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

Zomwe zimayambitsa zolaula zimakhala mu mphotho yoyendayenda

NDEMANGA: Ndemanga yochokera kwa mkulu wa National Institute on Drug Abuse, Nora Volkow, ndi gulu lake. Ndemanga iyi ikuwonetsa mavuto atatu akuluakulu a ubongo omwe amakhudzidwa ndi zizolowezi zonse. Mwachidule ndi awa: a) Kutaya chidwi : yankho losasangalatsa chifukwa cha kuchepa kwa dopamine signaling; b) Kuzindikira : yankho lowonjezereka la dopamine ku zizindikiro za zizolowezi, zoyambitsa kapena kupsinjika; ndi c) Kusaganizira bwino : kufooka kwa ma circuits odziletsa chifukwa cha kuchepa kwa voliyumu ndi magwiridwe antchito a frontal cortex. Kusintha komweku kwa ubongo kunafotokozedwa ndi American Society for Addiction Medicine (ASAM) mu tanthauzo lawo latsopano la zizolowezi zomwe zinatulutsidwa mu Ogasiti, 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

Chizolowezi choledzera, choyamba, ndi matenda a dongosolo la mphotho muubongo. Dongosololi limagwiritsa ntchito neurotransmitter dopamine (DA) ngati ndalama yake yayikulu yotumizira uthenga. Brain DA imagwira ntchito yofunika kwambiri pakugwiritsa ntchito chidziwitso chokhudza kusakhazikika [ 1 , 2 ], chomwe chili pakati pa kuthekera kwake kulamulira kapena kukhudza mphotho [ 3 , 4 ], kuyembekezera mphotho [ 5 ], chilimbikitso, malingaliro, ndi malingaliro a chisangalalo. Kutulutsidwa kwakanthawi kwa DA mu ventral striatum yaubongo ndi chochitika chofunikira, ngakhale chosakwanira, munjira zovuta zomwe zimapangitsa kuti munthu amve mphotho: kuwonjezeka kwa DA kumawoneka kuti kukugwirizana bwino ndi mphamvu ya "kukwera" komwe anthu amakumana nako. Mayankho okhazikika amangobwera pamene DA imatulutsidwa mobwerezabwereza pamene izi zikukwera mwachangu, kwakanthawi, poyankha mankhwala osokoneza bongo kapena zizindikiro zokhudzana ndi mankhwala osokoneza bongo.

Chochititsa chidwi, mwachindunji kapena mwanjira ina, mankhwala onse osokoneza bongo amagwira ntchito poyambitsa kuwonjezeka kwakukulu koma kwakanthawi kwa DA yakunja m'dera lofunika kwambiri la dongosolo la mphotho (limbic) [ 6 , 7 ], makamaka, mu nucleus accumbens (Nac) yomwe ili mu ventral striatum. Kukwera kwa DA kotereku kumafanana, ndipo nthawi zina kumaposa kwambiri, kuwonjezeka kwa thupi komwe kumachitika chifukwa cha zinthu zosangalatsa zachilengedwe (zomwe nthawi zambiri zimatchedwa zolimbikitsa zachilengedwe kapena mphotho). Monga momwe timayembekezera, maphunziro owunikira ubongo wa anthu pogwiritsa ntchito positron emission tomography (PET), awonetsa momveka bwino kuti kuwonjezeka kwa DA komwe kumachitika chifukwa cha magulu osiyanasiyana a mankhwala ( monga zolimbikitsa ( Chithunzi 1A ), [ 8 , 9 ], nikotini [ 10 ], ndi mowa [ 11 ]) mkati mwa ventral striatum, zimagwirizanitsidwa ndi zomwe zimachitika munthu akamamwa mowa kwambiri [ 12 , 13 , 14 ]. Popeza maphunziro a PET amatha kuchitika mwa anthu omwe ali maso, ndizothekanso kufotokozera ubale pakati pa malipoti okhudza zotsatira za mankhwala ndi kusintha kwa milingo ya DA. Kafukufuku wambiri wanena kuti omwe akuwonetsa kuwonjezeka kwakukulu kwa DA pambuyo pomwa mankhwala osokoneza bongo [amphetamine, nikotini, mowa, methylphenidate (MPH)] amanenanso kuti ali ndi vuto lapamwamba kwambiri kapena chisangalalo chachikulu ( Chithunzi 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 ...

Kafukufuku wa nyama ndi anthu wasonyeza kuti liwiro lomwe mankhwala amalowa, kugwira ntchito, ndikutuluka muubongo ( mwachitsanzo, mbiri yake ya mankhwala) imachita gawo lofunikira pakuzindikira mphamvu zake. Zoonadi, mankhwala aliwonse ogwiritsidwa ntchito molakwika omwe mankhwala omwe ubongo wawo umayesa ndi PET (cocaine, MPH, methamphetamine, ndi nicotine) amawonetsa mbiri yomweyo pamene mankhwalawo aperekedwa kudzera m'mitsempha, mwachitsanzo , kuchuluka kwa mankhwalawa muubongo wa munthu kumafika mkati mwa mphindi 10 ( Chithunzi 2A ) ndipo kuyamwa mwachangu kumeneku kumalumikizidwa ndi "kukwera" ( Chithunzi 2B ). Kutengera ndi mgwirizanowu, zikutsatira kuti kuonetsetsa kuti mankhwala osokoneza bongo amalowa muubongo pang'onopang'ono momwe angathere kuyenera kukhala njira yothandiza yochepetsera mphamvu zake, motero udindo wake wogwiritsa ntchito molakwika. Tinapanga kuyesera kuti tiyese bwino lingaliro ili ndi mankhwala olimbikitsa MPH, omwe, monga cocaine, amawonjezera DA pochepetsa kuyitanidwa kwake kubwerera ku presynaptic neuron ( mwachitsanzo poletsa zonyamula za DA), motero kukulitsa chizindikiro cha DA. Zoonadi, tapeza kuti, ngakhale kuti kuperekedwa kwa MPH m'mitsempha nthawi zambiri kumakhala kosangalatsa, komwe kumawonjezera DA mu striatum [ 15 ], koma ndi pharmacokinetics yocheperako ka 6 mpaka 12, nthawi zambiri sikumawonedwa ngati kulimbikitsa [ 16 , 17 ]. Chifukwa chake, kulephera kwa MPH m'kamwa - kapena amphetamine [ 18 ] mwanjira imeneyo - kuyambitsa kukwera kwambiri mwina ndi chizindikiro cha kuyamwa kwawo pang'onopang'ono muubongo [ 19 ]. Chifukwa chake, ndikoyenera kunena kuti pali mgwirizano wapafupi pakati pa liwiro lomwe mankhwala osokoneza bongo amalowa muubongo, lomwe limatsimikiza liwiro lomwe DA imawonjezeka mu ventral striatum, ndi zotsatira zake zolimbitsa [ 20 , 21 , 22 ]. Mwanjira ina, kuti mankhwala achite zolimbitsa ayenera kukweza DA mwadzidzidzi. Nchifukwa 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" ...

Kutengera kukula ndi nthawi ya kuwombera kwa mitsempha, DA signaling ikhoza kukhala imodzi mwa mitundu iwiri yoyambira: phasic kapena tonic. Phasic signaling imadziwika ndi amplitude yapamwamba komanso short burst firing, pomwe tonic signaling nthawi zambiri imakhala ndi amplitude yotsika komanso nthawi yayitali kapena yopitilira. Kusiyanaku ndikofunikira chifukwa zimawoneka kuti phasic DA signaling ndiyofunikira kuti mankhwala osokoneza bongo ayambe "mayankho okhazikika," omwe ndi amodzi mwa ma neuroadaptations oyamba omwe amatsatira kukhudzidwa ndi zolimbikitsa (kuphatikiza mankhwala). Chimodzi mwazinthu zosiyanitsa zomwe zimagwirizanitsa phasic signaling ndi conditioning ndi kutenga nawo mbali kwa D2R ndi glutamate n -methyl- d -aspartic acid (NMDA) receptors [ 23 ]. Kumbali ina, tonic DA signaling imagwira ntchito pakusinthasintha kwa kukumbukira kogwira ntchito ndi njira zina zoyendetsera. Zina mwa zinthu zomwe zimasiyanitsa njira iyi yolumikizirana ndi mtundu wa phasic ndikuti imagwira ntchito makamaka kudzera mu lower affinity DA receptors (DA D1 receptors). Komabe, ngakhale kuti pali njira zosiyanasiyana zomwe zimagwiritsidwa ntchito, kuwonetsedwa kwa mankhwala kwa nthawi yayitali (ndi kusintha kwa zizindikiro za tonic DA kudzera mu ma receptor awa) kwakhalanso ndi zotsatirapo pa kusintha kwa mitsempha komwe kumabweretsa kukhazikika [ 25 ] kudzera mu kusintha kwa NMDA ndi alpha-amino-3-hydroxyl-5-methyl-4-isoxazone-propionate (AMPA) glutamate receptors [ 24 ].

Umboni ukusonyeza kuti kuwonjezeka kwadzidzidzi kwa DA chifukwa cha mankhwala osokoneza bongo kumatsanzira kuphulika kwa maselo a DA. Izi zimathandiza kufotokoza chifukwa chake kugwiritsa ntchito mankhwala osokoneza bongo nthawi zonse kungayambitse mayankho amphamvu kwambiri ku mankhwalawo, zomwe amayembekezera, ndi zizindikiro zambiri (anthu, zinthu ndi malo) zokhudzana ndi kugwiritsa ntchito kwake. Komabe, ngakhale kuti zotsatira zolimbikitsa kwambiri za mankhwala osokoneza bongo zomwe zimadalira kuwonjezeka kwa DA mwachangu koteroko mwina "zofunikira" pakukula kwa chizolowezi, sizokwanira. Kuwonetsedwa mobwerezabwereza kwa mankhwala osokoneza bongo kumayambitsa kusintha kwa ntchito ya ubongo wa DA komwe kumatenga nthawi kuti kukule chifukwa kumachitika chifukwa cha kusintha kwa ma neuroadaptations m'machitidwe ena a neurotransmitter ( monga glutamate [ 26 ] komanso mwina γ-aminobutyiric acid (GABA)) zomwe, pamapeto pake, zimakhudza ma circuits ena a ubongo omwe amasinthidwa ndi DA. Ma circuits awa ndi omwe akuyang'ana kwambiri magawo otsatirawa.

Pitani ku:

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

Mfundo yakuti kugwiritsa ntchito mankhwala osokoneza bongo kuyenera kukhala kosatha musanayambe kuledzera ndi umboni womveka bwino wakuti matendawa amachokera, mwa anthu omwe ali pachiwopsezo, pa kusokonezeka mobwerezabwereza kwa dongosolo la mphotho. Kusokonezeka kumeneku kumatha kuyambitsa neuroadaptations m'magawo ena ambiri (chilimbikitso/kuyendetsa, kuletsa kulamulira/ntchito yoyendetsa, ndi kukumbukira/kukonza) zomwe zimasinthidwanso ndi DA [ 27 ]. Pakati pa kusintha kwa mitsempha komwe kwanenedwa nthawi zonse mwa anthu omwe ali ndi vutoli ndi kuchepa kwakukulu kwa milingo ya ma D2R (high affinity) receptors ndi kuchuluka kwa DA komwe kumatulutsidwa ndi maselo a DA [ 28 ] ( Chithunzi 3 ). Chofunika kwambiri, kusowa kumeneku kumagwirizanitsidwa ndi kuchepa kwa ntchito ya kagayidwe kachakudya m'madera a prefrontal cortex (PFC) omwe ndi ofunikira kwambiri pakugwira ntchito bwino kwa executive ( monga anterior cingulate gyrus (CG) ndi orbitofrontal cortex (OFC)) ( Chithunzi 4A ). Kuwona kumeneku kunatipangitsa kuganiza kuti iyi ikhoza kukhala njira imodzi yomwe imagwirizanitsa kusokonezeka kwa mankhwala mu DA signaling ndi kuperekedwa kwa mankhwala mokakamiza komanso kusowa kwa ulamuliro pa kumwa mankhwala komwe kumadziwika ndi kuledzera [ 29 ]. Komanso, mkhalidwe wotsatira wa hypodopaminergic ungafotokoze kuchepa kwa chidwi cha munthu woledzera ku mphotho zachilengedwe (monga chakudya, kugonana, ndi zina) komanso kupitiriza kugwiritsa ntchito mankhwala ngati njira yolipirira kwakanthawi kuchepa kumeneku [ 30 ]. Chotsatira chofunikira cha chidziwitsochi ndikuti kuthana ndi zofooka izi (mwa kuwonjezera milingo ya D2R yoyambira ndikuwonjezera kutulutsidwa kwa DA m'madera a striatum ndi prefrontal) kungapereke njira yachipatala yochepetsera zotsatira za kuledzera [ 31 ]. Kodi pali umboni uliwonse woti kusintha mkhalidwe wa hypodopaminergic kungakhale ndi zotsatira zabwino pamakhalidwe okhudzana ndi kugwiritsa ntchito mankhwala osokoneza bongo? Yankho ndi inde. Kafukufuku wathu akuwonetsa kuti pokakamiza kupanga mopitirira muyeso kwa D2R, mkati mwa dongosolo la mphotho la makoswe omwe ali ndi cocaine kapena mowa, titha kuchepetsa kwambiri kudzipatsa cocaine [ 31 ] kapena mowa [ 32 ], motsatana. Komanso, m'makoswe, komanso mwa anthu omwe amagwiritsa ntchito mankhwala osokoneza bongo a methamphetamine [ 33 ], kuchepa kwa D2R m'mimba kumagwirizanitsidwanso ndi kusakhazikika, ndipo m'makoswe amalosera machitidwe okakamiza a kudzipangira mankhwala (onani pansipa).

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 wokhudza zithunzi wasonyezanso kuti, mwa anthu, chizolowezi chimagwirizana ndi kuchepa kwa kutulutsidwa kwa DA mu ventral striatum ndi m'madera ena a striatum, komanso mayankho osangalatsa a mankhwalawa mwa ogwiritsa ntchito mankhwala osokoneza bongo omwe ali ndi vuto la detox ( Chithunzi 5 ) [ 34 ]. Izi zinali zosayembekezereka popeza zidaganiziridwa kuti chizolowezicho chikuwonetsa kukhudzidwa kwakukulu ndi mayankho opindulitsa (ndipo motero dopaminergic) ku mankhwala osokoneza bongo. Mwa ogwiritsa ntchito mankhwala osokoneza bongo, kuchepa kwa kutulutsidwa kwa DA kungawonetse kusokonezeka kwa neurophysiology mkati mwa magawo olipira ( monga mu ma neurons a DA omwe amatulutsa DA mu striatum) kapena, mwanjira ina, kusokonezeka kwa mayankho a gawo la mphotho ndi prefrontal (executive control) kapena amygdalar (maganizo) njira (njira za prefrontal-striatal, amygdalarstriatal glutamatergic). Popeza kusokonekera kwa dopaminergic mu striatum, monga momwe kumawonedwera mwa ogwiritsa ntchito mankhwala osokoneza bongo osatha, sikutha kufotokoza makhalidwe omwe amadziwika ndi machitidwe osokoneza bongo, monga kulakalaka, zilakolako, ndi kubwereranso komwe kumayamba chifukwa cha zizindikiro za mankhwala osokoneza bongo, ndizotheka kuti madera a prefrontal (komanso amygdala) nawonso akukhudzidwa pano, chifukwa kusokonezeka kwawo kungathandize kapena kukhudza makhalidwe awa.

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

Zaganiziridwa kuti kulephera kulamulira machitidwe ogwiritsira ntchito mankhwala osokoneza bongo omwe amadziwika ndi chizolowezi kungakhale chifukwa cha zovuta zinazake m'madera akutsogolo kwa ubongo [ 35 ]. Tsopano pali umboni wochuluka womwe umachirikiza lingaliro ili, kuyambira ndi maphunziro a nyama omwe amafufuza kulumikizana pakati pa D2R ndi kuwongolera khalidwe. Kuyesera kwa makoswe kukuwonetsa bwino mgwirizano pakati pa D2R yotsika ndi kusakhazikika [ 36 ], komanso pakati pa kusakhazikika ndi kudzipatsa mankhwala [ 37 ]. Koma kodi kulumikizanako ndi kotani? Monga tanenera kale, mwa ogwiritsa ntchito mankhwala osokoneza bongo, D2R yotsika kwambiri imagwirizana kwambiri ndi kagayidwe ka shuga m'magazi m'madera ofunikira a PFC, monga OFC (yokhudzana ndi salience attribution ndipo yomwe kusokonezeka kwake kumabweretsa machitidwe okakamiza) ndi mu CG (yokhudzana ndi kuletsa kuwongolera ndi kuyang'anira zolakwika ndipo yomwe kusokonezeka kwake kumabweretsa kusakhazikika) ( Chithunzi 4B ) [ 38 , 39 ]. Komanso, mu kafukufuku amene tinachita mwa anthu (avereji ya SD ± zaka, zaka 24 ± 3) mbiri ya banja la anthu omwe anali ndi vuto la uchidakwa, koma omwe sanali ndi vuto la uchidakwa, tinapezanso mgwirizano wofunikira pakati pa striatal D2R ndi kagayidwe kachakudya m'madera akutsogolo (CG, OFC, ndi dorsolateral PFC) komanso m'malo obisika akunja (omwe amakhudzidwa ndi kulowererana, kudzidziwa, komanso chilakolako cha mankhwala osokoneza bongo) [ 40 ] ( Chithunzi 6 ). Chochititsa chidwi n'chakuti, anthuwa anali ndi striatal D2R yapamwamba kuposa yolamulira yofanana ndi yomwe inalibe mbiri ya banja ya uchidakwa, ngakhale kuti sanali osiyana mu frontal metabolism. Komanso, mu zolamulira, striatal D2R sinagwirizane ndi frontal metabolism. Izi zinatipangitsa kuganiza kuti striatal D2R yapamwamba kuposa yachibadwa mwa anthu omwe ali ndi chiopsezo chachikulu cha majini cha uchidakwa imawateteza ku uchidakwa pang'ono mwa kulimbikitsa zochita m'madera akutsogolo. Zikaphatikizidwa, deta iyi ikusonyeza kuti kuchuluka kwa D2R mu striatum kungateteze ku kugwiritsa ntchito mankhwala osokoneza bongo ndi kuledzera mwa kusunga makhalidwe osafuna kuchitapo kanthu, mwachitsanzo , mwa kuwongolera ma circuits omwe amakhudzidwa ndi kuletsa mayankho a khalidwe komanso kuwongolera malingaliro.

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, tinaganiza kuti madera a prefrontal nawonso akukhudzidwa ndi kuchepetsa kutulutsidwa kwa DA (ndi kulimbitsa) komwe kumawonedwa mwa anthu omwe ali ndi vuto la kuledzera chifukwa amawongolera kuwombera kwa maselo a DA mu ubongo wapakati ndi kutulutsidwa kwa DA mu striatum. Kuti tiyese lingaliro ili tinayesa ubale pakati pa kagayidwe kachakudya koyambira mu PFC ndi kuwonjezeka kwa DA yoyambira komwe kumayambitsidwa ndi kuperekedwa kwa MPH m'mitsempha mwa olamulira komanso mwa oledzera omwe adachotsedwa. Mogwirizana ndi lingaliroli, mwa oledzera sitinazindikire mgwirizano wabwinobwino pakati pa kagayidwe kachakudya koyambira koyambirira ndi kutulutsidwa kwa DA mu striatum, zomwe zikusonyeza kuti kuchepa kwakukulu kwa kutulutsidwa kwa DA mu striatum komwe kumawonedwa mwa oledzera kukuwonetsa pang'ono kulamulira kosayenera kwa ntchito ya ubongo ndi madera a prefrontal 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.

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Zomwe zimakumbukiridwa ndi zizoloŵezi zosasinthika zimalowetsa "pamwamba" kukhala dalaivala

Kulimbikitsa kwambiri maselo a DA mu ventral striatum pamapeto pake kumakhazikitsa kulumikizana kwatsopano muubongo pakati pa kuchitapo kanthu kokhutiritsa chilakolakocho, ndi zochitika zomwe zimazungulira (monga chilengedwe, chizolowezi chokonzekera mankhwala, ndi zina zotero), kukhazikitsa maubwenzi atsopano, amphamvu ophunzirira omwe angayambitse khalidwe. Pomaliza, kukumbukira kapena kuyembekezera mankhwala kungayambitse machitidwe osakhazikika omwe amazindikiritsa anthu omwe ali ndi vutoli. Pogwiritsa ntchito mankhwala osokoneza bongo mobwerezabwereza, kuwombera maselo a DA mu striatum kumayamba kusintha ubongo womwe umayambitsa kuphunzira kogwirizana. Izi zimathandiza kuphatikiza zizindikiro zosakumbukira bwino zomwe zimagwirizanitsidwa ndi mankhwala osokoneza bongo, zomwe zimathandiza kufotokoza kuthekera kwa mitundu yonse ya zoyambitsa zokhudzana ndi mankhwala osokoneza bongo (mu chiyembekezo chophunzirira cholandira mphotho ya mankhwala akakumana ndi zoyambitsazi) [ 41 ] kuyambitsa mosavuta maselo a DA kuwombera. Ndipo chifukwa cha udindo wa DA pakulimbikitsa, kuwonjezeka kwa DA kumeneku kumayambitsa chilimbikitso chofunikira kuti apeze mphotho [ 42 ]. Zoonadi, pamene makoswe akumana mobwerezabwereza ndi chilimbikitso chosalowerera chomwe chimagwirizanitsidwa ndi mankhwala (chokhazikika), chingayambitse kuwonjezeka kwa DA ndikubwezeretsanso kudzipangira mankhwala [ 43 ]. Mayankho oterewa ndi ofunikira kwambiri pa matenda ogwiritsira ntchito mankhwala osokoneza bongo chifukwa ndi omwe amachititsa kuti munthu amene ali ndi vutoli abwererenso ku mankhwala osokoneza bongo ngakhale atakhala nthawi yayitali atachotsa poizoni m'thupi. Tsopano, njira zojambulira ubongo zimatithandiza kuyesa ngati anthu angapeze zizindikiro zokhudzana ndi mankhwala osokoneza bongo zomwe zingayambitse chilakolako cha mankhwala osokoneza bongo monga momwe zasonyezedwera m'zinyama za m'ma laboratories.

Pogwiritsa ntchito mankhwala osokoneza bongo mobwerezabwereza, kuwombera kwa maselo a DA mu striatum kumayamba kusintha kayendedwe ka ubongo komwe kamayambitsa kuphunzira kogwirizana. Izi zimathandiza kuphatikiza zizindikiro zokumbukira zosasinthika zomwe zimagwirizanitsidwa ndi mankhwalawa, zomwe zimathandiza kufotokoza kuthekera kwa mitundu yonse ya zinthu zokhudzana ndi mankhwala osokoneza bongo (mu chiyembekezo chophunzira cholandira mphotho ya mankhwala osokoneza bongo akakumana ndi zinthuzi) [ 41 ] kuyambitsa mosavuta kuwombera kwa maselo a DA. Ndipo chifukwa cha udindo wa DA pakulimbikitsa, kuwonjezeka kwa DA kumeneku kumayambitsa chilimbikitso chofunikira kuti apeze mphotho [ 42 ]. Zoonadi, pamene makoswe akumana mobwerezabwereza ndi chinthu cholimbikitsa chomwe chimagwirizanitsidwa ndi mankhwala osokoneza bongo (chokhazikika), chingayambitse kuwonjezeka kwa DA ndikubwezeretsanso kudzipatsa mankhwala [ 43 ]. Mayankho oterewa ndi ofunikira kwambiri pa matenda ogwiritsa ntchito mankhwala osokoneza bongo chifukwa ndi omwe amachititsa kuti munthu woledzera abwererenso ngakhale atakhala nthawi yayitali akuchotsa poizoni m'thupi. Tsopano, njira zojambulira ubongo zimatithandiza kuyesa ngati anthu omwe akumana ndi zizindikiro zokhudzana ndi mankhwala osokoneza bongo angayambitse chilakolako cha mankhwala osokoneza bongo monga momwe zasonyezedwera m'zinyama za labotale.

Funso ili lafufuzidwa mwa anthu omwe amagwiritsa ntchito mankhwala osokoneza bongo a cocaine. Pogwiritsa ntchito PET ndi [ 11 C]raclopride, maphunziro awiri odziyimira pawokha adawonetsa kuti kuwonetsedwa pa kanema wa cocaine-cues (wa anthu omwe amasuta cocaine) koma osati kanema wosalowererapo (wa zochitika zachilengedwe) kunawonjezera DA mwa anthu omwe amamwa cocaine ( Chithunzi 7 ) ndipo kuti kuwonjezeka kwa DA kunalumikizidwa ndi malipoti aumwini a chilakolako cha mankhwala osokoneza bongo [ 44 , 45 ]. Kuwonjezeka kwa DA komwe kumachitika chifukwa chowonera kanema wa cocaine-cues, chilakolako cha mankhwala osokoneza bongo chimakulanso. Kuphatikiza apo, kukula kwa kuwonjezeka kwa DA kunagwirizananso ndi kuchuluka kwa kuopsa kwa chizolowezi, kuwonetsa kufunika kwa mayankho omwe ali mu matenda amisala.

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 ...

Komabe, ndikofunikira kutsindika kuti ngakhale kuti pali kugwirizana kolakwika kumeneku, posachedwapa tasonkhanitsa umboni watsopano wosonyeza kuti anthu omwe amagwiritsa ntchito cocaine molakwika amakhala ndi mphamvu zina zoletsa chilakolako cha kugonana. Chifukwa chake, njira zolimbikitsira malamulo okhudza fronto-striatal zitha kupereka zabwino zothandizira [ 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 chizolowezi [ 47 ] chomwe chimafotokoza za momwe matendawa alili m'njira zambiri mwa kupereka ulalo wa ma circuits anayi ogwirizana, omwe zotsatira zake zosagwirizana zimatha kufotokoza zambiri za makhalidwe a chizolowezi: (a) mphotho, kuphatikiza ma nuclei angapo mu basal ganglia, makamaka ventral striatum, yomwe Nac imalandira malingaliro kuchokera ku dera la ventral tegmental ndikutumiza chidziwitsocho ku ventral pallidum (VP); (b) chilimbikitso/kuyendetsa, chomwe chili mu OFC, subcallosal cortex, dorsal striatum ndi motor cortex; (c) kukumbukira ndi kuphunzira, komwe kuli mu amygdala ndi hippocampus; ndi (d) kukonzekera ndi kulamulira, komwe kuli mu dorsolateral prefrontal cortex, anterior CG ndi inferior frontal cortex. Ma circuits anayiwa amalandira ma innervations ochokera ku ma neurons a DA koma amalumikizidwanso kudzera mu ma projections olunjika kapena osalunjika (makamaka glutamatergic).

Ma circuits anayi mu chitsanzo ichi amagwira ntchito limodzi ndipo ntchito zawo zimasintha malinga ndi zomwe akumana nazo. Chilichonse chimalumikizidwa ndi lingaliro lofunika, motsatana: saliency (mphoto), mkhalidwe wamkati (chilimbikitso/chilimbikitso), mayanjano ophunzirira (kukumbukira, kukonza), ndi kuthetsa mikangano (kulamulira). Kuphatikiza apo, ma circuits awa amalumikizananso ndi ma circuits omwe amakhudzidwa ndi malingaliro (kuphatikiza kupsinjika maganizo) [ 48 ] komanso ndi interception (zomwe zimapangitsa kuti munthu adziwe za chilakolako cha mankhwala osokoneza bongo ndi malingaliro) [ 49 ]. Tanena kuti kachitidwe ka zochita mu netiweki ya ma circuits anayi omwe afotokozedwa pano kamakhudza momwe munthu wamba amasankhira pakati pa njira zina zopikisana. Zosankha izi zimakhudzidwa mwadongosolo ndi mphotho, kukumbukira/kuwongolera, chilimbikitso, ndi ma circuits olamulira ndipo izi zimasinthidwa ndi ma circuits omwe ali pansi pa malingaliro ndi kuzindikira ( Chithunzi 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 ...

Kuyankha kwa chinthu cholimbikitsa kumakhudzidwa ndi mphamvu yake yakanthawi, mwachitsanzo mphotho yake yomwe imayembekezeredwa. Kenako, chiyembekezo cha mphotho chimakonzedwa pang'ono ndi ma neurons a DA omwe amalowa mu ventral striatum ndikukhudzidwa ndi ma glutamatergic projections ochokera ku OFC (yomwe imapatsa saliency value ngati ntchito ya nkhani) ndi amygdala/hippocampus (yomwe imayang'anira mayankho okhazikika ndi kukumbukira kukumbukira). Mtengo wa cholimbikitsacho umayesedwa (poyerekeza) poyerekeza ndi wa zinthu zina zoyambitsa, komanso umasintha ngati ntchito ya zosowa zamkati za munthu, zomwe zimasinthidwa ndi malingaliro (kuphatikiza stress reactivity) ndi kuzindikira kwa interceptive. Makamaka, kupsinjika kumawonjezera saliency value ya mankhwala pomwe nthawi yomweyo kumachepetsa prefrontal regulation ya amygdala [ 50 ]. Kuphatikiza apo, popeza kupsinjika kwanthawi yayitali kumalumikizidwa ndi kukhudzidwa kowonjezereka kwa mayankho a kupsinjika, izi zikufotokoza chifukwa chake kupsinjika kungayambitse kubwereranso kwa mankhwala nthawi zambiri m'mikhalidwe yachipatala. Kulimba kwa saliency ya cholimbikitsacho, komwe kumapangidwa pang'ono ndi zomwe zidakumbukiridwa kale, kumayambitsa kuyendetsa bwino kwa dera lolimbikitsa komanso kufunitsitsa kulipeza. Chisankho chanzeru chochitapo kanthu (kapena ayi) kuti chipeze chilimbikitsocho chimakonzedwa pang'ono ndi PFC ndi CG, zomwe zimayesa kulinganiza pakati pa zotsatira zabwino zomwe zachitika nthawi yomweyo poyerekeza ndi zotsatira zoyipa zomwe zachedwa, komanso ndi inferior frontal cortex (Broadmann Area 44), yomwe imagwira ntchito yoletsa kuyankha koyambirira kuchitapo kanthu [ 51 ].

Malinga ndi chitsanzo ichi, mu munthu woledzera ( Chithunzi 8B ), mphamvu ya mankhwala osokoneza bongo ndi zizindikiro zake zimawonjezeka potengera mphotho zina (zachilengedwe), zomwe mphamvu zake zimachepa kwambiri. Izi zikufotokozera kuwonjezeka kwa chilimbikitso chofuna mankhwala osokoneza bongo. Komabe, kupezeka mwachangu kwa mankhwala osokoneza bongo kumabwezeretsanso malire a mphotho, zomwe zimapangitsa kuti kuchepa kwa mphamvu ya mphotho kuzinthu zolimbitsa thupi [ 52 ], zomwe zimathandizanso kufotokoza kuchepa kwa mphamvu ya mankhwala osalimbikitsa mwa munthu woledzera. Chifukwa china chowonjezera mphamvu ya mankhwala osokoneza bongo ndi kusowa kwa chizolowezi cha mayankho a DA ku mankhwala osokoneza bongo (kulekerera) poyerekeza ndi chizolowezi chachizolowezi chomwe chilipo cha mphotho zachilengedwe ndipo chimabweretsa kukhuta [ 53 ].

Kuphatikiza apo, kukumana ndi zinthu zolimbikitsa thupi ndikokwanira kuwonjezera malire a mphotho [ 54 ]; motero, tinganene kuti mwa munthu woledzera, kukumana ndi malo okhala ndi zizindikiro zokhazikika kungawonjezere kuchepa kwa chidwi chawo ku mphotho zachilengedwe. Popanda mpikisano ndi ena olimbikitsa, kuphunzira kokhazikika kumakweza kupeza mankhwalawa kufika pamlingo wa chilimbikitso chachikulu kwa munthuyo. Tikuganiza kuti zizindikiro za mankhwala (kapena kupsinjika) zimapangitsa kuti DA ikule mwachangu mu Nac mu ventral striatum ndi mu dorsal striatum zomwe zimayambitsa chilimbikitso chomwa mankhwalawa ndipo sizingatsutsidwe bwino ndi PFC yosagwira ntchito. Chifukwa chake, pakumwa mankhwala osokoneza bongo ndi kuledzera, kuwonjezeka kwa zizindikiro za DA kungayambitse kuwonjezereka kwa ma circuits olimbikitsa/oyendetsa ndi kukumbukira, zomwe zimaletsa PFC (kuletsa prefrontal kumachitika ndi amygdala activation yayikulu) [ 50 ], kuletsa mphamvu ya PFC kuti ilamulire dera lolimbikitsa/oyendetsa. Popanda kuletsa kumeneku, kuzungulira kwa mayankho abwino kumakhazikitsidwa, komwe kumabweretsa kumwa mankhwala mokakamiza. Popeza kuyanjana pakati pa ma circuits kumakhala mbali ziwiri, kuyatsa kwa netiweki panthawi yoledzera kumathandizira kulimbitsa mphamvu ya mankhwalawo komanso momwe amagwirizanirana ndi zizindikiro za mankhwalawo.

Pitani ku:

Mawuwo

Mwachidule, tikupereka chitsanzo chomwe chimafotokoza za kuledzera motere: Pa nthawi ya kuledzera, kufunika kowonjezereka kwa zizindikiro za mankhwala mu memori circuit kumayendetsa chiyembekezo cha mphotho ndikuwonjezera chilimbikitso chogwiritsa ntchito mankhwalawa, kugonjetsa kuletsa komwe kumachitika ndi PFC yomwe ili kale yosagwira ntchito. Ngakhale kuti kuwonjezeka kwa DA komwe kumabwera chifukwa cha mankhwala osokoneza bongo kumachepa kwambiri mwa anthu omwe ali ndi mankhwala osokoneza bongo, zotsatira za mankhwala a mankhwalawa zimakhala mayankho okhazikika mwa iwo okha, zomwe zimapangitsa kuti chilimbikitso chomwa mankhwalawa chikhale chokhazikika komanso cholimbikitsa njira yabwino yoyankhira yomwe tsopano siikutsutsidwa, chifukwa cha kusagwirizana kwa circuit yolamulira prefrontal. Nthawi yomweyo, kuledzera kungabwezeretsenso madera omwe amalimbikitsa malingaliro ndi kuzindikira (komwe kumayimiridwa ndi mithunzi yakuda ya imvi) ( Chithunzi 8B ) m'njira zomwe, ngati zitatsimikiziridwa mwachiyembekezo, zingachepetse kwambiri kuletsa kuletsa ndikupita ku chilakolako ndi kumwa mankhwala osokoneza bongo mokakamiza.

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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