Hoʻopili pū ʻia nā Deptamine Striatal D2 Receptors haʻahaʻa me nā metabolism prefrontal ma nā kumuhana obese: nā mea hiki ke hāʻawi ʻia (2008)

KĀNUI: ʻO kēia aʻo ʻana i ka momona, i manaʻo ʻia i nā mea hoʻokele dopamine (D2) a me kā lākou pilina e hana ana i ka lobe mua. ʻO kēia noiʻi, ma ke poʻo o ka NIDA, hōʻike ʻia nā puʻuwai overeaters e like me nā mea hoʻohālikelike i ka lāʻau lapaʻau i loko o nā hana ʻelua i hōʻike ʻia. E like me ka mikouka lāʻau, loaʻa i ka obese nā haʻahaʻa D2 haʻahaʻa, a me hypofrontality. ʻO ka meaʻoi loa o ka D2 ka mea nui i ka desensitization (ke kiʻi ʻoluʻolu i hoʻowahāwahā ʻia) o ka kaila uku. ʻO ka hypyprontality ʻoi aku ka liʻiliʻi o ka metabolism ma mua o ka cortex frontal, i pili i ka kontrol impulse maikaʻi, hoʻonui i ka naʻau, a i ʻole ka hoʻoholo ʻana o nā hopena. Aia i kahi pilina ma waena o nā mea hoʻololi haʻahaʻa D2 a me ka hana haʻahaʻa o nā lob mua. ʻO ia ke kumu, overstimulation e alakaʻi i kahi kahe ʻana o nā kākoi D2 e hoʻopilikia ana i ka lobes mua.

KĀHIKE piha: E pili ana nā mea hoʻokele Dopamine Striatal D2 me nā Metabolism prefrontal i nā kumuhana Kuhi.

Neuroimage. 2008 October 1; 42 (4): 1537-1543.
Hoʻouna ʻia ka pūnaewele 2008 Iune 13. doi: 10.1016 / j.neuroimage.2008.06.002.

Nora D. Volkow, ab * Gene-Jack Wang, c Frank Telang, b Joanna S. Fowler, c Panayotis K. Thanos, Jean Logan, c David Alexoff, c Yu-Shin Ding, d Christopher Wong, c Yeming Ma, b a ʻo Kith Pradhanc
he National Institute on Drug Abuse, Bethesda MD 20892, USA
b National Institute on Alcohol Abuse and Alcoholism, Bethesda MD 20892, USA
c Medical Department Brookhaven National Laboratory, Upton NY 11973, USA
d Department of Diagnostic Radiology, Yale University School of Medicine La Haven, CT 06520-8042, USA
* Palapala kākau. National Institute on Drug Abuse, 6001 Executive Boulevard, lumi 5274, Bethesda, MD 20892, USA. Fax: + 1 301 443 9127. Wā leka uila: Email: [pale ʻia ka leka uila] , Email: [pale ʻia ka leka uila] (ND Volkow).

Hōʻuluʻulu Manaʻo

Hoʻomaopopo maikaʻi ʻia ka kuleana o Dopamine i ka kāohi inhibitory a hiki i kāna disruption ke kōkua i nā maʻi o ke kaohi e like me ka momona. Eia nō naʻe, ʻike maʻalahi ʻole ʻia ke ʻano hana e hoʻopili ai nā neurotransmission dopamine hōʻino. Ua hoʻopaʻa mākou ma mua i ka hoʻoliʻiliʻi o nā mea loaʻa nā dopamine D2 i nā kumuhana momona. No ka loiloi inā pili nā hoʻoliʻiliʻi i nā mea loaʻa i ka dopamine D2 me ka hana ma nā wahi lolo mua i hoʻopili ʻia i ka kaohi inhibitory ua loiloi mākou i ka pilina ma waena o ka loaʻa ʻana o ka mea loaʻa ka dopamine D2 i striatum me ka metabolism glucose glucose (marker o ka hana o ka lolo) i nā kumuhana he ʻumi morbidly (BMI> 40 kg / m2) a hoʻohālikelike iā ia i kēlā me ʻumikūmālua mau mana hoʻokipa ʻole. Ua hoʻohana ʻia ʻo PET me [11C] raclopride e nānā i nā mea loaʻa D2 a me [18F] FDG e nānā i ka metabolism glucose glucose ʻāina. I nā kumuhana obese striatal D2 receptor loaʻa ʻoi aku ka haʻahaʻa ma mua o nā kaohi a hoʻopili maikaʻi ʻia me ka metabolism i dorsolateral prefrontal, medial orbitofrontal, anterior cingulate gyrus a somatosensory cortices. I ka hoʻopili ʻana i nā hoʻopili ʻana me nā ʻōnaehana prefrontal ʻaʻole mea nui akā ʻaʻole hoʻohālikelike ka hoʻohālikelike ʻana me nā mea i nā kumuhana momona, ʻaʻole ʻae ia e kapa i nā hui i kū hoʻokahi i ka momona. ʻO nā hui ma waena o nā streparant D2 a me nā ʻōnaehana prefrontal i nā kumuhana obese e hōʻike i ka hōʻemi ʻana o ka striatal D2 i nā mea loaʻa i hiki ke hāʻawi i ka ʻai nui ma o kā lākou modulate o nā ala prefrontal striatal, i komo i ka kaohi inhibitory a me ka hoʻoilina. ʻO ka hui ma waena o nā mea loaʻa D2 striatal a me ka metabolism i loko o nā cortic somatosensory (nā ʻāpana e hana i ka palatability) hiki ke hoʻokumu i kekahi o nā ʻano hana e hoʻoponopono ai ka dopamine i nā mea hoʻoikaika i ka meaʻai.

Huaʻōlelo: Orbitofrontal cortex, Cingulate gyrus, Dorsolateral prefrontal, Dopamine transporters, Raclopride, PET

ʻO ka hoʻonui nui i nā maʻi ʻeha a me nā maʻi metabolic i ʻike ʻia i ka makahiki i hala aku nei, ua hūnā i ka hopohopo inā inā ʻaʻole i mālama i kēia mea e lilo i ka nui o ka hoʻoweliweli olakino ākea no ka 21st abad (Sturm, 2002). ʻOiai ke kōkua nei ka nui o nā mea nui i kēia piʻi ʻana i ka momona a hiki i ka ulu ʻana o ke ʻano a me ka ʻae ʻana i ka meaʻai palatable ʻaʻole hiki ke hoʻomaloʻo ʻia (Wardle, 2007). Mai ka loaʻa ʻana o ka ʻai a me nā ʻano like ʻole o ka ʻai nui (e pili ana iā Wardle, 2007) ke komo maʻalahi ʻana i ka meaʻai ʻoluʻolu e koi pinepine ai i ka makemake e ʻai i ka ʻai (Berthoud, 2007). ʻO ka nui o ka mea ʻē aʻe i ko lākou hiki ke hoʻokaʻawale i kēia mau pane a mālama i ka nui o kā lākou ʻai ʻana e hoʻololi paha i ko lākou hopena no ka nui ʻana o ka ʻai o kā mākou kai ʻōpala o kēia manawa (Berthoud, 2007).

Ua hōʻike mākou i loko o ka poʻe olakino D2 receptor i loaʻa i ka striatum modulate ʻai i nā hanana hana (Volkow et al., 2003). Ua kiko loa ka makemake o ka ʻai ʻana i ka wā i ʻike ʻia i nā manaʻo ʻino ʻole me ka loaʻa ʻole o ka D2 receptor (ʻo ka haʻahaʻa o ka D2 receptors e hoʻonui i ka loli no ka mea ʻai kekahi me ke kīpī ʻana). Eia kekahi, ma kahi noiʻi ʻē aʻe, ua hōʻike mākou he mau haʻahaʻa haʻahaʻa loa (BMI> 40) he haʻahaʻa ma mua o ka loaʻa ʻana o ka D2 maʻamau a ua hoʻohālikelike ʻia kēia mau hana ma kā BMI (Wang et al., 2001). Ua alakaʻi ʻia kēia mau hopena iā mākou e hoʻomau i ka loaʻa o ka mea i loaʻa i ka D2 ka mea i loaʻa i ka mea i pilikia no ka overeating. Ma kēia ʻoiai ua kūlike kēia i nā ʻike i hōʻike ʻia o ka hoʻopaʻa ʻana i nā kākoi D2 (nā lāʻau lapaʻau antipsychotic) e hoʻonui ai i ka hoʻokomo o ka meaʻai a hoʻonui i ka hopena i ka momona (Allison et al., 1999). Eia nō naʻe ka hoʻomaopopo ʻana i nā hana o ka mea ʻae a me ka mea i loaʻa i ka D2.

I kēia mau lā ua hōʻike ʻia i loko o nā kaola olakino polymorphism i loko o ka ʻaoʻao receptor D2 e pili ana i nā ana o ke kaohi o ke kaohi (Klein et al., 2007). ʻO nā mea kikoʻī, nā kānaka me ka ʻokoʻa ʻano e pili ana me ka ʻōlelo D2 haʻahaʻa i ʻoi aku ka liʻiliʻi o ka kaohi inhibitory ma mua o nā kānaka me ka ʻokoʻa gen e pili ana me ka ʻōlelo D2 receptor kiʻekiʻe aʻe a ua pili kēia mau pane ʻano me ka ʻokoʻa o ka hoʻoulu ʻana o ka cingulate gyrus (CG) a me dorsolateral prefrontal. cortex (DLPFC), nā wahi lolo i hoʻopili ʻia i nā ʻāpana like ʻole o ka kaohi pāpā (Dalley et al., 2004). Ua alakaʻi mākou iā mākou e noʻonoʻo hou i ka hiki i ka nui o ka makaʻu no ka ʻai nui ʻana i nā kumuhana me ka loaʻa ʻana o ka receptor D2 liʻiliʻi e hoʻokele ʻia e ka rula a DA o DLPFC a me nā wahi prefrontal medial, i hōʻike ʻia e komo i ka pāpā ʻana i nā ʻano pane kūpono ʻole (Mesulam , 1985; Le Doux, 1987; Goldstein a me Volkow, 2002). Pēlā mākou i hana ai i ka loiloi lua e pili ana i ka ʻikepili mai nā kumuhana i kiʻi mua ʻia ma ke ʻano he ʻāpana o nā noi e loiloi i nā loli o nā mea loaʻa D2 (Wang et al., 2001) a me ka metabolism glucose glucose i ka momona (Wang et al., 2002) a me nā ʻike mai hoʻohālikelike ʻia nā makahiki. ʻO kā mākou kuhiakau hana ʻo ia ka loaʻa ʻana o ka receptor D2 i nā kumuhana obese e pili ana i ka hana hoʻohaunaele i nā wahi ma mua.

No kēia noiʻi nā loiloi morbidly obese a me nā kumuhana o obese i loiloi i ka Positron Emission Tomography (PET) i hui pū me [11C] raclopride e ana i ka ʻae ʻana i nā mea hoʻohana o DA D2 (Volkow et al., 1993a) a me [18F] FDG e ana i ka lolo. kaūʻana o ka glucose (Wang et al., 1992). Ua hoʻohoka ʻia mākou e pili pū ana nā mea komo me D DNNUMX me ka metabolism ma nā wahi prefrontal (DLPFC, CG a me nā orbitofrontal cortex).

hana

Nā Kaupapa
He ʻumi mau kumuhana morbidly obese (5 mau wahine a me 5 mau kāne, ke ʻano 35.9 ± 10 mau makahiki) me ka nui o ke kino (BMI: kaupaona ʻia i nā kilokika i hoʻokaʻawale ʻia e ka square o ke kiʻekiʻe i nā mika) o 51 ± 5 kg / m2 i wae ʻia mai kahi loko wai. o nā kumuhana momona i pane i kahi hoʻolaha. Ua koho ʻia he ʻumikūmālua mau kumuhana non-obese (6 wahine a me 6 kāne, mean 33.2 ± 8 mau makahiki) me mean BMI o 25 ± 3 kg / m2 no ka hoʻohālikelike. Ua nānā akahele ʻia nā mea komo me ka moʻolelo olakino kikoʻī, ka hoʻokolohua kino a me ka neurological, EKG, nā hoʻokolohua koko maʻamau, a me ka wai ʻona toxology no nā lāʻau psychotropic e hōʻoia ai ua hoʻokō lākou i nā pae hoʻohui a me ka hoʻoneʻe. ʻO nā pae hoʻohālikelike: 1) hiki ke hoʻomaopopo a hāʻawi i ka ʻae ʻike. 2) BMI> 40 kg / m2 no nā mea momona a me BMI <30 kg / m2 no nā kumuhana hoʻohālikelike a me 3) 20-55 mau makahiki o ka makahiki. ʻO nā pae hoʻohālikelike i: o nā lāʻau anorexic a i ʻole nā kaʻina hana no ke kaupaona ʻana i nā mahina 1 i hala iho nei, (2) nā lāʻau i kuhikuhi ʻia i nā pule he 30 i hala, (3) ka mōʻaukala i hala a i ʻole ka hoʻohana ʻana i ka lāʻau ʻona (me ka uahi paka). Ua kauoha ʻia nā kumuhana e hoʻopau i kekahi lāʻau lapaʻau a i ʻole nā mea hoʻopihapiha hoʻopihapiha ma mua o ka scan. Ua hana ʻia nā hōʻike mimi pr-scan e hōʻoia i ka hoʻohana ʻole ʻana o ka lāʻau psychoactive. Ua loaʻa nā ʻae ʻike pūlima ʻia mai nā kumuhana ma mua o ke komo ʻana e like me ka mea i ʻae ʻia e ka Board Review Board ma Brookhaven National Laboratory.PET kiʻi kiʻi
Ua hana ʻia nā scan pēpē me CTI-931 (Computer Technologies, Incorporated, Knoxville, Tenn.) Tomograph (hoʻoholo 6 × 6 × 6.5 mm FWHM, ʻoki 15) me ka raclopride [11C] a me [18F] FDG. Ua hoʻopuka ʻia nā ʻike kikoʻī e pili ana i nā kaʻina hana, ka pono a me ka catheterization venous, ka helu ʻana o ka radiotracer a me ka hoʻouna ʻana a me nā mea e hoʻokuʻu ana i ka emission no [11C] raclopride (Volkow et al., 1993a), a no [18F] FDG (Wang et al., 1992) . ^ E Ha yM. ʻO ka pōkole no ka [11C] raclopride, hoʻomaka ʻia nā haki ikaika ma hope o ka hōʻono ʻia ʻana o ka make ʻana o 4 – 10 mCi (hana kūikawā> 0.25 Ci / μmol i ka manawa inikua) no ka huina o 60 min. No [18F] FDG, hoʻokahi hoʻoiho (20 min) i lawe ʻia ma 35 min ma hope o kahi maʻi injection o 4-6 mCi o [18F] FDG. Ua hana ia ka hoʻopaʻi ʻia ma ka lā like; ka [11C] raclopride scan mua a hana ʻia a [18F] FDG, ka mea i paʻi ʻia e 2 h ma hope o [11C] raclopride e ʻae ai no ka hōʻea o 11C (hapalua ola 20 min). I ka wā o ke aʻo ʻana ua mālama ʻia ma ke kāmela pēpē me ka maka o ko lākou mau maka; ua aniani nā lumi a ua mālama ʻia ke kani ʻana ma ka liʻiliʻi. Ua noho mau kahi kahu hānai me nā kumuhana āpau i ke kaʻina hana e ʻike ai ʻaʻole i hiamoe ka kumuhana i ka wā o ke aʻo ʻana.

Kaʻikepili kiʻi a me kaʻikepili
Loaʻa nā pāʻina hoihoi (ROI) i nā kiʻi raclopride [11C] i loaʻa no ka striatum (caudate a putamen) a no ka cerebellum. Ua koho mua ʻia ka ROI ma kahi scan ʻokoʻa (kahi kikowaena mai 10-60 min no [11C] raclopride), a laila hāʻawi ʻia i nā kikowaena neʻe e like me ka mea i hōʻike mua ʻia (Volkow et al., 1993a). ʻO nā kuʻina hana manawa no ka [11C] raclopride i striatum, a me cerebellum a me nā ʻāpana o ka manawa no ka tracer i hoʻololi ʻole ʻia ma ka papa hana i hoʻohana ʻia ai nā puʻu hoʻohele (DV) e hoʻohana ana i kahi kaʻina hana kiʻi kiʻiʻenehana no kahi reversible system (Logan Plots) (Logan et al ., 1990). Ua loaʻa ke ʻano Bmax / Kd i ka ratio o ke DV ma ka striatum i kēlā me ka cerebellum (DVstriatum / DVcerebellum) minus 1, i hoʻohana ʻia ma ke ʻano hoʻohālike o ka loaʻa ʻana o ka mea loaʻa ʻĀkī DA D2. He ʻokoʻa ka lula i ka loli i ka kahe koko o cerebral (Logan et al., 1994).

No ka loiloi i ka pilina ma waena o ka loaʻa ʻana o ka loaʻa D2 a me ka metabolism glucose o ka lolo, ua helu mākou i nā correlations me ka hoʻohana ʻana i Statistical Parametric Mapping (SPM) (Friston et al., 1995). Ua hoʻopaʻa ʻia nā hualoaʻa SPM me nā wahi hoihoi kūʻokoʻa (ROI); ʻo ia hoʻi, nā ʻāpana i loaʻa me ka hoʻohana ʻana i kahi mamana i alakaʻi ʻole ʻia e nā koina i loaʻa mai ka SPM. No ka nānā ʻana o ka SPM, ua hoʻomaʻamaʻa ʻia nā kiʻi o ka metabolic me ka hoʻohana ʻana i ka template i hāʻawi ʻia i loko o ka pūʻolo SPM 99 a laila hoʻomaʻamaʻa ʻia me ka 16 mm isotropic Gaussian kernel. Ua hoʻonohonohoʻia ka mea nui no ka hoʻoponoponoʻana i P <0.005 (uncorrected, 100 voxels) a ua uhiʻia nā palapala'āina helu ma kahi kiʻi hoʻolālā MRI. 1992). Ma waho o kēia hoʻohālike, ua koho mākou i nā ROI no ka medial a me ka lateral orbitofrontal cortex (OFC), anterior cingulate gyrus (CG) a me ka dorsolateral prefrontal cortex (DLPFC) a mākou i manaʻo ai he "a priori" kahi hui me DA D2 receptors, nā ROI no ka caudate. a me ka putamen, ʻo ia nā ROI he mau mea loaʻa D2 striatal, a ua ana ʻia nā ROI ma parietal (somatosensory cortex a me angular gyrus), kino (kiʻekiʻe a haʻahaʻa kino gyri a me hippocampus), a me nā cortices occipital, thalamus a me cerebellum, i koho ʻia ROIs kūʻokoʻa. Ua hana ʻia nā loiloi hoʻoponopono ʻana o ka manawa huahana Pearson ma waena o ka loaʻa ʻana o ka loaʻa ʻana o D2 i ka striatum a me nā ana metabolic kūloko. ʻO ka pae koʻikoʻi no ka hoʻoponopono ʻana ma waena o D2 receptors a me ka metabolism kūloko mai ka ROI i hoʻonohonoho ʻia ma P<0.01 a hōʻike ʻia nā waiwai o P<0.05 e like me nā ʻano. Ua ho'āʻoʻia nāʻokoʻa o ka pilina ma waena o nā hui me ka hoʻohanaʻana i ka ho'āʻo holoʻokoʻa o nā coincidences no nā regressions a ua hoʻonohonohoʻia ka nui ma P <0.05.

Results

ʻO nā ana o ka loaʻa ʻana o ka loaʻa D2 striatal (Bmax / Kd) i haʻahaʻa loa i nā kumuhana obese ma mua o nā mana non-obese (2.72 ± 0.5 versus 3.14 ± 0.40, Student t test = 2.2, P <0.05). ʻO ka loiloi SPM i hana ʻia ma nā mea momona e loiloi i ka pilina ma waena o ka loaʻa ʻana o ka loaʻa ʻana o D2 a me ka metabolism glucose o ka lolo kūloko i hōʻike ʻia he mea koʻikoʻi ia i nā pūʻulu 4 i hoʻokumu ʻia ma (1) hema a me ka ʻākau mua (BA 9), CG (BA 32) a ʻaoʻao hema orbitofrontal cortices (BA 45): (2) hema a ʻākau mua (BA 10); (3) ventral cingulate gyrus (BA 25) a me ka medial orbitofrontal cortex (BA 11); a me (4) somatosensory cortex akau (BA 1, 2 a me 3) (Fig. 1, Table 1).Fig. 1 Loaʻa nā palapala ʻāina lolo me SPM e hōʻike ana i nā wahi i koʻikoʻi ka pilina ma waena o ka loaʻa ʻana o ka loaʻa D2 striatal a me ka metabolism glucose o ka lolo. Pili ka manaʻo nui i ka P<0.005, hoʻoponopono ʻole ʻia, ka nui puʻupuʻu>100 voxels.

1 Pūnaewele
ʻO nā wahi o ka lolo kahi i hōʻike ai ka SPM i nā pilina koʻikoʻi (P <0.005) ma waena o ka loaʻa ʻana o ka loaʻa D2 striatal a me ka metabolism glucose. Ua hōʻike kēia hōʻike i ka nui o nā correlations ma ka hema a me ka ʻākau DLPFC (e pili ana i ka BA 2 a me 9), mua CG (e pili ana i ka BA 10 a me 32) a me ka medial orbitofrontal cortex (medial BA 25). Ua hoʻokūpaʻa pū kekahi i kahi pilina koʻikoʻi me ka cortex somatosensory kūpono (postcentral parietal cortex) (Table 11, Fig. 2). Papa 2 Correlation coefficients (r values) and significance levels (P values) no ka pilina ma waena o nā ana o striatal DA D2 loaʻa ka loaʻa ʻana o ka mea hoʻokipa (Bmax / Kd) a me ka metabolism lolo kūloko i nā kumuhana obese a me nā controlsFig. 2 Regression slopes ma waena o ka loaʻa ʻana o ka loaʻa ʻana o ka loaʻa ʻana o DA D2 (Bmax / Kd) a me ka metabolism glucose kūloko (μmol / 2 g / min) ma nā wahi prefrontal a ma ka somatosensory cortex. Hōʻike ʻia nā waiwai no kēia mau pilina ma ka Papa 100. Eia kekahi, ua hōʻike ʻia ka loiloi e hoʻohana ana i ka ROI i nā pilina koʻikoʻi me ka somatosensory cortex hema a hōʻike i kahi ʻano i ka gyrus angular akau a me ka caudate ʻākau (Table 2, Fig. 2). ʻO ka pilina me nā cortical ʻē aʻe (occipital, temporal and lateral orbitofrontal cortex), subcortical (thalamus, striatum) a me nā ʻāpana cerebellar ʻaʻole i koʻikoʻi. aia ma ka gyrus postcentral hema. Aia kekahi ʻano no ka hoʻopili ʻana ma ka ʻaoʻao orbitofrontal cortex a me ka gyrus angular ʻākau.

kūkākūkā

Maanei mākou e hōʻike ai i nā kumuhana morbidly obese ʻO DA D2 ka mea i loaʻa i ka mea pili me ka hana metabola ma nā wahi mua (DLPFC, medial orbitofrontal cortex a me ka CG anterior). Ua hoʻolako ʻia kēia mau ʻāina i ka hoʻoponopono ʻana i ka ʻai o ka meaʻai a ma ka hyperphagia o nā poʻe hānai (Tataranni et al., 1999, Tataranni a me DelParigi, 2003). Ke hōʻike pū nei mākou i kahi pilina koʻikoʻi me ka hana metabolism ma somatosensory cortex (postcentral cortices) i mea nui nui i ka obese a i nā ʻonanō ʻole-obese (nā wahi i waiho wale ʻia). Ma kahi mākou i hoʻokaʻawale i nā mea pili me nā ʻāina prefrontal o ka hui pū me ka cortex somatosensory i loaʻa ʻole.

ʻO ka hui ma waena o nā'onike D2 a me ke kūlike o ke kuhi mua

ʻO ka hui nui ma waena o ka loaʻa o ka D2 receptors a me ka metabolism ma nā wahi prefrontal e like me kā mākou ʻike ma mua o nā mea i hoʻohui ʻia i ka lāʻau (cocaine, methamphetamine a me ka waiʻona) i hōʻike mākou e pili ana i nā hōʻemi o nā mea i loaʻa i ka D2 e pili ana i ka hoʻemi ʻana i ka metabolism ma nā wahi cortical prefrontal ( Volkow et al., 1993b; Volkow et al., 2001; Volkow et al., 2007). Pēlā nō i loko o ka poʻe i ʻike ʻia ma ka helu ʻohana nui no ka ʻalaka, ua kākau mākou i kahi hui ma waena o ka loaʻa o ka mea i loaʻa i D2 a me ka prefrontal metabolism (Volkow et al., 2006). Maʻa like ka momona a me nā mea hōʻalo i ka hiki ʻole ke kaohi i ka lawena me ka ʻike ʻole i nā hopena maikaʻi ʻole. ʻOiai nā ʻāpana mua i hoʻopili ʻia i nā ʻāpana like ʻole o ka kaohi inhibitory (Dalley et al., 2004) hōʻike mākou i ka loaʻa o ka receptor D2 haʻahaʻa i ka striatum o nā mea momona (Wang et al., 2001) a me nā rodent models o ka momona (Hamdi et al., 1992; Huang et al., 2006; Thanos et al., 2008) hiki ke hāʻawi i ka momona i kahi ʻāpana ma o ka hoʻololi ʻana o DA i nā wahi mua i komo i ka kaohi inhibitory.

Ua hōʻikeʻia nā hopena e hiki ke noʻonoʻoʻia nā hoʻoponopono dopamineric o nā'āpana mua e pili ana i ka pilikia no ka momona ma waena o nā mea loaʻaʻo D2. Ua kūlike kēia i ka noiʻi genetic, nāna i hoʻopuka pono i ka gen receptor D2 (TAQ-IA polymorphism), ʻoiai he mea pili i ka nāwaliwali i ka obesity (Fang et al., 2005; Pohjalainen et al., 1998; Bowirrat a Oscar- Berman, 2005). Eia nō kekahi, ko ka polymorphism TAQ-IA, ka mea i ʻike ʻia ma nā haʻahaʻa D2 lalo o ka pae ma ka lolo (striatum) (Ritchie a me Noble, 2003; Pohjalainen et al., 1998; Jonsson et al., 1999) i kēia manawa ua ʻike pū ia me ka pili me ka pili ʻana. hoʻemi i ka hiki ke hoʻokaʻawale i nā ʻano kūpono e hopena i nā hopena maikaʻiʻole a me ka hoʻōla lima ʻana o nā wahi prefrontal (Klein et al., 2007). Ua hōʻike pū ʻia nā haʻawina preclinical ka holoholona me ka haʻahaʻa D2 kiʻekiʻe iki ka nui o nā mea i hōʻemi ʻia ma mua o ko lākou littermates me nā kiʻekiʻe D2 receptor (Dalley et al., 2007). Pēlā nā ʻike mai kā mākou noiʻi e hāʻawi i nā hōʻike hou aʻe e hui pū ana ka hui o nā D2 receptors me ka pale o ka inhibitory a me ka impulsivity i hoʻopili ʻia i kekahi ma o kā lākou hoʻololi ʻana i nā wahi prefrontal. Ma kēia ʻike kūpono i ka mea kupaianaha i hōʻike ʻia i nā haʻawina morphological haʻahaʻa ua hōʻike i ka nui o nā mea hina hina i loko o ka cortex prefrontal i nā kumumanaʻo i ka wā i hoʻohālikelike ʻia i nā poʻe kūloko (Pannacciulli et al., 2006)

ʻO ka pilina ma waena o nā mea loaʻa ʻo D2 a me ka DLPFC mea hoihoi loa no ka mea ua hoʻopili ʻia kēia ʻāina i ka hopena endogenous o ka hana i manaʻo ʻia (Brass and Haggard, 2007). ʻO nā hōʻike e pili ana i ka hana neuronal ma mua o ka ʻike o kēlā me kēia kanaka i ka manaʻo e 200-500 ms (Libet et al., 1983), ua alakaʻi i kekahi e nīnau i ke kumumanaʻo o ka "freelance" ma hope o nā hana i manaʻo ʻia a no ka noi ʻana i ka mana e hōʻike i ka hiki kāohi i nā hana a mākou e makemake ʻole ai. ʻOiaʻiʻo, ua ʻōlelo ʻia ʻo kēia mana veto a i ʻole "manuahi ʻaʻole" e like me ke ʻano o kā mākou hana ʻana i ka "freel" (Mirabella, 2007). I ka hihia o ka momona hiki i kekahi ke hoʻolaha i ka hōʻike ʻana i ka meaʻai a i ʻole nā meaʻai i hōʻona ʻia nā hopena e hopena i ka hana ʻole volitional o nā ʻōnaehana neuronal e pili ana i ka loaʻa ʻana a me ka ʻai ʻana i ka meaʻai a hōʻike ka mana i ka hiki ke kāohi i kēia mau hana i makemake e ʻai. ka mea 'ai. Hiki i kekahi ke noʻonoʻo pehea pehea ka hana kūpono o ka DLPFC, ka mea e hiki ai ke pale aku i nā hana e hopena i ka hopena maikaʻi ʻole, e like me ka ʻai ʻana i ka pōloli ʻole no ka makemake ʻole e kau i ka paona, hiki ke hoʻopiʻi. Ke hōʻike nei i nā ʻike ʻike nui loa i ka hoʻohaʻahaʻa ʻana i ka DLPFC ma hope o ka ʻai ʻana i nā kumumanaʻo obese ma mua o nā mea kūlohelohe e kākoʻo i kēia hypothesis (Le et al., 2006).

Ua hui pū ka hui ma waena o ka loaʻa o ka receptor D2 a me ka cortex medial orbitofrontal (OFC) a me ka anterior CG i ko lākou komo ʻana i ka hoʻoponopono lula (Pliquett et al., 2006). Nui nā ʻano e hiki i kekahi ke hāpai i ka hana i ka hana dopaminergic hiki i ka CC ke hiki i ka CG ke hoʻonui i ka hopena no ka overeating.

ʻO ka hui medial OFC e pili pū ana me ka hoʻohanohano salience e pili ana i ka waiwai o ka meaʻai (Rolls and McCabe, 2007; Grabenhorst et al., 2007; Tremblay and Schultz, 1999) a no laila ka hoʻōla ʻana i ka waena o ka hoʻoulu ʻana i ka meaʻai me ka hoʻōla ʻana iā DA. e hoʻopau i ka meaʻai me ka hiki ʻole o ka hiki ke pale ʻia. Eia kekahi, no ka hoʻonāukiuki ʻana i ka hana o ka OFC hopena i ka hoʻopulapula ʻana i ka hoʻokaʻina ʻana o nā ʻoihana aʻo ke hoʻokaʻawale ʻia kekahi mea hoʻoikaika (Gallagher et al., 1999) hiki ke hopena i ka ʻai ʻana i ka wā i hoʻowalewale ʻia ka waiwai o ka meaʻai e ka satiety a hiki ke wehewehe no ke aha e pili ai ka hoʻopilikia ʻana o ka OFC me nā mea hoʻohālike e koi ana me ka overeating (Butter et al., 1963, Johnson, 1971). Hoʻopili pū ka ʻāpala OFC i ke aʻo ʻana o ka hoʻoulu ʻana me ka hoʻoulu ʻana i ka naʻau (Schingenbaum et al., 1998, Hugdahl et al., 1995) a no laila hiki iā ia ke komo i ka hānai i nā mea e hānai me ke ʻano (Weingarten, 1983). He kūpono kēia no ka mea e pili ana nā pane a me nā mea e pili ana i ka meaʻai me ka nui o ka hapanui o nā hōʻailona pōloli (Ogden a Wardle, 1990).

Hoʻopili ʻia ka dorsal CG (BA 32) i ka pale ʻana i loko o nā kūlana e koi ana i ka nānā ʻana i ka hana a pēlā ke ʻano i haʻalele ʻia ai me ke ʻano o ka DLPFC e pili pū ana me (Gehring a me Knight 2000) e hoʻopiʻi hou paha i ka hiki ke hoʻopiʻi ʻia e hoʻohiolo i ka akee i luna nui. Hōʻike ʻia ka ventral CG (BA 25) i ka hoʻopiʻi ʻana i nā pane kū i ka ʻalāʻau salient (he uku a he aversive) (Elliott et al., 2000) a me nā haʻawina imaging ua hōʻike ʻia ʻo BA 25 e hoʻolaʻa ʻia e nā kūlohelohe a kūlohelohe (Breiter et al., 1997, Francis et al., 1999; Berns et al., 2001). No laila ʻo ka maikaʻi o ka pilina ma waena o nā mea uʻi a D2 a me ka ulu ʻana o ka ʻai i ka wā i hōʻike ʻia i nā manaʻo ʻino ʻole i hōʻike mua ʻia e mākou ma nā mana palekana (Volkow et al., 2003) hiki ke hoʻopaʻa ʻia e ka loli ʻana o ka BA 25.

ʻO ka pilina ma waena o ka hana metabola ma nā wahi prefrontal a me nā koina D2 hiki ke hōʻike i nā projections i ka cortex prefrontal mai ka ventral a me ka dorsal striatum (Ray a me nā kumukūʻai, 1993), ʻo ia nā wahi i hoʻopili ʻia i nā hopena hoʻoikaika a me ka manaʻo o ka meaʻai (Koob a me Bloom, 1988) a / a mai kahi mai ana i ka hoʻokaumaha ventral (VTA) a me substantia nigra (SN), ʻo ia nā mea nui ʻo DA e kuhi ai i ka striatum (ʻOades and Halliday, 1987). Akā, hoʻouna ka cortex prefrontal i ka striatum i hiki i ka hui ke hoʻomohala i nā palena prefrontal o ka hana striatal DA (Murase et al., 1993).

I loko o nā kaohi obese, ʻaʻole i koʻikoʻi nā mea hoʻoponopono ma waena o D2 receptor a me nā metabolism prefrontal. Ma nā hōʻike mua i hōʻike mākou i ka pilina nui ma waena o ka mea hoʻokae D2 a me ka metabolism prefrontal i nā kumumanaʻo i lawe pū me ka loaʻa ʻole o ka D2 ʻae akā ʻaʻole i nā kuleana (Volkow et al., 2007)Eia nō naʻe, ʻaʻole koʻikoʻi ka hoʻohālikelike o ka hoʻoponopono ʻana ma waena o ka obese a me nā pūʻali mana. He mea maopopo ʻole ka manaʻo like ʻole o ka pilina ma waena o nā mea makemake a D2 a me ka metabolism prefrontal e like me ka obesity (a i ka hoʻohui i nā lā ʻo Volkow et al., 2007). A ʻoi aku paha ka hōʻike ʻana o nā kaila ikaika i ʻike ʻia i ka poʻe kūlima i ka nui o nā koina DriNUMX recepty striatal (Bmax / Kd range 2-2.1) ma mua o nā kumuhana paʻa (Bmax / Kd range 3.7-2.7).

I ka unuhi ʻana i kēia mau ʻike, he mea nui hoʻi e noʻonoʻo i ka raclopride [11C] he radiotracer nona ka hoʻopaʻa ʻana i ka ʻĀina D2 e makaʻala i ka endogenous DA (Volkow et al., 1994) a no laila ke hoʻokaʻawale ʻia nā hōʻemi D2 i loaʻa i nā kumuhana obese e hiki ke noʻonoʻo i ka haʻahaʻa nā ʻae ʻeka a hoʻonui paha i ka hoʻokuʻu ʻana DA. Ua hōʻike ʻia nā haʻawina mua i nā holoholona o ka momona i ka hoʻohaʻahaʻa ʻana i nā kaila o D2 (Thanos et al., 2008), ke hōʻike nei i nā hōʻemi o nā haʻawina lohi i hōʻike i ka hōʻemi ma nā pae kiʻekiʻe o D2.

Ka hoʻoponoponoʻana ma waena o D2R a me ka cortex somatosensory

ʻAʻole mākou i "a priori" i kuhiakau i kahi hui ma waena o nā mea loaʻa ʻo D2 a me ka metabolism i somatosensory cortex. Ke hoʻohālikelike ʻia me nā ʻaoʻao mua a kūlohelohe paha he mea liʻiliʻi e ʻike ʻia e pili ana i ka mana o DA i ka parietal cortex. I ka lolo o ke kanaka ka manaʻo nui o nā mea loaʻa D2 a me D2 mRNA i ka parietal cortex ʻoiai ʻoi aku ka haʻahaʻa ma mua o nā wahi subcortical e like me ka mea i hōʻike ʻia i mua o ka mua (Suhara et al., 1999; Mukherjee et al., 2002; Hurd et al., 2001). ʻOiai he kaupalena ʻia nā puke e pili ana i ka hana o ka somatosensory cortex i ka lawe ʻana i ka meaʻai a me ka momona. Ua hōʻike ʻia nā noiʻi kiʻi ʻana i ka hoʻāla ʻana o ka cortex somatosensory i nā kumuhana kaupaona maʻamau me ka hōʻike ʻana i nā kiʻi ʻike o nā meaʻai caloric haʻahaʻa (Killgore et al., 2003) a me ka satiety (Tataranni et al., 1999), a ua hōʻike mākou i ʻoi aku ka kiʻekiʻe ma mua o ka metabolism maʻamau maʻamau. i ka cortex somatosensory i nā kumuhana momona (Wang et al., 2002). Ua hōʻike pū ʻia kahi noiʻi hou e pili ana i nā poʻe momona me ka leptin def deficit administration o leptin maʻamau i ko lākou kino kaumaha a hoʻemi i ka hoʻoulu ʻana o ka lolo i ka parietal cortex ʻoiai ke nānā nei i nā stimulus e pili ana i ka meaʻai (Baicy et al., 2007). ʻO ka pilina o ka pilina ma waena o ka striatum a me ka somatosensory cortex i hoʻopaʻa ʻia no ka lolo o ke kanaka e kahi noiʻi meta-analysis ma 126 haʻawina kiʻi paʻi kiʻi, i hoʻopaʻa ʻia me ka hoʻouluulu ʻana o ka cortex somatosensory me ka dorsal striatum (Postuma and Dagher, 2006 ). Eia nō naʻe, mai nā hoʻopili ʻana i kā mākou noi ʻana ʻaʻole hiki iā mākou ke ʻike i ke kuhikuhi o ka hui; no laila ʻaʻole hiki iā mākou ke hoʻoholo inā pili ka hui me nā mea loaʻa ʻo D2 i ka modulate a DA o ka somatosensory cortex a me / a i ʻole ka hopena o ka somatosensory cortex ma ka loaʻa D2 receptor loaʻa. ʻOiai he nui nā hōʻike e pili ana ka somatosensory cortex i ka hana DA a me ka hoʻokuʻu DA striatal (Huttunen et al., 2003; Rossini et al., 1995; Chen et al., 2007). Aia kekahi hōʻike e hoʻololi ana ʻo DA i ka somatosensory cortex i ka lolo kanaka (Kuo et al., 2007). ʻOiai ʻo DA e hoʻonāukiuki i nā hōʻailona a me ka hoʻomaʻamaʻa ʻana i ka hoʻoikaika ʻana (Zink et al., 2003, Kelley, 2004), DA's modulate of the somatosensory cortex's pane i ka meaʻai e hoʻokau paha i ka hana o ka hui pilikino ma waena o nā meaʻai a me nā kai e pili ana i ka meaʻai. nā kuhi a me ka hoʻonui i ka waiwai o ka meaʻai i kū i ka momona (Epstein et al., 2007).

Nā palena aʻo

ʻO ka kaupalena no kēia noiʻi ʻana, ʻaʻole i loaʻa iā mākou nā hana neuropsychological a no laila ʻaʻole hiki iā mākou ke loiloi inā pili ʻia ka hana ma nā wahi prefrontal me nā hanana kūpono o ka nānā cognitive i kēia mau kumumanaʻo. ʻOiai nā kaupalena neuropsychological e pili ana i ka momona ua hoʻohālikelike ʻia a ʻike ʻia nā ʻike e nā maʻi lapaʻau o ka momona (ʻo ia hoʻi ka maʻi diabetes a me hypertension), aia nō nā hōʻike e pili ana i nā kumumeao i ka hapai i ka paleʻana. Kūlana loa, i ka wā e hoʻohālikelike ʻia me nā pilikino maʻamau, ʻoi aku nā mea momona o ka lā i ke koho ʻana, ʻo ia ka mea e loaʻa ai ka hana me ka pale o ka neʻe ʻana o ka pale a me ka prefrontal dysfunction (Pignatti et al., 2006). A ʻoi aku ka nui o ka nānā ʻana i ka maʻi maʻamau (ADHD) e pili ana i ka haunaele, a hoʻokiʻekiʻe ʻia i ka poʻe momona (Altfas, 2002). Hoʻohālike ʻo ka impulsivity me ka BMI kiʻekiʻe ma kekahi mau lehulehu (Fassino et al., 2003) a i ka hoʻopale olakino ʻē aʻe nō hoʻi ua pili pū kekahi BMI i ka hana ma nā hana o ka hoʻokō e lawelawe i ka impulsivity (Gunstad et al., 2007).

Eia nō naʻe i loko o kēia pepa ke nānā nei mākou i ka hana a ka prefrontal cortex ma ka pale ʻana i ka pale a me ka impulsivity ua ʻike mākou ua pili ʻia nā cortex prefrontal me ka nui o nā hana cognitive he nui ka mea i hoʻopilikia ʻole i nā kumuhana obese (Kuo et al., 2006, Wolf et al., 2007). Hiki ke kūpono i nā hana o ka prefrontal cortex e pili ana i ka obesity i ka mea pili i ka mod pu ʻana o DA ma o nā ala stratal prefrontal pathway (Robbins, 2007; Zgaljardic et al., 2006).

ʻAʻole hoʻi ka disregulation o ka hana prefrontal a i ʻole ka hōʻino ʻana o ka hana luna i kikoʻī no ka momona. ʻOiai ʻo nā mea kūpono ʻole i ka prefrontal metabolism a me ka hōʻino ʻana i ka hana a ka luna i kākau ʻia i loko o nā ʻano maʻi like ʻole me nā mea me ka hoʻopili ʻia ʻana o ka dopaminergic e like me ka hoʻāla ʻana i ka lāʻau, schizophrenia, maʻi ʻo Parkinson a me ADHD (Volkow et al., 1993b; Gur et al., 2000; Robbins, 2007; Zgaljardic et al., 2006).

ʻO kekahi palena ʻē aʻe ʻo ka palena palena spatial o ka pā raclopride o ka pā [11C] i ʻole e ʻae iā mākou e ana i ka loaʻa ʻana o ka ʻāpono D2 i nā wahi liʻiliʻi o ka lolo e mea nui i ka hānai ʻana i nā ʻano pili o ka meaʻai e like me ka hypothalamus.

ʻO ka hopena,ʻaʻole i hōʻikeʻia nā hoʻoponoponoʻana i nā hui kaiaulu a me nā aʻo hou aku e noʻonoʻo i nā hopena o ka hoʻopiʻiʻana i ka lolo ma ka hana mua ma nā mea kikowaena.

hōʻuluʻulu manaʻo

Hōʻike kēia haʻawina i kahi hui nui o nā kumumeao ma waena o nā mea mālama D2 i striatum a me ka hana i loko o DLPF, medial OFC a me CG (nā wahi ulu o ka naʻau i hoʻomalu i ka hoʻomālamalama, salience attribution a me ka hoʻoneʻe i nā hopena a me ko lākou haunaele nā hopena i ka hana hoʻomālamalama a me ka hoʻopiʻi). ua manaʻo e hiki kēia i kekahi o nā hana e hiki ai i nā mea kāhea D2 haʻahaʻa i ka momona i hiki ke kōkua i ka overeating a me ka momona. Eia kekahi mea mākou i palapala pū ai i kahi hui nui ma waena o nā mea hoʻolohe a D2 a me ka metabolism i loko o kahi cortex somatosensory hiki ke hoʻololi i nā mea hoʻoikaika o ka ʻai (Epstein et al., 2007) a me ke ʻano o ka hoʻokolokolo hou ʻia.

mau hoomaikai ana
Mahalo mākou iā David Schlyer, David Alexoff, Paul Vaska, Colleen Shea, Youwen Xu, Pauline Carter, Karen Apelskog, a me Linda Thomas no kā lākou hāʻawi. Ua kākoʻo ʻia kēia noiʻi e ka NIH's Intramural Research Program (NIAAA) a me DOE (DE-AC01-76CH00016).

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Keʻaeʻia nei nā D2 Hoʻohālikelike me ka Preabality Metabolism i nā Obese Subjects:ʻO nā mea kōkua kumu (2008)