Kutsekemera kwa insulin kumagwirizana ndi Dopamine yochepa yochepa ku D2 / 3 Alandira mu Ventral Striatum ya Anthu Omwe Amakhala Amtendere Osobese (2015)

Int J Neuropsychopharmacol. 2015 Feb 25. pii: pyv014. onetsani: 10.1093 / ijnp / pyv014.

Caravaggio F1, Borlido C1, Hahn M1, Feng Z1, Fervaha G1, Gerretsen P1, Nakajima S1, Plitman E1, Chung JK1, Iwata Y1, Wilson A1, Remington G1, Graff-Guerrero A2.

Kudalirika

MALANGIZO:

Kuledzera kwa zakudya ndi mutu wotsutsana pa sayansi. Umboni wosonyeza kuti matenda a shuga ndi ofanana ndi kuchepa kwa dalamine m'munsi mwa nucleus accumbens, ofanana ndi anthu omwe ali ndi vuto loledzera. Sidziwika ngati mphamvu ya insulini yokhudzana ndi matenda a dopamine m'magulu a anthu. Tinafufuza izi pogwiritsa ntchito agonist dopamine D2/3 zojambula zam'madzi [11C] - (+) - PHNO ndi vuto lalikulu la kutha kwa dopamine. Muchitsanzo chosiyana cha anthu wathanzi, tinayesa ngati dopamine kuwonongeka kungasinthe insulini mphamvu.

ZITSANZO:

Kutsimikizika kwa insulini kunayesedwa pa phunziro lirilonse pogwiritsa ntchito kusala kwa magazi m'magazi ndi insulini pogwiritsira ntchito Homeostasis Model Assessment II. Anthu khumi ndi anayi omwe ali ndi thanzi labwino komanso osagwirizana nawo (3 akazi) anapereka mzere woyamba [11C] - (+) - PHNO scan, 9 yomwe inapangidwira pansi pa dopamine kutaya, kulola kuti chiwerengero cha dopamine chosasinthika pa dopamine D2/3 phwando. Kutaya kwa dopamine kunapindula kudzera mwa alpha-methyl-para-tyrosine (64mg / kg, PO). Mu 25 anthu omwe ali ndi thanzi labwino (9 female), kusala magazi ndi shuga kunaperekedwa musanafike komanso pambuyo poti dopamine iwonongeke.

ZOKHUDZA:

Dopamine yodalirika pa ventral striatum dopamine D2/3 receptor inali yogwirizana kwambiri ndi kutengeka kwa insulini (r(7) =. 84, P = .005) ndipo sagwirizana kwambiri ndi ma insulini (r (7) = -. 85, P = .004). Masewu a shuga sanali ogwirizana ndi dopamine yodalirika pa ventral striatum dopamine D2/3 phwando (r (7) = -. 49, P = .18). Momwemonso, chiwopsezo chachikulu cha dopamine chitayika kwa anthu abwinobwino chinachepetsa kwambiri kuteteza insulini (t (24) = 2.82, P = .01), kuwonjezeka kwa insulini (t (24) = - 2.62, P = .01), ndipo sanasinthe ma glucose (t (24) = - 0.93, P = .36).

POMALIZA:

Anthu omwe ali ndi thanzi labwino, kuchepa kwa mphamvu ya insulini kumagwirizana ndi dopamine yomwe imakhala yochepa kwambiri pa dopamine D2/3 phwando mu ventral striatum. Komanso, kupweteka kwambiri kwa dopamine kumachepetsa kuchepa kwa insulini. Zotsatirazi zikhoza kukhala ndi zofunikira zofunika kwa anthu odwala matendawa omwe ali ndi zovuta zamadzimadzi.

© The Author 2015. Lofalitsidwa ndi Oxford University Press m'malo mwa CINP.

MAFUNSO:

D2; shuga; dopamine; shuga; insulini

Introduction

Kuwonjezereka kochulukira kwa kuchuluka kwa kunenepa kwambiri ndi shuga ku North America, kuganiza kuti ikugwirizana ndi kuwonjezeka kwa zakudya zapamwamba-mafuta / shuga, kumabweretsa mavuto aakulu a anthu onse (Mokdad et al., 2001; Seaquist, 2014). Lingaliro la kuledzera kwa zakudya, kumene zakudya zabwino kwambiri zimawoneka zopindulitsa monga mankhwala osokoneza bongo (Lenoir et al., 2007), imakhalabe mutu wotsutsana kwambiri (Ziauddeen et al., 2012; Volkow et al., 2013a). Mu vivo zojambula zojambula za ubongo mwa anthu zathandizira lingaliro ili, kusonyeza ubongo wofananana ukusintha pakati pa anthu ovuta kwambiri ndi anthu omwe ali ndi vuto la mankhwala osokoneza bongo (Volkow et al., 2013a, 2013b). Zowonjezereka, zakhala zikuwonetsedwa pogwiritsira ntchito positron emission tomography (PET) yomwe anthu olemera kwambiri komanso anthu omwe ali ndi vuto la mankhwala osokoneza bongo ali ndi dopamine yochepa D2/3 receptor (D2/3R) kupezeka mu striatum (Wang et al., 2001), chizoloŵezi cha mankhwala osokoneza bongo (neural marker) chomwechi chikuwonanso mu makoswe omwe amawonjezera zakudya zokoma (Johnson ndi Kenny, 2010).

Dopamine yakufa, makamaka mu ventral striatum (VS), ndizofunika kwambiri kuti mukhale ndi zakudya komanso mankhwala osokoneza bongo (Palmiter, 2007). Pali maumboni angapo omwe amasonyeza kuti shuga ndi kuchepa kwa mphamvu ya insulini (IS) zingagwirizane ndi kuchepa kwa dopamine yodalirika mu VS. Kuchepetsa ubongo wa dopaminergic wakhala ukuwoneka mu makoswe a shuga ndi postmortem ubongo waumunthu, monga momwe amasonyezera ndi kuchepa kwa dopamine kaphatikizidwe ka chiwerengero (Crandall ndi Fernstrom, 1983; Trulson ndi Himmel, 1983; Saller, 1984; Bitar et al., 1986; Bradberry et al., 1989; Kono ndi Takada, 1994) ndi metabolism (Saller, 1984; Kwok et al., 1985; Bitar et al., 1986; Kwok ndi Juorio, 1986; Lackovic et al., 1990; Chen ndi Yang, 1991; Lim et al., 1994). Nthiti zomwe zimapangitsa kuti thupi likhale lopweteka kudzera mu streptozotocin limasonyeza kuchepa kwa dopamine m'munsi mwa nucleus accumbens (Murzi et al., 1996; O'Dell et al., 2014) komanso amamasulidwe a dopamine poyankha amphetamine (Murzi et al., 1996; O'Dell et al., 2014). Mwachidziŵikire, insulini imayendetsa mawonekedwe a maselo (Garcia et al., 2005; Daws et al., 2011) ndi ntchito (Owens et al., 2005; Sevak et al., 2007; Williams et al., 2007; Schoffelmeer et al., 2011) wa dopamine transporter (DAT). Komanso, insulin receptors amasonyezedwa mu nucleus accumbens ndi midbrain dopaminergic neurons (Werther et al., 1987; Figlewicz et al., 2003), komwe angapange mpweya wothamanga, mphamvu zowonjezera mphamvu, komanso mayendedwe a makhalidwe omwe amapereka mphoto monga chakudya, cocaine, ndi amphetamine (Galici et al., 2003; Konner et al., 2011; Schoffelmeer et al., 2011; Mebel et al., 2012; Labouebe et al., 2013). Pamodzi, deta izi zikusonyeza kuti kuchepa kwa IS kungakhale kofanana ndi zochepa za dopamine zolephereka mu VS.

Pakadali pano, maphunziro a 2 PET apenda kufufuza ubale pakati pa abambo a Dopamine D2/3R kupezeka ndi kuchuluka kwa kudya mahomoni a neuroendocrine (Dunn et al., 2012; Guo et al., 2014). Pogwiritsa ntchito antagonist radiotracer [18F] -mwiniwake, Dunn ndi anzake (2012) anasonyeza kuti dopamine D2/3Kupezeka kwa VS kunayanjanitsidwa kwambiri ndi IS mu chitsanzo cha akazi obisala komanso osobese. Popeza kumangiriza mafilimu kumagwirizana ndi dopamine yodalirika pazotsatira (Laruelle et al., 1997; Verhoeff et al., 2001), chinthu chimodzi chotheka chomwe chimapezeka pazimenezi ndi chakuti anthu omwe amachepetsedwa ali ndi dopamine yochepa kwambiri yomwe imakhalapo D2/3R mu VS ndipo motero kumangiriza kwa radiotracer pamsana woyambira. Izi zawonetsedwanso ndi PET kuti anthu omwe ali ndi vuto la cocaine ali ndi dopamine yochepa kwambiri ku D2/3R mu VS (Martinez et al., 2009). Umboni wakuti anthu omwe ali ndi insulin yowonjezera amakhalanso ndi dopamine yochepa kwambiri ku D2/3R mu VS idzawathandiza kuti thupi liziyenda moyenera pa insulini ku dopaminergic mphotho za mphotho za ubongo (Daws et al., 2011) ndi makhalidwe ofunafuna chakudya (Pal et al., 2002). Komabe, palibe kafukufuku wina amene adafufuza momwe kulingalira kwapadera kwa dopamine ku D2/3R mu VS ikukhudzana ndi kuyerekezera kwa YEHOVA mwa anthu.

Kugwiritsira ntchito PET ndi ma radioligands a D2/3R, n'zotheka kukwaniritsa zowonongeka za dopamine yokhazikika D2/3R mwa anthu mu vivo. Izi zingatheke poyerekeza ndi kusintha kwapakati pazomwe mungakwanitse (BPND) pakati pa pET yoyamba ya PET ndikuyang'ana pansi pa dopamine yowonongeka kwambiri (Laruelle et al., 1997; Verhoeff et al., 2001). Malingana ndi chitsanzo chokhalamo, kuyambira pa radiotracer kumangiriza ku D2/3R imagwirizana ndi madera a dopamine pachiyambi, kusintha kwa BPND pambuyo poti dopamine ikutha kuwonetsa momwe dopamine inalikugwiritsira ntchito mapulogalamu pazotsatira (Laruelle et al., 1997; Verhoeff et al., 2001). Kuchuluka kwa dopamine kumatha kupezeka mwa anthu mwa kuletsa dopamine kaphatikizidwe kudzera mwa tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). Paradigm iyi yagwiritsidwa ntchito pofuna kusiyanitsa kusiyana pakati pa ma dopamine omwe amakhala ovuta kudera D2/3R mu statum ya anthu omwe ali ndi matenda a neuropsychiatric (Martinez et al., 2009).

Gulu lathu lapanga [11C] - (+) - PHNO, woyamba PET radiotracer wa D agonist2/3R (Wilson et al., 2005; Graff-Guerrero et al., 2008; Caravaggio et al., 2014). Kugwiritsidwa ntchito kwa agonist radiotracer, yomwe iyenera kufanana mofanana ndi kumangiriza kwa ligand endogenous, ingapereke chiwerengero chodziwika bwino komanso chogwira ntchito kwambiri cha dopamine yodalirika mwa anthu. Komanso, posachedwapa tatsimikizira kugwiritsa ntchito [11C] - (+) - PHNO kuti aone ngati pali dopamine osakwanira pa D2/3R pogwiritsa ntchito vuto la AMPT (Caravaggio et al., 2014). Pamodzi, deta ya anthu imasonyeza kuti wojambulayu amamvetsetsa kusiyana kwa zovuta zedi za dopamine kuposa zotsutsana ndi radiotracers monga [11C] -chilopride (Shotbolt et al., 2012; Caravaggio et al., 2014) ndipo motero zingakhale bwino kuthetsa kusiyana pakati pa magulu oopsa a dopamine ku D2/3R mwa anthu. Kugwiritsa ntchito [11C] - (+) - PHNO mtundu waukulu wa thupi (BMI) mkati mwa malo osabese umapezeka kuti ukugwirizana bwino ndi BPND mu VS koma osati dorsal striatum (Caravaggio et al., 2015). Zomwe mungathe kuzipeza ndizakuti anthu omwe ali ndi BMI ali ndi dopamine yochepa kwambiri yomwe imakhalapo D2/3R mu VS. Kufufuza koyambirira kumeneku kumaphatikizapo kufufulira za ubale umene uli pakati pa IS ndi wodalirika wa dopamine makamaka mu VS monga momwe anayezera ndi [11C] - (+) - PHNO.

Kugwiritsa ntchito [11C] - (+) - PHNO ndi poddimm yowonongeka kwambiri ya dopamine, tinayesetsa kufufuza nthawi yoyamba ngati kulingalira kwa dopamine kosatha ku D2/3R mu VS ya anthu abwino, osobese akugwirizana ndi IS. Tinkaganiza kuti anthu omwe ali ndi kachilombo ka HIV angakhale ndi dopamine yochepa kwambiri yomwe imakhalapo D2/3R mu VS pachiyambi. Ophunzira omwe ali ndi thanzi adayesedwa kuti apereke: 1) chitsimikizo cha lingaliro la ubale pakati pa IS ndi ubongo wa dopamine popanda kukhalapo kosokoneza kusintha komwe kungabwere chifukwa cha matenda; ndi 2) chiwerengero cha mtsogolo poyerekezera ndi anthu odwala. Tinayesetsanso kudziwa ngati kuchepetsa dopamine yokhazikika ndi AMPT kungawononge kusintha kwa anthu omwe ali ndi thanzi labwino. Kufotokozera mgwirizano pakati pa IS ndi ma dopamine mu ubongo wa anthu mu vivo ukayimira chinthu chofunikira choyamba kumvetsetsa kusiyana pakati pa thanzi lamagetsi, mphamvu za homeostasis, ndi maulendo opereka ubongo mu thanzi ndi matenda (Volkow et al., 2013a, 2013b).

Njira ndi Zipangizo

ophunzira

Deta ya 9 ya ophunzira, omwe amapereka gawo la kuphunzira kuti kulingalira kuti dopamine yodalirika ndi PET, idanenedwa kale (Caravaggio et al., 2014). Otsatira onse anali ndi manja abwino komanso opanda vuto lililonse lachipatala kapena la matenda omwe amachitidwa ndi apilo, a Mini International Neuropsychiatric Interview, oyesa ma laboratory, ndi ma electrocardiography. Ophunzirawo anali osasamala ndipo ankayenera kukhala ndi minofu yoipa yogwiritsira ntchito mankhwala osokoneza bongo komanso / kapena kutenga mimba pokhapokha asanayambe kujambulidwa PET. Phunzirolo linavomerezedwa ndi bungwe la Research Ethics Board la Center for Addiction ndi Mental Health, Toronto, ndi onse omwe adapereka chidziwitso chodziwitsidwa.

Utsogoleri wa Metyrosine / AMPT

Ndondomeko ya AMPT-inachititsa kuti dopamine iwonongeke yasindikizidwa kwina (Verhoeff et al., 2001; Caravaggio et al., 2014). Mwachidule, kuchepa kwa dopamine kunayambitsidwa ndikuwongolera pakamwa kwa 64mg metyrosine pa kilogalamu yolemera thupi kwamaola 25. Odziyimira pawokha, sanatenge nawo gawo> 4500mg. Metyrosine idaperekedwa muyezo 6 wofanana nthawi izi: 9:00 am, 12:30 pm (post 3.5 hours), 5:00 pm (post 8 hours), ndi 9:00 pm (post 12 hours) tsiku 1 , ndi 6: 00am (post 21 hours) ndi 10:00 am (post 25 hours) patsiku 2. The post AMPT PET scan inakonzedwa nthawi ya 12 pm, maola 28 pambuyo pa metyrosine yoyamba. Omwe adayang'aniridwa moyang'aniridwa muulamuliro wa AMPT ndipo adagona usiku m'mabedi ofufuzidwira kuchipatala kuti athetse dongosolo la AMPT ndikuwunika zomwe zingachitike. Kuphatikiza apo, maphunziro adalangizidwa kuti azimwa madzi osachepera 4L panthawi yolandila masiku awiri kuti ateteze kupangidwa kwa timibulu ta AMPT mumkodzo, komanso kuyamwa kwamadzi kumayang'aniridwa kuti zitsimikizire kutsatira. Kuphatikiza apo, kuti alkalinize mkodzo, womwe umakulitsa kusungunuka kwa AMPT, sodium bicarbonate (2g) idaperekedwa pakamwa pa 1.25: 10 pm madzulo asanakwane 00 ndi 1: 7 am patsiku 00 la utsogoleri.

Kusuta Plasma Data

Ophunzira adafunsidwa kuti asadye ndi kumwa zakumwa kupatula madzi a 10 kwa maola 12 musanayambe kugwira ntchito ya magazi, yomwe inasonkhanitsidwa ku 9: 00 am. Kwa omwe adapereka PET scans (n ​​= 11), ntchito yowirira magazi inasonkhanitsidwa pa tsiku la PET. Otsatira makumi awiri ndi asanu omwe ali ndi thanzi labwino (9 azimayi, a zaka zakubadwa = 31 ± 11, BMI: 22-28) amapereka ntchito yowonjezera magazi (9: 00 am) pazotsatira ndipo atalandira madongosolo a 5 a AMPT. Kwa 13 za nkhanizi, zinkatheka kusonkhanitsa magazi pogwiritsa ntchito maola a 24. Pazinthu zotsalira, 4 inapereka magazi ku 6 masiku osachepera 7, 4 inapereka 10 masiku a 14 pambali, ndipo 2 inapereka 36 masiku a 43 padera. Magazi a m'magazi a 4-ML omwe anali ndi sodium fluorate anali okosijeni ndi osakaniza monga potassium. Plasma inayesedwa ndi shuga pa EXL 200 Analyzer (Siemens) pogwiritsa ntchito njira ya hexokinase-glucose-6-phosphate dehydrogenase njira. Magazi a insulini ankayengedwa mu tube ya 6-mL yofiira yofiira popanda zowonjezera. Seramu inafufuzidwa pa Access 2 Analyzer (Beckman Coulter) pogwiritsira ntchito paramagnetic particle, chemiluminescent immunoassay kuti chiwerengero cha insulini chitetezeke mu seramu yaumunthu. Chizindikiro cha kuyamwa kwa glucose chimawerengedwa pa phunziro lirilonse pogwiritsa ntchito kusala kwa magazi m'magazi ndi insulini pogwiritsa ntchito Homeostasis Model Assessment II (HOMA2), yowerengedwa ndi University of Oxford HOMA2 calculator (v2.2.2; http://www.dtu.ox.ac.uk/homacalculator/) (Wallace et al., 2004). Chiwerengero cha ZIMENE chimachitika pogwiritsa ntchito HOMA2 chimagwirizanitsidwa kwambiri ndi zomwe zimapezeka ndi njira yowonongeka ya hyperinsulinemic-euglycemic method (Matthews ndi al., 1985; Levy et al., 1998).

PET Imaging

Ophunzira adalandira 2 [11C] - (+) - PHNO PET imafufuza, imodzi pansi pa zochitika zoyambira ndipo ina pa maola 25 pambuyo pa kuchepetsa dopamine AMPT. Radiyoyynthesis ya [11C] - (+) - PHNO ndi kupeza zithunzi za PET zakhala zikufotokozedwa mwatsatanetsatane (Wilson et al., 2000, 2005; Graff-Guerrero et al., 2010). Mwachidule, mafano adapezedwa pogwiritsa ntchito njira yamakono yopangira makamera a PET (CPS-HRRT; Siemens Molecular Imaging) poyerekeza ndi chidziwitso pazithupi za 207 ndi ubweya wa 1.2mm aliyense. Kukonzekera kwa ndegeyi kunali ~ 2.8mm full-width at theka-maximum. Zojambula zotumizira zinapezedwa pogwiritsa ntchito 137Cs (T1/2 = 30.2 yr, E = 662 KeV) gwero lamodzi lokha la photon loperekera kukonzekera kuchepetsa, ndipo deta ya deta inapezedwa mndandanda wa mndandanda. Deta yofiira inamangidwanso ndi kuyang'aniridwa kumbuyo. Kwa maziko [11C] - (+) - PHNO imafufuza (n = 11), mlingo wa radioactivity ndi 9 (± 1.5) mCi, ndi ntchito yapadera ya 1087 (± 341) mCi / μmol ndi jekeseni wa 2.2 (± 0.4) μg. Kuyeza kwa dopamine (n = 9), mlingo wa radioactivity ndi 9 (± 1.6) mCi, ndi ntchito yapadera ya 1044 (± 310) mCi / μmol ndi jekeseni wa 2.1 (± 0.4) μg. Panalibe kusiyana pakati pa nthenda ya radioactivity dose (t(8) = 0.98, P= .36), ntchito yapadera (t(8) = 1.09, P= .31), kapena injected mass (t(8) = - 0.61, P= .56) pakati pa zowonongeka ndi dopamine zowonongeka (n = 9). [11C] - (+) - PHNO data yowunikira inapezedwa kwa 90 maminiti pambuyo pake. Kamangidwe kameneka kanali kozaza, detayi idasinthidwanso muzithunzi za 30 (1-15 ya mphindi ya 1 ndi 16-30 ya mphindi ya 5).

Zithunzi Zamatsenga

Chigawo chochititsa chidwi (ROI) -kutsutsana kozama kwa [11C] - (+) - PHNO yakhala ikufotokozedwa mwatsatanetsatane (Graff-Guerrero et al., 2008; Tziortzi et al., 2011). Mwachidule, nthawi yothandizira nthawi (TACs) yochokera ku ROI imapezeka kuchokera ku zithunzi za PET zowonongeka pazithunzi za MRI. Kulembetsa kwa mgwirizano wa MRI uliwonse mpaka PET malo unapezedwa pogwiritsa ntchito njira yolumikizirana yovomerezeka (Studholme et al., 1997), monga momwe anagwiritsiridwa ntchito mu SPM2 (SPM2, Dipatimenti ya Wellcome Dipatimenti Yodziŵa Zogwirizana ndi Nzeru, London; http://www.fil.ion.ucl.ac.uk/spm). TACs idasanthuledwa pogwiritsira ntchito Yowonjezera Buku la Tissue Method (Lammertsma ndi Hume, 1996) pogwiritsa ntchito cerebellum monga malo owonetsera, kuti atenge chiwerengero chokwanira cha kumangiriza: kumanga zinthu zogwirizana ndi chipinda chosasunthika (BP)ND), monga kutanthauzira mawu ovomerezeka a maumboni omwe amawagwiritsira ntchito mobwerezabwereza (Innis et al., 2007). Maziko ogwira ntchito kukhazikitsidwa kwa Ndondomeko Yowonjezera Yophatikiza Njira Yopangira (Gunn et al., 1997) anagwiritsidwa ntchito pa zithunzi zolimba za PET kuti apange mauthenga apamwamba a voxelND mapu ogwiritsa ntchito PMOD (v2.7, PMOD Technologies, Zurich, Switzerland). Mtundu umene maziko ake amagwiritsidwa ntchito (K2mphindi - K2max) anali 0.006 kwa 0.6. Zithunzi izi zinali zosawerengeka ku malo a ubongo wa MNI ndi malo oyandikana nawo oyandikana nawo pafupi ndi kukula kwa voxel okonzedwa ku 2 × 2 × 2mm3 pogwiritsa ntchito SPM2. Regional BPND Zomwe zimayesedwa ndiye zinachokera ku ROI zomwe zimatchulidwa mu MNI space. VS ndi dorsal striatum (dorsal caudate, hereafter caudate ndi dorsal putamen, pano) Mawlawi et al. (2001).

Kuyesa Mipingo Yopanda Dopamine

Chiwerengero cha ma dopamine osakwanira pa D2/3R ankagwiritsidwa ntchito pachithunzi chokhala ndi malo omwe amakhala ndi radiotracers monga [11C] - (+) - PHNO kwa D2/3R imagwirizana ndi ma dopamine (Laruelle et al., 1997; Verhoeff et al., 2001; Cumming et al., 2002). Zimaganiziridwa ndi chitsanzo ichi: 1) maziko D2/3R BPND amavutitsidwa ndi dopamine yodalirika, ndiko kuti, yapamwamba kwambiri ya dopamine, pansipa phindu la D2/3R BPND; 2) D2/3R BPND pansi pazomwe zikuwonetsa molondola chiwerengero chenicheni cha D2/3R; ndi 3) kuwonjezeka kochepa mu D2/3R BPND Dopamine itatha [ie, 100 * (Depletion BPND - Baseline BPND) / Baseline BPND = % ΔBPND] ali ofanana mofanana ndi ndondomeko yoyamba ya dopamine ku D2/3R, pokhapokha ndondomeko yothetsera dopamine sikusintha chiwerengero ndi kugwirizana kwa D2/3R. Choncho,% ΔBPND, pamaganizo oyenera, amaonedwa kuti ndi ofanana kwambiri ndi ma dopamine omwe ali ovuta kwambiri pa D2/3R (Verhoeff et al., 2001). Malingana ndi kafukufuku wathu wakale, sitinathe kulingalira dopamine yodalirika mu nambala ya nigra, komanso sitinathe kulingalira moyenera dopamine yodalirika mu hypothalamus ndi ventral pallidum pa maphunziro onse (Caravaggio et al., 2014). Choncho, ma ROI awa sanafufuzidwe panopa.

Chiwerengero cha Kusanthula

Cholinga chathu choyambirira chinali kuyesa mgwirizano pakati pa IS ndi zovuta kwambiri za dopamine mu VS. Tinayesa kufufuza pakati pa IS ndi dopamine yodalirika m'mbali yonse ya striatum: caudate, putamen, ndi globus pallidus.

Ubale pakati pa BP yoyambaND ndipo IS anafufuzidwa mu ROI kuti afotokoze zovuta zilizonse ndi mapepala osakanikirana a dopamine (ngati alipo). Zomwe zimagwiritsidwa ntchito pogwiritsa ntchito SPSS (v.12.0; SPSS, Chicago, IL) ndi GraphPad (v.5.0; GraphPad Software, La Jolla, CA). Chizoloŵezi cha mitunduyi chinatsimikiziridwa pogwiritsa ntchito mayeso a D'Agostino-Pearson. Mbali yofunika ya mayesero onse adayikidwa P<.05 (2-mchira).

Results

Anthu khumi ndi anayi ali ndi thanzi labwino, osabedi komanso osaphunzira (3 akazi) adagwira nawo gawo la PET la phunzirolo; ndondomeko ya deta iyi yakhala ikufotokozedwa kale (Gulu 1) (Caravaggio et al., 2014). Pogwiritsa ntchito zitsanzo zonse (n = 11), kuyesa mgwirizano pakati pa magulu owonetserako owonetsetsawo akuwonetsa kuti zaka zakhala zikugwirizana bwino ndi chiuno (r(9) =. 76, P= .007), ndipo chiuno chapafupi chinali chogwirizana kwambiri ndi msangamsanga wa insulini (r(9) =. 80, P= .003) (Gulu 2).

Gulu 1. 

Chiwerengero cha Owerengera

  Otsatira a PET PET 

(n = 11)

 AMPT-PET 

ophunzira

(n = 9)
Zaka (zaka) 29 (8) 29 (9)
mitundu: 20-43 20-43
Kusakaniza shuga (mmol / L) 5 (0.3) 5 (0.3)
mitundu: 4.3-5.3 4.3-5.3
Kusuta insulini (pmol / L) 31 (25) 34 (26)
mitundu: 15-101 15-101
Kutsimikizika kwa insulini (% S) 211 (70) 197 (70)
mitundu: 53-276 53-276
Thupi la Misa ya Thupi (kg / m2) 25 (2.4) 25 (2.4)
mitundu: 22-28 22-28
Chiuno chozungulira (cm) 35 (6) 36 (7)
mitundu: 27-52 27-52

  • Makhalidwe amawonetsera njira ndi kupotoza kwabwino pakati pa makolo.

    Mafasho: AMPT, alpha-methyl-para-tyrosine; PET, positron emission tomography.

Gulu 2. 

Pearson Mgwirizano pakati pa Mabaibulo a Mitambo

  Age BMI Chiuno Kusadulidwa Gulu wa Kusala Kusuta kwa insulini
Insulin mphamvu -0.179 (P= .599) -0.571 (P = .067) -0.602† (P = .050) -0.517 (P = .103) -0.926*** (P = .0001)
Kusuta insulini 0.422 (P = .196) 0.529 (P = .095) 0.795** (P = .003) 0.598† (P = .052)  
Kusakaniza shuga 0.420 (P = .199) 0.063 (P = .855) 0.516 (P = .104)    
Chiuno chozungulira 0.756** (P = .007) 0.466 (P = .149)      
Thupi Misa Index 0.050 (P = .883)        

  • †Mgwirizano uli pamtundu wofunika kwambiri: 0.05 (2-tailed).

  • **Kugwirizana kuli kofunika pa msinkhu wa 0.01 (2-tailed).

  • ***Kugwirizana kuli kofunika pa msinkhu wa 0.001 (2-tailed).

Nkhani zisanu ndi zinayi za 11 zinapereka zonsezi PET ndikuyang'ana pang'onopang'ono pansi pa chiopsezo chachikulu cha AMPT chosokoneza dopamine; izi zimaperekedwa zoganizira za dopamine yosasamala yomwe ikugwira ntchito D2/3R mu VS pachiyambi (ie, peresenti amasintha [11C] - (+) - PHNO BPND dopamine isanafike komanso pambuyo pake. Kuwerengedwa kwa dopamine kumapeto kwa D2/3R mu VS inali yolumikizidwa bwino ndi IS (r(7) =. 84, P= .005) (Chithunzi 1), a Chigwirizano chomwe chinatsalira pambuyo pa chiwerengero cholamulira popanda ufulu kwa zaka (r(6) =. 86, P= .007), BMI (r(6) =. 72, P= .04), chiuno chozungulira (r (6) =. 75, P= .03), ndi ma plasma a AMPT (r(6) =. 84, P= .009). Panthawi yomweyo, akuti dopamine amayamba kukhala D2/3R mu VS idagwirizana kwambiri ndi kusala kudya kwa insulini (r(7) = -. 85, P= .004) koma silinagwirizanitsidwe ndi msanga wa shuga (r(7) = -. 49, P= .18). Dopamine amene amakhala mu VS sanali ogwirizana ndi BMI (r(7) =. 09, P= .80) kapena chiuno chozungulira (r(7) = -. 30, P= .41).

Chithunzi 1. 

Kugwirizana pakati pa kuyerekezedwa kwa insulini (IS) ndi dopamine yodalirika pa D2/3 mapulogalamu (D2/3R) mu ventral striatum (VS) ya 9 anthu wathanzi.

Zowonjezereka, izi zokhudzana ndipamwamba zomwe zili ndi dopamine yoyamba kukhala D2/3R ankatsatiridwa makamaka ndi dopamine okhala mu VS yoyenera koma osati VS kumanzere. Mwachindunji, dopamine yomwe ili kumanzere kwa VS sinayanjane ndi IS (r(7) =. 41, P= .28), msinkhu wa kudya wa insulini (r(7) = -. 46, P= .22), kapena shuga (r(7) = -. 33, P= .39), pamene dopamine amakhala mu VS yolondola anali ogwirizana kwambiri ndi IS (r(7) =. 75, P= .01), yosagwirizana kwambiri ndi msangamsanga wa insulini (r(7) = -. 73, P= .02), ndipo sichigwirizana ndi magulu a shuga (r(7) = - 39., P= .31).

Muzitsanzo zonse (n = 11), maziko oyambirira [11C] - (+) - PHNO BPND mu VS yolondola inagwirizanitsidwa kwambiri ndi estimation IS (r(9) = -. 65, P= .02) (Chithunzi 2). Potero, anthu omwe ali ndi dopamine ochepa kwambiri omwe akukhalapo D2/3R anali ndi BP wapamwamba kwambiriND pazotsatira, mogwirizana ndi kuchepetsa mpikisano wa zovuta zomwe zimamangidwa ndi dopamine yodalirika ndi kuchepa kwa IS. Panthaŵi imodzimodziyo, kusala kudya kwa insulini kunkagwirizana kwambiri ndi [11C] - (+) - PHNO BPND mu VS yoyenera (r(9) =. 77, P= .006), pomwe panalibe mgwirizano ndi mazira a kudya shuga (r(9) =. 27, P= .43). Mwachidziwikire, [11C] - (+) - PHNO BPND kumanzere kwa VS sikunayanjane ndi IS (r(9) = -. 35, P= .29) kapena msinkhu wa kudya insulini (r(9) =. 53, P= .09) ndi shugar(9) =. 08, P= .81).

Chithunzi 2. 

Chiyanjano pakati pa dopamine D2/3 receptor (D2/3R) kupezeka - [11C] - (+) - PHNO BPND - komanso kuti mphamvu ya insulini (IS) mu 11 anthu wathanzi.

Kufufuza kosanthula kunawonetsa kuti chiwerengero cha ISI sichinagwirizane ndi kuyerekezera kwa dopamine yodalirika pa D2/3R mu zovuta (r(7) =. 47, P= .20), putamen (r(7) =. 52, P= .15), kapena globus pallidus (r(7) =. 33, P= .40). Panalibenso mgwirizano pakati pa kuyerekezera dopamine kukhala m'madera awa ndi kusala kudya kwa insulini kapena shuga, komanso BMI ndi chiuno chozungulira (zonse P> .05; deta yosawonetsedwa).

Kufufuza momwe kuchepetsa kupweteka kwa dopamine kumakhudza IS, 25 kulamulira wathanzi (zaka zowonjezereka = 31 ± 11; 9 yazimayi) inaperekanso kudya magazi a insulini ndi shuga pamaso ndi pambuyo pa AMPT dopamine kutha. AMPT yochuluka kwambiri yowonjezera mazira a plasma kusala kudya insulini (t(24) = - 2.62, P= .01) pamene sichimasintha kwambiri magulu a plasma a kusala kudya (t(24) = - 0.93, P= .36). Chodziwika, AMPT yacheperachepera chiwerengero cha IS (t(24) = 2.82, P= .01) (Chithunzi 3). Kuchotsa nkhani zomwe zinali ndi nthawi yoposa masabata a 2 pakati pa ntchito yosonkhanitsa magazi sizinasinthe kwambiri zotsatira zomwe tazitchula (data yosasonyezedwa).

Chithunzi 3. 

Mphamvu ya dopamine yovuta kwambiri kupyolera mwa alpha-methyl-para-tyrosine (AMPT) yomwe imayesedwa kuti imadziwika ndi insulini (IS), komanso kusala kudya m'magazi a insulini ndi shuga, mu 25 anthu wathanzi (zolakwitsa zimasonyeza SD). Kwazithunzithunzi za 8, chikhalidwe chawo chotsitsimula cha US chosagwirizana ndi kachitidwe kaŵirikaŵiri: 6 inakula ndipo 2 inakhala yofanana.

Kukambirana

Kugwiritsa ntchito agonist radiotracer [11C] - (+) - PHNO ndi poddimm yowonongeka kwambiri ya dopamine, timasonyeza kuti nthawi yoyamba idavomerezedwa bwino ndi ma dopamine omwe amatha ku D2/3R mu VS. Ngati kulibe kunenepa kwambiri kapena kuchepa kwa shuga, kuchepa kwa dopamine m'munsi mwa VS kumagwirizana ndi kuchepa kwa IS. Kufufuza kumeneku kukugwirizana ndi kale lomwe mu vivo PET kafukufuku wolemba D2/3Kupezeka kwa VS ya anthu olemera kwambiri (Dunn et al., 2012) ndipo imathandizira zotsatira zaposmortem zaumunthu (Lackovic et al., 1990) komanso zowonongeka kwa nyama (Murzi et al., 1996; O'Dell et al., 2014). Mogwirizana ndi kupeza kwa PET, kuyesa kuchepetsa kuchepa kwa dopamine mu chitsanzo cha anthu abwino omwe ankagwirizana ndi kuchepetsedwa kwa IS.

Umboni umasonyeza kuti ubongo wa insulin umatsutsana-umapezeka ndi pulogalamu ya insulin yokhazikika, ndi anthu omwe sagonjetsedwa ndi insulini omwe amasonyeza kuchepa kwa shuga m'magazi a VS ndi prefrontal cortex chifukwa cha pulogalamu ya insulin (Anthony et al., 2006). Chochititsa chidwi, chapakati D2/3R agonism mu makoswe amatha kuwonjezera kuchuluka kwa shuga m'mphepete mwake, osati mu ubongo (Arneric et al., 1984; Saller ndi Kreamer, 1991). M'nkhaniyi, zimapereka ndemanga yakuti bromocriptine, nonspecific dopamine receptor agonist, imasonyezedwa pochiza matenda a shuga (Grunberger, 2013; Kumar et al., 2013). Motero, kusintha kwapadera pakati pa dopamine / insulin receptor ogwira ntchito mu VS ya anthu kungakhale ndi zofunikira kwambiri pakuthana ndi matenda a kagayidwe kachakudya. Tiyenera kukumbukira kuti ngakhale dopamine mu accumbens amasinthidwa ndi kusintha kwa magazi m'magazi pogwiritsa ntchito hyperinsulinemia, ubale umenewu ukhoza kukhala wovuta, ndi nthawi (acute vs chronic) ndi dose (physiological vs supraphysiological) zotsatira zonse zikuwoneka ngati zofunika (Bello ndi Hajnal, 2006).

Zoperewera pa phunziro lathu lachidziwitso sizikutengera sampulumu anthu omwe ali ndi vuto la shuga; Choncho, zovuta zomwe zimapangitsa kuti anthu azikhala ndi matenda a cardiometabolic ndi ovuta kuyankhapo. Izi zikusonyezedwa kuti kafukufuku wamtsogolo adzafufuze momwe madigiri osiyana a shuga dysmetabolism (mwachitsanzo, insulin kukana, prediabetes, shuga) ndi ofanana ndi zowonongeka za dopamine ndi dopamine kumasulidwa mu VS ya anthu. Kuonjezera apo, kufufuza kwa m'tsogolo kuyenera kuwona ngati izi zikusintha pakadutsa chithandizo cha zoperewera zamagetsi. Komanso, n'kofunika kufufuza njira zosiyanasiyana za kuchepa kwa shuga kwa anthu momwe momwe mawerengedwe a dopamine ndi machitidwe a VS akukhudzira zokhudzana ndi maganizo, zolinga, ndi mphoto. Potsiriza, chitsanzo chathu mu phunziro la tsopano ndiloling'ono. Ngakhale kuti sitinayambe kuwonetsa mwachindunji kuti tifanizire zambiri, ndibwino kuti tizindikire kuti ubale wa pakati pa IS ndi wokonzeka kukhala ndi dopamine mu VS udzapulumuka kukonzedwa kwa Bonferroni (kukonzedwa P chiwerengero chamtengo wapatali: P= .01 (0.05 / 4 ROI). Maphunziro a AMPT amtsogolo akuyesa kuyanjana kwa mgwirizano pakati pa dopamine m'kati mwa ubongo ndipo iyenso ayesetse kugwiritsa ntchito kukula kwakukulu. Chifukwa cha kukula kwathu kochepa, sitinayese kufufuza maubwenzi pakati pa chiyambi [11C] - (+) - PHNO BPND ndipo ali mu ROI kupatula VS. Makamaka, tsogolo [11C] - (+) - PHNO kufufuza pogwiritsa ntchito makulidwe akuluakulu ayenera kuyang'ana mgwirizano pakati pa IS ndi BPND mu substantia nigra ndi hypothalamus: madera kumene 100% ya [11C] - (+) - PHNO BPND chizindikiro ndi chifukwa cha D3R vs D2R (Searle et al., 2010; Tziortzi et al., 2011). Kudziwa kwathu, maphunziro sanaganizire ngati pali kusiyana pakati pakati pa D3R vs D2R poyankhula ndi pulogalamu ya insulini kukana nyama kapena anthu. Izi zimafuna kufufuza, kuyambira D3R ikhoza kuthandizira kuchepetsa kuthamanga kwa insulini pena paliponse (Ustione ndi Pistoni, 2012), ndi D3R kugwedeza mbewa zakhala zikudziwika ngati kukhala ndi kunenepa kwambiri kowonjezera (phenonepe)McQuade et al., 2004).

Kodi mgwirizano wa pakati pa insulini ndi wotani, kusintha kwa dopamine, komanso mphotho ya chakudya? Kusintha kwa insulini kumawoneka kusintha ntchito ya masolimbic dopamine system, yomwe imakhudza chakudya ndi chakudya cha mphotho (Figlewicz et al., 2006; Labouebe et al., 2013). Anthu amanena kuti insulin ikhoza kuletsa dopamine neurons mu ventral tegmental area (VTA) kotero kuti kuchepetsa kutulutsa dopamine mu accumbens (Palmiter, 2007). Zowoneka kuti, majekisoni oopsa a insulin mu VTA awonetsedwa kuti alepheretsa kudya zakudya zamtengo wapatali kwambiri m'makoswe osasintha popanda kusinthana ndi njala (Mebel et al., 2012). Komanso, makoswe amadzimadzi amasonyeza kuwonjezeka kwa zakudya zokhudzana ndi kugwiritsidwa ntchito kosinthika kwa nucleus accumbens (Pal et al., 2002). Deta mu makoswe abwino amasonyeza kuti phokoso la insulini jekesoni limatha kuwonjezera dopamine kumasulidwa mu nucleus accumbens (Potter et al., 1999), ndipo insulini pa se imodzi ikhoza kukhala yopindulitsa (Jouhaneau ndi Le Magnen, 1980; Castonguay ndi Dubuc, 1989). Choncho, njira zenizeni zomwe zimakhala zovuta kwambiri kuti thupi likhale losavuta komanso lopanda matenda a insulini limakhudza masolimbic dopamine dongosolo komanso ma dopamine mmenemo siziri bwino. Kuonjezerapo, sizikudziwika bwino momwe machitidwewa angasinthire muzitsulo zowonongeka bwino ndi omwe ali ndi matenda.

Kafukufuku wochuluka afufuza momwe insulini imakhudzira DAT ndi makhalidwe okhudzana ndi mphotho kwa mankhwala osokoneza bongo omwe amachititsa DAT, monga cocaine ndi amphetamine (Daws et al., 2011). Mwachitsanzo, ntchentche zopanda mphamvu zimathandiza kuchepetsa amphetamine (Galici et al., 2003), pamene kuwonjezeka kwa insulini mu accumbens kumapangitsa kuti munthu asamangokhalira kumwa mankhwala a cocaine.Schoffelmeer et al., 2011). Komabe, pamene maselo omwe amachititsa kuti insulin isinthe DAT ntchito ndi mawu akudziwikiratu, zotsatira zotsatizana zakhala zikuwonedwa pa maphunziro omwe amagwiritsa ntchito mankhwala omwe amachititsa kuti atha kukhala ndi matenda a insulin (striatum)Galici et al., 2003; Owens et al., 2005; Sevak et al., 2007; Williams et al., 2007; Schoffelmeer et al., 2011; Owens et al., 2012; O'Dell et al., 2014) ndi VTA (Figlewicz et al., 1996, 2003; Mebel et al., 2012). Ambiri mwa maphunzirowa sanazindikire mosiyana momwe insulini imakhudzira DAT mu dorsal striatum vs VS, kapena accum accums core core shell. Izi zikhoza kukhala magwero a chisokonezo, chifukwa mawu, lamulo, ndi ntchito ya DAT zingakhale zosiyana m'madera osiyana siyana (Nirenberg et al., 1997; Siciliano et al., 2014). Kudziwa kwathu, palibe phunziro la ubongo la ubongo la umunthu lomwe lafufuza za ubale pakati pa insulin kukana ndi kupezeka kwa DAT. Zomwe zokhudzana ndi mgwirizano pakati pa BMI ndi kupezeka kwa DAT kwa anthu zakhala zosakanikirana (Chen et al., 2008; Thomsen et al., 2013; van de Giessen et al., 2013), ngakhale kuti maphunzirowa sanayambe kufufuza VS. N'zochititsa chidwi kuti ogwiritsa ntchito amphetamine amanena kuti kunenepa kwambiri kwa ubwana ndi matenda a psychopathology (Ricca et al., 2009), kuwonetseranso zofunikira zomwe zimachitika pakati pa chakudya ndi mankhwala.Volkow et al., 2013b).

Zomwe zikupezeka panopa kuti zochepa zomwe zimagwiritsidwa ntchito ndizomwe zimagwirizanitsidwa ndi kuchepetsedwa kwa dopamine mu VS zingakhale ndi zifukwa zokhudzana ndi zakudya ndi mankhwala osokoneza bongo. Zakhala zikuperekedwa kuti kuwonjezeka kwa BMI ndi khalidwe lodyera kumagwirizana ndi kuchepetsedwa kwa presynaptic dopamine kaphatikizidwe mphamvu mu statum ya anthu abwino (Wilcox et al., 2010; Wallace et al., 2014). Datha kuchokera Wang ndi anzake (2014) amasonyeza kuti anthu olemera kwambiri amasonyeza kuti amamasulidwa dopamine mu VS chifukwa cha kuchepetsa zakudya zamakono poyerekezera ndi anthu omwe sioobese. Kuwonjezera apo, pogwiritsa ntchito SPECT, awonetseredwa kuti owonjezera akazi amasonyeza kuchepa kwa dopamine kumasulidwa ndi amphetamine (van de Giessen et al., 2014). Izi zikhoza kuwonetsa kuti VS dopamine yomasulidwa yamasulidwe akuwoneka kuti ali ndi matenda a shuga komanso anthu omwe ali ndi vuto la mankhwala osokoneza bongo poyankha psychostimulants (Volkow et al., 2009). Zidzakhala zofunikira kufotokoza ngati anthu omwe ali ndi shuga amasonyezanso kusokoneza kwa dopamine kumasulidwa chifukwa cha chakudya, chakudya, ndi / kapena psychostimulants. Pogwiritsa ntchito, mu maphunziro a ubongo ubongo umasonyeza kuti kunenepa ndi mwinamwake kuteteza insulini kumagwirizanitsa ndi kuchepetsedwa kwa dopamine kaphatikizidwe, kumasulidwa, ndi mawu osayenerera mu VS.

Ngakhale kuti sitinapeze mgwirizano pakati pa IS ndi ma dopamine osakwanira mu dorsal striatum, ndikofunikira kufotokoza kuti ziwerengero za ziweto zambiri zasintha kusintha kwa dorsal striatal dopamine ndi kugwira ntchito kwa neurons mu substantia nigra poyerekeza ndi insulini kukana (Morris et al., 2011). Mwachidziŵikire, kwa anthu dopamine kumasulidwa chifukwa cha chakudya mu storal striatum yapezeka kuti ikugwirizana ndi ziyeso za chakudya chosangalatsa (Small et al., 2003). Mwinamwake, kuchepetsedwa kumakhudza VS dopamine kugwira ntchito yoyamba, ndi kusintha kwa dorsal striatal dopamine kumagwirira ntchito kokha poyera ndi insulini yotsutsa. N'zotheka kuti phunziroli lidayang'aniridwa ndi / kapena sanagwiritse ntchito mndandanda wa EN kuti awone zotsatira zake mu dorsal striatum.

Deta iyi ili ndi zofunikira zofunika pa matendawa a neuropsychiatric omwe insulin kukana akhoza kukhala ophatikizana kapena ophatikizana. Mwachitsanzo, maumboni angapo amasonyeza kuti amalumikizana pakati pa insulini kukana ndi chitukuko cha matenda a Parkinson (Santiago ndi Potashkin), matenda a Alzheimer's (Willette et al., 2014), ndi kuvutika maganizo (Pan et al., 2010). Mogwirizana ndi lingaliro lakuti insulin kukana ingagwirizane ndi kuchepa kwa dopamine yopweteka, zimayesa kulingalira kuti m'munsimu CH chingapereke chitetezo pa maganizo a anthu omwe ali ndi schizophrenia. Mwachitsanzo, mu chiyambi choyambirira cha Chitchaina, anthu osadziŵa mankhwala omwe ali ndi schizophrenia, kuthamanga kwakukulu kwa insulini kumagwirizana ndi kuchepa kwakukulu kwa zizindikiro zabwino (Chen et al., 2013). Zimatsimikiziridwa kuti anthu omwe ali ndi schizophrenia, komanso achibale awo osakhudzidwa (Fernandez-Egea et al., 2008), amakhala osowa kwambiri; izi zapezeka musanayambe kugwiritsira ntchito mankhwala osokoneza bongo ndipo mutatha kuyesetsa kuti muzikhala ndi makhalidwe (Kirkpatrick et al., 2012). Komanso, kusiyanasiyana pakati pa shuga kumaphatikizapo magulu a anthu omwe ali ndi matenda a schizophrenia omwe amadziwika ndi zizindikiro zosiyana siyana za zizindikiro zoopsa (Kirkpatrick et al., 2009). Malingana ndi zochitikazi, kuphatikizapo mbiri yakale yomwe insulin-inachititsa kuti kansalu ikhoze kuyambitsa zizindikiro za psychotic (West et al., 1955), zimakhala zosangalatsa kuganiza kuti pakatikati pa insulin kuwonetsa pa dopamine neurons kungathandize pa matenda ndi chithandizo cha schizophrenia (Lovestone et al., 2007). Maphunziro a PET amtsogolo akuyang'ana kuyanjana pakati pa matenda a maganizo ndi insulin kutsutsana pazitali za dopamine ndithudi zikuwoneka kuti ndi zoyenera.

Pomalizira, pogwiritsa ntchito PET ndi vuto lalikulu la kuthetsa vuto la dopamine, tawonetsa kwa nthawi yoyamba kuti kulingalira kwa IS kuli kofanana ndi ma dopamine othetsera D2/3R mu VS ya anthu abwino. Kuwonjezera pamenepo, kuchepetsa kuchepa kwa dopamine kwa anthu abwino kungasinthe momwe zilili. Kuphatikizidwa pamodzi, zotsatirazi zikuyimira chiyambi chofunikira pozindikira momwe chikhalidwe cha thupi chimagwirira ntchito ndi matenda akuluakulu a maganizo monga schizophrenia.

Chikhalidwe cha chidwi

Dr. Nakajima malipoti atalandira wapereka ku Japan Society kwa patsogolo Science ndi Inokashira Hospital Fund Research ndi honoraria wokamba kuchokera GlaxoSmith Kline, Janssen mankhwala, Pfizer, ndi Yoshitomiyakuhin m'zaka 3 zapitazi. Dr. Graff-Guerrerro akupeza thandizo lofufuzira kuchokera ku bungwe lopereka ndalama zowonjezera: Ma Institutes of Health Research, US National Institute of Health, ndi Mexico Instituto de Ciencia y Tecnologıa ku Capital del Conocimiento ku Distrito Federal (ICyTDF). Iye walandiridwanso ntchito zamalonda kuchokera ku Abbott Laboratories, Gedeon-Richter Plc, ndi Lundbeck; perekani thandizo kuchokera kwa Janssen; ndi malipiro okhudzana ndi Eli Lilly. Dr. Remington walandira thandizo la kafukufuku, malipiro othandizira, kapena ndalama za oyankhula ku bungwe laku Canada la matenda a shuga, Canadian Institutes of Health Research, Hoffman-La Roche, Laboratorios Farmacéuticos Rovi, Medicine, Neurocrine Biosciences, Novartis Canada, Research Research Fund-Canada Foundation kwa Innovation, ndi Society Schizophrenia ya Ontario. Olemba ena alibe mpikisano kuti awulule.

Kuvomereza

Phunziroli linalipidwa ndi a Canadian Institutes of Health Research (MOP-114989) ndi US National Institute of Health (RO1MH084886-01A2). Olembawo ayamika antchito a PET Center ku Center for Addiction ndi Mental Health kuti athandizidwe pothandizira deta. Amawathokoza ndi mtima wonse Yukiko Mihash, Akufuna Mar, Thushanthi Balakumar, ndi Danielle Uy kuti awathandize.

Ichi ndi nkhani yotsegulidwa yogawidwa pansi pa lamulo la Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), zomwe zimaloleza kubwezeretsa, kubwezeretsa, ndi kubwezeretsa mwakuya kulikonse, kupatula kuti ntchito yoyambirira imatchulidwa bwino.

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Onani Abstract