Maseŵera Osewera a Neuronal M'kuledzeretsa Ndi Kunenepa Kwambiri: Umboni Wachikhalidwe Chakumidzi (2008) Nora Volkow

MAFUNSO: Wolemba Volkow, yemwe ndi mutu wa NIDA. Kusavuta kwenikweni - kusokoneza bongo kumafanana ndi kusuta mankhwala osokoneza bongo munjira zosokoneza bongo komanso kusintha kwa ubongo. Umboni wina woti kusuta zakudya kumatha kusintha ubongo mofananamo ndi mankhwala osokoneza bongo. Funso lathu - ngati chakudya chingayambitse kusuta, kodi kuseweretsa maliseche ku zolaula sikungakhale bwanji kovuta? Makamaka poganizira kuti kugwiritsira ntchito zolaula kumakhala kolimbikitsa kwambiri komanso kwanthawi yayitali kuposa kudya.

Kuphatikiza Maulendo a Neuronal M'kuledzeretsa Ndi Kunenepa Kwambiri: Umboni Wopereka Mavuto Atsitsi

Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12; 363 (1507): 3191-3200.

Idasindikizidwa pa intaneti 2008 Jul 24. do:  10.1098 / rstb.2008.0107

PMCID: PMC2607335

Nora D Volkow,1,2,* Gene-Jack Wang,3 Joanna S Fowler,3 ndi Frank Telang2

Kudalirika

Mankhwala osokoneza bongo komanso chakudya chimalimbikitsa zina mwa kuwonjezera dopamine (DA) m'magawo amiyendo, zomwe zadzetsa chidwi chofuna kumvetsetsa momwe kugwiritsa ntchito mankhwala osokoneza bongo / chizolowezi chake kumakhudzira kunenepa kwambiri. Apa, tikuphatikiza zomwe zapezedwa kuchokera ku kafukufuku wa positron emission tomography pazochita za DA pakugwiritsa ntchito mankhwala osokoneza bongo / kuledzera komanso kunenepa kwambiri ndikupereka njira yofananira yazikhalidwe ziwirizi. Zonse mu nkhanza / chizolowezi komanso kunenepa kwambiri, pamakhala phindu lamtundu wina wamphamvu (mankhwala osokoneza bongo ndi chakudya, motsatana) pochotsera othandizira ena, zomwe ndi zotsatira za kuphunzira kokhazikika ndikukhazikitsanso malire a mphotho yachiwiri mpaka yolimbikitsidwa mobwerezabwereza mankhwala osokoneza bongo (kuzunza / kumwa) komanso chakudya chochuluka chokoma (kunenepa kwambiri) mwa anthu omwe ali pachiwopsezo (mwachitsanzo majini). Mwa mtunduwu, mukamakumana ndi cholimbikitsira kapena cholozera, mphotho yomwe ikuyembekezeredwa (yokonzedwa ndimasekondi okumbukira) imathandizira madongosolo olimbikitsa ndi olimbikitsira poletsa magwiridwe antchito azidziwitso, zomwe zimapangitsa kulephera kuyendetsa galimoto kuti idye mankhwala kapena chakudya ngakhale kuyesera kutero. Ma circonal a neuronal, omwe amasinthidwa ndi DA, amalumikizana wina ndi mnzake kuti kusokonezeka kwa dera limodzi kutheredwe ndi kwina, zomwe zikuwonetsa kufunikira kwa njira zingapo pakuthandizira kuzolowera komanso kunenepa kwambiri.

Keywords: dopamine, positron emission tomography, kujambula, kudziletsa, kukakamizidwa

1. Introduction

Kugwiritsa ntchito mankhwala osokoneza bongo komanso kuledzeretsa, ndipo mitundu ina ya kunenepa kwambiri imatha kumveka chifukwa cha zizoloŵezi zomwe zimalimbitsa ndi kubwerezabwereza kwa khalidwe ndipo zimakhala zovuta kwambiri kuti munthu azilamulira ngakhale kuti zotsatira zake zingakhale zoopsa. Kugwiritsira ntchito chakudya, kupatula kudya njala, ndi kugwiritsa ntchito mankhwala osokoneza bongo kumayendetsedwa ndi katundu wawo wopindulitsa, omwe muzochitika ziwirizi zimaphatikizapo kuyambitsa njira za mesolimbic dopamine (DA). Zakudya ndi kugwiritsa ntchito mankhwala osokoneza bongo zimayambitsa DA njira zosiyanasiyana (tebulo 1). Chakudya chimayambitsa mphoto za ubongo zomwe zimayambitsa matendawa (kuphatikizapo opioids osagwiritsidwa ntchito mopitirira malire) komanso chifukwa cha kuchuluka kwa shuga ndi insulini (kumaphatikizapo kuwonjezeka kwa DA), pomwe mankhwala osokoneza bongo amachititsa kuti izi zitheke pogwiritsa ntchito mankhwala awo (kudzera mwa maselo a DA kapena mwachindunji kudzera m'magetsi zomwe zimayambitsa DA maselo monga opiates, nicotine, γ-aminobutyric asidi kapena cannabinoids; Volkow & Wanzeru 2005).

Gulu 1  

Kuyerekezera chakudya ndi mankhwala monga olimbikitsa. (Kusinthidwa kuchokera Volkow & Wanzeru 2005.)

Anthu ambiri amakhulupirira kuti mphotho ya DA yomwe imapereka mphotho imayambitsa matenda a ubongo m'mabwalo ena omwe amachititsa kuti khalidweli likhale lopanikizika kwambiri. Pankhani ya kugwiritsa ntchito mankhwala osokoneza bongo, kubwereza kwapadera kwa DA kumagwiritsa ntchito mankhwala osagwiritsidwa ntchito nthawi zambiri kumakhulupirira kuti zimapangitsa kusintha kwa pulasitiki mu ubongo (kutanthauza kuti glutamatergic cortico-bereatal pathways), zomwe zimapangitsa kuti kugwirizanitsa maganizo ndi mankhwala kapena mankhwala awo, kutetezedwa kwa mankhwala osokoneza bongo komanso kudya mankhwala osokoneza bongo (Volkow & Li 2004). Mofanana, dopaminergic kukakamiza panthawi yaledzera kumapangitsa munthu kukhala ndi chizolowezi chogwiritsa ntchito mankhwala osokoneza bongo komanso mankhwala osokoneza bongo, komanso kulimbitsa zizoloŵezi zomwe zimapangitsa kuti munthu azitha kumwa mankhwala osokoneza bongo atakhala ndi nkhawa. Mofananamo, kubwereza ku zakudya zina (makamaka, chakudya chokwanira cha mphamvu ndi mafuta ndi shuga; Oats Et al. 2008) kwa anthu omwe ali pachiopsezo angayambitsenso kudya zakudya zoperewera, kuchepetsa zakudya zopatsa thanzi komanso zakudya zolimbitsa thupi. Anthu omwe ali pachiopsezo (mwachitsanzo, omwe ali ndi ziwalo zamtundu kapena zowonjezera), izi zingachititse kunenepa (chakudya) kapena kumwa mankhwala osokoneza bongo.

Nthenda yamagetsi ya kudya ndi yovuta kwambiri kusiyana ndi kayendedwe ka kugwiritsa ntchito mankhwala osokoneza bongo, popeza chakudya chimayendetsedwa osati pokhapokha mphotho komanso mowonjezereka, zowonjezereka ndi zowonjezereka kuposa zomwe zimapereka mphotho (Levine Et al. 2003). Papepala lino, timangoganizira kwambiri za tizilombo toyambitsa matenda zomwe zimakhudzana ndi chakudya chopatsa thanzi, chifukwa chiyenera kukhala chothandizira kwambiri pakuwerengera ndalama chifukwa cha kuchuluka kwakukulu kwa kunenepa kwambiri kumene kwachitika zaka makumi atatu zapitazi. Lingaliro lathu ndilokuti kusintha kwa dera la mphotho komanso ku maulendo olimbikitsa, kukumbukira ndi kuyang'anira omwe amapezeka mobwerezabwereza ndi chakudya chochuluka chokongola kwambiri ndi chimodzimodzi ndi chimene amachiwona mobwerezabwereza mankhwala osokoneza bongo (tebulo 2). Timapatsanso kuti kusiyana pakati pa anthu pa ntchito za maulendowa musanayambe kudya kapena kugwiritsa ntchito mankhwala osokoneza bongo amachititsa kuti pakhale kusiyana pakati pa chiwopsezo cha zakudya kapena mankhwala monga chitsimikizo chofunikila. Izi zimaphatikizapo kusiyana pakati pa zokhudzana ndi kupatsa malipiro a zakudya monga mankhwala; Kusiyana kwa mphamvu zawo zowononga kuchepetsa cholinga chawo chodyera chakudya chokongola pambali pa zotsatira zake zoipa (kulemera) kapena kutenga mankhwala osayenera (choletsedwa); komanso kusiyana pakati pa kukhala ndi mayankho olimbitsa thupi pakakhala chakudya ndi mankhwala.

Gulu 2  

Anasokoneza ntchito za ubongo zomwe zimakhudzidwa ndi khalidwe la phenyope la chizolowezi choledzeretsa ndi kunenepa kwambiri komanso malo omwe ubongo umaganizira kuti umasokonezeka. (Kusinthidwa kuchokera Volkow & O'Brien 2007.)

2. Madera a mphoto / saliency oledzera ndi kunenepa kwambiri

Popeza kuti DA imakhala ndi chakudya chopatsa thanzi komanso mankhwala ambiri, timayankha kuti kusiyana komweku kuchitika kwadongosolo la DA kukhala chakudya kapena mankhwala osokoneza bongo kungachititse kuti anthu azigwiritsa ntchito mankhwala osokoneza bongo. Poyesa izi, timagwiritsa ntchito positron emission tomography (PET) ndi njira zambiri zofufuza njira za DA mu ubongo waumunthu muzitsulo zowonongeka komanso nkhani zomwe zimagwiritsidwa ntchito mankhwala osokoneza bongo komanso omwe ali ovuta kwambiri. Zomwe zimagwiritsidwa ntchito ndi synaptic za DA neurotransmission, kupezeka kwa DA D2 zovomerezeka mu striatum zimadziwika kuti zikhazikitse zowonjezera mayankho kwa mankhwala ndi chakudya.

(a) Mayankho a mankhwala osokoneza bongo ndi chiopsezo cha kugwiritsa ntchito mankhwala osokoneza bongo

Muzitsulo zosagwiritsira ntchito mankhwala osokoneza bongo, tinasonyeza kuti D2 kupezeka kwapadera ku statum kunayankha njira zawo zowonetsera ku mankhwala osokoneza bongo methylphenidate (MP). Zolinga zokhudzana ndi zochitika zomwe zinali zosangalatsa zili ndi ziwerengero zochepa zowonjezereka poyerekeza ndi zomwe zikufotokozera MP ngati zosasangalatsa (Volkow Et al. 1999a, 2002a). Izi zikusonyeza kuti mgwirizano pakati pa makanema a DA ndi kuyimitsa mayankho kumatsatira mpikisano wofanana ndi U: zochepa kwambiri sizingagwiritsidwe bwino kuti zitsimikizidwe koma zowonjezereka sizitsutsa. Motero, mkulu D2 Maseŵera okhudzidwa akhoza kutetezedwa kuntchito yokonza mankhwala. Chithandizo cha izi chimaperekedwa ndi maphunziro odziwika bwino omwe akuwonetsa kuti kusinthidwa kwa D2 Zomwe zimapezeka mu nucleus accumbens (NAc; m'dera mwa striatum zovuta mu mankhwala ndi chakudya mphotho) kwambiri kuchepetsa kumwa mowa nyama zomwe poyamba anaphunzitsidwa kudziletsa mowa (Thanos Et al. 2001), ndi maphunziro a zachipatala omwe amasonyeza kuti omwe omwe ali ndi mbiri ya banja losagwiritsa ntchito mankhwala osokoneza bongo anali osakanizidwa ndi D2 ovomerezeka mu striatum kuposa anthu opanda mbiri mbiri ya banja (Mintun Et al. 2003; Volkow Et al. 2006a).

Kugwiritsa ntchito PET ndi D2 mapulogalamu othandizira mauthenga, ife ndi ochita kafukufuku ena tawonetsa kuti nkhani zomwe zimakhala ndi mankhwala osokoneza bongo (cocaine, heroin, alcohol ndi methamphetamine) zimachepetsa kwambiri D2 kupezeka kwapadera ku striatum yomwe imapitirira patapita miyezi itatha nthawi yaitali yowonongeka Volkow Et al. 2004). Kuonjezera apo, anthu ogwiritsira ntchito mankhwala osokoneza bongo (cocaine ndi mowa) akuwonetsanso kuchepa kwa DA, zomwe zikhoza kusonyeza kuwombera kwa DA kachetechete (Volkow Et al. 1997; Martínez Et al. 2005). DA itamasulidwa pogwiritsa ntchito PET ndi [11C] raclopride, yomwe ndi D2 receptor radioligand yomwe imapikisana ndi DA wodalirika pomangirira D2 mapuloteni ndipo potero angagwiritsidwe ntchito kuyesa kusintha kwa DA koyambitsa mankhwala. Dera la DA likuwonjezeka kwambiri (likuwoneka ngati kuchepetsedwa pamtundu wina wa [11C] raclopride) chifukwa cha kusokonezeka kwa mankhwala osokoneza bongo (MP kapena amphetamine) owononga mankhwala a cocaine ndi zakumwa zauchidakwa zinali zochepa poyerekeza ndi maulamuliro (kuposa 50% m'munsi; Volkow et al. 1997, 2007a; Martinez Et al. 2005, 2007). Chifukwa chakuti DA ikuwonjezeredwa ndi MP imadalira DA kumasulidwa, ntchito ya ma cell DA kuwombera, ife tikuganiza kusiyana uku mwinamwake kunasonyeza kuchepa kwa maselo a DA m'zochita za cocaine oledzera ndi zidakwa.

Kafukufukuyu akusonyeza zovuta ziwiri zomwe zimakhala zovuta kwambiri zomwe zingachititse kuchepa kwa madera a mphoto kwa DA: kuchepa kwa DA D2 kulandila, ndi DA kumasulidwa ku striatum (kuphatikizapo NAc). Aliyense amathandizira kuchepetsa kukhudzidwa mtima kwa anthu osokonezeka. Inde, anthu omwe amagwiritsira ntchito mankhwala osokoneza bongo amawoneka kuti akuvutika chifukwa cha kuchepa kwa maulendo awo opereka mphotho kwa anthu olimbitsa thupi. Mwachitsanzo, kafukufuku wogwiritsa ntchito magnetic resonance akuwonetsa kuchepa kwa ubongo chifukwa cha kugonana kwa anthu osokoneza bongo (Garavan Et al. 2000). Mofananamo, kafukufuku wa PET adapeza umboni wosonyeza kuti ubongo wa osuta umagwira ntchito mosiyana ndi malipiro a ndalama ndi osakhala osuta (osasuta)Martin-Solch Et al. 2001). Popeza mankhwala osokoneza bongo ndi ovuta kwambiri polimbikitsa madera a mphoto ya DA kuposa machitidwe olimbitsa thupi, iwo adzalandirabe madera ozungulira mphoto. Kuchepetsa kuchepa kwa madera a mphoto kungachititse kuchepa kwa chidwi cha chilengedwe, mwinamwake zowonongeka kuti mupeze mankhwala osokoneza bongo ngati njira yowonjezera maulendo a mphotho.

(b) Kudya miyambo ya chikhalidwe ndi chiopsezo cha kunenepa kwambiri

Muzitsulo zoyenera zolemera, D2 Kupezeka kwa phwando mu striatum kumayendera kudya makhalidwe (Volkow Et al. 2003a). Mwapadera, chizoloŵezi chodya pakadandaula chidasokonezeka kwambiri ndi D2 kupezeka kwapadera (kumunsi kwa D2 mapepala othandizira, amatha kukhala ndi mwayi woti nkhaniyo idye ngati mukudandaula).

M'maphunziro onenepa kwambiri (body mass index (BMI)> 40), tawonetsa zocheperako kuposa D.2 kupezeka kwapadera ndi kuchepetsa kumeneku kunali kofanana ndi BMI yawo (Wang Et al. 2001). Izi zikutanthauza kuti ndizomwe zili ndi m'munsimu D2 amalandila anali ndi BMI apamwamba. Zotsatira zofanana za kuchepa D2 mapulogalamu obwera m'mabuku ovuta kwambiri adakambidwa posachedwa (Haltia Et al. 2007). Zotsatirazi zinatipangitsa kuti tilembere kuti D2 kupezeka kwapadera kungapangitse munthu kukhala pachiopsezo chodyera. Ndipotu, izi zikugwirizana ndi zofukufuku zosonyeza kuti kuletsa D2 mapuloteni (antipsychotic mankhwala) amachulukitsa chakudya komanso amadzetsa chiopsezo cha kunenepa kwambiri (Allison Et al. 1999). Komabe, njira zomwe D2 kupezeka kwapadera kungapangitse chiopsezo chodyera (kapena momwe amachulukitsa chiopsezo cha kugwiritsa ntchito mankhwala osokoneza bongo) sichimvetsetsedwa bwino.

3. Kuletsa kulepheretsa / kutengeka maganizo kumayendedwe ndi kunenepa kwambiri

(a) Kugwiritsa ntchito mankhwala osokoneza bongo komanso kuledzera

Kukhalapo kwa mankhwala kumabweretsa mwayi wa kuyesera ndi kuzunza (Volkow & Wanzeru 2005). Choncho, kuthetsa mayankho omwe angakhalepo m'madera omwe amapezeka mosavuta, amatha kugwiritsa ntchito mankhwala osokoneza bongo. Mofananamo, zovuta zowononga zachilengedwe (ie, zosokoneza za anthu) zimathandizanso kuyesa mankhwala ndi kuzunza. Popeza kuti si nkhani zonse zomwe zimachitanso zofanana ndi zovuta, zosiyana m'maganizo okhudzidwa ndi zochitika zina zakhala zikuphatikizapo chinthu chomwe chimayambitsa chiopsezo cha mankhwala osokoneza bongo (Piazza Et al. 1991).

Phunziro pa ogwiritsira ntchito mankhwala osokoneza bongo komanso omwe ali pa chiopsezo choledzera, tawonanso mgwirizano pakati pa kupezeka kwa D2 zovomerezeka ndi chigawo cha ubongo glucose metabolism (chizindikiro cha ubongo ntchito) kuyesa malo a ubongo omwe atha kuchepetsedwa pamene D2 zovomerezeka zatsika. Ife tawonetsa kuti kuchepa kwa D striater2 Zolandira za mankhwala osokoneza bongo zowonongeka zimagwirizanitsidwa ndi kuchepa kwa maselo opangidwa ndi orbitofrontal cortex (OFC), anterior cingulate gyrus (CG) ndi dorsolateral prefrontal cortex (DLPFC; chiwerengero cha 1; Volkow Et al. 1993, 2001, 2007a). Popeza OFC, CG ndi DLPFC zikuphatikizidwa ndi kuchepetsa mphamvu (Goldstein & Volkow 2002) komanso pogwiritsa ntchito maganizo (Phan Et al. 2002), tinadandaula kuti malamulo awo olakwika ndi a DA omwe ali osokoneza bongo angawononge kuwonongeka kwa mankhwala osokoneza bongo komanso kusadziletsa kwawo. Zoonadi, mu zidakwa, kuchepetsa D2 Kupezeka kwa receptor mu ventral striatum kumagwirizana ndi chilakolako chowopsa ndi kuwonjezereka kwakukulu kochitidwa ndi mphambano yamakono yamakono ndi CG (Heinz Et al. 2004). Kuonjezera apo, chifukwa kuwonongeka kwa OFC kumabweretsa makhalidwe opirira (Rolls 2000) komanso kuwonongeka kwa anthu mu OFC ndi CG zimagwirizana ndi khalidwe lodzikakamiza (Nyama 1992), tinanenanso kuti kuwonongeka kwa DA kwa madera amenewa kungakhale kudyetsa mankhwala osokoneza bongo omwe amachititsa kuti munthu akhale ndi vutoli.Volkow Et al. 2005).

Chithunzi 1  

(a) Zithunzi za DA D2 zovomerezeka (zoyezedwa ndi [11C] raclopride mu striatum) mu (i) chiwongolero ndi (ii) owononga mankhwala a cocaine. (b) Chithunzi chomwe chikusonyeza kumene kagayidwe ka shuga kogwirizanitsidwa ndi DA D2 anthu odwala mankhwala a cocaine, omwe anali ndi orbitofrontal ...

Komabe, bungwe likhoza kutanthauzanso kuti kusokoneza ntchito m'dera la prefrontal kungapangitse anthu omwe ali pangozi yogwiritsira ntchito mankhwala osokoneza bongo ndipo kenaka kubwereza mankhwala osokoneza bongo kungabweretse mavuto a D2 zovomerezeka. Zoonadi, kuthandizira zomwe zingatheke kumaperekedwa ndi maphunziro athu, mitu yomwe ngakhale kuti ali ndi chiopsezo chokwanira chauchidakwa (chifukwa cha chiwerengero cha mabanja oledzeretsa) sichinali chakumwa chauchidakwa: mwa izi, tawonetsa D2 olandiridwa mu striatum kuposa anthu omwe alibe mbiri ya banjaVolkow Et al. 2006a). M'mitu iyi, apamwamba D2 mapuloteni, apamwamba kwambiri a metabolism mu OFC, CG ndi DLPFC. Kuwonjezera apo, OFC kagayidwe kameneka kanalinso kogwirizana bwino ndi umunthu wa zochitika zabwino. Potero, timayimitsa madera akuluakulu a D2 mapulogalamu otha kulandira mankhwala amatha kuteteza kusokoneza bongo poyendetsa zigawo zapadera zomwe zimakhala zoletsa kulepheretsa anthu kugwiritsira ntchito mankhwalawa.

(b) Kudya chakudya ndi kunenepa kwambiri

Popeza kupezeka kwa chakudya ndi kuonjezera kuonjezera chakudya chokwanira (Wardle 2007), kupeza mosavuta chakudya chokongola kumafuna kuti kawirikawiri izilepheretsa chilakolako chodya (Berthoud 2007). Mtengo umene anthu amasiyana nawo kuthetsa mayankhowa ndikuwongolera kuchuluka kwa zomwe amadya angathe kuwonetsa chiwopsezo chawo chodyera zakudya zamakono zomwe tili nazo panopa (Berthoud 2007).

Monga tafotokozera pamwambapa, tidalemba kale kuchepetsa D2 mapulogalamu obwera m'magazi ochepa kwambiri. Izi zinatitsogolera kuika pansi D2 mapuloteni akhoza kuika munthu pa chiopsezo chodyera. Njira zomwe D2 mapulogalamu othandizira odwala amalandira chiopsezo cha kudya mopitirira malire koma sitinafotokoze kuti, monga momwe zilili ndi mankhwala osokoneza bongo / mankhwala osokoneza bongo, izi zingathekezedwe ndi D2 malamulo ovomerezeka omwe amalandiridwa ndi madera a prefrontal.

Kuwona ngati kuchepetsa D2 opezeka m'matenda odzaza kwambiri ophatikizidwa ankaphatikizidwa ndi ntchito m'madera a prefrontal (CG, DLPFC ndi OFC), tinayesa mgwirizano pakati pa D2 kupezeka kwapadera ku striatum ndi ubongo wa shuga mumatenda. Kufufuza kwa SPM onse (kuti aone mgwirizano pa pixel-pixel maziko osasankhidwa a madera) komanso malo omwe adakopeka nawo chidwi awonetseredwa kuti D2 Kupezeka kwa receptor kunkagwiritsidwa ntchito ndi metabolism ku malo osungirako zinthu (Brodmann) (BA) 9 ndi 10), pakati pa OFC (BA 11) ndi CG (BA 32 ndi 25; chiwerengero cha 2). Kuyanjana ndi thupi la prefrontal limasonyeza kuti kuchepa kwa D2 Zomwe zimapezeka m'mabuku opambana zimathandizira kudyetsa mbali zina mwa kudula malire a zigawo za prefrontal zomwe zimaphatikizapo kuletsa kuteteza komanso kusokoneza maganizo.

Chithunzi 2  

(a) Zithunzi zowerengedwa za DA D2 zovomerezeka (zoyezedwa ndi [11C] raclopride) mu gulu la (i) kulamulira (n= 10) ndi (ii) maphunziro ovuta kwambiri (n= 10). (b) Zotsatira kuchokera ku SPM zikutanthauzira zomwe zili mu ubongo kumene D2 kupezeka kwapadera kunagwirizanitsidwa ndi ...

4. Kulimbikitsa / kugwiritsa ntchito mankhwala osokoneza bongo / kuledzera ndi kunenepa kwambiri

(a) Kugwiritsa ntchito mankhwala osokoneza bongo komanso kuledzera

Mosiyana ndi kuchepa kwa ntchito zamagetsi m'dera la prefrontal mu detoxified cocaine abusers, izi zigawo ndi hypermetabolic mu yogwira cocaine abusers (Volkow Et al. 1991). Choncho, timapereka kuti nthawi ya kumwa mowa wa cocaine kapena kumwa mowa kumadwala, DA yomwe imapangidwanso ndi mankhwala imayamba kuwonjezereka mwa STRATum activate ndi CG, zomwe zimabweretsa chilakolako chofuna kudya mankhwala osokoneza bongo. Inde, tawonetsa kuti MP yowonjezera yowonjezera mphamvu yowonjezera mphamvu mu OFC kokha mwa ozunza a cocaine omwe amachititsa chidwi chachikulu (Volkow Et al. 1999b). Kugwira ntchito kwa OFC ndi CG kwa ogwiritsira ntchito mankhwala osokoneza bongo kunanenedwa kuti kumachitika panthawi yolakalaka zomwe adaziwona pakuwona kanema ya cocaine (Grant Et al. 1996) komanso pokumbukira zochitika zamankhwala zam'mbuyo (Wang Et al. 1999).

(b) Kunenepa kwambiri

Maphunziro a kufotokozera m'mabuku oposa ambiri awonetsa kuti kuwonjezeka kwa zigawo za prefrontal kumawunikira kudya, komwe kuli kovuta kwambiri kusiyana ndi maphunziro ochepa (Gautier Et al. 2000). Pamene zovuta zokhudzana ndi zakudya zimaperekedwa ku maphunziro omveka bwino (monga ngati mankhwala okhudzana ndi mankhwalawa amapatsidwa mankhwala osokoneza bongo; Volkow & Fowler 2000), chida chamakono choyendetsa chitetezo chimayambitsidwa ndipo zilakolako zimatchulidwa (Gautier Et al. 2000; Wang Et al. 2004; Miller Et al. 2007). Mbali zingapo za prefrontal cortex (kuphatikizapo OFC ndi CG) zakhala zikukhudzidwa ndi cholinga chodyetsa (Rolls 2004). Zigawo zimenezi zimatha kusonyeza gawo lopatsirana pogwiritsa ntchito mankhwala osokoneza bongo lomwe limayendera kudya kapena kumwa mankhwala osokoneza bongo. Zovuta za madera amenewa zikhoza kuyambitsa khalidwe kapena mankhwala, malingana ndi kukhudzidwa ndi mphotho ndi / kapena zikhazikitso za phunzirolo.

5. Kumbukirani, chikhalidwe ndi zizolowezi za mankhwala ndi mankhwala

(a) Kugwiritsa ntchito mankhwala osokoneza bongo komanso kuledzera

Maulendo oyandikana ndi chikumbumtima ndi maphunziro, kuphatikizapo maphunziro olimbitsa thupi, maphunziro a chizolowezi ndi kukumbukira kukumbukira (kukufotokozedwa Vanderschuren & Everitt 2005), adakonzedwa kuti azichita nawo mankhwala osokoneza bongo. Zotsatira za mankhwala osokoneza bongo akumbukira njira zomwe zosakhudzidwa ndi ndale zimatha kulimbitsa katundu ndi zolimbikitsana, mwachitsanzo, kupyolera mu maphunziro olimbitsa thupi. Kafukufuku wokhudzana ndi kubwerezabwereza, ndikofunikira kumvetsetsa chifukwa chomwe anthu ogwiritsira ntchito mankhwala osokoneza bongo ali ndi chilakolako champhamvu cha mankhwalawa pofika kumalo kumene adatenga mankhwalawa, kwa anthu amene adayamba kugwiritsa ntchito mankhwala osokoneza bongo komanso zinthu zina zomwe amagwiritsa ntchito mankhwalawa. Izi ndizofunikira kwambiri chifukwa chodziwika ndi mankhwala omwe amachititsa kuti mankhwalawa asokonezeke. Popeza DA ikukhudzidwa ndi kuneneratu kwa mphotho (yowonongedwa ndi Schultz 2002), tinaganiza kuti DA akhoza kukhala ndi mayankho omwe amachititsa chidwi. Maphunziro a zinyama zopanga ma laboratory amathandizira izi: Pamene zovuta zandale zimagwirizanitsidwa ndi mankhwala omwe, ndi mayanjano obwerezabwereza, amatha kuwonjezera DA ku NAc ndi dorsal striatum. Kuwonjezera pamenepo, mayankho a khunyu amathandizidwa ndi khalidwe lofunafuna mankhwala Vanderschuren & Everitt 2005).

Kwa anthu, maphunziro a PET ndi [11C] raclopride posachedwapa adatsimikizira izi ndi kusonyeza kuti mu cocaine olakwira mankhwala osokoneza bongo (mavidiyo a cocaine-cue mafilimu otenga cocaine) kwambiri anawonjezeka DA mu dorsal striatum ndipo kuonjezeraku kunkagwirizana ndi chikhumbo cha cocaine (chiwerengero cha 3; Volkow Et al. 2006b; Wong Et al. 2006). Chifukwa chakuti dorsal striatum imaphatikizapo kuphunzirira chizoloŵezi, kusonkhana kumeneku kungakhale kukuwonetseratu kulimbitsa zizoloŵezi monga momwe chizoloŵezi choledzerera chimayambira. Izi zikuwonetsa kuti vuto lalikulu la sayansi ya sayansi ya zokhudzana ndi chizoloŵezi cha mankhwala osokoneza bongo likhoza kukhala ndi DA-zomwe zimayambitsa mayankho omwe amachititsa zizolowezi zomwe zimayambitsa mankhwala osokoneza bongo. N'kutheka kuti mayankhowa akuphatikizapo kusintha kwa njira za cortico-striatal glutamatergic zomwe zimayambitsa DA release (zowonongeka Kalivas Et al. 2005). Choncho, ngakhale mankhwala osokoneza bongo (komanso chakudya) angayambitse DA kumasulidwa mu ventral striatum (kuwonetsa mphotho), ndi kulamulira mobwerezabwereza ndi zizolowezi zomwe zikuwonekera apo zikuwoneka kuti kusintha kwa DA kukuwonjezeka ku dorsal striatum.

Chithunzi 3  

(a) Zithunzi zowerengedwa za DA D2 zovomerezeka (zoyezedwa ndi [11C] raclopride) m'gulu la anthu omwe amamwa mankhwala osokoneza bongo (cocaine)n= 16) ayesedwa pamene akuwonera kanema wosalowerera komanso akuwonera kanema ya cocaine. (b) Histogram ikuwonetsa zochitika za DA D2 kupezeka kwapatsidwa ...

(b) Chakudya ndi kunenepa kwambiri

DA imayendetsa zakudya zokha osati kupyolera muzomwe zimapindulitsa (Martel & Fantino 1996) komanso powongolera kusintha kwa zakudya zomwe zimapangitsa kuti anthu adye chakudya (Kiyatkin & Gratton 1994; Mark Et al. 1994). Imodzi mwa mafotokozedwe oyambirira a yankho lovomerezeka ndi Pavlov amene adasonyeza kuti agalu akadziwombera kuti adzalumikizana mobwerezabwereza ndi kamvekedwe ka nyama kamvekedwe kake kamene kangapangitse kuti nyama izi zisamalire. Kuyambira apo, kufufuza kwa voltammetry kwawonetsa kuti kuwonetsa kusakhudzana ndi zakudya zomwe zakhala zikukonzekera ku chakudya kumabweretsa kuwonjezeka kwa chiwerengero cha DA komanso kuti kuwonjezeka kwa DA kumagwirizanitsidwa ndi khalidwe la motoric lomwe limayenera kupeza chakudya (kukanikiza; Roitman Et al. 2004).

Tagwiritsira ntchito PET kuti tiyang'ane mayankho omwe ali ndi machitidwe abwino. Timaganiza kuti chakudyacho chidzakulitsa DA extracellular mu striatum ndipo kuti kuwonjezeka kumeneku kudzaneneratu chikhumbo cha chakudya. Nkhani zoperewera za zakudya zinaphunzitsidwa pamene zinalimbikitsidwa ndi zochitika zapanda ndale kapena zochokera ku chakudya (zolembedwera). Kuti tiwone kusintha kwa DA, tinayambitsanso nkhaniyi ndi MP (20 mg oral), mankhwala osokoneza bongo omwe amalepheretsa anthu opititsa patsogolo DA (njira yaikulu yothetseratu DA; Giros Et al. 1996). Kulimbikitsana kwa chakudya kunakula kwambiri DA mu statum ndipo izi zikuwonjezereka ndi kuwonjezeka kwa kudzidzimva kwa njala ndi chilakolako cha chakudya (Volkow Et al. 2002b; chiwerengero cha 4). Zomwe anapezazo zinanenedwa pamene chakudya chapadera chinkaperekedwa ku machitidwe abwino popanda kutengeredwa ndi MP. Zofukufukuzi zimatsimikizira kuti kulimbikitsidwa kwa DA kugwidwa ndi mayankho pamayendedwe a chakudya komanso kutenga nawo mbali njirayi polimbikitsa chakudya. Popeza kuti mayankhowa anapezeka pamene maphunzirowa sanadye chakudya, izi zimayankha mayankho awa mosiyana ndi udindo wa DA pakukonza mphotho kudzera ku NAC.

Chithunzi 4  

(a) Zithunzi zowerengedwa za DA D2 zovomerezeka (zoyezedwa ndi [11C] raclopride) mu gulu la machitidwe (n= 10) kuyesedwa pamene akufotokozera za mzera wawo wa banja (kusalowerera ndale) kapena pamene akupezeka pa chakudya. (b) Histogram ikuwonetsa zochitika za DA D2 phwando ...

Pakalipano tikuyesa mayankho oyenerera pa maphunziro ovuta kwambiri omwe timakhulupirira kuti kuwonjezeka kwa DA kuwonjezereka kwakukulu poyerekeza ndi anthu omwe ali olemera.

6. Njira yowonongeka / kuledzera komanso kunenepa kwambiri

Monga tafotokozera kale, maulendo angapo omwe amapezeka m'magulu a ubongo amadziwika ndi maphunziro ojambula zithunzi monga othandizira pa matenda ozunguza bongo / kuledzera ndi kunenepa kwambiri. Pano, tikuonetsa maulendo anai awa: (i) mphoto / saliency, (ii) zolimbikitsa / magalimoto, iii) kuphunzira / chikhalidwe, ndi (iv) kuletsa kuteteza / kusintha maganizo / ntchito yapamwamba. Dziwani kuti maulendo ena awiri (mauthenga / kutengeka maganizo ndi kutengapo mbali) amathandizanso kuti azidya kapena kumwa mankhwala osokoneza bongo koma kuti asakhale ophweka sichiphatikizidwa mu chitsanzo. Tikufuna kuti zotsatira za kusokonezeka kwa maulendo anaiwa ndizofunika kwa mtundu wina wa reinforcer (mankhwala osokoneza bongo ndi chakudya chokwanira kwa munthu wambiri) potsalira ena othandizira, zomwe zimakhala zovomerezeka kuphunzira ndi kukhazikitsanso malipiro ochepa omwe amapitsidwanso mobwerezabwereza ndi mankhwala osokoneza bongo (mankhwala osokoneza bongo / osokoneza bongo) komanso chakudya chochuluka kwambiri.

Chotsatira cha kuwonongeka kwa dera / mphoto (njira yomwe imayimira pakati pa NAC, ventral pallidum, medial OFC ndi hypothalamus), yomwe imapangitsa kuti tiyankhe kwa onse omwe ali abwino ndi olakwika, ndizochepa zomwe zimapangitsa kuti zikhale zosiyana ndi zomwe zingakhudze makhalidwe zomwe zingakhale ndi zotsatira zabwino pamene mukupewa makhalidwe omwe angabweretse chilango. Pa nkhani ya kugwiritsa ntchito mankhwala ozunguza bongo, munthu akhoza kunena kuti chifukwa cha kusagwira ntchito mu chipatala ichi, munthu sangakhale wolimbikitsidwa kuti asagwiritse ntchito mankhwala osokoneza bongo chifukwa zowonjezereka zowonjezera (zosokoneza zachibadwa) sizikhala zosangalatsa komanso zotsatira zoipa ( Mwachitsanzo, kusamvana, kusudzulana) ndizochepa. Pa vuto la kunenepa kwambiri, munthu akhoza kuneneratu kuti chifukwa cholephera kugwira ntchito mu chipatala ichi, munthu sangakhale ndi zovuta kuti asadye chifukwa chakuti ena amathandizira (zochitika zolimbitsa thupi) komanso zotsatira zake zoipa (monga kupindula kulemera, shuga) ndizochepa.

Zotsatira za kusokonezeka kwa kayendetsedwe ka kayendedwe ka kayendedwe ka kayendedwe ka kayendedwe ka kayendedwe ka kayendedwe kake ndi kuwonongeka kwa munthu kukhala ndi mphamvu zowonongeka ndi kuwonetsa maganizo (njira zomwe zimagwirizanitsidwa pang'onopang'ono kupyolera mwa DLPFC, CG ndi kutsogolo kwa OFC), zomwe ndizofunikira kwambiri zigawo zoyenera kulepheretsa mayankho oyambirira monga chilakolako champhamvu cha kumwa mankhwala muzovuta kapena kudya chakudya chokwanira mu munthu wambiri. Chotsatira chake, munthuyo sangachite bwino kulepheretsa zochita zake mwachangu ndikuwongolera zomwe zimakhudzana ndi zikhumbo zamphamvu (mwina kutenga mankhwala kapena kudya chakudya).

Zotsatira za kusungidwa kwa chikumbumtima / chikhalidwe / chizoloŵezi chozungulira (zomwe zimagwiritsidwa ntchito pang'onopang'ono kupyolera mu hippocampus, amygdala ndi dorsal striatum) ndizo kugwiritsidwa ntchito mobwerezabwereza kwa mankhwala osokoneza bongo kapena kubwereza mobwerezabwereza chakudya chambiri ) zimapangitsa kuti pakhale mapangidwe atsopano okhudzana ndi zochitika (zomwe zimagwirizanitsidwa kudzera mu hippocampus ndi amygdala), zomwe zimapangitsa munthuyo kuti aziyembekeza mayankho osangalatsa, osati pokhapokha atagwiritsa ntchito mankhwala osokoneza bongo (kapena wodwalayo) komanso kuwonetsetsa kuti mankhwalawa akutsitsimutsa (ie fungo la ndudu) kapena kuti azikhala ndi chakudya (ie kuonera TV). Izi zimayambitsa mayankho omwe nthawi zambiri amachititsa kuti munthu amene akumwa mankhwala osokoneza bongo komanso amene amamwa mankhwala osokoneza bongo komanso kudya zakudya zowonjezera, ngakhale amene akulimbikitsidwa kusiya kumwa mankhwala osokoneza bongo kapena kuchepetsa thupi.

Dera lolimbikitsa / kuyendetsa ndi kuyendetsa kayendetsedwe kake (kumagwirizanitsa mbali ina kudzera mu OFC, dorsal striatum ndi makina owonjezera) zimaphatikizapo pochita zomwezo ndikuziletsa ndizochita zake zimadalira zomwe zimaperekedwa kuchokera ku mphoto / saliency, memory / conditioning and Kuletsa kuteteza / kutsegula maulendo a reactivity. Pamene phindu la mphotho likuwonjezeka chifukwa cha chikhalidwe chake chakale, chimakhala cholimbikitsana kwambiri ndipo ngati izi zikugwirizana ndi kusokonezeka kwa dera loyendetsa chitetezo, izi zingayambitse khalidwe mwachidziwitso (palibe chidziwitso; chiwerengero cha 5). Izi zikhoza kufotokoza chifukwa chomwe anthu ogwiritsira ntchito mankhwala osokoneza bongo amavomereza kumwa mankhwala osokoneza bongo ngakhale kuti sakudziwa kuti amachita zimenezi komanso chifukwa chake anthu ovutika kwambiri amakhala ndi nthawi yovuta kwambiri poyang'anira chakudya chawo komanso chifukwa chake anthu ena amati amamwa mankhwalawa kapena chakudya chokakamiza ngakhale pamene sizikuwoneka pa se monga zosangalatsa.

Chithunzi 5  

Zitsanzo za madera a ubongo zimakhala ndi chizolowezi choledzeretsa ndi kunenepa kwambiri: mphoto / saliency mothandizira / galimoto, kukumbukira / chikhalidwe ndi kuletsa kuletsa / malamulo maganizo. Kusokoneza ntchito m'madera a ubongo okhudzana ndi malamulo oletsa kuteteza / kusokoneza maganizo ...

Mu chitsanzochi, poyang'ana pa reinforcer kapena kwa cues yomwe imaperekedwa kwa reinforcer, mphoto yomwe amayembekezeredwa (yosinthidwa ndi kukumbukira kukumbukira) imawongolera kuwonjezereka kwa mphotho ndi maulendo olimbikitsako pamene kuchepetsa ntchitoyo kumagwirizanitsa dera. Izi zimapangitsa kuti sitingakwanitse kuletsa kuyendetsa galimoto ndikuyesa mankhwalawa (mankhwala osokoneza bongo / chizoloŵezi cha mankhwala osokoneza bongo) kapena chakudya (munthu wochuluka) ngakhale kuti ayesa kuchita zimenezi (chiwerengero cha 5). Chifukwa chakuti maulendo a neuronal, omwe akuyendetsedwa ndi DA, amayanjana, kusokonezeka pa dera limodzi kungathetsedwe ndi zochita za wina, zomwe zikutanthawuza chifukwa chake munthu akhoza kuyesetsa kulamulira khalidwe lawo kuti azitenga mankhwala kapena zakudya nthawi zina koma osati kwa ena.

7. Chofunika chachipatala

Chitsanzochi chiri ndi zotsatira zochiritsira zomwe zimapangitsa kuti izi ziwononge njira yowonjezerapo yomwe imayesera njira zowonjezereka: kuchepetsa zowonjezereka zowonjezera vuto (mankhwala kapena chakudya); Kuonjezerapo zinthu zopindulitsa zowonjezereka (mwachitsanzo, kugwirizana pakati pa anthu, zochitika zolimbitsa thupi); kusokoneza magulu ophunzitsidwa bwino (mwachitsanzo, kulimbikitsa zizolowezi zatsopano kuti alowe m'malo akale); ndi kulimbitsa mphamvu zoletsa (ie biofeedback), pochiza mowa / mankhwala osokoneza bongo komanso kunenepa kwambiri Volkow Et al. (2003b).

Mawu a M'munsi

Mgwirizano wina wa 17 ku Nkhani Yokambirana pazokambirana 'Kusowa kwa ubongo: zatsopano zatsopano.'

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