Neuropharmacology ya kudya mokakamiza (2018)

Philos Trans R Soc Lond B Biol Sci. 2018 Mar 19; 373 (1742). pii: 20170024. onetsani: 10.1098 / rstb.2017.0024.

Moore CF1,2, Panciera JI1,3,4, Sabino V1, Cottone P5.

Kudalirika

Khalidwe lokakamiza ndi kapangidwe kake ka transdiagnostic kamene kamapezeka munthawi zina za kunenepa kwambiri komanso zovuta pakudya, komanso pakupanga kwa 'kusuta'. Kudya mokakamiza kumatha kuganiziridwa monga zinthu zitatu: (i) kudya mopitirira muyeso, (ii) kudya mopitirira muyeso kuti muchepetse kukhumudwa, komanso (iii) kudya mopitilira muyeso ngakhale zitakhala zovuta. Njira za Neurobiological zomwe zimaphatikizira kupangika kwa zizolowezi zoyipa, kuwonekera kwakusokonekera, ndikuwonongeka kwa zoletsa kumaganiziridwa kuti kumayendetsa chitukuko ndikulimbikira kwakudya kosakhazikika. Njira zovuta za psychobehavioural izi zimayang'aniridwa ndi machitidwe osiyanasiyana a neuropharmacological. Apa, tikulongosola umboni waposachedwa womwe ukupangitsa machitidwewa kukhala okakamira pakudya, ndikuwasanjikiza m'zinthu zitatuzi. Kumvetsetsa bwino magawo a neuropharmacological a kudya mopitirira muyeso kumatha kupititsa patsogolo kwambiri mankhwala opatsirana pogonana. Nkhaniyi ndi gawo limodzi lazokambirana pamisonkhano 'Za mbewa ndi thanzi lam'mutu: kutsogolera zokambirana pakati pa asayansi oyambira ndi azachipatala'.

MAFUNSO:  chidutswa; chotsutsana; kudya; chizolowezi; chiletso choletsa; kuchotsa

Nkhaniyi ndi mbali ya zokambirana zokambirana za "Mphepete ndi umoyo waumphawi: kuyambitsa kukambirana pakati pa akatswiri a zachipatala.

1. Introduction

Kukakamizidwa kumatanthauzidwa ngati cholimba champhamvu, chosaletseka choyendetsa mkati kuti muchitepo kanthu, mosemphana ndi chifuniro cha munthu [1]. Pogwiritsa ntchito kudyetsa, khalidwe loyendetsa kudya limayesedwa ngati njira yowonongeka ya mitundu yambiri ya kunenepa kwambiri komanso matenda ovutika kudya, komanso kusokoneza zakudya [2-4]. Kulemera kwa thupi kumatanthauzidwa ngati thupi lolemera mthupi (BMI) lalikulu kapena lofanana ndi 30 kg m-2 [5], ndipo kaŵirikaŵiri zimakhala chifukwa cha kudya mopitirira nthawi [6]. Matenda obwera chifukwa chodya zakudya (BED) amatanthauzidwa ndi khalidwe losazolowereka komanso mopitirira muyeso m'magawo odziwika bwino, ambiri kuphatikizapo kudya chakudya chokoma (ie chakudya cha mafuta ndi / kapena shuga) [7]. Posachedwapa, chidwi chabweretsedwa ku zokonzedweratu zopangira zakudya, zomwe zimabwera kuchokera ku lingaliro lakuti zakudya zina zingakhale ndi zovuta zowonjezera, komanso kuti kudya kwambiri kungakhale khalidwe lopweteka [8]. Chizoloŵezi cha zakudya chimapezeka kudzera mu Yale Food Addiction Scale (YFAS), yomwe imagwiritsira ntchito njira zoyenera kugwiritsira ntchito Matenda okhudzana ndi Kugwiritsira Ntchito Magulu kuchokera ku Gawo la Kuzindikira ndi Kusanthula kwa Mental Disorders (DSM) kusinthidwa kuti ziwonetsetse makhalidwe oipa pa chakudya [7-9], ngakhale n'kofunika kuzindikira kuti lingaliro limeneli silinadziwidwe ngati vuto la boma mu DSM. Kunenepa kwambiri, BED ndi zakudya zolimbitsa thupi zimakhala zovuta kwambiri monga, mwachitsanzo, 40-70% ya anthu omwe ali ndi BED ndi ovuta kwambiri [10,11], ndipo chiwerengero cha zizoloŵezi zogwiritsira ntchito zakudya kumakhala pafupifupi 25% mwa anthu olemera kwambiri [12,13]. Choncho, ndikofunika kwambiri kumvetsetsa njira za neuropharmacological zomwe zimapanga njira zowonjezera zowonongeka, monga chizolowezi chodya kudya, kuti adziwe momwe angagwiritsire ntchito zovuta zothandizira.

Posachedwapa timaganizira zofunikira zitatu, osati zofanana, zomwe zimalongosola zoyenera kudya kudya: (i) kudya kudya, (ii) kudya mopitirira malire, komanso (iii) kudya mopanda mavuto ngakhale [2]. Phunziroli, timayesetsa kufufuza kumvetsetsa kwatsopano kwa machitidwe ambiri a neuropharmacological omwe akutsatila magawo atatu a chizoloŵezi chodya kudya. Cholinga cha ndondomekoyi, tikukambirana za umboni wochokera ku zinyama zomwe siziphatikizapo kuperewera kapena kusamalidwa kwa chakudya pokhapokha zitatchulidwa, ndikuyembekeza kutembenuzidwa kowonjezereka kwa neuropharmacology ya chizolowezi chodyera.

2. Njira zamaganizo ndi njira zogwirira ntchito zomwe zimayambira pachikhalidwe cha khalidwe lofuna kudya

Zinthu zitatu zomwe zimachitika kuti munthu azidya moyenera zimatha kupangidwira kuti asamayambe kudwala matendawa.2]. Chigawo choyambirira, kudya mopitirira muyeso, kumatanthawuza njira yomwe kamodzi kachitidwe kachitidwe kameneka kamakhala kovuta,14]. Mzinda wa Basal ganglia, malo akuluakulu ophunzirako, kuphatikizapo ventral striatum (kapena nucleus accumbens, NAc), omwe amadziwika kuti ali ndi mphoto ndi mphamvu, komanso zigawo zina zomwe zimagwiritsidwa ntchito pochita zinthu (monga dorsolateral striatum, DLS), zomwe zimaganiziridwa malo a mapangidwe a zizoloŵezi [14]. Mofanana ndi zomwe zakhala zikugwiritsidwa ntchito ponena za mankhwala osokoneza bongo, osasokonezeka, obwerezabwereza akulimbikitsanso dopaminergic system mu NAC ndi chakudya chokoma komanso zomwe zimagwiritsidwa ntchito potsata njira zowonongeka za dopaminergic zomwe zimayambitsa kupanga zizoloŵezi [15]. Choncho, kudya mokakamiza kumaganiziridwa kukhala ndi chizoloŵezi choyambitsa matenda, chomwe chimadutsa mwadzidzidzi, zochitika zolinga.

Chigawo chachiwiri, kudya kwambiri pofuna kuthetsa vuto la maganizo, limatanthauzidwa kukhala kuchita khalidwe (kudya chakudya chokoma) kuti athetse vuto la maganizo [16,17]. Izi zimayambira kale mu zizindikiro zokhudzana ndi vuto lopanikizika kwambiri (OCD), ndipo zingaphatikizepo kuchita nawo chizoloŵezi chodziletsa kuti athetse nkhawa, nkhawa kapena nkhawa asanayambe kuchita nawo kanthu kapena kupereka mpumulo ku zowawa, nkhawa kapena kupanikizika panthawi yomwe mukuchita. [7,18,19]. Njira zokhudzana ndi matenda a ubongo zomwe zimayambira pazigawozi ndi ziwiri: mkati mwa njira zowonongeka zimapangitsa kuti anthu asagwiritsidwe ntchito molakwika ndi mesocorticolimbic dopaminergic system, komanso njira zomwe zimagwiritsa ntchito njira zomwe zimaphatikizapo kugwiritsidwa ntchito kwa ubongo m'mayendedwe a amygdala [20]. Momwemo, kutengeka mtima kosasokonezeka maganizo kumaphatikizapo kuchepa kwa mphotho, kutaya zifukwa zowonjezera mphotho [17] ndi nkhawa yowonjezereka [20]. Choncho, kusintha kwa chakudya chokakamiza kumadodometsedwa chifukwa cha chakudya chomwe chimakhala ndi zinthu zolakwika zowonjezereka (ie kudya mopitirira malire)17,20-22]. Chofunika kwambiri, kuchotsa zinthu pambaliyi ndi kosiyana ndi tanthauzo lachikhalidwe cha kuchotsa mankhwala (mwachitsanzo, zizindikiro zowonongeka), ndipo zimatanthawuza kuti munthu ali ndi matenda oterewa, omwe amakhala ndi nkhawa,2,16].

Gawo lachitatu, kudya mopanda mavuto, limafotokoza kuwonongedwa kwa akuluakulu oyang'anira za zakudya zomwe zimawonedwa ngati kupitiliza kudya mopitirira muyeso chifukwa cha zotsatira zovulaza zakuthupi, zamaganizo ndi zachikhalidwe, komwe makhalidwe amatha kuchepetsedwa [23-25]. 'Kutaya chiwongolero' akuti awonetse zoperewera mu njira zoletsa zoletsa zomwe cholinga chake ndi kupondereza zosayenera. Njira zoletsa zoletsa zimasungidwa ndi makina akulu awiri mkati mwa preortal cortex (PFC), yodziwika ngati 'GO' system (dorsolateral PFC (dlPFC), anterior cingate (ACC) ndi orbitofrontal (OFC) cortices) ndi 'STOP' system ( ventromedial PFC, vmPFC). Kusasinthasintha kwa dongosolo la GO komanso kusachita bwino kwa STOP kumaganiziridwa kuti kumapangitsa kuti muchepetse mphamvu zowononga kudya mopitirira muyeso ngakhale zitakhala zovuta [26].

3. Mapulogalamu a Neuropharmacological omwe amachititsa kuti zinthu zikhale zovuta kudya

(a) Dopamine dongosolo

Njira ya mesocorticolimbic dopaminergic imathandiza kwambiri pa khalidwe lolimbikitsana, ndipo kupweteka kwake kumagwiritsidwa ntchito kuti zitha kugwiritsidwa ntchito kuzinthu zitatu zomwe zimadalira kudya: kudya mopitirira muyeso, kudya mopweteketsa mtima komanso kudya mopweteketsa ngakhale zovuta. Mu maphunziro opititsa patsogolo, kupanga mapangidwe ka chizolowezi kumafuna chizindikiro cha dopaminergic m'kati mwa DLS [27]. Dopamine mtundu-1 receptor (D1R) neurons, omwe amapanga mwachindunji, njira ya striatonigral, galimoto yopititsa patsogolo dendritic excitability [28], ndi kulamulira kwake kofanana poyerekeza ndi dopamine mtundu-2 receptor (D2R) kuwonetsera ndi njira imodzi yokha ya kapangidwe ka chizolowezi chogwiritsa ntchito mankhwala osokoneza bongo ndi zakudya zokoma [29,30]. Nyama zomwe zili ndi mbiri yopezera chakudya chokoma zimasonyeza khalidwe lozoloŵera la kudya, pamene maulamuliro odyetsa amatha kukhala ndi cholinga-chakudya chotsogoleredwa chotsatira pambuyo poyerekeza [29]. Mu DLS, nyama zomwe zimazoloŵera kudya kwambiri zawonjezeka c-fos activation mu non-D2R-containing neurons, kutanthauza kuti D1R neurons amasinthidwa mwakhama kudya [29]. Kuwonjezera apo, majekeseni a SCH-23390, wotsutsa D1R, kulowa mu DLS amalephera kudya chakudya [29] ndi kubwezeretsa kuzindikirika kwa zinyama zinyama zomwe zili ndi mbiri ya chakudya chokoma.

M'kupita kwa nthawi, kudalira kwambiri ma mesocorticolimbic dopaminergic system kuchokera ku chitsimikiziro cha chakudya chamtengo wapatali, chokoma mtima chimagwiritsidwanso ntchito kuti chiwonongeke / kuchepetsa, zomwe zimapangitsa kuti ahedonia ayambe kusokonezeka ndi zofooketsa [16,21]. Kudyetsa kudya moyenera kumakhala ngati njira yodzipangira mankhwala kuti athetse zizindikirozi. Pali umboni wina wosonyeza kuti pali dopamine yosavomerezeka mwa anthu olemera kwambiri, monga kupezeka kwa D2Rs [31-33] komanso kuyankha mafunso osokoneza bongo ku chakudya chokoma [34] apezeka kuti akugwirizana kwambiri ndi BMI. Mofananamo, makoswe amaloledwa kuti akhale olemera kwambiri-omwe amawonetseredwa kuti awonongeke mphoto yomwe ikugwira ntchito isanakwane [35] ndikutsatira kukula kwa kunenepa kwambiri [36]. Pambuyo popita kwa nthawi yaitali chakudya chokwanira, mafuta amphongo amawonetsanso khalidwe loperekera kudya komanso amachepetsa D2R zakupha [36]. Kugogoda pansi pa D2Rs mkati mwa mkaka wa makoswe musanayambe kudya zakudya zamtengo wapatali kunapeza kuwonongeka kwa malipiro owonjezereka ndikupangitsa kuti anthu azikhala ndi makhalidwe okakamiza [36], kusonyeza mbali yogwira ntchito ya D2R yoberekera mwa kudya mokakamiza. Choncho, kusokonezeka kwa dopamine chizindikiro kungayambitse kudya mopitirira malipiro a mphotho. Lisdexamfetamine (LDX), pulojekiti ya d-Amphetamine, ndi mankhwala okhawo omwe amavomerezedwa kuchiza BED, ndipo amagwiritsira ntchito kupititsa patsogolo monoamine, kuphatikizapo dopamine. LDX yasonyezedwa kuti ichepetse kusokoneza kudya mwa makoswe [37] komanso anthu, monga anayesedwa ndi Yale-Brown osaganizira kwambiri kuti asinthidwe kudya (Y-BOCS-BE) [38]. Ulamuliro wa LDX umapitiriza kuwonjezeka mwakuya kwa dopamine m'matumbo [39], yomwe ikhoza kubwezeretsa pansi dopaminergic zizindikiro zomwe zimapangitsa kuti munthu asamangokhalira kudya mopitirira malire kuti athetse vuto la maganizo.

Zowonongeka kapena njira zogwiritsira ntchito mapulaneti a prefronto-cortical dopaminergic akuganiza kuti zimapangitsa kuti asapitirize kulamulira zomwe zimapangitsa kuti azidya mopitirirabe ngakhale zotsatira zake zoipa [4,40]. Pakati pa PFC, makamaka mu OFC ndi ACC, kuchepa kwa dopamine ntchito yoledzera ndi kunenepa kwambiri kumagwirizanitsidwa ndi kuchepetsa kutetezedwa koletsa [41]. D2Rs yochepa kwambiri, chifukwa cha kunenepa kwambiri, imagwirizananso ndi kuchepa kofanana pa ntchito ya prefrontal [32,42]. Kuwonjezera apo, mwina powonjezera kuchuluka kwa dopamine mu PFC [39,43], LDX yowonjezera mavutidwe oletsa kuletsa anthu mwa BED [38] zomwe zimagwirizana ndi kudya mopanda mavuto. Choncho, powonjezera kuchuluka kwa dopamine m'magulu a basal komanso malo omwe amakonda, LDX ikhoza kubwezeretsanso vuto la dopaminergic lomwe limagwirizanitsidwa ndi zinthu ziwiri ndi zitatu zomwe zimakhala zovuta kudya.

(b) Opioid dongosolo

Mu-ndi kappa-opioid receptor subtypes zakhala zikukhudzidwa ndi khalidwe loperekera kudya mwa madigiri osiyanasiyana. Mchitidwe wa o-opioid umadziwika kawirikawiri kuti umathandiza kuti azidyetsa, ngakhale posachedwa posachedwapa watenga chidwi monga wotsogolera wotsitsimula chakudya chokwanira ndi chakudya chogwirizana [44-46], othandizira kwambiri kusintha kwa zotsatira-zotsatila motsatizana ndi zolimbikitsa, zomwe zimakonda kudya [47]. Kwa anthu omwe ali ndi BED, munthu wotsutsana ndi opioid receptor antkistro GSK1521498 adachepetsa kugwiritsidwa ntchito kwa chakudya chokoma komanso chidwi cha chakudya chokoma [48,49]. Naltrexone, wotsutsana ndi opioid receptor antagonist, adachepetsa mphuno zokhudzana ndi zakudya pazinthu zabwino, monga momwe kusinthira kwa ACC ndi dorsal striatum [50]. Mayesero osinthika omwe akuyendetsa naltrexone asonyeza zowonongeka pa kudya chakudya chambiri [51]. Kuphatikizidwa kwa naltrexone ndi bupropion, norepinephrine-dopamine reuptake inhibitor, ndi imodzi mwa njira zabwino kwambiri [52,53], kuwonetsa kuti phindu la mankhwala osokoneza bongo amalumikizana ndi njira zambiri zokhudzana ndi matenda opatsirana pogwiritsa ntchito mankhwala amodzi.

Kusintha kwa ma-opioid receptor machitidwe amakhalanso panthawi yochotsa chakudya chokoma, ndipo amatha kutenga nawo mbali pa vuto la maganizo omwe amachititsa kuti munthu asadye zakudya zoyenera. Mphuno zomwe zimapatsidwa mwayi wothandizana ndi sucrose zimasonyeza kuti mu-opioid receptor imamangirira komanso imalembetsa ekephalin mRNA mu NAC, yomwe imamasuliridwa kuti ikuwonetseratu njira yowonjezereka ya kumasulidwa kwa opioid kwa nthawi yayitali [54]. Chifukwa chake, dziko lotha kuchoka likhoza kuchepetsedwa mu makoswe kudzera mu kuyang'anira mdani wa mu-opioid, naloxone, zomwe zimayambitsa zizindikiro zaumtima ndi khalidwe losautsa [55]. Chithandizo cha Naloxone chinasonyezedwanso kuti chimapangitsa dontho la extracellular dopamine (-18 ku 27%) ndi kuchulukitsa acetylcholine kumasulidwa (+ 15 kwa 34%) mu makoswe othamangitsidwa ndi sucrose ndi magetsi odyetsa [55].

Palinso umboni wa machitidwe a mu-and kappao- opioid m'thupi mwa PFC pakukakamiza kudya, kuyerekezeredwa kuti ziwonongeke mwa njira zowonongeka zomwe zimayambitsa kudya mopanda mavuto. Kupweteka kwa opioid receptor mu vmPFC inasonyezedwa kuti onse akulimbikitsa kudyetsa [56] ndikupangitsani zolepheretsa kuletsa [57], zomwe zinadza chifukwa cha kuchulukitsidwa kwa chakudya chokhudzidwa ndi kuwonongera khalidwe labwino [58]. Kuwonjezera pamenepo, mkati mwa PFC (mPFC), kuyang'anira naltrexone-kudalira moyenera ndi kuchepetsa kugwiritsiridwa ntchito, ndi cholinga cha chakudya chokoma mwachitsanzo chodyera nyama [59,60]. Mosiyana ndi zimenezi, naltrexone microinfusion mu NAC osakakamizika kudya zakudya zokhazokha komanso chakudya chokoma [60], kusonyeza kusankhidwa kwa njira zogwiritsira ntchito opouraal opioid signaling (motsutsana ndi kubala) pa kudya kwambiri chakudya chokoma. Kuwonjezera apo, nyama zomwe zili ndifupipafupi zowonjezera zakudya zowonjezera zinawonetsetsa kuti jini ikuyimira peptide pro-dynorphin (PDyn) ndi kuchepetsedwa kwa jekeseni wa pro-enkephalin (PEnk) mu mPFC. Zotsatira izi zimasonyeza kuti njira zogwiritsira ntchito mankhwala opangidwira opioid zimathandiza kuti kudya zakudya zowonongeka, mwinamwake kupyolera mu njira zowonongeka zowonongeka [56].

(c) Chinthu cha corticotropin-release factor (CRF) -CRF1 receptor system

Pali umboni wokhutiritsa wakuti chinthu chowonjezera cha corticotropin-release factor (CRF) -CRF1 receptor system ndicho choyendetsa galimoto yokakamiza kuti athetse vuto la maganizo [20,61]. Zakudya zamakono zosawerengeka, zomwe zimakhala zosavuta komanso zowonongeka zimagwiritsidwa ntchito kuti zipeze pulogalamu ya CRF-CRF1 receptor [20], adawona ngati kuwonjezeka kwa CRF pakati pa mtima wa amygdala (CeA) wa nyama panthawi ya kudya zakudya zosavuta [20,62]. Kukhazikitsidwa kwa dongosolo la CRF-CRF1 kumaganiziridwa kuti pamapeto pake kumatulutsa mkhalidwe wosasangalatsa womwe umawoneka pakusiya womwe umatchedwa 'mbali yakuda' ya chizolowezi [17,20,61]. Makoswe okhala ndi mbiri ya chakudya chosakanikirana amasonyeza nkhaŵa-ndi makhalidwe opsinjika maganizo ngati chakudya chokoma sichinali kupezeka (ie kutaya) [20,21,63,64]. Kuwonjezeredwa kwazowonjezera kunapangitsa kuti pakhale chakudya chokoma kwambiri komanso kuthetsa vuto loipa la maganizo [21]. Choncho, kayendetsedwe ka CRF1 chotsutsana ndi R121919 mu CeA inalepheretsa khalidwe lopanda nkhawa komanso lopangitsa munthu kuti adye chakudya chopatsa thanzi.20,61].

Chipangizo cha CRF-CRF1 pamutu wa bedi wa stria terminals (BNST) chingathenso kudya zakudya zolimbitsa thupi zomwe zimayambitsidwa ndi nkhawa muchitsanzo chowombera ndi mbiri ya chakudya choletsa zakudya [65]. BNST ikukhudzidwa ndi kupanikizika, ndipo imayambitsidwa ndi njira yowonjezera ya chakudya chokoma mwachitsanzo cha nyama chomwe chimagwiritsanso ntchito zolemetsa zazing'ono [65]. Kulowetsedwa kwa R121919 mu BNST kunatha kulepheretsa kudya zakudya zolimbitsa thupi; kupyolera mwa mbiriyakale ya choletsa chakudya [65]. Mu zosiyana ndi zinyama zosiyana siyana zomwe zimayambitsa matenda, zimakhala zovuta kuti ubongo umve mawu a CRF mRNA mu BNST ya kudya zakudya zolimbitsa thupi, koma osati makoswe odyera [66]. Choncho, CRF mu BNST ikhoza kuyesetsanso kudya zakudya zolimbitsa thupi zomwe zimayendetsedwa ndi zovuta ndipo zingayambane ndi CeA kuti ziwonongeke.

Kutsogozedwa ndi umboni wolonjeza wamitundu yazinyama, mu 2016, kafukufuku wosasinthika, wakhungu kawiri, wowongoleredwa ndi placebo adasanthula zovuta za CRF1 wotsutsana ndi pexacerfont pakudya komwe kumayambitsa kupsinjika kwa omwe amadya omwe ali ndi thanzi labwino la achikulire. Ngakhale kuti kafukufukuyu adathetsedwa koyambirira pazifukwa zosagwirizana ndi zovuta zilizonse za pexacerfont, ofufuza adapeza zotsatira zabwino pakuchepetsa kuchuluka kwamavuto azakudya / chidwi chogwiritsa ntchito YFAS, komanso kuchepa kwa kulakalaka ndi kudya, ngakhale osadalira kupsinjika [67]. Ngakhalenso ndi kuchepetsa kukula kwazitsulo, kuyesedwa kwachipatalachi kunawonetsa mphamvu zabwino za antchito a CRF1 pofuna kuchepetsa chilakolako cha zakudya m'zambiri za dieters,67]. Otsutsana a CRF1 akufunsidwa kukhala ovuta kwambiri m'mabungwe ena a matenda aumphawi makamaka kuwonetsa kuti CRF isasinthidwe; Choncho, mayesero amtsogolo omwe angayang'anire zogwira mtima za antchito a CRF1 omwe ali ndi vuto linalake, zochitika, kapena magulu a odwala akhala akuitanidwa [68,69].

(d) Mchitidwe wa Cannabinoid receptor 1

Dongosolo la cannabinoid receptor-1 (CB1) receptor mkati mwa amygdala limathandizira kusakhazikika kwamaganizidwe okhudzana ndi kudya mokakamiza. Pogwiritsa ntchito mankhwala osokoneza bongo, kuledzera mobwerezabwereza ndikuchoka kumabweretsa ntchito ya endocannabinoid mkati mwa ma circy amygdalar, omwe amadziwika kuti ndi 'buffer system' ku CRF-CRF1 receptor system overactivation [70,71]. Mofananamo, panthawi ya kudya zakudya zosavuta, matendawa amatha kuwonjezeka mu CeA [72]. Kutsekemera kwasinthidwe ndi Kea komwe kumakhalako kwa CB1 kulandira chithandizo cha agonist chosakanikirana ndi chikhalidwe cha agonist chokhalira ndi nkhawa komanso matenda a anorexia a zakudya zoyenera kudya pa nthawi yochotsa chakudya chokoma [72,73]. Chofunika kwambiri, rimonabant sichinawonjezere nkhawa-monga khalidwe la nyama zowonongeka [72,73]. Choncho, njira ya amygdala yotchedwa endocannabinoid imayesedwa kuti ikhale yolembedwera panthawi yochotsa chakudya chokoma ngati njira yothetsera nkhawa. Momwemonso, matenda othetsera matendawa amathandiza kuchepetsa vuto la maganizo lomwe likukhudzana ndi kuchotsa chakudya, ndipo mankhwalawa amachititsa kuti anthu asamakhale ndi chakudya chokwanira pamene akuyesera kuchepa (mwachitsanzo, kudya). Izi zimatha kufotokozera kuopsa kwa zotsatira za matenda opatsirana pogwiritsa ntchito mankhwala osokoneza bongo omwe amachititsa kuti odwala ambiri azidwala kwambiri [74].

Mchitidwe wa CB1 umathandizanso kudya mopitirira muyeso ngakhale zovuta. Mu makoswe omwe ali ndi mbiri yopezera chakudya chokoma, zakudya zamchere zimachepetsa chakudya chokwanira kwambiri kuposa chakudya chowongolera komanso amalepheretsa kudya chakudya chokoma pamayesero /75]. Ngakhale malo enieni omwe akutsutsana ndi zotsatirazi sadziwika, ali ndi rimonabant yowonjezera makateni amtundu monga dopamine mu PFC [76], motero kubwezeretsanso zovuta zomwe zimachitika mu njira zoletsa kutetezera zomwe zimagwirizanitsidwa ndi chizindikiro chochepa chapopalal dopamine.

(e) dongosolo la Glutamatergic

Maphunziro awiri a glutamatergic (a-amino-3-hyrxy-5-methyl-4isoxazolepropionic acid (AMPA), ndi N-methyl-d aspartate (NMDA) receptors) apezeka kuti akukhudzidwa ndi makhalidwe odyetsa, makamaka kudya ndi kudya mopitirira muyeso ngakhale zotsatira zovuta. Kudya chakudya chokoma kumadalira ma AMPAR mu DLS, imodzi mwa malo akuluakulu a ubongo omwe amagwira ntchito popanga zizolowezi. Kulowetsedwa kwa amphasana a AMPA / kainate receptor, CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) kulowa mu DLS inalepheretsa kudya kachitidwe, kubwezeretsa mphamvu zowononga chakudya chokoma [29].

Ma NMDAR amaganiza kuti akhoza kuphatikizidwa ndi zomwe zimayambitsa kudya mopitilira muyeso ngakhale zitakhala zovuta chifukwa cholumikizana ndi njira zoletsa zoletsa. Memantine, wotsutsana ndi NMDAR wosapikisana, adachepetsa kudya kwambiri komanso 'kudziletsa' pamakhalidwe oyeserera poyeserera, komwe kungayesedwe ndi anthu [77]. Chikumbutso chinasonyezedwanso kuti chichepetse kutengeka ndi kupititsa patsogolo chidziwitso cha chidziwitso kwa ogulitsa okakamiza [78], chizoloŵezi chokhala ndi chizoloŵezi chokhala ndi zofanana ndi zovuta kudya. M'magulu odyetsa odyetserako mankhwala omwe amatha kupeza chakudya chamtundu uliwonse tsiku lililonse, kachilomboka kakang'ono ka memantine mu khungu la NAc kamachepetsa kudya monga kudya [23], kusonyeza kuti dongosolo la NMDAR mu chipolopolo cha NAc likuyendetsedwa mwachangu kuti adye makoswe. Ntchito mkati mwa NAc ikuyendetsedwa ndi ziwonetsero zowonongeka kuchokera ku PFC [79-81]. Memantine inalepheretsanso kufunafuna zakudya komanso kusala kudya chakudya chokoma [23].

Mukatikati mwa NAC, kudya kwambiri kwa mafuta kunayambitsa kunenepa kunayambitsa kusinthika kwapadera m'matumbo, kuphatikizapo kuwonjezeka kwa mphamvu zowonjezereka m'matumbo, kutaya mphamvu kwa mphamvu zoterezi kuti zikhale ndi nthawi yaitali yovutika maganizo komanso mitsempha yothamanga ya NMDA [82]. Kulephera kwasinthati kunayanjanitsidwa ndi khalidwe lokonda kusuta, kuphatikizapo kuwonjezereka, kukhuta kwambiri ndi kufunafuna chakudya chowonjezeka pamene chakudya sichinapezeke [82]. Kuwonetsa kosawonongeka pamagwiridwe a cortico-accumbens amachititsa kuti asokoneze chidziwitso chodziwika bwino chokhudzidwa ndi chidziwitso ndi kulepheretsa kuyankha [83], mwinanso chifukwa cha kusowa mphamvu pa kudya ndi kudya mopanda mavuto.

(f) Chizindikiro cha Sigma-1

Zizindikiro za Sigma-1 (Sig-1Rs) zakhala zikuphatikizidwa mu matenda opatsirana omwe amachititsa kuti anthu azizunza [84-90], komanso awonetsedweratu kuti azisamaliranso mopitirira malire ngakhale kuti zotsatira zake ndi zoipa [59]. Zinyama zokhudzana ndi chakudya chokoma, tsiku ndi tsiku, zosakanikirana ndi mankhwala a Sig-1R BD-1063 zatsala pang'ono kuchepetsa chakudya chodalirika chodalira [59]. Kuonjezerapo, mu phunziro lomwelo, BD-1063 inaletsa khalidwe loyenera la kudya pakadakhala zovuta [59]. Kuwongolera, kudya mokakamiza makoswe kunakulirakulira kuwirikiza kawiri mu mapuloteni a Sig-1R mu ACC [59]. Motero, dongosolo la prefrontal Sig-1R lingakhale ndi gawo la kudya mokakamiza [59], mwinamwake chifukwa cha kusintha kwa dopamine ndi chizindikiro cha glutamate [91,92].

(g) Cholinergic system

Kusayenerera kwa acetylcholine (ACh) kuzindikiritsa mu NAC ndi chizindikiro cha kuchotsa kumwa mankhwala osokoneza bongo [93], komanso zawonetsedwa panthawi yopuma zakudya zosavuta [55], kutanthawuzira dongosolo lino ngati mtsogoleri wofunikira muzochitika zosokoneza maganizo. Mofananamo, mu makoswe omwe amatha kupeza njira yowonjezeramo mankhwala ndi chow chakudya, amatsatiridwa ndi 12 h omwe alibe chakudya chokwanira kuti azidya mowa, komanso nthawi yomweyo kuchotsedwa kwa naloxone kunayambitsa kuchuluka kwa ACs mu NAC [55,94]. Izi zinawonjezeredwa ndi ACh komanso zinachepetsedwa ndi chizindikiro cha dopaminergic, komanso zizindikiro zowonongeka komanso khalidwe losautsa [55]. M'kati mwa NAc, kuyanjana kwa ntchito pakati pa dopaminergic ndi cholinergic systems kumakhala kovuta kwambiri pa zokakamiza kudya [95,96], makoswe osowa aja anasiya kudyetsa ngati malire pakati pa awiriwo adasinthira kuti awonongeke [97]. Makhalidwe apamwamba a ACh mu NAC amachititsanso kusokonezeka panthawi yochepa yotchedwa dopamine [96], ndipo motero zingapangitse kusokonezeka kwa kuchotsedwa.

(h) Tsatirani dongosolo la receptor-1 la amine

Umboni waposachedwapa umasonyeza kuti dongosolo la amine-logwirizana ndi receptor-1 (TAAR1) likugwira nawo ntchito yodetsa nkhaŵa mopitirirabe ngakhale zotsatira zovuta, mwinamwake kudzera mwa maulendo a PFC. TAAR1 ndi G-mapuloteni ogwirizana ndi receptor omwe amachitidwa ndi amines komanso ena amtundu wotchedwa dopamine ndi serotonin [98]. Ndondomeko ya TAAR1 yatsatiridwa posachedwapa pa umboni wa ntchito yake pakulamulira zochita za psychostimulants [99] komanso khalidwe lodzidzimutsa [100]. Kafukufuku waposachedwapa [101] anafufuza ntchito ya TAAR1 kawirikawiri ndikudyera makoswe amatsenga akutsatira chakudya chamtundu uliwonse. Majekeseni owoneka bwino a TAAR1 agonist RO5256390 mokwanira ndipo mwachindunji analetsedwa kudya chakudya chokoma, malingaliro a malo okonda chakudya chokoma, komanso kudya zakudya zolimbitsa thupi [101]. Kuwonjezera pamenepo, nyama zodyera zatsika puloteni kutchulidwa kwa TAAR1 receptors mu PFC [101]. Majekeseni a RO5256390 amatchulidwa mwachindunji mu infralimbic, koma osati prelimbic, cortex inachititsa kuti anthu asamale kudya zakudya zamphongo [101]. Zotsatira izi zimasonyeza kuti TAAR1 ikhoza kukhala ndi chiletso choletsa kudyetsa khalidwe, ndipo kutayika kwa ntchitoyi kungakhale ndi udindo wokakamiza kudya. N'zochititsa chidwi kuti TAAR1s imathandizanso ndi amphetamine [98], yogwira ntchito ya metabolite mu BED achire LDX [102]. LDX ndi TAAR1 agonism, motero, amagwiritsa ntchito njira zofanana zobwezeretsa chilakolako choyendetsa chisamaliro cha makhalidwe abwino.

(i) Chipangizo cha Serotonin

Serotonin (5-hydroxytrptamine, 5-HT) kupatsirana kwadzidzidzi kwaphunzira kwambiri pakudyetsa ndi kudyetsa zakudya, kuphatikizapo BED [103], ndipo wagwirizanitsidwa ndi zizoloŵezi zochititsa manyazi ku OCD ndi bulimia nervosa [104,105]. Odwala omwe ali ndi BED anasonyeza kuchepetsedwa kwa 5-HT mu hypothalamus, otsika kwambiri 5-HT yotumiza katundu mkatikatikatikati, ndi apamwamba 5-HT2a ndi 5-HT5 omanga mu NAC shell [106-108]. Mankhwala otchedwa serotonergic, monga seleotonin osakanikirana, amawerengedwa ngati njira zothandizira BED [109,110]. Pali mbali yodziwikiratu kwa dongosolo la serotonin mu nkhaŵa ndi matenda osokonezeka; ndi kuchepetsa ntchito ya 5-HT inapezeka kuti inaneneratu kuti simungathe kudya chakudya chambiri [111]. Njira imodzi yothetsera mankhwala osokoneza bongo 5-HT inapezedwa kudzera mwa 5-HT2c kulandira mankhwala a dopamine neurons mu ventral tegmental area (VTA) [112]. Mankhwala olemera kwambiri a lorcaserin (a 5HT-2c osakaniza agonist) awonetseredwa kuti achepetse chakudya cha homeostatic komanso chakudya cholimbikitsira kupyolera mwa VTA 5-HT2c kuyambitsa [113]. d-Amphetamine, yomwe imaletsa monoamine reuptake, kuphatikizapo serotonin, yasonyezedwa kuonjezera kuika kwa 5-HT mu striatum [114]. Choncho, LDX ikhoza kubwezeretsanso ntchito yotentha yomwe imathandiza kuti athe kuchepetsa khalidwe la kudya.

(j) Orexin

Udindo wa orexin (hypocretin) umakhala ndi chizoloŵezi chokhala ndi makhalidwe oledzera [115], kuphatikizapo kudya mowa mwauchidakwa komanso kudya chakudya chokakamiza, mwinamwake mwa kugwiritsa ntchito chakudya chokoma mtima komanso khalidwe lofuna kudya chakudya [116]. Orexin-1 receptor (OX1R) wotsutsa amasonyezedwa kuti asachepetse kudya mowa kwambiri kudya chakudya chokoma [117,118]. Kuphatikizanso apo, orexin neurons mu lateral hypothalamus amavomerezedwa ndi chakudya cues [119,120], ndikugwirizanitsa zowonjezera zomwe zimapangitsa kuti azidya [119] ndi kubwezeretsedwa-kubwezeretsedwanso kwa khalidwe lofunafuna chakudya [120]. Motero, orexin kuwonetsera mwachindunji kumapangitsa kuti anthu azikhala ndi zakudya zogwiritsira ntchito zizoloŵezi zowonongeka, ndipo amatha kugwira nawo ntchito yowonongeka, yozoloŵera kudya.

Pali zodziwika za zotsatira za orexin dongosolo pa kuvutika maganizo ndi khalidwe lodzidetsa [121]; ngakhale kuti izi sizinaphunzire mozama pa nkhani yochotsa chakudya chokoma. Komabe, mu zinyama zodyera kudya zomwe zimaphatikizapo mbiri ya caloric restriction ndi / kapena nkhawa zapeza kuwonjezeka kwa orexin kufotokoza mu lateral hypothalamus [117,122]. Zimagwirizanitsa kuti chiletso cha caloric ndi nkhawa zimagwirizanitsa kuti zikonzekerere orexigenic njira ndikulimbikitsanso kudya. Infusions a OX1Wotsutsana amalepheretsa kudya mowa mumsampha uwu wa choletsedwa kupsinjika-kudyetsedwa kudya [117]; kuwonetsa kuganiza molakwika pokakamiza kudya kuti athetse nkhawa. Komabe, tisaiwale kuti kudziletsa komweko kungayambitse matenda omwe amachititsa kuti anthu azidya zakudya zolimbitsa thupi [123,124] osiyana ndi mbiri ya kufotokozera ndi kudya chakudya chokoma [23,59,64].

4. Kukambirana

Matenda omwe amachititsa kuti munthu asamadye zakudya zamadzimadzi amachititsa kuti azikhala ndi matenda osiyanasiyana m'magulu osiyanasiyana a neurotransmitter ndi neuropeptide. Pali zambiri zomwe zatsala pang'ono kumvetsa za zovuta za makhalidwe amenewa ndi zovuta zokhudzana ndi matenda, komanso matenda. Kukonzekera kwa kudya mokakamizidwa kwangoyamba kuchitidwa chidwi, ndipo kukangana pachitanthawuzo cha chizoloŵezi chokakamiza ndi njira yake yothetsera vutoli ndipitirizabe. Choncho, kafukufuku wamakono akugogomezera njira zomwe masiku ano zimaganizira za neuropharmacological njira zomwe zimayambitsa zovuta kudya, monga momwe posachedwapa zalembedwera ndi olemba [2]. Kuwongolera pakudya mokakamiza mwa kuwonjezeka kwa kafufuzidwe kafukufuku ndi kukambirana pakati pa asayansi kudzawatsogolera ku umboni wa machitidwe ena owonjezera.

Matenda ovuta, monga kunenepa kwambiri ndi matenda ovutika, amafunika kuchita khama kuti apeze kafukufuku wokhudzana ndi khalidwe labwino (mwachitsanzo, zizoloŵezi, nkhawa, kutetezetsa mphamvu), makamaka kofunikira kwambiri kuwonjezera kunenepa kwambiri, matenda oopsa kwambiri, kumene maphunziro ambiri apeza zotsatira zotsutsana ndi neuropharmacological [125]. Pomalizira pake, kufotokoza mankhwala ochiritsira omwe amachititsa chinthu chimodzi kapena zingapo zomwe zimapangitsa munthu kukhala ndi khalidwe lodziletsa kwambiri, amakhala ndi mphamvu zothandizira anthu mamiliyoni ambiri omwe ali ndi vuto la kunenepa kwambiri komanso / kapena matenda.

Kupezeka kwa deta

Nkhaniyi ilibe deta yina.

Zopereka za olemba

Olemba onse anapanga zopereka zowathandiza kulera ndi kulinganiza kwawongosoledwe. CM ndi JP analemba zolembedwazo, ndipo PC ndi VS zinakonzanso mwatsatanetsatane kuti zikhale ndi nzeru. Olemba onse apereka chivomerezo chomaliza cha kuwonetsera kwake

Zosangalatsa zovuta

Timalengeza kuti tilibe mpikisano.

ndalama

Ntchitoyi inathandizidwa ndi National Institutes of Health (kupereka manambala DA030425 (PC), MH091945 (PC), MH093650 (VS), AA024439 (VS), AA025038 (VS) ndi DA044664 (CM)); Peter Paul Career Development Professor (PC); McManus Charitable Trust (VS); ndi Bungwe la Burroughs Wellcome (CM) kupyolera mu Transformative Training Program mu Addiction Sciences [nambala ya 1011479]. Zomwe zili m'bukuli ndizo udindo wa olemba ndipo sizikuimira ziwonetsero za bungwe la National Institutes of Health.

Zothokoza

Tili othokoza ku Royal Society chifukwa chothandizira pamtengo wopezeka pamsonkhanowu 'Wa mbewa ndi thanzi lam'mutu: kutsogolera zokambirana pakati pa asayansi oyambira ndi azachipatala omwe adayitanitsidwa ndi Amy Milton ndi Emily A. Holmes.

Mawu a M'munsi

  • Adalandira August 4, 2017.
http://royalsocietypublishing.org/licence 

Lofalitsidwa ndi Royal Society. Maumwini onse ndi otetezedwa.

Zothandizira

  1. ↵
    Wokakamiza (nd). Mu dikishonale ya pa intaneti ya Merriam-Webster (11th ed.). Kuchokera ku http://www.merriam-webster.com/dictionary/compulsive.
  2. ↵
    1. Moore CF,
    2. Sabino V,
    3. Koob GF,
    4. Cottone P

    . Zokwanira za 2017: Kuwonetsa umboni kwa kukakamiza kumanga. Neuropsychopharmacology 42, 1375-1389. (onetsani: 10.1038 / npp.2016.269)

    1. Davis C

    . 2013 Kuchokera pa kudya mopitirira muyeso kuti 'zakudya zowonjezera': kukakamizidwa kwakukulu ndi kuuma. Zosamba za ISRN. 2013, 435027. (onetsani: 10.1155 / 2013 / 435027)

  4. ↵
    1. Volkow ND,
    2. Wang GJ,
    3. Tomasi D,
    4. Wowonongeka RD

    . 2013 Kukula kwa chikhalidwe cha kunenepa kwambiri. Ubweya. Psychiatry 73, 811-818. (onetsani: 10.1016 / j.biopsych.2012.12.020)

  5. ↵
    Bungwe la World Health Organization. Kuchuluka kwa 2000: kuteteza ndi kuyendetsa mliri wa padziko lonse. Lipoti la bungwe la WHO. Bungwe la World Health Organization. 894, i-xii, 1-253.
  6. ↵
    1. Hill JO,
    2. Wyatt HR,
    3. Reed GW,
    4. Peters JC

    . Kulemera kwa 2003 ndi chilengedwe: kodi timachokera kuti? Science 299, 853-855. (yani: 10.1126 / sayansi.1079857)

  7. ↵
    Association of Psychiatric Association. Buku la 2013 lofufuza ndi chiwerengero cha matenda a m'maganizo, 5th edn. Washington, DC: Association of American Psychiatric Association.
  8. ↵
    1. Gearhardt AN,
    2. Corbin WR,
    3. Brownell KD

    . 2009 Yotsimikiziridwa koyambirira kwa Yale chakudya choyendetsa msinkhu. Kudya 52, 430-436. (onetsani: 10.1016 / j.appet.2008.12.003)

  9. ↵
    1. Gearhardt AN,
    2. Corbin WR,
    3. Brownell KD

    . 2016 Kukula kwa Yale zakudya zowonjezera kukula kwa 2.0. Psychol. Kusokoneza. Behav. 30, 113-121. (yani: 10.1037 / adb0000136)

  10. ↵
    1. Ma Dingemani AE,
    2. van Furth EF

    . 2012 Kudya zakudya zolimbana ndi matenda a psychopathology m'thupi lolemera komanso olemera kwambiri. Int. J. Idyani. Kusokonezeka. 45, 135-138. (yani: 10.1002 / idyani.20905)

  11. ↵
    1. Kessler RC et al

    . 2013 Kufalikira ndi mgwirizano wa matenda oledzeretsa mudziko lapansi bungwe la zaumoyo padziko lonse lapansi. Ubweya. Psychiatry 73, 904-914. (onetsani: 10.1016 / j.biopsych.2012.11.020)

  12. ↵
    1. Davis C,
    2. Curtis C,
    3. Levitan RD,
    4. Carter JC,
    5. Kaplan AS,
    6. Kennedy JL

    . Umboni wa 2011 woti 'kusokoneza bongo' ndi mtundu wovomerezeka wa kunenepa kwambiri. Kudya 57, 711-717. (onetsani: 10.1016 / j.appet.2011.08.017)

  13. ↵
    1. Pursey KM,
    2. Stanwell P,
    3. Gearhardt AN,
    4. Collins CE,
    5. Mizere TL

    . 2014 Kukula kwa chizoloŵezi cha zakudya monga kuyesedwa ndi Yale zakudya zowonongeka: kuwonongeka mwatsatanetsatane. Mavitamini 6, 4552-4590. (onetsani: 10.3390 / nu6104552)

  14. ↵
    1. Everitt BJ,
    2. Robbins TW

    . 2005 Neural systems zowonjezeretsa kuledzera: kuchokera ku zochita mpaka ku chizoloŵezi. Nat. Neurosci. 8, 1481-1489. (onetsani: 10.1038 / nn1579)

  15. ↵
    1. Everitt BJ,
    2. Robbins TW

    . Kugwiritsa ntchito mankhwala osokoneza bongo a 2016: Kukonza zochita kumangoyamba zaka khumi. Annu. Rev. Psychol. 67, 23-50. (yani: 10.1146 / annurev-psych-122414-033457)

  16. ↵
    1. Koob GF,
    2. Volkow ND

    . 2010 Neurocircuitry yakuledzera. Neuropsychopharmacology 35, 217-238. (onetsani: 10.1038 / npp.2009.110)

  17. ↵
    1. Parylak SL,
    2. Koob GF,
    3. Zorrilla EP

    . 2011 Mbali yamdima ya kuledzera kwa zakudya. Physiol. Behav. 104, 149-156. (yani: 10.1016 / j.physbeh.2011.04.063)

  18. ↵
    1. el-guebaly n,
    2. Mudry T,
    3. Zohar J,
    4. Tavares H,
    5. Potenza MN

    . 2012 Zosakanikirana pazochita zowonongeka: vuto la kutchova njuga. Bongo 107, 1726-1734. (onetsani: 10.1111 / j.1360-0443.2011.03546.x)

  19. ↵
    1. Abramowitz JS,
    2. Jacoby RJ

    . 2015 Matenda osokoneza maganizo ndi ofanana. Annu. Rev. Clin. Psychol. 11, 165-186. (yani: 10.1146 / annurev-clinpsy-032813-153713)

  20. ↵
    1. Cottone P et al

    . 2009 CRF system recruitment amalumikizana ndi mdima wakukakamiza kudya. Proc. Natl Acad. Sci. USA 106, 20 016-20 020. (onetsani: 10.1073 / pnas.0908789106)

  21. ↵
    1. Iemolo A,
    2. Valenza M,
    3. Tozier L,
    4. Knapp CM,
    5. Kornetsky C,
    6. Steardo L,
    7. Sabino V,
    8. Cottone P

    . 2012 Kuchokera ku matenda osapitirira, kwapakatikati kwa chakudya chokoma kwambiri kumapangitsa khalidwe losautsa ngati lopanda kudya makoswe. Behav. Pharmacol. 23, 593-602. (yani: 10.1097 / FBP.0b013e328357697f)

  22. ↵
    1. Teegarden SL,
    2. Bale TL

    . 2007 Kuchuluka kwa zakudya zokonda zakudya kumabala malingaliro owonjezereka komanso chiopsezo cha kuchepetsa kudya. Ubweya. Psychiatry 61, 1021-1029. (onetsani: 10.1016 / j.biopsych.2006.09.032)

  23. ↵
    1. Smith KL,
    2. Rao RR,
    3. Velazquez-Sanchez C,
    4. Valenza M,
    5. Giuliano C,
    6. Everitt BJ,
    7. Sabino V,
    8. Cottone P

    . 2015 Wosagonjetsa N-methyl-D-Aspartate wotsutsa mementine amachepetsa kudya, kufunafuna chakudya, ndi kudya mokakamiza: udindo wa nucleus accumbens shell. Neuropsychopharmacology 40, 1163-1171. (onetsani: 10.1038 / npp.2014.299)

    1. Velazquez-Sanchez C,
    2. Ferragud A,
    3. Moore CF,
    4. Everitt BJ,
    5. Sabino V,
    6. Cottone P

    . 2014 Makhalidwe apamwamba amatanthawuza chizoloŵezi cha zakudya-monga khalidwe mu khola. Neuropsychopharmacology 39, 2463-2472. (onetsani: 10.1038 / npp.2014.98)

  25. ↵
    1. Rossetti C,
    2. Spena G,
    3. Halfon O,
    4. Boutrel B

    . Umboni wa 2014 chifukwa cha khalidwe lodzikakamiza mu makoswe omwe amatha kupeza njira yowonjezera chakudya chokoma kwambiri. Kusokoneza. Ubweya. 19, 975-985. (onetsani: 10.1111 / adb.12065)

  26. ↵
    1. Koob GF,
    2. Volkow ND

    . 2016 Neurobiology ya kuledzera: kuyerekezera kwa ubongo. Lancet Psychiatry 3, 760-773. (doi:10.1016/S2215-0366(16)00104-8)

  27. ↵
    1. Yin HH,
    2. Knowlton BJ

    . 2006 Udindo wa basal gangla mu mapangidwe apangidwe. Nat. Rev. Neurosci. 7, 464-476. (onetsani: 10.1038 / nrn1919)

  28. ↵
    1. Surmeier DJ,
    2. Ding J,
    3. Tsiku M,
    4. Wang Z,
    5. Shen W

    . 2007 D1 ndi D2 dopamine-receptor modulation of scraper glutamatericic in signal spider spiny neurons. Miyambo ya Neurosci. 30, 228-235. (onetsani: 10.1016 / j.tins.2007.03.008)

  29. ↵
    1. Furlong TM,
    2. Jayaweera HK,
    3. Balleine BW,
    4. Corbit LH

    . 2014 Kulimbitsa thupi ngati chakudya chokoma kumachepetsa chizoloŵezi chokhala ndi khalidwe labwino ndipo kumadalira kuchitapo kanthu kowonongeka kwa dorsolateral striatum. J. Neurosci. 34, 5012-5022. (onetsani: 10.1523 / JNEUROSCI.3707-13.2014)

  30. ↵
    1. Volkow ND,
    2. Wang GJ,
    3. Tomasi D,
    4. Wowonongeka RD

    . Ma 2013 osagwirizana ndi maulendo oledzera. Curr. Opin Neurobiol. 23, 639-648. (onetsani: 10.1016 / j.conb.2013.01.002)

  31. ↵
    1. Wang GJ,
    2. Volkow ND,
    3. Logan J,
    4. Pappas NR,
    5. Wong CT,
    6. Zhu W,
    7. Netusll N,
    8. Fowler JS

    . 2001 ubongo dopamine ndi kunenepa kwambiri. Lancet 357, 354-357. (doi:10.1016/S0140-6736(00)03643-6)

  32. ↵
    1. Volkow ND et al

    . 2008 Low dopamine yopweteka D2 receptors imagwirizanitsidwa ndi mankhwala a prefrontal mu nkhani zowonjezereka: zomwe zingatheke zowonjezera. Neuroimage 42, 1537-1543. (yani: 10.1016 / j.neuroimage.2008.06.002)

  33. ↵
    1. van de Giessen E,
    2. Celik F,
    3. Schweitzer DH,
    4. van den brink w,
    5. Booij J

    . 2014 Dopamine D2 / 3 kupezeka kwapezeka ndi amphetamine-inachititsa dopamine kumasulidwa mu kunenepa kwambiri. J. Psychopharmacol. 28, 866-873. (pitani: 10.1177 / 0269881114531664)

  34. ↵
    1. Stice E,
    2. Spoor S,
    3. Bohon C,
    4. DM yaying'ono

    . 2008 Chiyanjano pakati pa kunenepa kwambiri ndi yankho lopwetekedwa ndi chakudya chimayesedwa ndi TaqIA A1. Science 322, 449-452. (yani: 10.1126 / sayansi.1161550)

  35. ↵
    1. Valenza M,
    2. Steardo L,
    3. Cottone P,
    4. Sabino V

    . Mankhwala a 2015 okhudzana ndi kudya zakudya komanso makoswe osagwidwa ndi zakudya: kusiyana kwa zotsatira zopindulitsa komanso zopanda mphamvu za D-amphetamine. Psychopharmacology 232, 3215-3226. (doi:10.1007/s00213-015-3981-3)

  36. ↵
    1. Johnson PM,
    2. Kenny PJ

    . 2010 Dopamine D2 receptors mu zowonongeka monga mphotho zopanda ntchito ndi kudya mokakamiza mu makoswe oposa. Nat. Neurosci. 13, 635-641. (onetsani: 10.1038 / nn.2519)

  37. ↵
    1. Chiritsani DJ,
    2. Goddard S,
    3. Brammer RJ,
    4. Hutson PH,
    5. Vickers SP

    . 2016 Lisdexamfetamine amachepetsa khalidwe lodzikakamiza ndi lokhalitsa la kudya makoswe muzakudya zowonjezera. J. Psychopharmacol. 30, 662-675. (pitani: 10.1177 / 0269881116647506)

  38. ↵
    1. McElroy SL,
    2. Mitchell YES,
    3. Wilfley D,
    4. Gasior M,
    5. Ferreira-Cornwell MC,
    6. McKay M,
    7. Wang J,
    8. Whitaker T,
    9. Hudson JI

    . 2016 Lisdexamfetamine zimayambitsa zotsatira pa kudya zakudya zolimbitsa thupi komanso kuchita zinthu mopanda malire ndi akuluakulu omwe ali ndi vuto lodyera kudya. EUR. Idyani. Kusokonezeka. Chiv. 24, 223-231. (onetsani: 10.1002 / erv.2418)

  39. ↵
    1. Rowley HL,
    2. Kulkarni R,
    3. Gosden J,
    4. Brammer R,
    5. Hackett D,
    6. Chiritsani DJ

    . 2012 Lisdexamfetamine ndikutulutsidwa mwachangu kwa d-amfetamine - kusiyana kwamaubwenzi a pharmacokinetic / pharmacodynamic kuwululidwa ndi striatal microdialysis mu makoswe osunthira mosasunthika munthawi yomweyo kuchuluka kwa mankhwala osokoneza bongo a plasma ndi zochitika za locomotor. Neuropharmacology 63, 1064-1074. (yani: 10.1016 / j.neuropharm.2012.07.008)

  40. ↵
    1. Tomasi D,
    2. Volkow ND

    . Njira ya 2013 yovuta kugwiritsira ntchito mowa ndi kunenepa kwambiri: kusiyana ndi kufanana. Chotsutsa. Rev. Biochem. Mol. Ubweya. 48, 1-19. (pitani: 10.3109 / 10409238.2012.735642)

  41. ↵
    1. Volkow ND,
    2. RA wanzeru

    . 2005 Kodi kumwa mankhwala osokoneza bongo kungatithandize bwanji kumvetsa kunenepa kwambiri? Nat. Neurosci. 8, 555-560. (onetsani: 10.1038 / nn1452)

  42. ↵
    doi:10.1002/(SICI)1096-8628(19970418)74:2<162::AID-AJMG9>3.0.CO;2-W)

  • ↵
    1. Chiritsani DJ,
    2. Cheetham SC,
    3. Smith SL

    . 2009 The neuropharmacology ya mankhwala a ADHD mu vivo: zowunika pazothandiza ndi chitetezo. Neuropharmacology 57, 608-618. (yani: 10.1016 / j.neuropharm.2009.08.020)

  • ↵
    1. Laurent V,
    2. Morse AK,
    3. Balleine BW

    . 2015 Ntchito ya opioid mu mphoto ndi kupanga kupanga. Br. J. Pharmacol. 172, 449-459. (onetsani: 10.1111 / bph.12818)

    1. Giuliano C,
    2. Cottone P

    . 2015 Udindo wa opioid mu matenda odyera kudya. CNS Wopenya. 20, 537-545. (yesani: 10.1017 / S1092852915000668)

  • ↵
    1. Wassum KM,
    2. Cely IC,
    3. Matumbo NT,
    4. Balleine BW

    . Kusokonezeka kwa 2009 ya ntchito yambiri ya opioid panthawi yophunzira molimbika kumapangitsanso kupeza chizolowezi. Neuroscience 163, 770-780. (yani: 10.1016 / j.neuroscience.2009.06.071)

  • ↵
    1. Corbit LH

    . Zotsatira za 2016 za zakudya zowopsya pa kuphunzira ndi kachitidwe kachitidwe. Curr. Opin. Behav. Sci. 9, 84-90. (yani: 10.1016 / j.cobeha.2016.02.010)

  • ↵
    1. Chamberlain SR ndi al

    . Zotsatira za 2012 za chiopsezo cha opioid receptor kuti chizindikiridwe mwa anthu ambiri odyera. Psychopharmacology 224, 501-509. (onetsani: 10.1007 / s00213-012-2778-x)

  • ↵
    1. de Zwaan M,
    2. Mitchell JE

    . Otsutsa a 1992 Opiate ndi khalidwe la kudya mwa anthu: ndemanga. J. Clin. Pharmacol. 32, 1060-1072.

  • ↵
    1. Murray E,
    2. Brouwer S,
    3. McCutcheon R,
    4. Kuvulaza CJ,
    5. Cowen PJ,
    6. McCabe C

    . 2014 Kutsutsana ndi neural zotsatira za naltrexone pa chakudya mphotho ndi chisokonezo: zotsatira za chithandizo cha kunenepa kwambiri. Psychopharmacology 231, 4323-4335. (doi:10.1007/s00213-014-3573-7)

  • ↵
    1. Alger SA,
    2. Schwalberg MD,
    3. Bigaouette JM,
    4. Michalek AV,
    5. Howard LJ

    . Mmene 1991 Zimakhudzidwira ndi munthu wotsutsa odwala matenda ozunguza maganizo komanso opiate. Am. J. Clin. Mankhwala. 53, 865-871.

  • ↵
    1. Greenway FL,
    2. Dunayevich E,
    3. Tollefson G,
    4. Erickson J,
    5. Guttadauria M,
    6. Fujioka K,
    7. Cowley MA

    . 2009 Kuyerekeza kwa bupropion pamodzi ndi naltrexone mankhwala opatsirana kwambiri ndi monotherapy ndi placebo. J. Clin. Endocrinol. Metab. 94, 4898-4906. (yani: 10.1210 / jc.2009-1350)

  • ↵
    1. Greenway FL,
    2. Fujioka K,
    3. Plodkowski RA,
    4. Mudaliar S,
    5. Guttadauria M,
    6. Erickson J,
    7. Kim DD,
    8. Dunayevich E

    . Zotsatira za 2010 Zomwe zimachititsa kuti munthu asamakhale ndi kachilombo koyambitsa matenda olemera kwambiri (akuluakulu olemera kwambiri), odwala kwambiri (COR-I): ma multicentre, randomized, double-blind, a placebo-controlled, trial 3. Lancet 376, 595-605. (doi:10.1016/S0140-6736(10)60888-4)

  • ↵
    1. Hoebel BG,
    2. Avena NM,
    3. Bocarsly ME,
    4. Rada P

    . 2009 Chizoloŵezi chakuthupi: khalidwe lachikhalidwe ndi dera lomwe limayambira kuwonetsa shuga mu makoswe. J. Addict. Med. 3, 33-41. (doi:10.1097/ADM.0b013e31819aa621)

  • ↵
    1. Colantuoni C,
    2. Rada P,
    3. McCarthy J,
    4. Patten C,
    5. Avena NM,
    6. Chadeayne A,
    7. Hoebel BG

    . Umboni wa 2002 kuti pakati, shuga wochuluka wa shuga umayambitsa kudalira kwambiri kwa opioid. Obes. Res. 10, 478-488. (onetsani: 10.1038 / oby.2002.66)

  • ↵
    1. Mena JD,
    2. Sadeghian K,
    3. Baldo BA

    . Kuchepetsa 2011 ya hyperphagia ndi chakudya chamagulu chifukwa chotsitsimula mu-opioid receptor m'madera ozungulira a cortex. J. Neurosci. 31, 3249-3260. (onetsani: 10.1523 / JNEUROSCI.2050-10.2011)

  • ↵
    1. Selleck RA,
    2. Nyanja C,
    3. Estrada V,
    4. Riederer J,
    5. Andrzejewski M,
    6. Sadeghian K,
    7. Baldo BA

    . Chizindikiro cha 2015 chodziwika bwino cha opioid m'kati mwa mapiritsi oyendera bwino amafunika kuti chiwonetsero chochitidwa ndi njala chichitike. Neuropsychopharmacology 40, 2464-2474. (onetsani: 10.1038 / npp.2015.97)

  • ↵
    1. Selleck RA,
    2. Baldo BA

    . Zotsatira za 2017 Zomwe zimayambitsa matenda a mu-opioids mu kondomu yoyendetsera zakuthambo: kafukufuku wa zomwe zachitika posachedwapa ndi kuyerekeza ndi zochitika za opioid mu nucleus accumbens. Psychopharmacology 234, 1439-1449. (doi:10.1007/s00213-016-4522-4)

  • ↵
    1. Cottone P et al

    . Kugonana kwa 2012 ya sigma-1 receptors imatseka kudya monga kumadya. Neuropsychopharmacology 37, 2593-2604. (onetsani: 10.1038 / npp.2012.89)

  • ↵
    1. Blasio A,
    2. Steardo L,
    3. Sabino V,
    4. Cottone P

    . Njira ya 2014 Opioid yomwe imakhala mkati mwa mapepala apakati omwe imakhala ngati kudya. Kusokoneza. Ubweya. 19, 652-662. (onetsani: 10.1111 / adb.12033)

  • ↵
    1. Iemolo A,
    2. Blasio A,
    3. St Cyr SA,
    4. Jiang F,
    5. Mpunga KC,
    6. Sabino V,
    7. Cottone P

    . 2013 CRF-CRF1 receptor system m'katikati ndi basolateral nuclei ya amygdala mosiyana imatsutsana kwambiri kudya chakudya chokoma. Neuropsychopharmacology 38, 2456-2466. (onetsani: 10.1038 / npp.2013.147)

  • ↵
    1. Zorrilla EP,
    2. Logrip ML,
    3. Koob GF

    . Chotsalira cha 2014 Corticotropin: gawo lofunika kwambiri mu njira yokhudzana ndi mankhwala ozunguza bongo. Front Neuroendocrinol. 35, 234-244. (yani: 10.1016 / j.yfrne.2014.01.001)

  • ↵
    1. Cottone P,
    2. Sabino V,
    3. Steardo L,
    4. Zorrilla EP

    . 2008 Kufikira kwapadera kwa chakudya chocheperachepera kumachepetsa mphamvu yowonjezera ya makoswe. Am. J. Physiol. Regul. Kugwirizana. Kuphatikiza. Physiol. 295, R1066-R1076. (onetsani: 10.1152 / ajpregu.90309.2008)

  • ↵
    1. Cottone P,
    2. Sabino V,
    3. Steardo L,
    4. Zorrilla EP

    . 2009 Kudyetsa, kukhudzana ndi nkhawa ndi kagayidwe kachakudya mu makoswe aakazi ndi kusandulika mwayi wopeza chakudya. Psychoneuroendocrinology 34, 38-49. (onetsani: 10.1016 / j.psyneuen.2008.08.010)

  • ↵
    1. Micioni Di Bonaventura MV et al

    . 2014 Udindo wa pedi la bedi la stria terminalis corticotrophin-kutulutsa zinthu zotengera zomwe zimakhumudwitsa kwambiri-zomwe zimapangitsa kuti azidya zakudya zolimbitsa thupi m'madzi amphongo ndi mbiri ya chakudya choletsedwa. J. Neurosci. 34, 11 316-11 324. (onetsani: 10.1523 / JNEUROSCI.1854-14.2014)

  • ↵
    1. Calvez J,
    2. de Avila C,
    3. Guevremont G,
    4. Timofeeva E

    . Zovuta za 2016 zimayambitsa ubongo wa corticotropin-kumasula chinthu chowongolera-ngati kudya makoswe omwe amawoneka bwino komanso osagonjetsedwa. Kudya 107, 585-595. (onetsani: 10.1016 / j.appet.2016.09.010)

  • ↵
    1. Epstein DH,
    2. Kennedy AP,
    3. Furnari M,
    4. Heilig M,
    5. Shaham Y,
    6. Phillips KA,
    7. Preston KL

    . Zotsatira za 2016 Mtsutso wa CRF1-receptor pexacerfont pa kudya ndi kulakalaka chakudya. Psychopharmacology 233, 3921-3932. (doi:10.1007/s00213-016-4424-5)

  • ↵
    1. Spierling SR,
    2. Zorrilla EP

    . 2017 Osadandaula za CRF: kuwunika zolephera za kumasulira kwa CRF1antagonists. Psychopharmacology 234, 1467-1481. (doi:10.1007/s00213-017-4556-2)

  • ↵
    1. Koob GF,
    2. Zorrilla EP

    . 2012 Kukonzekera pa corticotropin-releasing factor pharmacotherapy kwa matenda a maganizo: munthu wokonzanso zinthu. Neuropsychopharmacology 37, 308-309. (onetsani: 10.1038 / npp.2011.213)

  • ↵
    1. Koob GF

    . 2015 Mbali yamdima ya kutengeka: kuledzera. EUR. J. Pharmacol. 753, 73-87. (onetsani: 10.1016 / j.ejphar.2014.11.044)

  • ↵
    1. Patel S,
    2. Cravatt BF,
    3. Hillard CJ

    . Kuyanjana kwa 2005 Synergistic pakati pa zowonongeka ndi kusokonezeka kwa chilengedwe pakuyambitsa pakati pa amygdala. Neuropsychopharmacology 30, 497-507. (onetsani: 10.1038 / sj.npp.1300535)

  • ↵
    1. Blasio A et al

    . 2013 Rimonabant imabweretsa nkhawa m'makoswe omwe achotsedwa ku chakudya chokoma: gawo lalikulu pakati pa amygdala. Neuropsychopharmacology 38, 2498-2507. (onetsani: 10.1038 / npp.2013.153)

  • ↵
    1. Blasio A,
    2. Mpunga KC,
    3. Sabino V,
    4. Cottone P

    . Zithunzi za 2014 za njira yochepetsedwera ya zakudya zowonjezereka m'magulu aakazi: zotsatira za CB1 zotsutsana ndi zotsutsana ndi zakudya zomwe zimadya zakudya komanso khalidwe lodzidetsa nkhaŵa. Behav. Pharmacol. 25, 609-617. (yesani: 10.1097 / FBP.0000000000000059)

  • ↵
    1. Christensen R,
    2. Kristensen PK,
    3. Bartels EM,
    4. Bliddal H,
    5. Osowa AV

    . 2007 Meta yofufuza za mphamvu ndi chitetezo cha wothandizira wodwala kunenepa kwambiri Rimonabant. Ugeskr. Laeger. 169, 4360-4363.

  • ↵
    1. Dore R,
    2. Valenza M,
    3. Wang X,
    4. Mpunga KC,
    5. Sabino V,
    6. Cottone P

    . 2014 Mgwirizano wa agonist wa CB1 receptor SR141716 amaletsa kudya chakudya chokoma. Kusokoneza. Ubweya. 19, 849-861. (onetsani: 10.1111 / adb.12056)

  • ↵
    1. Tzavara ET,
    2. Davis RJ,
    3. Perry KW,
    4. Li X,
    5. Salhoff C,
    6. Bymaster FP,
    7. Witkin JM,
    8. Nomikos GG

    . 2003 Mtsutso wa CB1 wolandira SR141716A umatulutsa monoaminergic neurotransmission pamtanda woyendera bwino: zotsatira za zochiritsira. Br. J. Pharmacol. 138, 544-553. (yani: 10.1038 / sj.bjp.0705100)

  • ↵
    1. Brennan BP,
    2. Roberts JL,
    3. Fogarty KV,
    4. Reynolds KA,
    5. Jonas JM,
    6. Hudson JI

    . Memphine ya 2008 pochiza matenda oledzeretsa: chizindikiro chotseguka, akuyembekezera. Int. J. Idyani. Kusokonezeka. 41, 520-526. (yani: 10.1002 / idyani.20541)

  • ↵
    1. Grant JE,
    2. Odlaug BL,
    3. Mooney M,
    4. O'Brien R,
    5. Kim SW

    . Phunziro la 2012 loyendetsa malemba la memantine pakulandila kukakamiza kugula. Ann. Kliniki. Psychiatry 24, 119-126.

  • ↵
    1. Brog JS,
    2. Salyapongse A,
    3. Deutch AY,
    4. Zahm DS

    . 1993 Mchitidwe wa kusungidwa kosasunthika kwa chiyambi ndi chipolopolo mu gawo la 'accumbens' la makoswe ventralum: kudziwika kwa immunohistochemical ya kutengedwera kwamtundu wa fluoro-golide. J. Comp. Neurol. 338, 255-278. (onetsani: 10.1002 / cne.903380209)

    1. McGeorge AJ,
    2. Faull RL

    . 1989 Mapangidwe a chiwonetserocho kuchokera ku cerebral cortex kupita ku striatum mu khola. Neuroscience 29, 503-537. (doi:10.1016/0306-4522(89)90128-0)

  • ↵
    1. Zahm DS,
    2. Brog JS

    . 1992 Pa kufunikira kwa magulu akuluakulu mu gawo la 'accumbens' la pirat ventral striatum. Neuroscience 50, 751-767. (doi:10.1016/0306-4522(92)90202-D)

  • ↵
    1. Brown RM et al.

    Matenda a 2015 monga osokoneza bongo omwe amachititsa kuti munthu adye kwambiri. Ubweya. Psychiatry 81, 797-806. (onetsani: 10.1016 / j.biopsych.2015.11.019)

  • ↵
    1. Gipson CD,
    2. Kupchik YM,
    3. Kalivas PW

    . 2014 Rapid, yapadera ya syntaptic plastiki muzoledzeretsa. Neuropharmacology 76, 276-286. (yani: 10.1016 / j.neuropharm.2013.04.032)

  • ↵
    1. Valenza M,
    2. DiLeo A,
    3. Steardo L,
    4. Cottone P,
    5. Sabino V

    . Zotsatira za 2016 za Ethanol m'magulu opanda sigma-1 receptor. Behav. Resin ya ubongo. 297, 196-203. (yani: 10.1016 / j.bbr.2015.10.013)

    1. Sabino V,
    2. Hicks C,
    3. Cottone P

    . Zilonda za 2017 Sigma ndi matenda ogwiritsira ntchito mankhwala. Malangizo. Exp. Med. Ubweya. 964, 177-199. (doi:10.1007/978-3-319-50174-1_13)

    1. Sabino V,
    2. Cottone P

    . Zilonda za 2016 Sigma ndi matenda osokoneza bongo. Chida. Exp. Pharmacol. 244, 219-236. (yani: 10.1007 / 164_2016_97)

    1. Katz JL,
    2. Su TP,
    3. Hiranita T,
    4. Hayashi T,
    5. Tanda G,
    6. Kopajtic T,
    7. Tsai SY

    . 2011 Udindo wokhudzana ndi zizindikiro za sigma muzokhalitsa zokhazokha. asatayike 4, 880-914. (onetsani: 10.3390 / ph4060880)

    1. Blasio A,
    2. Valenza M,
    3. Iyer MR,
    4. Mpunga KC,
    5. Steardo L,
    6. Hayashi T,
    7. Cottone P,
    8. Sabino V

    . 2015 Sigma-1 receptor imayitanitsa kupeza zakumwa za mowa ndi kufunafuna khalidwe mowa-kusankha makoswe. Behav. Resin ya ubongo. 287, 315-322. (yani: 10.1016 / j.bbr.2015.03.065)

    1. Sabino V,
    2. Cottone P,
    3. Blasio A,
    4. Iyer MR,
    5. Steardo L,
    6. Mpunga KC,
    7. Conti B,
    8. Koob GF,
    9. Zorrilla EP

    . Kugwiritsidwa ntchito kwa 2011 ya sigma-receptors kumapangitsa kumwa mowa ngati mowa ku Sardinian mowa-kukonda makoswe. Neuropsychopharmacology 36, 1207-1218. (onetsani: 10.1038 / npp.2011.5)

  • ↵
    1. Robson MJ,
    2. Noorbakhsh B,
    3. Seminerio MJ,
    4. Matsumoto RR

    . Zilonda za 2012 Sigma-1: Zolinga zomwe zingatheke pochiza mankhwala osokoneza bongo. Curr. Pharm. Zovuta 18, 902-919. (pitani: 10.2174 / 138161212799436601)

  • ↵
    1. Bastianetto S,
    2. Rouquier L,
    3. Perrault G,
    4. Sanger DJ

    . Kuzungulira kwa 1995 DTG chifukwa cha makoswe kungaphatikizepo kugwirizana pakati pa sigma sites ndi njira za nigro-striatal dopaminergic. Neuropharmacology 34, 281-287. (doi:10.1016/0028-3908(94)00156-M)

  • ↵
    1. Dong LY,
    2. Cheng ZX,
    3. Fu YM,
    4. Wang ZM,
    5. Zhu YH,
    6. Sun JL,
    7. Dong Y,
    8. Zheng P

    . 2007 Neurosteroid dehydroepiandrostoneone sulphate imapangitsa kuti glutamate osasunthika atuluke mu khola la prelimbic cortex pogwiritsa ntchito dopamine D1 ndi sigma-1 receptor. Neuropharmacology 52, 966-974. (yani: 10.1016 / j.neuropharm.2006.10.015)

  • ↵
    1. Rada PV,
    2. Mark GP,
    3. Taylor KM,
    4. Hoebel BG

    . 1996 Morphine ndi naloxone, ip kapena kwanuko, zimakhudza acetylcholine yochulukirapo mu accumcums ndi prefrontal cortex. Pharmacol. Chilengedwe. Behav. 53, 809-816. (doi:10.1016/0091-3057(95)02078-0)

  • ↵
    1. Avena NM,
    2. Bocarsly ME,
    3. Rada P,
    4. Kim A,
    5. Hoebel BG

    . 2008 Pambuyo pa kudya tsiku ndi tsiku, chakudya chochepa chimayambitsa nkhawa ndipo chimakhala chosayerekezera cha dopamine / acetylcholine. Physiol. Behav. 94, 309-315. (yani: 10.1016 / j.physbeh.2008.01.008)

  • ↵
    1. Hernandez L,
    2. Hoebel BG

    . Chakudya cha 1988 mphoto ndi cocaine amachulukitsa extracellular dopamine mu nucleus accumbens monga momwe anayesera ndi microdialysis. Moyo Sci. 42, 1705-1712. (doi:10.1016/0024-3205(88)90036-7)

  • ↵
    1. Hoebel BG,
    2. Avena NM,
    3. Rada P

    . 2007 Accumbens dopamine-acetylcholine muyeso ndi njira yopewera. Curr. Opin Pharmacol. 7, 617-627. (yani: 10.1016 / j.coph.2007.10.014)

  • ↵
    1. Mark GP,
    2. Shabani S,
    3. Dobbs LK,
    4. Hansen ST

    . 2011 Cholinergic modulation ya mesolimbic dopamine ntchito ndi mphoto. Physiol. Behav. 104, 76-81. (yani: 10.1016 / j.physbeh.2011.04.052)

  • ↵
    1. Borowsky B et al

    . 2001 Fufuzani amines: kudziwika kwa banja la mapuloteni othandizira mapuloteni a G mammalian. Proc. Natl Acad. Sci. USA 98, 8966-8971. (onetsani: 10.1073 / pnas.151105198)

  • ↵
    1. DK Wamkulu,
    2. Miller GM,
    3. Li JX

    . 2016 'TAARgeting bongo'- alamo akuchitira umboni kusintha kwina: kuwunika mwachidule za msonkhano wonse wa msonkhano wa 2015, biology ndi chemistry. Mankhwala Osokoneza Bongo Amadalira. 159, 9-16. (yani: 10.1016 / j.drugalcdep.2015.11.014)

  • ↵
    1. Espinoza S et al

    . 2015 TAAR1 imagwira ntchito yokhala ndi cortical glutamate kugwira ntchito kwa NMDA. Neuropsychopharmacology 40, 2217-2227. (onetsani: 10.1038 / npp.2015.65)

  • ↵
    1. Ferragud A,
    2. Howell AD,
    3. Moore CF,
    4. Ta TL,
    5. Kufotokozera MC,
    6. Sabino V,
    7. Cottone P

    . 2016 Chidule cha amine-cholumikizira receptor 1 agonist RO5256390 zimasokoneza, kumangokhala ngati kudya makoswe. Neuropsychopharmacology 42, 1458-1470. (onetsani: 10.1038 / npp.2016.233)

  • ↵
    1. Goodman DW

    . 2010 Lisdexamfetamine dimesylate (vyvanse), wogulitsa mankhwala osokoneza bongo. Pharm. Ther. 35, 273-287.

  • ↵
    1. Jimerson DC,
    2. Lesem MD,
    3. Kaye WH,
    4. Brewerton TD

    . 1992 Low serotonin ndi dopamine metabolite kwambiri mu cerebrospinal fluid kuchokera ku bulimic odwala omwe nthawi zambiri amakhala m'magulu. Mzere. Gen. Psychiatry 49, 132-138. (onetsani: 10.1001 / archpsyc.1992.01820020052007)

  • ↵
    1. Fineberg NA,
    2. Roberts A,
    3. Montgomery SA,
    4. Cowen PJ

    . 1997 ubongo 5-HT ntchito mu chisokonezo-chokakamiza matenda. Ma prolactin amayankha d-fenfluramine. Br. J. Psychiatry 171, 280-282. (onetsani: 10.1192 / bjp.171.3.280)

  • ↵
    1. Steiger H,
    2. Israeli M,
    3. Gauvin L,
    4. Ng Ying Kin NM,
    5. Young SN

    . Zotsatira za 2003 za zipsyinjo ndi zosafuna kuchita za serotonin mu amai omwe ali ndi bulimia nervosa. Kupuma kwa maganizo. 120, 219-229. (doi:10.1016/S0165-1781(03)00195-1)

  • ↵
    1. De Fanti BA,
    2. Gavel DA,
    3. Hamilton JS,
    4. Horwitz BA

    . 2000 Extracellular hypothalamic serotonin m'magulu atatha kupwetekedwa mtima kwa khungu (Fa / Fa) ndi ochepa (fa / fa) makoswe a Zucker. Resin ya ubongo. 869, 6-14. (doi:10.1016/S0006-8993(00)02308-8)

    1. Ratner C,
    2. Ettrup A,
    3. Bueter M,
    4. Nditsutseni,
    5. Compan V,
    6. le Roux CW,
    7. Levin B,
    8. Hansen HH,
    9. Knudsen GM

    . Zolemba za 2012 Zolemba za serotonergic zowonongeka kwambiri ndipo pambuyo pa roux-en-Y chapamimba chimadutsa. kunenepa 20, 2133-2141. (onetsani: 10.1038 / oby.2012.75)

  • ↵
    1. Kuikka JT ndi al.

    2001 Wothandizira wotenga serotonin amamanga kudya mowa kwambiri. Psychopharmacology 155, 310-314. (onetsani: 10.1007 / s002130100716)

  • ↵
    1. McElroy SL,
    2. Guerdjikova AI,
    3. Mori N,
    4. Keck Jr PE

    . 2015 Psychopharmacologic chithandizo cha matenda osowa: zotsatira zotulukira. Curr. Psychiatry Rep. 17, 35. (doi:10.1007/s11920-015-0573-1)

  • ↵
    1. Milano W,
    2. Petrella C,
    3. Casella A,
    4. Capasso A,
    5. Carrino S,
    6. Milano L

    . 2005 Kugwiritsa ntchito sibutramine, mankhwala oletsa kubwezeretsa serotonin ndi noradrenaline, pochiza matenda osokoneza bongo. Malangizo. Ther. 22, 25-31. (yesani: 10.1007 / BF02850181)

  • ↵
    1. Steiger H,
    2. Gauvin L,
    3. Engelberg MJ,
    4. Ying Kin NM,
    5. Israeli M,
    6. Wonderlich SA,
    7. Richardson J

    . 2005 Mood- ndi zolemba zotsalira zotsalira kuti zikhale zovuta mu bulimia nervosa: zotsatila zotheka za dongosolo la serotonin. Psychol. Med. 35, 1553-1562. (yesani: 10.1017 / S0033291705005817)

  • ↵
    1. Xu P et al

    . Kugwiritsidwa ntchito kwa 2017 kwa serotonin 2C receptors mu dopamine neurons amalepheretsa kudya mofanana ngati kudya pice. Ubweya. Psychiatry 81, 737-747. (onetsani: 10.1016 / j.biopsych.2016.06.005)

  • ↵
    1. Valencia-Torres L,
    2. Olarte-Sanchez CM,
    3. Lyons DJ,
    4. Georgescu T,
    5. Greenwald-Yarnell M,
    6. Myers Jr MG,
    7. Bradshaw CM,
    8. Heisler LK

    . Kugwiritsidwa ntchito kwa 2017 ya ventral tegmental m'dera 5-HT2C receptors amachepetsa zolimbikitsa. Neuropsychopharmacology 42, 1511-1521. (onetsani: 10.1038 / npp.2016.264)

  • ↵
    1. Hernandez L,
    2. Lee F,
    3. Hoebel BG

    . 1987 microdialysis imodzimodziyo ndi amphetamine kulowetsedwa mu nucleus accumbens ndi striatum ya makoswe omasuka kusuntha: kuwonjezera mu extracellular dopamine ndi serotonin. Resin ya ubongo. Bull. 19, 623-628. (doi:10.1016/0361-9230(87)90047-5)

  • ↵
    1. Boutrel B,
    2. de Lecea L

    . 2008 Kuledzera ndi kuukitsa: kugwirizana kwa hypocretin. Physiol. Behav. 93, 947-951. (yani: 10.1016 / j.physbeh.2007.11.022)

  • ↵
    1. Cason AM,
    2. Smith RJ,
    3. Tahsili-Fahadan P,
    4. Moorman DE,
    5. GC woyenda,
    6. Aston-Jones G

    . 2010 Udindo wa orexin / hypocretin mu kufunafuna mphoto ndi kuledzera: zotsatira za kunenepa kwambiri. Physiol. Behav. 100, 419-428. (yani: 10.1016 / j.physbeh.2010.03.009)

  • ↵
    1. Piccoli L et al

    . Ntchito ya 2012 ya orexin-1 njira zotengera zakudya zopanikizika mu chitsanzo cha kudya mowa mwa makoswe aakazi. Neuropsychopharmacology 37, 1999-2011. (onetsani: 10.1038 / npp.2012.48)

  • ↵
    1. Alcaraz-Iborra M,
    2. Carvajal F,
    3. Lerma-Cabrera JM,
    4. Valor LM,
    5. Cubero I

    . 2014 Kulimbitsa thupi monga zakudya zamakono komanso zopanda phokoso m'zinthu zamakono C57BL / 6 J mbewa: umboni wamagulu ndi maselo okhudza kuloŵerera kwa orexin. Behav. Resin ya ubongo. 272, 93-99. (yani: 10.1016 / j.bbr.2014.06.049)

  • ↵
    1. Petrovich GD,
    2. Hobin MP,
    3. Reppucci CJ

    . Mafuta a 2012 osankhidwa m'thupi mwa hypothalamic orexin / hypocretin, koma osati mankhwala a melanin omwe amachititsa kuti azidyera makoswe. Neuroscience 224, 70-80. (yani: 10.1016 / j.neuroscience.2012.08.036)

  • ↵
    1. Campbell EJ,
    2. Barker DJ,
    3. Nasser HM,
    4. Kaganovsky K,
    5. CV ca Dayas,
    6. Marchant NJ

    . Chakudya cha 2017 chomwe chimapangidwira chilango chofuna kulangidwa chimagwirizanitsidwa ndi kuwonjezeka kwa kufotokozera kwa Fos mu lateral hypothalamus ndi amygdala yamkati ndi yamkati. Behav. Neurosci. 131, 155-167. (onetsani: 10.1037 / bne0000185)

  • ↵
    1. Yeoh JW,
    2. Campbell EJ,
    3. James MH,
    4. Graham BA,
    5. Dayas CV

    . Otsutsana a 2014 Orexin kwa matenda a neuropsychiatric: kupita patsogolo komanso mavuto. Kutsogolo. Neurosci. 8, 36. (pitani: 10.3389 / fnins.2014.00036)

  • ↵
    1. Pankevich DE,
    2. Teegarden SL,
    3. Hedin AD,
    4. Jensen CL,
    5. Bale TL

    . Mchitidwe wa 2010 wa caloric umakumana ndi zovuta zowonongeka ndi njira zolimbitsa thupi komanso zimalimbikitsa kudya zakudya zolimbitsa thupi. J. Neurosci. 30, 16 399-16 407. (onetsani: 10.1523 / JNEUROSCI.1955-10.2010)

  • ↵
    1. Shalev U

    . 2012 Chizoloŵezi cha zakudya zowonongeka chimayambitsa kubwezeretsedwa kwa khalidwe lozimitsa heroin pamadzi. Kusokoneza. Ubweya. 17, 691-693. (onetsani: 10.1111 / j.1369-1600.2010.00303.x)

  • ↵
    1. Carr KD

    . Nkhono ya 2016 imagwira ntchito yoletsa malonda kwa AMPA ndi chakudya choletsedwa: Cholinga chosayenera cha mankhwala osokoneza bongo ndi zakudya zoletsedwa. Curr. Opin. Behav. Sci. 9, 32-39. (yani: 10.1016 / j.cobeha.2015.11.019)

  • ↵
    1. Karlsson HK,
    2. Tuominen L,
    3. Tuulari JJ,
    4. Hirvonen J,
    5. Parkkola R,
    6. Helin S,
    7. Salminen P,
    8. Nuutila P,
    9. Numma L

    . Kulemera kwa 2015 kumagwirizanitsidwa ndi kuchepa mu-opioid koma osasinthika dopamine D2 receptor kupezeka mu ubongo. J. Neurosci. 35, 3959-3965. (onetsani: 10.1523 / JNEUROSCI.4744-14.2015)

    •