Chizoloŵezi: Kuchepetsa Kulingalira kwa Mphoto ndi Kuwonjezeka Kuyembekeza Kukhazikika Kumalimbikitsa Kugonjetsa Brain's Control Circuit (2010)

Zomwe zimayambitsa zolaula zimakhala mu mphotho yoyendayenda

MAFUNSO: Kuwunikiridwa ndi mutu wa National Institute on Abuse, Nora Volkow, ndi gulu lake. Kuwunikaku kukuwonetsa zovuta zazikulu za 3 zokhudzana ndi neurobiological zomwe zimakhudzidwa ndi zovuta zonse. Mwachidule ndi awa: a) Kusokoneza maganizo: chiwonongeko chosangalatsa kwambiri chifukwa cha kuchepa kwa chizindikiro cha dopamine; b) Kutsegula: Kupititsa patsogolo mphamvu ya dopamine ku zizolowezi zoledzeretsa, zokopa kapena nkhawa; ndi c) Kusasamala: kufooketsa mayendedwe odziletsa chifukwa chakuchepa kwama voliyumu ndi magwiridwe antchito a kotekisi yakutsogolo. Kusintha komweku kwaubongo kunaperekedwa ndi American Society for Addiction Medicine (ASAM) mwawo malingaliro atsopano oledzera inatulutsidwa mu August, 2011.

Volkow ND, Wang GJ, Fowler JS, Tomasi D, Telang F, R. R. Bioessays. 2010 Sep; 32 (9): 748-55.

National Institute on Abuse, NIH, Bethesda, MD 20892, USA.

[imelo ndiotetezedwa]

KUPHUNZIRA KWAMBIRI - Chizolowezi: Kuchepetsa Mphotho Kukhudzidwa ndi Kuyembekeza Kowonjezeka Kukhazikika Kumayesa Kugonjetsa Bwalo Loyang'anira Brain

Kudalirika

Malingana ndi zofufuza za ubongo, timapereka chitsanzo molingana ndi momwe chizoloŵezi chimawonekera ngati kusamvetsetsana pakati pa kusamalidwa ndi kuyanjana pakati pa maulendo osiyanasiyana a ubongo ndi ntchito.

Mavutowa amasonyeza:

(a) kuchepetsa kuchepa kwa madera a mphotho,

(b) kumvetsetsa kwa maulendo okumbukira kuti zikhale zoyembekezereka kwa mankhwala osokoneza bongo ndi mankhwala, mankhwala okhwima maganizo,

(c) ndi dera lowongolera lolamulira.

Ngakhale kuti poyamba kuyesa kugwiritsa ntchito mankhwala osokoneza bongo ndi khalidwe lodzikonda, kugwiritsa ntchito mankhwala osokoneza bongo kungawononge mapulaneti a neuronal mu ubongo omwe amagwiritsidwa ntchito mwa ufulu wakudzisankhira, kutembenuza ntchito mankhwala osokoneza bongo. Kukhoza kwa mankhwala osokoneza bongo kuti asankhe chizindikiro cha neurotransmitter pakati pa neurons (kuphatikizapo dopamine, glutamate, ndi GABA) amasintha ntchito za maulendo osiyana a neuronal, omwe amayamba kugwedezeka pazigawo zosiyana siyana za mankhwala osokoneza bongo. Pambuyo poona mankhwala, mankhwala osokoneza bongo kapena kupsinjika maganizo, izi zimabweretsa kusokoneza maganizo kwa dera lolimbikitsa / kuyendetsa galimoto zomwe zimayambitsa kumwa mankhwala osokoneza bongo omwe amachititsa kuti munthu akhale ndi chizolowezi choledzera.

Keywords: kuledzera, matenda a ubongo, dopamine, dera la mphoto
Pitani ku:

Introduction

Zaka zotsiriza za 25 za kafukufuku wa sayansi ya ubongo zatulutsa umboni wakuti kuledzera ndi matenda a ubongo, kumapereka ndemanga yamphamvu yochirikiza miyezo yomweyi ya chithandizo chamankhwala kwa wodwalayo monga omwe amapezeka kwa matenda ena omwe ali ndi mphamvu yaikulu ya anthu, monga matenda a shuga. Inde, kafufuzidwe pa zauchidakwa wayamba kufotokozera zochitika zomwe zimakhalapo ndi sequelae zosatha zomwe zingabwere chifukwa cha kugwiritsa ntchito molakwa mankhwala osokoneza bongo. Kafukufukuyu wasonyeza momwe kugwiritsa ntchito mankhwala mobwerezabwereza kumawombera mamolekyu akuluakulu ndi maulendo a ubongo, ndipo pamapeto pake kumasokoneza njira zowonjezereka zomwe zimapangitsa kukhala ndi maganizo, kuzindikira ndi khalidwe. Taphunzira kuti kuledzera kumachitika ndi ubongo wa ubongo. Kuwonongeka kwenikweni kumayambira m'madera ambiri a ubongo omwe amakonza mphotho, kenako amasunthira kumadera ena omwe ali ndi ntchito zovuta kumvetsetsa. Choncho, kuwonjezera pa mphotho, anthu omwe amamwa mowa mwauchidakwa angathe kukhumudwa kwambiri pakuphunzira (kukumbukira, kugwirizanitsa, chizoloŵezi), executive function (kusokoneza maganizo, kusokoneza maganizo, kuchepetsa kukhutira) ntchito.

Kujambula makamaka kuchokera ku zotsatira za maphunziro opanga ubongo omwe amagwiritsira ntchito positron emission tomography (PET), timayambitsa maulendo akuluakulu a ubongo omwe amakhudzidwa ndi mankhwala osokoneza bongo osagwiritsidwa ntchito mobwerezabwereza ndipo kenako amapereka chitsanzo chogwirizana, malinga ndi momwe chizoloŵezi chimayambira monga zotsatira za kusamvetsetsa kusinthidwa kwa nkhani mkati ndi pakati pa maulendo awa. Kumvetsetsa bwino njira za ubongo zomwe zimatha kusintha mosavuta, komanso zowonongeka za chilengedwe ndi zachilengedwe zomwe zimakhudza mwayi wawo, ndizofunika kuti pakhale njira zothandiza kupewa ndi mankhwala kuti athetse vutoli.

Pitani ku:

Dopamine yapamwamba, koma yochepa, imayenera kuledzera

Chizoloŵezi ndicho, choyamba, matenda a mphotho ya mphotho. Njirayi imagwiritsa ntchito neurotransmitter dopamine (DA) ngati ndalama yake yayikulu kutumiza zambiri. Ubongo DA umagwira gawo lofunikira pakukonza zambiri zokhudzana ndi kusakhazikika [1, 2], yomwe ili pamtima wokhoza kulamulira kapena kukopa mphoto [3, 4], mphoto zoyembekezera [5], chilimbikitso, zotengeka, komanso chisangalalo. Kutulutsidwa kwakanthawi kwa DA mu ubongo wa ventral striatum ndikofunikira, ngakhale sikokwanira, pamachitidwe ovuta omwe amachititsa chidwi cha mphotho: kuwonjezeka kwa DA kumawoneka kuti kukugwirizana kwambiri ndi kukula kwa "okwera" komwe maphunziro amakumana nawo. Mayankho omwe ali ndi mayankho amangopezeka DA ikamamasulidwa mobwerezabwereza ngati izi, zakanthawi kochepa, ma surges, poyankha mankhwala osokoneza bongo.

Chochititsa chidwi ndi chakuti, mwachindunji kapena molakwika, mankhwala osokoneza bongo amachititsa kuti ayambe kukokomeza koma nthawi zina amawonjezeka mu DA chowonjezera pa gawo lalikulu la mphotho (chiwalo)6, 7], makamaka, mu nucleus accumbens (Nac) yomwe ili mu ventral striatum. Dongosolo la DA limeneli likufanana, ndipo nthawi zina zimakhala zopambana, kuwonjezeka kwa thupi kumayamba chifukwa cha zokondweretsa zachilengedwe (zomwe zimatchulidwa kuti zowonjezera zachilengedwe kapena mphotho). Monga momwe tingayembekezere, ubongo waumunthu ukulingalira maphunziro pogwiritsa ntchito positron emission tomato (PET), wasonyeza bwino kuti DA ikuwonjezeredwa ndi magulu osiyanasiyana a mankhwala (mwachitsanzo. zolimbikitsa (Fanizo la 1A), [8, 9], nicotine [10], ndi mowa [11]) mkati mwa ventral striatum, zimagwirizanitsidwa ndi zochitika zomwe zimakhala zosavuta (panthawi yapamwamba) poledzera [12, 13, 14]. Popeza maphunziro a PET angathe kuchititsidwa mwakuuka m'mitu ya anthu ndizotheka kukonza chiyanjano pakati pa zifukwa zovomerezeka za zotsatira za mankhwala ndi kusintha komwe kumachitika m'magulu a DA. Kafukufuku ambiri adafotokoza kuti omwe akuwonetsa DA wamkulu kwambiri amatsatira zotsatira za mankhwala [amphetamine, nicotine, mowa, methylphenidate (MPH)] amanenanso zapamwamba kwambiri kapena zokoma (Fanizo la 1B).

Chithunzi 1

DA yodalirika kwambiri yowonjezera pa striatum imagwirizana ndi kumverera kwa "pamwamba." A: Zithunzi za kufalitsa (DV) za [11C] raclopride mwa imodzi mwa nkhanizo pazotsatira ndipo mutatha kuyang'anira 0.025 ndi 0.1 mg / kg iv ...

Maphunziro a zinyama ndi anthu awonetsa kuti liwiro limene mankhwala alowa, amachitapo kanthu, ndipo amasiya ubongo (mwachitsanzo mbiri yake ya mankhwala) imasewera mbali yaikulu pakuzindikiritsa zotsatira zake. Ndipotu, mankhwala osokoneza bongo omwe agwiritsidwe ntchito ndi ubongo wamagetsi ndi PET (cocaine, MPH, methamphetamine, ndi nicotine) amasonyeza mbiri yomweyi pamene maulamuliro amatha, mwachitsanzo, nsonga zapamwamba mu ubongo wa munthu zimafikira mkati mwa 10 min (Fanizo la 2A) ndipo izi zowonjezera zimagwirizanitsidwa ndi "mkulu" (Fanizo la 2B). Malingana ndi mgwirizano umenewu, zikutsatira kuti kuonetsetsa kuti mankhwala osokoneza bongo amalowerera mu ubongo pang'onopang'ono mwakuyenera ayenera kukhala njira yowonjezerapo yochepetsera mphamvu zowonjezeretsa, motero kuchitidwa nkhanza. Tinapanga mayesero kuti tiyese bwino chongopeka ichi ndi mankhwala osokoneza bongo MPH, omwe, monga cocaine, amachulukitsa DA pochepetsera kayendedwe kake kuti alowe m'thupi (presynaptic neuron)mwachitsanzo mwa kulepheretsa otsogolera a DA), motero akukulitsa chizindikiro cha DA. Inde, tapeza kuti, ngakhale kutumiza kwa MPH kawirikawiri kumakhala kosiyana, kumakhala ndi MPH, yomwe imapangitsanso DA mu statum [15], koma ndi 6- mpaka 12 pang'onopang'ono pharmacokinetics, sizikuwoneka kuti zikuwongolera [16, 17]. Choncho, kulephera kwa oral MPH - kapena amphetamine [18] chifukwa cha nkhaniyi - kukakamiza pamwamba ndi chizindikiro cha kuchepa kwawo mu ubongo [19]. Choncho, ndizomveka kufotokozera kukhalapo kwa mgwirizano pakati pa chiwerengero cha mankhwala osokoneza bongo chomwe chimalowa mu ubongo, chomwe chimapangitsa kuti DA iwonjezeke mu ventral striatum, ndi zotsatira zake zowonjezera [20, 21, 22]. Mwa kuyankhula kwina, kuti mankhwala akulimbikitseni kuwonjezereka kumachititsa DA mwamsanga. Chifukwa chiyani izi ziyenera kukhala choncho?

Chithunzi 2

A: Axial ubongo zithunzi za kufalitsidwa kwa [11C] methamphetamine nthawi zosiyana (mphindi) pambuyo pake. B: Ntchito yam'mbuyo yamakono [11C] methamphetamine mu striatum motsatira njira yachimake ya "mkulu" ...

Malingana ndi kukula kwake kwa nthawi yaitali, kuzindikiritsa DA kungatenge chimodzi mwa mitundu iwiri yofunikira: phasi kapena tonic. Kuwonekera kwa phasic kumadziwika ndi kutalika kwapamwamba komanso kuthamanga kwafupipafupi, pamene chizindikiro cha tonic chili ndi matalikidwe otsika komanso nthawi yowonjezereka. Kusiyanitsa n'kofunikira chifukwa zimasonyeza kuti kuwonetsa kwa DA n'kofunika kuti mankhwala osokoneza bongo apangitse "mayankho ogwira ntchito," omwe ndi amodzi omwe amachititsa kuti asamangidwe (kuphatikizapo mankhwala). Chimodzi mwa zinthu zosiyanitsa zomwe zimagwirizanitsa kufalikira ndi chikhalidwe ndikutengeka kwa D2R ndi glutamate n-methyl-d-aspartic asidi (NMDA) receptors [23]. Kumbali inayi, kuwonetsa DA kuwonetsera kumawathandiza kugwira ntchito kukumbukira komanso njira zina zoyendetsera ntchito. Zina mwa zinthu zomwe zimasiyanitsa mtundu uwu wa chizindikiro kuchokera ku mtundu wa phasic ndizoti zimagwira ntchito makamaka kudzera m'magulu otsika a DA receptors (DA D1 receptors). Komabe, ngakhale mosagwirizana ndi njira zosiyanasiyana zomwe zimagwiritsidwa ntchito, mankhwala osokoneza bongo omwe amatha nthawi yaitali (komanso kusintha kwa DA tonic kupyolera mwa mapulogalamuwa) kumatanthauziranso kusintha kwa mapuloteni omwe amachititsa kuti zikhale bwino [25] mwa kusintha kwa NMDA komanso alpha-amino-3-hydroxyl-5-methyl-4-isoxazone-propionate (AMPA) glutamate receptors [24].

Umboni umasonyeza kuti kuwonjezereka kwa mankhwala osokoneza bongo kuwonjezeka kwa DA kumapangitsa kuti DA ayambe kuwombera. Izi zimathandizira chifukwa chake kugwiritsa ntchito mankhwala osokoneza bongo kosatha kungachititse kuti mayendedwe amphamvuwa adziwe mankhwala, chiyembekezero chake, ndi zizindikiro zambiri (anthu, zinthu ndi malo) ogwirizana ndi ntchito yake. Komabe, ngakhale kuwonjezereka koopsa kwa mankhwala osokoneza bongo kumene kumadalira kuwonjezereka kwa DA kotereku kumawoneka kuti "kofunikira" kuti chitukuko chikhale chonchi, siziwonekere "zosakwanira." Kuwonetsa mankhwala mobwerezabwereza kumayambitsa kusintha kwa ntchito za ubongo zomwe zimatenga nthawi kukula chifukwa zimachokera ku mafilimu achiwiri m'magulu ena a ubongo (mwachitsanzo glutamate [26] komanso mwinamwake γ-aminobutyiric acid (GABA) yomwe potsirizira pake imakhudza maulendo ena a ubongo omwe DA. Maulendo awa ndilo gawo la magawo otsatirawa.

Pitani ku:

Kugwiritsira ntchito mankhwala osokoneza bongo kumachepetsanso dopamine receptors ndi dopamine kupanga: The "high" iphwanyika

Mfundo yakuti mankhwala osokoneza bongo ayenera kukhala ochiritsika musanayambe kumwa mowa ndizowonekera momveka bwino kuti matendawa akulosedweratu, mwa anthu omwe ali pachiopsezo, pakuwonongeka mobwerezabwereza kwa mphoto. Izi zowonongeka zimatha kutsogoloza maulendo ena ambiri (zolimbikitsa / kuyendetsa, kuletsa kuteteza / kulamulira ntchito, ndi kukumbukira / kugwirizanitsa) zomwe zimapangidwanso ndi DA [27]. Zina mwazinthu zomwe zakhala zikuchitika mobwerezabwereza m'nkhani zovuta kwambiri ndizochepetsetsa kwambiri m'magulu a D2R (high affinity) receptors ndi kuchuluka kwa DA yotulutsidwa ndi maselo a DA [28] (Chith. 3). Chofunika kwambiri, kuchepetsa izi kumagwirizanitsidwa ndi ntchito zochepa zowonongeka zamagetsi m'madera a prefrontal cortex (PFC) omwe ndi ofunikira kuti azigwira bwino ntchito (mwachitsanzo Anterior cingulate gyrus (CG) ndi orbitofrontal cortex (OFC)) (Fanizo la 4A). Izi zikutipangitsa kuti tiwonetsetse kuti izi zikhoza kukhala chimodzi mwa njira zomwe zimagwirizanitsa kusokonezeka kwa mankhwala osokoneza bongo mu DA kuwonetsera ndi kukakamizidwa kwa mankhwala osokoneza bongo komanso kusowa kwa mphamvu pa kudya mankhwala osokoneza bongo omwe amachititsa munthu kukhala ndi chizoloŵezi choledzera [29]. Komanso, zomwe zimachitika chifukwa cha hypodopaminergic zitha kufotokozera kuchepa kwa chidwi cha omwe amalandila mphotho zachilengedwe (monga chakudya, kugonana, ndi zina) ndikupitiliza kugwiritsa ntchito mankhwala osokoneza bongo ngati njira yobwezera kwakanthawi kwakusowa kumeneku [30]. Chofunika chodziwitsa chidziwitso chimenechi ndikutchula zolephera izi (poonjezera miyeso ya D2R yakupha ndi kuwonjezereka kwa DA kumasulidwa ku striatum ndi zigawo za prefrontal) zingapereke njira zothandizira kuti athetse vutoli.31]. Kodi pali umboni uliwonse wosinthira chikhalidwe cha hypodopaminergic chingakhale ndi zotsatira zabwino pamakhalidwe ogwiritsira ntchito mankhwala osokoneza bongo? Yankho ndilo inde. Maphunziro athu amasonyeza kuti mwa kukakamiza kuchulukitsidwa kwa D2R, mkatikati mwa mphotho ya cocaine-kapena makoswe omwe amadziŵa moŵa, tikhoza kuchepetsa kwambiri kudziletsa kwa cocaine [31] kapena mowa [32], motero. Komanso, mu makoswe, komanso anthu othamanga a methamphetamine [33], kuchepa kwa D2R kumaphatikizidwanso ndi kutengeka, ndipo mu makoswe imaneneratu njira zowonongeka za mankhwala osokoneza bongo (onani m'munsimu).

Chithunzi 3

Zithunzi za ubongo za DA D2 receptors (D2R) pa mlingo wa striatum muzolamulira ndi osokoneza bongo. Zithunzi zinapezeka ndi [11C] raclopride. Kusinthidwa ndi chilolezo kuchokera ku Volkow Et al. [30].

Chithunzi 4

A: Zithunzi zomwe zimapezeka ndi fluorodeoxyglucose (FDG) kuti muyese ubongo wa metabolism muzowononga komanso mowa mankhwala osokoneza bongo. Tawonani kuchepa kwa kagayidwe kake kamene kamakhala kochepetsedwa mu orbitofrontal cortex (OFC) mu cocaine wozunza poyerekeza ndi kulamulira. B: Mgwirizano pakati ...

Kafukufuku akuwonetsanso kuti, mwa anthu, kuledzera kumagwirizana ndi kuchepetsedwa kwa DA ku ventral striatum ndi m'madera ena a striatum, komanso kuyankha mosangalatsa kwa mankhwala omwe amagwira ntchito ndi ogwiritsira ntchito mankhwala osokoneza bongo (Chith. 5) [34]. Ichi chinali chidziwitso chosayembekezereka chifukwa chakuti adayamba kuganiza kuti kuledzeretsa kunasonyeza kuti kulimbikitsidwa kwapindulitsa (ndipo chotero dopaminergic) mayankho a mankhwala. Anthu ogwiritsa ntchito mankhwala osokoneza bongo, amachepetsedwa ku DA kumasulidwa kungathe kusokoneza ubongo wodwalayo m'madera ozungulira mphoto (mwachitsanzo m'magulu a DA omwe amamasula DA ku statum) kapena, kusokoneza maganizo pazochitika za circuit reward ndi prefrontal (executive control) kapena njira za amygdalar (zamaganizo) (njira zamakono zapamwamba zamakono). Popeza vuto lopanda dopaminergic mu striatum, monga momwe likuwonera munthu wodwala mankhwala osokoneza bongo, amalephera kuwerengera makhalidwe omwe amachititsa makhalidwe oipa, monga kukhumba, zolakalaka, ndi kubwerera chifukwa cha mankhwala osokoneza bongo, zikutheka kuti zigawo zapamwamba (monga komanso amygdala) akuphatikizidwanso apa, chifukwa kusokonezeka kwawo kungathandize kapena kusokoneza makhalidwe amenewa.

Chithunzi 5

MPH idakulitsa kuwonjezeka (kuyesedwa ndi kulepheretsa kumangika kwa raclopride kapena Bmax / Kd) pakuwongolera komanso moledzeretsa. Zidakwa zikuwonetsa kuchepa kwa kumasulidwa kwa DA. Kusinthidwa ndi chilolezo kuchokera ku Volkow Et al. [34].
Pitani ku:

Mankhwala opatsirana a dopamine receptor (DR2) amalepheretsa kutengeka kwa chilakolako choyendetsa makina a prefrontal cortex

Zakhala zikudodometsedwa kuti zolepheretsa kulamulira makhalidwe osokoneza bongo omwe amadziwika ndi chizolowezi choledzeretsa akhoza kukhala chifukwa cha zovuta zina zomwe zili m'madera a ubongo [35]. Panopa pali umboni wochuluka wotsimikizira mfundo imeneyi, kuyambira ndi maphunziro a zinyama omwe amafufuza kugwirizana pakati pa D2R ndi kuyendetsa khalidwe. Zotsatira za makoswe zimasonyeza bwino mgwirizano pakati pa D2R yochepa ndi kutengeka [36], komanso pakati pa kukhudzidwa ndi kudzikonda kwadongosolo [37]. Koma kugwirizana ndi chiyani? Monga tanenera kale, ogwiritsira ntchito mankhwala osokoneza bongo, D2R yochepa kwambiri imagwirizanitsa kwambiri ndi ubongo m'magulu akuluakulu a PFC, monga OFC (wogwirizana ndi kuthandizira komanso kusokonezeka komwe kumabweretsa zizoloŵezi zozizwitsa) ndi CG ndi kuwunika kolakwika ndi omwe chisokonezo chimayambitsa chikoka) (Fanizo la 4B) [38, 39]. Kuwonjezera apo, mu phunziro lomwe tinalipanga mwa anthu pawokha (kutanthauza SD ± zaka, 24 ± 3 zaka) mbiri ya banja yauchidakwa, koma omwe analibe zidakwa, tinapezanso mgwirizano waukulu pakati pa D2R yoyamba ndi metabolism m'madera akutali (CG , OFC, ndi dorsolateral PFC) komanso kumalo osungirako zida za m'madzi (kugwirizanitsa ntchito, kudzidziwitsa, ndi kulakalaka mankhwala osokoneza bongo) [40] (Chith. 6). Chochititsa chidwi n'chakuti, anthuwa anali ndi D2R yowononga kwambiri kusiyana ndi mbiri ya banja yauchidakwa, ngakhale kuti sizinali zosiyana ndi zamagetsi. Ndiponso, mu maulamuliro, D2R yopweteka sinagwirizanitse ndi kagayidwe kamene kamayambitsa matenda. Izi zinatipangitsa kulingalira kuti D2R yodalirika kwambiri m'mitu yomwe ili ndi chiopsezo chachikulu chauchidakwa kumawatetezera kuledzera mbali imodzi mwa kulimbikitsa ntchito ku madera a prefrontal. Pogwirizana, ma datawa akusonyeza kuti D2R yapamwamba mu striatum ingateteze kusagwiritsira ntchito mankhwala osokoneza bongo ndi chizoloŵezi choletsa kusunga khalidwe lodziletsa, mwachitsanzo, poyendetsa maulendo okhudzana ndi khalidwe loletsa makhalidwe komanso kuyang'anira maganizo.

Chithunzi 6

Malo a ubongo kumene DA D2 receptors (D2R) anali ofanana kwambiri ndi ubongo metabolism mu nkhani ndi mbiri ya banja la uchidakwa. Kusinthidwa ndi chilolezo kuchokera ku Volkow Et al. [40].

Mofananamo, timaganiza kuti zigawo za m'madera oyandikana nawo zimathandizanso kuchepetsa kutsegulidwa kwa DA. Poyesa izi, ife tinayesa kugwirizana pakati pa kagwiritsidwe kake ka mphamvu m'thupi mwa PFC komanso kuwonjezereka kwa DA kuyambitsa chifukwa cha kulamulira kwa MPH muzitsulo komanso kuledzera. Mogwirizana ndi maganizo, mu zakumwa zoledzeretsa sitinathe kuona mgwirizanowu wa pakati pa chiyero choyambirira chokhazikika ndi DA kuchoka mu striatum, kutanthauza kuti chilembacho chicheperachepera DA kuchotsedwa mu striatum mu zidakwa zikuwonetsera mu gawo lina lolakwika la ntchito ubongo ndi prefrontal m'madera ubongo [34].

Choncho, tapeza mgwirizano pakati pa ntchito zochepa zochepa mu PFC ndikuchepetsanso D2R yovulazira m'mabuku omwe amamwa mankhwala osokoneza bongo, komanso pakati pa ntchito yapadera ya PFC ndi kuwonetsedwa kwa DA komwe kulibe anthu osokoneza bongo. Mabungwe amenewa amavomereza kuti mgwirizanowu ulipo pakati pa PFC ndi njira zochepa zowonongeka m'dongosolo la DA ndi zolimbikitsa, mwina chifukwa cha mphamvu ya PFC chifukwa chofuna kuchita zinthu mosaganizira. Komabe, izi zimalephera kuwerengera zochitika zina zowonjezera, monga zotsatira za mankhwala okhudzana ndi mankhwala omwe amachititsa chidwi chilakolako, zomwe zingakhale zovuta kukumbukira ndi kuphunzira maulendo.

Pitani ku:

Zomwe zimakumbukiridwa ndi zizoloŵezi zosasinthika zimalowetsa "pamwamba" kukhala dalaivala

Kuwonjezera pa kukakamizidwa kwa maselo a DA mu ventral striatum pamapeto pake kumakhazikitsa malumikizano atsopano mu ubongo pakati pa zochitika zokhutiritsa, ndi zochitika zomwe zikuzungulirapo (mwachitsanzo, chilengedwe, chizolowezi chokonzekera mankhwala, etc.), kukhazikitsa zatsopano , mabungwe amphamvu ophunzira omwe angayambe khalidwe. Pomalizira pake, kukumbukira chabe kapena kuyembekezera kwa mankhwala kungayambitse makhalidwe omwe amakhudzidwa ndi anthu osokonezeka. Mobwerezabwereza kugwiritsa ntchito mankhwala osokoneza bongo, kuwombera kwa maselo a DA mu striatum kumayamba kusintha khunyu ya ubongo. Izi zimathandizira kukhazikitsa zochitika zapamwamba zomwe zimagwiritsidwa ntchito ndi mankhwala, zomwe zimathandiza kufotokoza kuthekera kwa mitundu yonse ya mankhwala okhudzana ndi mankhwala osokoneza bongo (mwa chiyembekezero chodziwitsidwa cholandira mphotho ya mankhwala pakadutsa zovuta izi) [41] kuti atha kuyambitsa moto wa DA. Ndipo chifukwa cha udindo wa DA motsogoleredwa, DAzi ikuwonjezereka ndikuyendetsa galimoto kuti ipeze mphoto [42]. Inde, pamene makoswe amavomerezedwa mobwerezabwereza kumalo osatetezeka omwe akugwiritsidwa ntchito ndi mankhwala (ovomerezeka), akhoza kuwonjezera DA kuwonjezeka ndi kubwezeretsanso mankhwala oyendetsa mankhwala [43]. Mayankho oterewa ndi okhudzana ndi matenda omwe amagwiritsidwa ntchito kwambiri chifukwa ali ndi udindo waukulu wa munthu wosokonezeka kuti abwererenso ngakhale atatha nthawi yaitali. Tsopano, njira zoganizira ubongo zimatipangitsa ife kuyesa ngati kuwonetsa kwa anthu kuti azigwiritsira ntchito mankhwala osokoneza bongo kungayambitse chilakolako cha mankhwala monga momwe zikusonyezedwera mu nyama za ma laboratory.

Mobwerezabwereza kugwiritsa ntchito mankhwala osokoneza bongo, kuwombera kwa maselo a DA mu striatum kumayamba kusintha khunyu ya ubongo. Izi zimathandizira kukhazikitsa zochitika zapamwamba zomwe zimagwiritsidwa ntchito ndi mankhwala, zomwe zimathandiza kufotokoza kuthekera kwa mitundu yonse ya mankhwala okhudzana ndi mankhwala osokoneza bongo (mwa chiyembekezero chodziwitsidwa cholandira mphotho ya mankhwala pakadutsa zovuta izi) [41] kuti atha kuyambitsa moto wa DA. Ndipo chifukwa cha udindo wa DA motsogoleredwa, DAzi ikuwonjezereka ndikuyendetsa galimoto kuti ipeze mphoto [42]. Inde, pamene makoswe amavomerezedwa mobwerezabwereza kumalo osatetezeka omwe akugwiritsidwa ntchito ndi mankhwala (ovomerezeka), akhoza kuwonjezera DA kuwonjezeka ndi kubwezeretsanso mankhwala oyendetsa mankhwala [43]. Mayankho oterewa ndi okhudzana ndi matenda omwe amagwiritsidwa ntchito kwambiri chifukwa ali ndi udindo waukulu wa munthu wosokonezeka kuti abwererenso ngakhale atatha nthawi yaitali. Tsopano, njira zoganizira ubongo zimatipangitsa ife kuyesa ngati kuwonetsa kwa anthu kuti azigwiritsira ntchito mankhwala osokoneza bongo kungayambitse chilakolako cha mankhwala monga momwe zikusonyezedwera mu nyama za ma laboratory.

Funso limeneli lafufuzidwa ndi owononga cocaine ovutitsa. Kugwiritsa ntchito PET ndi [11C] raclopride, mafukufuku awiri odziwonetsera okha adasonyeza kuti kuwonetsa kanema ya cocaine-cues (ya maphunziro osuta cocaine) koma osati pa kanema kosaloŵerera (za masoka a chirengedwe) kuwonjezeka kwa DA kupha anthu m'mutu mwa anthu omwe amamwa mankhwala a cocaine (Chith. 7) komanso kuti kuwonjezeka kwa DA kunagwirizanitsidwa ndi zidziwitso zoyenera za chilakolako cha mankhwala [44, 45]. Kuwonjezereka kwa DA kukuwonjezeka chifukwa chodziwika ndi kanema ya cocaine, makamaka chikhumbo cha mankhwala. Kuwonjezera apo, kukula kwa DA kumawonjezereka kunagwirizananso ndi chizoloŵezi chokhwima kwambiri, kuwonetsa kufunikira kwa mayankho omwe ali nawo mu matenda oledzera.

Chithunzi 7

A: Average DV zithunzi za [11C] raclopride mu gulu la owononga cocaine (n = 17) ayesedwa pamene ayang'ana (B) mavidiyo osalowererapo (masewero achilengedwe), komanso pamene akuwonera (C) kanema ndi mankhwala a cocaine (maphunziro opatsa komanso akupatsa cocaine). Kusinthidwa ndi ...

Ndikofunika kuti tigogomeze, ngakhale, ngakhale kuti magulu amenewa ali ndi mphamvu zowonongeka, tafika posonkhanitsa umboni watsopano wosonyeza kuti owononga mankhwala a cocaine amakhalabe ndi mphamvu zowononga chilakolako. Choncho, njira zothandizira malamulo a fronto-striatal angapereke thandizo lochiritsira [46].

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Kuziyika zonse pamodzi

Zina mwazoopsa kwambiri za mankhwala osokoneza bongo ndizolakalaka kwambiri kugwiritsa ntchito mankhwala osokoneza bongo omwe angathe kukumbukira ngakhale atakhala ndi zaka zambiri, komanso kuti anthu omwe amamwa mankhwala osokoneza bongo amalepheretsa kufunafuna mankhwala osokoneza bongo pomwe chilakolakochi chikufalikira ngakhale kuti zotsatira zake zimakhala zoipa.

Tapereka chitsanzo cha chizoloŵezi choledzera [47] lomwe limalongosola mchitidwe wambiri wa matendawa poyambitsa maulendo anayi ophatikizana, omwe amagwirizanitsa ntchito zowonongeka angathe kufotokozera makhalidwe ambiri oledzeretsa: (a) mphotho, kuphatikizapo nuclei zingapo m'magulu a basal, makamaka ventral striatum, yemwe Nac amalandira zopereka kuchokera ku gawo la ventral tegmental ndikutumizira uthenga ku ventral pallidum (VP); (b) Kulimbikitsa / kuyendetsa galimoto, yomwe ili mu OFC, corcalx, suborlosal cortex, dorsal striatum ndi motor cortex; (c) kukumbukira ndi kuphunzira, komwe kuli amygdala ndi hippocampus; ndipo (d) kukonzekera ndi kuyendetsa, yomwe ili mu kondomu yapamwamba yapamwamba, CG yapansi ndi yotsika pansi. Maulendo anaiwa amalandira mauthenga ochokera kwa DA neurons koma amalumikizana wina ndi mzake kudzera muzowonetsera molunjika kapena mosagwirizana (makamaka glutamatergic).

Maulendo anayi mu chitsanzochi amagwira ntchito limodzi ndipo ntchito zawo zimasintha ndi zodziwa. Chilichonse chimagwirizana ndi mfundo yofunikira, motere: saliency (mphoto), mkati mwa dziko (zolimbikitsa / kuyendetsa), mayanjano ophunzira (kukumbukira, chikhalidwe), ndi kukonza mkangano (ulamuliro). Kuwonjezera apo, maulendowa amathandizananso ndi maulendo omwe amakhudzidwa ndi maganizo (kuphatikizapo kusokonezeka maganizo) [48] komanso ndi interoception (zomwe zimachititsa kuzindikira za chilakolako cha mankhwala ndi maganizo) [49]. Ife tawonetsa kuti chitsanzo cha ntchito mu intaneti zinayi zotchulidwa apa zikukhudza momwe munthu wamba amasankhira pakati pa njira zotsutsana. Zosankhazi zimakhudzidwa mwatsatanetsatane ndi mphotho, kukumbukira / kukonzekera, zolimbikitsa, ndi maulendo oyendetsa komanso izi zimayendetsedwa ndi maulendo omwe ali ndi maganizo komanso kuzindikira (Fanizo la 8A).

Chithunzi 8

Chitsanzo chokonzekera zokopa za maulendo anayi omwe akuyambitsidwa: mphoto (yofiira: ili mu nucleus accumbens ya ventral astriatum ndi VP); Chothandizira (chobiriwira: chili mu OFC, subcallosal cortex, dorsal striatum, ndi motor cortex); kukumbukira (golide: ilipo ...

Yankho lachithupi limakhudzidwa ndi mphindi yake yamphindi, mwachitsanzo, mphotho yake. Momwemonso, kuyembekezera mphoto kumagwiritsidwa ntchito ndi mbali za DA neurons zomwe zimagwira ntchito ku ventral striatum ndipo zimakhudzidwa ndi zizindikiro za glutamatergic kuchokera ku OFC (zomwe zimapereka saliency mtengo monga ntchito ya nkhani) ndi amygdala / hippocampus (yomwe imayankha mayankho ndi kukumbukira kukumbukira). Mtengo wa zokopazo ndi wolemera (poyerekeza) ndi wina wa zovuta zina, komanso umasintha monga ntchito ya zosowa za munthu, zomwe zimasinthidwa ndi maganizo (kuphatikizapo kusokonezeka maganizo) ndi kuzindikira kwina. Makamaka, kuika maganizo pafupipafupi kumawonjezera kufunika kwa mankhwala osokoneza bongo panthawi imodzimodziyo kumachepetsa malamulo oyendetsa amygdala [50]. Kuonjezerapo, popeza kuti mankhwala osokoneza bongo amatha kugwiritsidwa ntchito polimbikitsana kuti asamapanikizidwe, izi zimalongosola chifukwa chake kupanikizika kungayambitsenso mankhwala osokoneza bongo nthawi zambiri m'maganizo. Pamene mphamvuyi ikufunika kwambiri, zomwe zimapangidwanso ndi zochitika zomwe zinachitika pamtima, zimakhala zolimbikitsa kwambiri kuyendetsa dera lolimbikitsana komanso kulimbikitsa kuti lipeze. Chisankho cha chisankho chochitapo kanthu (kapena ayi) kuti chikhale chokonzekera chikugwiritsidwa ntchito ndi mbali ndi PFC ndi CG, yomwe imayeza kuchuluka pakati pa zotsatira zabwino zowonongeka, ndi corrox yapansi (Broadmann Area 44), zomwe zimathandiza kulepheretsa yankho loyambirira lachitapo kanthu [51].

Malingana ndi chitsanzo ichi, mu phunziro lovuta (Fanizo la 8B), kufunika koyipa kwa mankhwala osokoneza bongo ndi zomwe zimagwirizanitsidwa zimapangidwanso pokhapokha mphotho zina (zachilengedwe), zomwe saliency yake yachepetsa. Izi zikhoza kufotokoza kuwonjezereka kwakukulu kofuna mankhwalawa. Komabe, kugwiritsidwa ntchito kwa mankhwala osokoneza bongo kumabweretsanso malipiro a mphotho, zomwe zimapangitsa kuchepa kwa dera la mphoto kuti likhale lothandizira [52], komwe kumathandizanso kufotokozera kuchepa kwa phindu la osagwiritsa ntchito mankhwala osokoneza bongo mwa munthu wosokonezeka. Chifukwa chinanso chokhazikika cha mankhwala osokoneza bongo ndi kusowa kwa chizoloŵezi cha mayankho a DA ku mankhwala osokoneza bongo (kulekerera) poyerekeza ndi chizoloŵezi chozoloŵera chomwe chiripo chifukwa cha madalitso achilengedwe ndipo zomwe zimapangitsa kuti munthu asamangoganizira [53].

Kuwonjezera apo, kufotokozera zokakamiza ndizokwanira kuwonjezera malire a malipiro [54]; Choncho, tikaneneratu kuti munthu amene ali ndi chizoloŵezi chowongolera, kuwonetsa malo omwe ali ndi vutoli akhoza kupititsa patsogolo kuchepa kwawo kwa madalitso achilengedwe. Popanda mpikisano ndi ena othandizira, kuphunzira kumapangitsa kuti munthu akhale ndi mankhwala osokoneza bongo. Timaganiza kuti mankhwalawa amachititsa kuti DA iwonjezeke ku Nac mu ventral striatum komanso mu dorsal striatum yomwe imayambitsa chida cha mankhwala ndipo sitingatsutsane ndi PFC yosavomerezeka. Choncho, kumwa mankhwala osokoneza bongo komanso kumwa mowa mwauchidakwa kuwonjezereka kwa zizindikiro za DA kungapangitse kuwonjezereka kwa maulendo olimbikitsako / magalimoto ndi ma memory, zomwe zimalepheretsa PFC (chiopsezo cha prefrontal chikhale ndi mphamvu yayikulu ya amygdala) [50], kulepheretsa mphamvu ya PFC kuyendetsa dera lolimbikitsa. Pokhapokha kutetezedwa kotereku, chitsimikizo chotsimikizika chimakhazikitsidwa, chomwe chimapangitsa kuti munthu adye mankhwala osokoneza bongo. Chifukwa kuyankhulana pakati pa maulendowa ndi mbali ziwiri, kutsegula kwa intaneti pakuledzera kumatithandiza kulimbikitsa kufunika kwa mankhwala ndi chikhalidwe cha mankhwala.

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Mawuwo

Mwachidule, timapereka chitsanzo chomwe chimayambitsa chizolowezi choledzera motere: Panthawi ya chizoloŵezi, kufunika kokhala ndi mankhwala osokoneza bongo kumalo okumbukira mankhwala kumapereka mphotho ya kuyembekezera komanso kumapangitsa kuti anthu adye mankhwalawa, powonjetsa chiletso choletsedwa ndi PFC. Ngakhale kuti chiwerengero cha DA chowonjezereka ndi mankhwala omwe amachititsa kuti mankhwalawa asokonezedwe kwambiri, mankhwalawa amachititsa kuti mayankho awo azikhala mwaokha, kupititsa patsogolo zida zogwiritsira ntchito mankhwalawa ndi kulandira ndondomeko yabwino yotsutsa ndondomekoyi, chifukwa cha kuchotsedwa wa dera loyang'anira dera. Pa nthawi yomweyi, chizoloŵezi choledzeretsa chikhoza kubwezeretsanso maulendo omwe amatsitsimutsa mtima ndi kuzindikira (zomwe zimaimiridwa ndi mdima wakuda)Fanizo la 8B) mwa njira zomwe, ngati atayesedwa, amayesetsa kupititsa patsogolo kutalika kwa chiletso choletsedwa ndi kulakalaka ndi kukakamiza kumwa mankhwala osokoneza bongo.

Timavomereza kuti ichi ndi chosavuta: Timadziwa kuti mbali zina za ubongo ziyenera kuchitiranso nawo maulendowa, dera limodzilo lingapereke maulendo angapo, ndipo maulendo enawo akhoza kukhala oledzera. Kuonjezerapo, ngakhale kuti chitsanzo ichi chimalingalira za DA, zikuwoneka kuchokera ku maphunziro ovomerezeka omwe amasinthidwa kuti agwirizane ndi zomwe zimayambitsa matendawa komanso zomwe takambirana pano. Zikuwonekeranso kuchokera kuzipangizo zamakono zomwe odwala ena amachititsa kuti mankhwalawa asokonezedwe monga mankhwala osokoneza bongo komanso opioids. Mwamwayi, mpaka posachedwa, kupeza koperewera kwa opanga mafilimu pa kujambula kwa PET kulibe mphamvu yokha kufufuza momwe magulu ena opatsirana mankhwala amathandizira mu mphotho ya mankhwala ndi mowa.

Pitani ku:

achidule

AMPA
α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate
CG
kumvetsetsa gyrus
CTX
kortex
D2R
mtundu wa dopamine 2 / 3 receptor
DA
dopamine
FDG
fluorodeoxyglucose
GABA
γ-aminobutyiric asidi
HPA
hypothalamic pituitary axis
mph
methylphenidate
Nac
nucleus accumbens
NMDA
n-methyl-d-asittic acid
OFC
orbitofrontal cortex
PET
positron emission tomography
PFC
prefrontal cortex
VP
ventral pallidum
Pitani ku:

Zothandizira

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