ntchito ya prefrontal yolembedwa mu detoxified cocaine abusers pamene sichikulimbikitsidwa ndi mankhwala kapena mankhwala osokoneza bongo [onani ndemanga (Volkow et al. 2009a)], zigawo izi zimayambitsidwa pamene ophera mankhwala a cocaine ali ndi chilakolako chofuna kukakamiza (mwina mankhwala kapena cues) (Grant et al. 1996; Volkow et al. 1999a; Wang et al. 1999). Chotsatira ichi ndi kukumbukira kuti anthu omwe amagwiritsa ntchito mankhwalawa a cocaine, atangophunzira patangotha kanthawi kochepa chabe, akuwonetsa kuwonjezeka kwa ntchito zamagetsi mu OFC ndi ACC (komanso dorsal striatum) yomwe inkagwirizana ndi chikhumbo (Volkow et al. 1991).
Komanso, pamene mayankho a iv MP amafaniziridwa pakati pa anthu omwe amagwiritsidwa ntchito ndi mankhwala a cocaine ndi osagwiritsidwa ntchito, omwe kale adayankha kuwonjezeka kwa kagetsi koyambitsa matenda a ACC and mediation OFC (zotsatira zokhudzana ndi chilakolako), pamene otsogolerawo akuwonetsa kusiyana kwake, Matenda a shuga m'madera amenewa (Volkow et al. 2005). Izi zikusonyeza kuti kuyambitsidwa kwa madera amenewa ndi kusokoneza mankhwala kungakhale koyenera kuledzera komanso kugwirizana ndi chilakolako chowopsa cha mankhwala. Kuwonjezera apo, kafukufuku yemwe adachititsa kuti anthu omwe ali ndi vuto la cocaine adziletse kuti asakonde chilakolako chofuna kugwiritsira ntchito mankhwala osokoneza bongo, amasonyeza kuti anthu omwe adakali ndi chilakolako choletsa chilakolako amachepetsa kuchepa kwa thupi la mkati mwa OFC. mphotho) (Volkow et al. 2009b). Zofukufukuzi zikutsindika kuti OFC, ACC, ndi striatum zikugwira ntchito mwachangu pofuna kupeza mankhwala osokoneza bongo.
Zomwe zakhala zikuchitika, OFC yakhala ikugwiritsidwanso ntchito pofotokoza kufunika kwa chakudya (Grabenhorst et al. 2008; Rolls ndi McCabe 2007), kuthandizira kuwona chisangalalo chake choyembekezeredwa ndi kulumikiza monga ntchito yake. Maphunziro a PET ndi FDG kuti awonetse ubongo wa shuga m'magulu olemera omwe amawonetsa kuti kukhudzana ndi zakudya zowonjezera kuwonjezereka kwa thupi ku OFC, komwe kunakhudzidwa ndi kuwona njala ndi chilakolako cha chakudya (Wang et al. 2004). Kuonjezera kwa OFC kuyambitsa ndi kukonzekera chakudya kumakhala kukuwonetsa zotsatira zochepa za dopaminergic ndikugwira nawo mbali pa DA pakuyendetsa chakudya. OfC imachita nawo mbali pophunzitsa makampani othandiza anthu kuti azikhala olimbitsa thupi (Cox et al. 2005; Gallagher et al. 1999), zothandizira zochitika zomwe zinkapangitsa kuti tizidyetsa (Weingarten 1983), ndipo mwinamwake zimapangitsa kuti adye mopitirirabe kanthu zozizwitsa za njala (Ogden ndi Wardle 1990). Zoonadi, OFC imalephera kugwiritsira ntchito kudya (Machado ndi Bachevalier) 2007).
Ngakhale kusagwirizana pakati pa maphunziro, ubongo woganizira deta imathandizanso lingaliro lakuti kusintha kwa kayendetsedwe ka kayendetsedwe kake ndi kagwiridwe ka ntchito m'madera a ubongo omwe amagwira ntchito yaikulu (kuphatikizapo kuchepetsa mphamvu) kungayambane ndi BMI popanda anthu ena wathanzi. Mwachitsanzo, kafukufuku wa MRI wochitidwa ndi akazi achikulire, pogwiritsa ntchito vofiel based based morphometry, anapeza mgwirizano wosagwirizana pakati pa BMI ndi mitu yoyera (kuphatikizapo m'madera akutali), omwe, mu OFC, ankagwirizanitsa ndi olamulira akuluakulu (Walther et al. 2010). Kugwiritsa ntchito PET poyeza ubongo wa shuga m'magazi abwino, tinalumikiza kusagwirizana pakati pa BMI ndi ntchito zamagetsi ku DLPFC, OFC, ndi ACC. Phunziroli, ntchito yamagetsi m'madera oyandikana ndi dziko lapansi inaneneratu kuti zotsatirazi zikuchitika pa mayesero akuluakulu (Volkow et al. 2009c). Mofananamo, kuwerengera kwa nyukiliya magnetic resonance (NMR) yopenda bwino m'zaka zapakatikati ndi maulendo achikulire kunawonetsa kuti BMI inagwirizanitsidwa kwambiri ndi n-acetyl aspartate (chizindikiro cha neuronal integrity) pambali ya ACCAL (Gazdzinski et al. 2008; Volkow et al. 2009c).
Maphunziro a kuganiza kwa ubongo poyerekeza anthu okhwima ndi oonda adanenanso kuti kuchepa kwapakati pamapiri (kutsogolo kwa operculum ndi gyrus ya kutsogolo kwapakati) ndi kumbuyo pakati pa gyrus ndi putamen (Pannacciulli et al. 2006). Kafukufuku wina, sanapeze kusiyana pakati pa mutu wa imvi pakati pa nkhani zowopsya komanso zoonda, izo zinalemba mgwirizano wovomerezeka pakati pa nkhani yoyera ya ubongo m'magulu a ubongo ndi chiuno kuti chiwonongeke, zomwe zinasinthidwa pang'ono ndi zakudya (Haltia et al. 2007b). N'zochititsa chidwi kuti madera a cortical, monga DPFC ndi OFC omwe akuphatikizidwa kuchitetezo, amapezedwanso kuti athandizidwe pogwiritsa ntchito zakudya zopatsa thanzi (DelParigi et al. 2007), kutanthauza kuti zomwe zingakhale zofuna kuti munthu azikhala ndi khalidwe labwino kwambiri komanso kuti ali ndi vutoli.
6 Kuphatikizidwa kwa Zokambirana zapakati
Kafukufuku wa Neuroimaging atsimikizira kuti insula yapakati imakhala yovuta kwambiri pa zofuna za chakudya, cocaine, ndi ndudu (Bonson et al. 2002; Pelchat et al. 2004; Wang et al. 2007). Kufunika kwa insula kwafotokozedwanso ndi kafukufuku amene adawonetsa kuti anthu osuta fodya akuwonongeka ku dera lino (koma osasuta fodya amene adamva zovuta zina) adatha kusuta fodya mosavuta komanso popanda kukhumba kapena kubwerera m'mbuyo (Naqvi et al . 2007). Nkhalangoyi, makamaka m'madera ake osiyana kwambiri, imagwirizananso ndi zigawo zingapo (monga, ventromedial prefrontal cortex, amygdala, ndi ventral striatum) ndipo imawoneka kuti ili ndi ntchito yogwirizana, kuphatikizapo chidziwitso chodziwika ndi zozizwitsa zomwe zimakhala ndi maganizo ndi zolimbikitsa, motero zimapereka Kuzindikira zokhuza izi (Naqvi ndi Bechara 2009). Zoonadi, kafukufuku wamagulu a ubongo amasonyeza kuti zowonjezera za PFC ndi insula ndizofunikira zigawo zofunikira zomwe zimapereka mauthenga othandizira kupanga maganizo (Clark et al. 2008). Mogwirizana ndi lingaliro limeneli, kufufuza zojambula kumasonyezeratu nthawi zonse kusinthika kwa insula pakulakalaka (Brody et al. 2009; Goudriaan et al. 2010; Naqvi ndi Bechara 2009; Wang et al. 1999). Choncho, kuyanjananso kwa dera la ubongoli kwatchulidwa kuti ndipangidwe ngati chithunzithunzi chothandizira kubwereza kubwereza (Janes et al. 2010).
Nkhalangoyi ndi malo oyamba kudya, omwe amachitira mbali zambiri za makhalidwe, monga kukoma. Kuonjezerapo, chombo cha rostral (chogwirizanitsidwa ndi choyambirira cha cortex) chimapereka chidziwitso kwa OFC chomwe chimakhudza kuimira kwake kwa mulingo wa chisangalalo kapena mphoto ya chakudya chomwe chimabwera (Zojambula 2008). Chifukwa cha chigwirizano cha insula mkati mwa thupi la thupi, pakuzindikira zamalingaliro (Craig 2003) komanso mothandizidwa ndi kutengeka 2008), kuyembekezera kufooka kwapakati pa kunenepa kwambiri kungayembekezereke. Zoonadi, kutsekedwa kwa mimba kumabweretsa zotsatira za kukhazikitsidwa kwa insula, zomwe zikhoza kusonyeza mbali yake pakuzindikira za thupi (mu nkhaniyi ya chidzalo) (Wang et al. 2008). Komanso, potsitsimutsa, koma osati mowonjezereka, kumangidwe kosakanikirana kumapangitsa kuti amygdala ndi kutsekedwa kwa insula (Tomasi et al. 2009). Kulephera kwa yankho la amygdala mu nkhani zowonjezereka kungapangitse kuzindikira kosavuta kumvetsetsa kwa maiko akuthupi omwe ali ndi satiety (m'mimba mokwanira). Ngakhale kuti ntchito yolemba ntchito ya DA inalembedwa bwino, ikudziwika kuti DA ikukhudzidwa ndi mayankho ola kudya zakudya zomwe zimakhala zovomerezeka kudzera mu insula (Hajnal ndi Norgren) 2005). Kafukufuku wa anthu akuwonetsa kuti kulawa zakudya zopatsa mphamvu kunayambitsa malo a insula ndi midbrain (DelParigi et al. 2005; Frank et al. 2008). Komabe, zizindikiro za DA zingakhale zofunikira pozindikira kuti kalori ndi chakudya. Mwachitsanzo, pamene amayi olemera omwe anali olemera ankalawa zokoma ndi calories (sucrose), madera onse a insula ndi dopaminergic midbrain anayamba kuchitidwa, koma kulawa kosakaniza kalora (sucralose) kunangowonjezera insula (Frank et al. 2008). Ophunzira omwe amamveka bwino amawonetsa mphamvu zowonjezera zowonjezereka kusiyana ndi zowonongeka pamene mukudya chakudya chamchere chomwe chili ndi shuga ndi mafuta (DelParigi et al. 2005). Mosiyana ndi zimenezi, anthu omwe amachiritsidwa kuchokera ku anorexia nervosa amavomereza kusagwiritsidwa ntchito mosungirako mankhwalawa pamene akulawa sucrose komanso palibe mgwirizano wokhala ndi chisangalalo chokhazikika mwachangu monga Wagner et al. 2008). Zogwirizanitsa, zotsatirazi zimapangitsa kuti kusokonezeka kwa chitukukochi kuchitapo kanthu ndi zovuta zomwe zingakhudzidwe ndi zovuta zosiyana siyana.
7 The Circuitry of Aversion
Monga tanenera kale, kuphunzitsidwa (chikhalidwe) pa chidziwitso chomwe chikulosera mphoto kumabweretsa maselo a dopaminergic akuwombera poyankha kulosera kwa mphotho, osati ku mphotho yokha. Kumbali ina, ndipo zogwirizana ndi lingaliro ili, tawonedwa kuti maselo a dopaminergic adzawotchepera pang'ono kuposa momwe chiyembekezero choyembekezereka sichidzapangidwira (Schultz et al. 1997). Umboni wochuluka (Christoph et al. 1986; Lisoprawski et al. 1980; Matsumoto ndi Hikosaka 2007; Nishikawa et al. 1986) amasonyeza kuti habenula ndi chimodzi mwa zigawo zomwe zimayambitsa kuwombera kwa maselo a dopaminergic ku VTA omwe angatsatire kulephera kulandira mphoto yomwe ikuyembekezeredwa (Kimura et al. 2007). Choncho, kumvetsetsa kochititsa chidwi kwa habenula, chifukwa cha mankhwala osokoneza bongo, kungachititse kuti anthu azigwiritsa ntchito mankhwala osokoneza bongo. Inde, kuyambitsa habenula, mu maphunziro a cocaine-osokonezeka, wakhala akugwirizananso ndi khalidwe lobwezeretsa mankhwala osokoneza bongo (brown et al. 2011; Zhang et al. 2005). Pankhani ya chikonga, α5 nicotinic receptors mu habenula ikuwonekera kuti athetse mayankho akuluakulu a nicotine (Fowler et al. 2011); ndipo α5 ndi α2 receptors mu habenula zimakhudzidwa ndi kuchotsa chikonga (Salas et al. 2009). Chifukwa cha kusintha kwa habenula kwa a DA neurons kuti apereke mphotho (kutsegula) ndi kuchitapo kanthu pazowonekera ku zovuta zowonongeka, timatchula pano pa habenula kuwonetsera ngati wina akupereka "kulowerera".
The habenula ikuwoneka kukhala ndi gawo lomwelo ponena za mphotho ya chakudya. Chakudya chokoma kwambiri chingayambitse kunenepa mu makoswe, ndi kulemera kwake kumawonjezereka kuwonjezeka ndi kuwonjezeka kwa μ-opioid peptide kumangiriza muzitsulo zam'madzi ndi zowonongeka. Chochititsa chidwi n'chakuti, habenula yamkati imasonyeza kwambiri kuti μ-opioid peptide imamanga (pafupifupi pafupifupi 40%) pambuyo poyang'ana chakudya chokoma mu makoswe omwe analemera (omwe amadya chakudya chochuluka) koma osati omwe sanali (Smith et al. 2002). Izi zikutanthauza kuti habenula akhoza kutenga nawo mbali pakudya mopitirira muyezo wa chakudya chokoma. Kuwonjezera pamenepo, neurons mu pulogalamu ya rostromedial tegmental, yomwe imalandira chithandizo chachikulu kuchokera ku lateral habenula, ntchito ku VTA DA neurons ndipo imatulutsidwa pambuyo potsalira chakudya (Jhou et al. 2009). Zotsatirazi zikugwirizana ndi gawo la habenula pakuyanjanitsa mayankho ku zovuta kapena zochitika zowoneka ngati zomwe zimachitika pakudya kapena kuchotsa mankhwala.
Kuphatikizidwa kwa habenula ngati malo ochepetsera mauthenga m'maganizo kumagwirizana ndi zitsanzo zamakono zomwe zimapangitsa kuti anthu asamapindule kwambiri ndi mayankho omwe amachititsa kuti anthu asamapindule ndi mphotho zawo. (Koob ndi Le Moal 2008). Mayankho ofanana omwe angakhale nawo angapangitsenso kudyetsa zakudya mopitirira muyeso.
8 Mankhwala Osokoneza Matenda ndi Mphoto ya Chakudya: Njira Yopangidwira Yogwira Ntchito
Tiye amatha kukana chilakolako chogwiritsa ntchito mankhwala kapena kudya kudutsa panthawi yomwe amafuna kuti azichita bwino, amafunika kuyendetsa bwino ma ciriteti omwe amachititsa kuti asamangogwiritsira ntchito mankhwala ozunguza bongo. chakudya / mankhwala. Pano, tawonetsa maulendo asanu ndi limodzi mwa izi: mphotho / saliency, chikhalidwe / zizoloŵezi, kuletsa mphamvu / ntchito, udindo, kuyendetsa, kutsekereza, ndi kusokoneza maganizo (mkuyu. 8). Malinga ndi deta yomwe imagwiritsidwa ntchito pano, timapereka kuti pali kusiyana pakati pa kuyembekezera kwa mankhwala / zakudya (zowonongeka) ndi zotsatira zolakwika za ubongo zomwe zimapangitsa kumwa mankhwala osokoneza bongo kapena kudyetsa zakudya poyesa kupeza mphoto yoyembekezeredwa. Komanso, ngati atayesedwa nthawi yoyamba kapena yanthaŵi yaitali yosiya / kudya, maphunziro ozunguliridwa / obedi amasonyeza m'munsimu D2R mu striatum (kuphatikizapo NAc), zomwe zimagwirizanitsidwa ndi kuchepa kwa ntchito yoyamba m'madera a ubongo omwe amachitidwa ndi orbitofrontal cortex. (ACC ndi DLPFC), omwe kusokonezeka kwawo kumadzetsa kukhwima ndi kukhudzidwa. FPomwepo, umboni wawonetseranso pa ntchito yongoganizira zapakati ndi zowonongeka m'zinthu zosiyana siyana zomwe zimapangitsa kuti mankhwala osokoneza bongo kapena zakudya zisamangidwe.
Chith. 8 Chitsanzo chopanga mauthenga a maulendo ophatikizana, zosokoneza zomwe zimapangitsa kuti zikhale zovuta zokhudzana ndi chizolowezi cha mankhwala osokoneza bongo komanso kudya mopitirira muyeso: mphotho (nucleus accumbens, VTA, ventral pallidum), chikhalidwe / kukumbukira (amygdala, OFC yapakati pothandizira kuti azidziwika bwino, hippocampus, ndi dorsal striatum), control control (DLPFC, ACC, low cortex cortex, ndi lateral OFC) zofuna / kuyendetsa (mediation OFC chifukwa cha kupatsidwa kwa saliency, ventral ACC, VTA, SN, dorsal striatum, ndi motor cortex). Nac, nucleus accumbens, interoception (Insula ndi ACC), ndi kusokonezeka / kupeŵa (Habenula). A Pamene madera amenewa ali oyenerera, izi zimapangitsa kuti mukhale woyenera kuletsa komanso kusankha zochita. b Panthawi ya chizoloŵezi, pamene chiwerengero cha mankhwalawa, mphotho, ndi maulendo am'mbuyo amatha kugonjetsa dera loyendetsa bwalo, kulandira chithandizo chabwino choyambitsa ndondomeko choyambitsidwa ndi kugwiritsa ntchito mankhwala osokoneza bongo komanso kupititsa patsogolo kuyendetsa galimoto. ndi maulendo achikumbutso. Maulendowa amathandizananso ndi maulendo okhudzana ndi kusintha maganizo, kuphatikizapo reactivity (zomwe zimaphatikizapo amygdala, hypothalamus, habenula) ndi kuyanjana pakati (zomwe zikuphatikizapo insula ndi ACC komanso zimathandizira kuzindikira za kukhumba). Mapepala angapo amadzimadzi amachititsa chidwi m'matendawa, kuphatikizapo glutamate, GABA, norepinephrine, factor corticotropin-releasing, ndi opioid receptors. CRF, chochotsera-corticotropin-factor; NE, norepinephrine. Kusinthidwa ndi chilolezo kuchokera ku Volkow et al. (2011b)
Chifukwa cha kusokonezeka kwapadera m'maderawa, anthu amatha kupeza 1) chidziwitso cholimbikitsana cha mankhwala / chakudya (magulu ochepa omwe amaphunzira pogwiritsa ntchito chikhalidwe ndi zizoloŵezi) pothandizira ena opatsirana (kupititsa patsogolo kwa kuchepa kwa dera la mphoto ), 2) zovuta zomwe zingalepheretse kuchita zolinga (mwachangu) zomwe zimayambitsa chilakolako champhamvu cha kumwa mankhwala / chakudya (chomwe chimapangitsa kuti munthu asagwiritsidwe ntchito molakwika) komanso kuti 3) ikhale yovuta kwambiri. ndi kupeŵa mwatsatanetsatane komwe kumapangitsa kuti mankhwala osokoneza bongo asatengeke mosavuta.
Chitsanzochi chimapereka njira zambiri zothandizira mankhwala ozunguza bongo omwe amachititsa kuchepetsa mphamvu zowonjezereka za mankhwala / chakudya, kubwezeretsanso / kupititsa patsogolo zopindulitsa zowonjezera zachilengedwe, kulepheretsa mayanjano ophunzitsidwa bwino, kulimbikitsanso ntchito zosagwiritsidwa ntchito ndi mankhwala / kuchepetsa nkhawa. , kusintha maganizo, komanso kulimbitsa mphamvu zowonongeka.
Kuvomereza
Olembawo angafune kuyamika thandizo la NIAAA pulogalamu yazitsulo ya National Institutes of Health.
Zothandizira
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