Oledzeredwa ndi Zakudya Zowonjezereka: Kuyerekezera Neurobiology ya Bulimia Nervosa ndi ya Mankhwala Osokoneza Bongo (2014)

Natalie A. Hadad, MA ndi Lori A. Knackstedt, Ph.D.

Zolemba za Mlembi ► Chidziwitso cha Copyright ndi License ►

Keywords: Bulimia Nervosa, Addiction, Neurobiology, Dopamine, Glutamate, Opioid, Chakudya Chokhazikika, Kuphika, Shuga, Sucrose

Kujambula osasamba BN

Chitsanzo cha "choletsa zakudya / chosowa zakudya" chimagwiritsa ntchito makoswe kuti abwezeretse mtundu wosasamba wa BN mwa kuika nthawi yowonongeka kwa zakudya kapena kuperewera komanso nthawi yopezeka kwa zakudya zokoma kapena zovuta (mwachitsanzo, Hagan ndi Moss 1991; 1997). Pambuyo pazinthu zitatu zodyera zakudya ku 75% ya kulemera kwa thupi koyenera pambuyo pake ndi kupumula kwa kulemera kwake, makoswe amasonyeza kudya mofanana ndi ola pa ola loyamba la ad lib kudyetsa rat chow (Hagan ndi Moss 1991). Mofananamo, makoswe ogwiritsidwa ntchito pa masabata a 12 a tsiku la 4 tsiku loperekera chakudya potsatira nthawi ya 2- kwa 4 nthawi yopeza ufulu wa zakudya kapena zakudya zokoma zimakhala ndi hyperphagia panthawi yopeza ufulu (Hagan ndi Moss 1997). Zowoneka kuti, makoswewa amasonyeza zakudya zowonjezera kwa nthawi yaitali ndikupitiriza kusonyeza makhalidwe odyera ngakhale atabwerera ku nthawi yowonjezera chakudya ndi kulemera kwa thupi, makamaka pamene akupereka chakudya chokoma (Hagan ndi Moss 1997).

Mukhoza "shuga", makoswe amapatsidwa njira yothetsera shuga: Maola a 12-16 osowa chakudya chotsatiridwa ndi maola 8-12 opezeka ku 10% sucrose kapena 25% glucose ndi chow ndi madzi tsiku lililonse (mwachitsanzo, Avena et al. 2008a, b; Avena et al. 2006a; Colantuoni et al. 2002). Poyerekeza ndi makoswe, makoswe omwe amapatsidwa mwayi wambiri wofikira sucrose amachulukitsa sucrose kudya ndi kusonyeza khalidwe lopangidwira, lomwe limatanthauzidwa ndi kuchuluka kwa sucrose yomwe idya pa ola loyamba la nthawi iliyonse yofikira (Avena et al. 2008a; Avena et al. 2006a; Colantuoni et al. 2002). Makamaka, makoswe omwe anapatsidwa njira yowonjezereka ya mankhwala a sucrose mwadala amadya chow mocheperapo kuposa makoswe omwe amapatsidwa mankhwala osakanikirana kapena othandizana ndi chow (Avena et al. 2008a; Avena et al. 2006a). Izi hypophagia zikufanana ndi zakudya za BN-anthu omwe amaletsa kuletsa chakudya chamtsogolo ndi kutsatira mapiko (Association of Psychiatric Association 2013). Mphuno zomwe zimapatsidwa mwayi wa shuga (koma osati chow) zimasonyezanso zizindikiro za kutaya (mwachitsanzo, mano akugwedeza, kugwedeza mutu) pambuyo pa maola a 24-36 a chiwonongeko. Mtengo umenewu umapereka chidziwitso cha zinthu zomwe zimagwiritsidwa ntchito m'magazi panthawi ya kudya ndi kudya, zomwe zimatsanzira molondola zomwe sizikuyeretsa BN.

Mosiyana ndi zitsanzo zomwe tazitchula pamwambapa, "njira yoperewera" siyimitse makoswe kuti ayambe kudya kapena kuperewera. M'malo mwake, makoswe amapatsidwa libitum kupeza chow ndi madzi, komanso maulendo apakati pa chakudya chokoma chokhala ndi mafuta, shuga, kapena mafuta / shuga kuphatikiza maola 1-2 (mwachitsanzo, Corwin ndi Wojnicki 2006; Wong et al. 2009). Makoswe anapatsidwa mwayi wopezeka ku 100% masamba akuchepetsa kuchepetsa mafuta ndi kutaya mwadzidzidzi chow chakudya chokhazikika (Corwin ndi Wojnicki 2006). Izi zimachepetsa muyezo wa chow mofanana ndi makoswe omwe amapatsidwa mwayi wopita ku 10% sucrose solution (mwachitsanzo, Avena et al. 2008a) ndi hypophagia omwe amawonedwa mu BN-anthu (Association of Psychiatric Association 2013). Choncho, "njira yochepa yopeza" imathandizanso kudya zakudya zopanda kuyeretsa BN-anthu pokhapokha atagwiritsanso ntchito chilolezo chodzipangira okha kuphatikizapo kubisala.

Kuphatikizidwa pamodzi, chitsanzo "choletsa zakudya / chiwonongeko," chitsanzo cha "chizoloŵezi cha shuga", ndi "kayendedwe kochepa" komweko kumapangitsa kudya kudya mowa. Komanso, iwo amadziwika ndi kuyesa-kapena kudziletsa. Monga momwe tafotokozera pamwambapa, kubweretsa ndi kuletsa ndizo zigawo zikuluzikulu za kusasamba BN. Choncho, mwa kusinthanitsa nthawi ya kudya ndi kudya komanso kuchepetsa chakudya chokwanira, zitsanzozi zimakhala zogwiritsidwa ntchito zonyama zosasamba BN.

Kuyeretsa kutsanzira BN

Kupanga mtundu wanyama wa mtundu wa kutsuka kwa BN wakhala wovuta chifukwa makoswe alibe kusowa kwa mitsempha ya m'mimba kuti asanzire. Choncho, kuti adziwe momwe amachitira ndi nyama imodzi, ochita kafukufuku aphatikizirapo njira yogwiritsira ntchito nyamakazi pogwiritsa ntchito zakudya zolimbitsa thupi (mwachitsanzo, Avena et al. 2006b). Mchitidwe wa makoswe odyetsa, chifuwa cha fistula chimalowetsedwa m'mimba mwa piritsi kapena m'mimba, zomwe zimayambitsa kugwirizana pakati pa chakudya ndi chifuwa cha m'mimba ndi m'mimba. Chifukwa chifuwa cha fistula chimayambitsa madzi kuti achoke m'mimba, amatha kuchepetsa zakudya zamchere (Casper et al. 2008). Pogwiritsa ntchito makasitomala odyetserako njinga pamsana wa 12 ora la chakudya nthawi yotsatiridwa ndi maola a 12 kupeza ufulu kwa chakudya, makoswe amawotcha zakudya zokoma ndi kuyeretsa kudzera m'mimba ya fistula (Avena et al. 2006b). Njirayi yasinthidwa posachedwapa pakati pa BN-individuals (onani Klein ndi Smith 2013). Mwachindunji, amayi a BN omwe asinthidwa-kusokonezedwa ndi kupukuta ndi kupopera pa mankhwala amadzimadzi amakhala mu hyperphagia pomwe kulamulira koyenera ndi amayi omwe ali ndi Anorexia Nervosa samatero. Motero, ngakhale zitsanzo za nyama sizingagwire bwinobwino zovuta za matenda omwe anthu amadya (Avena ndi Bocarsly 2012), chitsanzo cha nyamayi chodyetsa pamodzi ndi kudya mowa mwauchidakwa kumagwiritsira ntchito molondola kupukuta BN.

Zolinga zowonjezera mu ndemanga yangapo

Zinyama zomwe tatchulidwa pamwambazi zimabweretsanso makhalidwe ofunika a BN. Kusakaniza osatsuka BN, "kuchepetsa zakudya / kunyalanyaza," "kusuta shuga," ndi "zochepera zochepa" zitsanzo zomwe zikuphatikizidwa ndi experimenter- kapena kudziletsa. Chofunika kwambiri, izi ndi zizindikiro ziwiri zapadera zosasamba BN (Association of Psychiatric Association 2000). Kutenga zigawo zikuluzikulu ziwiri za kuyeretsa BN (Association of Psychiatric Association 2000), kuyesa kudya / kumwa mowa mwauchidakwa kumaphatikizapo kudyerera pamodzi ndi kuyeretsa. Pali zitsanzo zina za BN, monga njira yoletsera yogonana yomwe imabweretsa chakudya chokwanira ndi nkhawa (mwachitsanzo, Hagan ndi al. 2002; Inoue et al. 1998). Komabe, zitsanzozi sizinagwiritsidwe ntchito kuti ziwone kusintha kwa maurobodolo omwe akulembedwa pamanjali ndipo, motero, iwo sangakambirane.

Kuwonanso kwapano kumaphatikizapo zitsanzo za nyama zomwe tazitchula pamwambapa Popeza kulekanitsidwa ndi kubwereka ndizo zigawo zazikulu za BN (Association of Psychiatric Association 2013), kuphatikizanso pano ndizopeza kuchokera ku maphunziro omwe akuphatikizapo mwina kusala kudya kapena kumwa mowa nyama zamatera. Timayerekezera zotsatira kuchokera ku maphunziro amenewa ndi omwe amapeza pogwiritsa ntchito mitundu yosiyanasiyana ya mankhwala osokoneza bongo omwe amatenga mbali zofunikira za chizoloŵezi cha anthu: chikhalidwe cha malo ogwiritsidwa ntchito, ogwiritsira ntchito mankhwala osokoneza bongo, kumwa mowa, komanso kubwezeretsedwa kwa mankhwala osokoneza bongo. Kufunafuna mankhwala. Chofunika kwambiri, mosiyana ndi ndemanga zatsopano zomwe zikufaniziranso zovuta zokhudzana ndi chizoloŵezi cha kudya mowa mwa nyama zomwe zimatsogolera kunenepa kwambiri (mwachitsanzo, DiLeone et al. 2012; Volkow et al. 2013), zomwe zafukufuku pogwiritsa ntchito zitsanzo za zinyama za kunenepa kwambiri sizinaphatikizidwe pano chifukwa BN payekha sali olemera kwambiri (Association of Psychiatric Association 2013).

Nucleus accumbens dopamine

Kulimbikitsidwa kwa DA neurons mu VTA kumayambitsa DA kutulutsidwa ku NAc ndikuyendetsa khalidwe lolimbikitsa komanso kugwiritsira ntchito mankhwala osokoneza bongo. Ethanol, nicotine, opiates, amphetamine, ndi cocaine amachulukitsa madera a DA ku NAC, koma mankhwala osagwiritsidwa ntchito ndi anthu samasintha ma DS muderali (Di Chiara ndi Imperato 1988). Kuwonjezera apo, pamene kumasulidwa kwa DA kumalimbikitsidwa potsata mobwerezabwereza kayendedwe ka mankhwala, zotsatira za chakudya pa kuwomboledwa kwa DA kumakhala nthawi pokhapokha ngati kupezeka kwa chakudya kuli kovuta kapena kosagwirizana (Ljungberg et al. 1992; Mirenowicz ndi Schultz 1994). Pano tikukambirana ma data omwe amachokera ku zitsamba za kuyeretsa ndi kusasamba BN zomwe zimasonyeza kuti yankho la NAC DA ndi chakudya chokoma chimasiyana ndi chow.

Pofufuza za sucrose makoswe odyetsa-sucrose-bingeing, Avena ndi anzanu (2006b) adafufuza ufulu wa NAC DA poyankha sucrose. Makoswe m'magulu odyetsedwa omwe mimba yawo imatseguka pa ola loyambirira la chakudya chowonetsetsa machitidwe a sucrose-kudya mowa komanso kudya kwambiri sucrose pa ola loyamba la kufika pa masiku onse oyesedwa (masiku 1, 2, ndi 21) poyerekeza ndi makoswe odyetseratu eni ake omwe mimba ya fistula inakhala yotsekedwa. Mu vivo microdialysis anavumbula kuti NAc zowonjezera madola DA zowonjezereka kwambiri kwa makoswe odyetsedwa komanso odyetseratu enieni chifukwa cha kulawa kwa sucrose masiku onse oyesedwa. Chofunika kwambiri, ngakhale kuti sucrose inadyedwa nthawi yoyamba kudya mofulumira yomwe imachotsedwa kumimba za makoswe odyetsa, kuyankha kwa DA ku NAC kunapitirizidwa kuchitika tsiku la 21. Zotsatira zofanana zapezeka pogwiritsa ntchito mitundu ya "shuga". Kuwonetsa makoswe ku nthawi ya chakudya cha ola limodzi la 12 potsatira nthawi yowonjezera shuga imabweretsa shuga wosakaniza tsiku ndi tsiku ndikupitiriza kuti DA atuluke mu nkhono ya NAc masiku 1, 2, ndi 21 ya kupeza shuga (Rada et al. 2005). Kusiyanitsa, makoswe oyendetsa malonda ndi ad adum chobitum kupeza chow ndi kupeza sucrose kwa 1 ola limodzi masiku awiri osadya shuga, kapena kusonyeza adasungidwa DA mu shell NAC. Phunziro lina, makoswe anasiya chakudya cha maola 16 amatsatiridwa ndi mwayi wopeza maola a 8 ndi 10% sucrose yankho la maola awiri oyambirira kwa masiku a 21, zomwe zimapangitsa shuga kuwedzeretsa komanso kuwonjezeka kwakukulu ku NAC DA tsiku lina 21 (Avena et al. 2008b). Patsiku la 28, patatha masiku 7 atachepetsedwa ku 85% ya kulemera kwake kwa thupi, makoswe omwe ankamwa sucrose anakulira ku NAC DA yomwe inali yopambana kwambiri kuposa NAC DA yomwe inatuluka chifukwa cha kumwa sucrose pa kulemera kwa thupi tsiku 21 (Avena et al. 2008b). Mu phunziro lina, makoswe a ma cycling kudzera m'masiku a 28 a protocol oledzera "shuga" otsatiridwa ndi maola a 36 osala kudya anawombera pansi kwambiri NAc shell DA yokhudzana ndi makoswe omwe anapatsidwa mankhwala osokoneza bongo (quittum)Avena et al. 2008a).

Kuphatikizidwa pokhapokha ngati kuletsedwa kapena kusamalidwa pamodzi ndi zotsatira za sucrose-kubweretsera kuwonjezeka kwa NAC DA komwe sikukhala kawirikawiri (mwachitsanzo, Avena et al. 2008b; Avena et al. 2006b; Colantuoni et al. 2001; Rada et al. 2005), Madera a DA amachepetsedwa mu chipolopolo cha NAC nthawi yosala kudya (mwachitsanzo, Avena et al. 2008a). Pamene maola ochepa a 2 amatha kupeza sucrose amapezedwanso pambuyo pa nthawi ya kusala kudya, mazamu owonjezera a NAC DA amaposa zomwe zimawoneka pa nyama zomwe zimapatsidwa mwayi wopeza sucrose, zomwe zikuwonetsa kuyankha kwa DA (mwachitsanzo, Avena et al. 2008b). Mofananamo, makoswe otchulidwa ku cocaine, morphine, nicotine, tetrahydrocannabinol, ndi heroin amachulukitsa kwambiri NAC DA (mwachitsanzo, Di Chiara ndi Imperato 1988; Gaddnas et al. 2002; Pothos et al. 1991; Tanda et al. 1997), pamene kuchotsa zinthu zimenezi kumachepetsa NAC DA (Acquas ndi Di Chiara 1992; Barak, Carnicella, Yowell, & Ron, 2011; Gaddnas et al. 2002; Mateo, Lack, Morgan, Roberts, & Jones, 2005; Natividad et al. 2010; Pothos et al. 1991; Rada, Jensen, & Hoebel, 2001; Weiss et al. 1992; Zhang et al. 2012). Momwemonso, kuchuluka kwa chiphaso cha VTA DA neurons kumachepa pa morphine (Diana et al. 1999) ndi kanema (Diana et al. 1998kuchotsa. Zofanana ndi ntchito ya DA poyankha sucrose patatha nthawi yoletsedwa (Avena et al. 2008b), Nthenda ya NAc DA ikuwonjezeka pamene makoswe amatsitsimikiziridwa ndi chikonga pambuyo pa 1 kapena 10-tsiku la kuchoka ku 4 kapena masabata a 12 a mphuno yaumwini wodzilamulira (Zhang et al. 2012). Kuwombera kwa VTA DA neurons kumawonjezeka kwambiri poyankha morphine (Diana et al. 1999) ndi kanema (Diana et al. 1998) kuyang'anira pambuyo pa kuchoka. Komabe, vuto la cocaine jekeseni pambuyo pa 1 kapena masiku 7 kuchoka pa kupititsa patsogolo ufulu wodziletsa sichitha kuwonjezera NAc DA, akusonyeza kukula kwa kulekerera osati kutonthozedwa (Mateo et al., 2005). Pambuyo pochita masewera olimbitsa thupi omwe ali ndi chikonga chowongolera, kuthamanga kwa chikonga pambuyo pa maola a 24 atachoka kumapangitsa kuti mapulitsi a NAC DA omwe ali ochepa kuposa omwe amapezeka mu makoswe a mankhwala osokoneza bongo, amasonyezanso kukula kwa kulekerera (Rahman, Zhang, Engleman, & Corrigall, 2004). Ngakhale kupititsa patsogolo mavitamini a methamphetamine (Le Cozannet, Markou, & Kuczenski, 2013) amapanga zotsatira motsatira Rahman et al. (2004), methamphetamine jekeseni yotsatila zotsatirazi zonse zosavuta komanso zochepa kuti zikhale ndi methamphetamine zokhazokha zimapangitsa kuti athandizidwe ndi DA kuti athetse mavutowa (Lominac, Sacramento, Szumlinski, & Kippin, 2012).

Mwachidule, pamene kubwezeretsedwa kwa chakudya chokoma pambuyo pa nthawi ya kuchepa kumabweretsa kuwonetseratu kutulutsidwa kwa DA, zotsatira zomwezo zimangowonongeka potsatira kuchoka kwa chikonga chodzitamandira, chokhalira ndi methamphetamine yochepa, komanso kasamalidwe ka mankhwala osokoneza bongo, morphine, ndi methamphetamine. Ntchito ya DAT imachepa pambuyo pa nthawi ya kusala (Patterson et al., 1998), zomwe zingapangitse DA kukwera kwambiri m'madera ena a ubongo pakupatsanso chakudya. Zotsatira zofanana zikuwoneka panthawi yochotsa ku experimer-administered methamphetamine (Wachijeremani, Hanson, & Fleckenstein, 2012).

Nucleus accumbens dopamine receptor mawu

Makoswe omwe amavomerezedwa mobwerezabwereza-refeeding cycle ndi kupeza kwa mitundu yonse ya shuga ndi chow kwa masiku 31 amachulukitsa chakudya cha shuga, koma osati chow kudya (Colantuoni et al. 2001). Maola 12 mpaka 15 maola atatha kudya, D1 receptor omanga mu NAc shell ndi pachimake ndi apamwamba kwambiri zakudya-zoletsedwa, shuga-bingeing makoswe olamulira. WXnUMX kwa maola 1.5 pambuyo pa kudya kwa sucrose, makoswe omwe ali chakudya choletsedwa ndipo amapatsidwa mwayi wochepa wa sucrose ndi chow kwa masiku 2.5 chiwonetsero chotsika kwambiri cha D7 mu NAC poyerekeza ndi makoswe omwe amapeza pang'ono kupeza chow (Bello et al. 2002). Malingana ndi kulamulira nyama zomwe zimapatsidwa chow, makoswe okhala ndifupikitsa kwa masiku a 21 amakhala otsitsila sucrose ndi kusonyeza kuchepa kwa D2 mRNA ndi kuwonjezeka kwa D3 mRNA m'nyengo ya NAc 1 mutatha kupeza sucrose ndi chow (Spangler et al. 2004).

Kuwonjezeka komweko ku NAc D1 kulandira mapulogalamu ndi / kapena mRNA miyezo yapezeka popita mobwerezabwereza kayendedwe ka cocaine (Unterwald et al. 2001), chikonga (Bahk et al. 2002), ndi amphetamine (Young et al. 2011). Komabe, Le Foll et al. (2003) adapeza kokha kuwonjezeka kwa D3 kumanga ndi mRNA koma palibe kusintha kwa D1 yotsatira chikonga chosagwira ntchito. Mofananamo, Metaxas et al. (2010) sanapeze kusintha mukulankhula kwa D1 kutsatira nicotine self-administration. Zonse zosalekeza komanso zosasokoneza zakumwa za mowa (Sari et al. 2006), ndi kupititsa patsogolo mwayi wa cocaine self-administration (Ben-Shahar ndi al. 2007) kuonjezera D1 mRNA komanso kufotokozera pamwamba pake (Conrad et al. 2010).

Kuwonjezeka kwa mawu a D1 mwinamwake kumapangitsa kuyankha kolimbikitsa kwa DA. Kutulutsidwa kwa DA ndi kukakamizidwa kwina kwa madokotala a D1 mu NAc zomwe zikuchitika pa kayendetsedwe ka mankhwala osokoneza bongo zimapangitsa kuwonetsa kovuta komwe kumaphatikizapo kuwonjezeka kwa kufotokozera zinthu zolembedwa ngati DFF Nestler et al. 2001). Kulepheretsa ntchito ya DFBB kumathandiza kuchepetsa zotsatira zopindulitsa za mankhwala osokoneza bongo (Zachariou et al. 2006) ndi mafotokozedwe owonjezereka amalimbikitsa mphotho ya mankhwala (Colby et al. 2003; Kelz et al. 1999; Zachariou et al. 2006). Kuletsedwa kwa zakudya kumapangitsanso ma fomu a DFBB ku NAC ya makoswe (Stamp et al. 2008; Vialou et al. 2011), zomwe zimapangitsa kuti munthu adzalandire chakudya chambiri chopatsa thanzi, monga momwe akuwonetsera kuti chidziwitso chodziwika bwino cha dFFB chimaonjezera chakudya chokoma (Vialou et al. 2011). THus, mwina BN ikuwonjezera ma DFFB ku NAC mwa njira yofanana ndi mankhwala osokoneza bongo, motero kumapindulitsa phindu lopindulitsa.

Kuwongolera kumawonetsanso kuchepa kwa D2 ku NAC (mwachitsanzo, Bello et al. 2002; Colantuoni et al. 2001; Spangler et al. 2004). Mwachidziŵikire, Taq1A, omwe amachititsa kuti mitundu yambiri yopanga mavitamini imapezeka pakati pa BN ndi anthu osokoneza bongo (Berggren et al. 2006; Connor et al. 2008; Nisoli et al. 2007), ikugwirizana ndi kuchepetsa mphamvu ya D2 receptor (Neville et al. 2004). Ngakhale cocaine imachepetsa D2 mawu mu NAc (Conrad et al. 2010), mobwerezabwereza mankhwala omwe amachitidwa ndi kasitini (Bahk et al. 2002), amphetamine omwe amagwiritsa ntchito experimenter (Mukda et al. 2009), ndi mowa wodzisamalira (Sari et al. 2006) kuwonjezera mawu a D2 pakati pa makoswe. Malingana ndi ntchito ndi mankhwala osokoneza bongo omwe amasonyeza kuchepetsa ku D2 kumanga (Volkow et al. 2001; Volkow et al. 1993), n'zodabwitsa kuti zochitika zomwezo sizikuwoneka pambuyo pa chikonga, amphetamine, kapena kuledzera kwa zinyama. Komabe, kuchepetsa kukakamizidwa kwa D2 komwe kumawoneka mwa anthu kungayambe kuwonetsa mankhwala, ndipo motero miyezo yafupi ya D2 sichiyenera kuwonetsedwa pambuyo poyang'ana nyama. Kuchepetsa kufotokoza kwa D2 kungapangitse kuwonjezeka kwa DA efflux yomwe ikhoza kuyendetsa galimoto kapena kufunafuna mankhwala osokoneza bongo.

Mwachidule, sucrose kudya zoweta zamtundu wa BN kumakhala kukwera kwa NAC DA, kuwonjezeka kwa D1 receptor kumanga ndi D3 mRNA, ndi kuchepetsa D2 receptor kumanga ndi mRNA mu NAc. Ngakhale kuti D1 ndi D3 zimasintha mogwirizana ndi zomwe zimayambitsidwa ndi mankhwala osokoneza bongo (pogwiritsa ntchito mankhwala osokoneza bongo a D1 kusintha), Kupepuka kwa D2 sikukuwonetsedwa mu maphunziro ambiri a zinyama za mankhwala osokoneza bongo. N'zotheka kuti ngakhale D2 kuchepa kwa anthu kumayendetsa galimoto, izi zimachepetsa kugwiritsa ntchito mankhwala osokoneza bongo ndipo sizimayambitsa.

Dopamine m'dera la ventral tegmental

Dopaminergic maselo mu VTA project kwa PFC, hippocampus, amygdala ndi NAc. Dongosolo la DA lotulutsidwa ndi Somatodendritic limapezanso mu VTA pazowunikira (Beckstead et al. 2004) ndipo zimakhudza kwambiri ntchito ya dopaminergic VTA neurons. Mawonekedwe awa a DA kumasulidwa amachititsa ovomerezeka a D2 am'deralo.Cragg ndi Greenfield 1997), motero kulepheretsa kuopsa kwa ma CD ku VTA (Bernardini et al. 1991; Wang 1981; White ndi Wang 1984) ndi DA kumasulidwa ku PFC ndi NAc malo osungirako malo (Kalivas ndi Duffy 1991; Zhang et al. 1994). Choncho, kumasulidwa kwa DA ku VTA kumapangitsa kuti ntchito yayikulu ikugwiritsidwe ntchito poyendetsa kayendedwe ka DA pamasom'pamaso a mesocorticolimbic.

Mu vivo microdialysis yagwiritsidwa ntchito kufufuza zowonjezera za VTA DA panthawi yopereka chakudya. Makoswe amaletsedwa chakudya ndi madzi kwa maola 36 asanafike nthawi yoti adzidyetsenso pamene microdialysis inkachitidwa (Yoshida et al. 1992). Kuwonjezeka kwakukulu kwa ma VTA DA kuwonetseredwa pakupatsanso chakudya ndi kumwa mofanana ndi zoyambira. Ma VTA DA anagwiritsidwa ntchito kwa 20-40 maminiti atatha kumapeto kwa nthawi yopatsa ndi kumwa. Mofananamo, injection ya IP ya ethanol imapangitsa kuti VTA DA ikhale yochulukitsa mkati mwa 20 maminiti, yomwe imayambanso maminiti a 40 pambuyo pa jekeseni ndikukwera kumkayi (Kohl et al. 1998). Chimodzimodzinso,Bradberry ndi Roth 1989) ndi IP (Reith et al. 1997; Zhang et al. 2001) cocaine administration ndi acute IP injection ya methamphetamine (Zhang et al. 2001) kuwonjezera DA extracellular mu VTA. Pamene zotsatira za Yoshida et al. (1992) Kafukufuku akusonyeza ntchito yofunika ya VTA DA pakudyetsa makhalidwe, makoswe mu phunziroli anali atangoyendetsa njinga pokhapokha panthawi imodzi ya chakudya choletsedwa ndi kubwezeretsa chakudya, ndipo makhalidwe odyera sanaganizidwe. Kuwonjezera apo, panalibe gulu lolamulira mu phunziroli, kotero sichidziwika ngati zotsatira zomwezo zikhoza kuoneka pakati pa makoswe omwe sali okhudzidwa ndi kuwonongeka kwa paradigm. Momwemo, kuyesa zomwezo pogwiritsa ntchito chitsanzo cha BN n'kofunikira.

Kutumiza pambali pa maolalimbic akuwonetseranso kumayendedwe ndi DATNA levels. DAT mRNA imapangidwira mu VTA ndipo imayendetsa kachidindo ka DA mu VTA. Zimatumizidwanso ku NAC kuti zikagwiritse ntchito synaptic reuptake ya DA. Pakalipano, kafukufuku mmodzi yekha adayesa kusintha kwa DAT mu VTA pogwiritsa ntchito chitsanzo cha BN (Bello et al. 2003). Mu phunziroli, makoswe anali chakudya choletsedwa kapena amapatsidwa mwayi wothandizira libitum ku sucrose kapena chow choyimira, wotsatira chakudya choyamba cha sucrose kapena chow standard. Makoswe oletsedwa odyetsa omwe anapatsidwa mwayi wopeza sucrose amadya kwambiri chow kuposa gulu lina lililonse la makoswe. Komabe, mosiyana ndi kafukufuku wammbuyo (mwachitsanzo, Avena et al. 2008a; Avena et al. 2006a; Colantuoni et al. 2002; Corwin ndi Wojnicki 2006; Hagan ndi Moss 1997), kusiyana pakati pa gulu mu sucrose kudya sikunapezeke (Bello et al. 2003). Zotsatira zotsutsana zingakhale chifukwa chakuti Bello ndi anzake amagwiritsa ntchito makoswe podutsa kamodzi kokha ndipo amapereka makoswe okhala ndi mphindi imodzi yokha ya 20 kupeza sucrose. Komabe, kusiyana kwa magulu mu sucrose kudya kumachitika pamene makoswe amachoka pamsasa chifukwa chosowa ndi kupeza nthawi zingapo ndipo amaloledwa kupeza sucrose kwa 1 kwa maola 12 (mwachitsanzo, Avena et al. 2008a; Avena et al. 2006a; Colantuoni et al. 2002; Corwin ndi Wojnicki 2006; Hagan ndi Moss 1997). Komabe, makoswe amapezeka kuti akuwonjezera katemera wawo katatu pamasiku a 7 (Bello et al. 2003), kusonyeza makhalidwe odzisunga. Malingana ndi maulamuliro ndi makoswe omwe anapatsidwa ufulu wothandizidwa pa chow, makoswe omwe anapatsidwa mwayi wopezeka ku sucrose omwe amachitikawo amasonyeza kwambiri DAT kumanga ndi mRNA miyezo ya VTA ndi DAT yomwe imamanga mu NAC (Bello et al. 2003). Monga tafotokozera pamwambapa, NAC DA ikuwonjezerapo pakuwonetsa chakudya chokoma, ndipo kuwonjezeka kwa mawu a DAT mu NAC kungakhale ngati kuyesa kubweza chiwerengero ichi. Izi zikusonyeza kuti kusasamba BN kuphatikizapo sucrose-bingeing kumapangitsa zotsatira pa VTA DA yomwe imasiyana ndi zomwe zimapangidwa ndi kumeza zakudya zosakoma. Kutchulidwa mobwerezabwereza kwa amphetamine (Lu ndi Wolf 1997; Shilling et al. 1997) ndi chikonga (Li et al. 2004) imachulukitsa VTA DAT mRNA. Mosiyanitsa, cocaine yopanda malire imachepa (Cerruti et al. 1994), pamene zonse zopanda malire-komanso kupititsa patsogolo kwa cocaine zokhazokha zilibe zotsatirapo (Ben-Shahar ndi al. 2006), DAT mRNA mawu mu VTA.

Kafufuzidwe pogwiritsa ntchito mitundu ya nyama yoletsa zakudya imasonyeza kuti dopaminergic VTA efferents ingathetsere khalidwe lofunika kwambiri la kusasamba BN. Malinga ndi kulamulira makoswe pokhala ndi ufulu wopeza chakudya, makoswe omwe akudya zakudya zambiri zowonongeka kuwonjezeka kwa VTA akuwonetsa ma vesi awiri omwe akugwiritsidwa ntchito mu DA synthesis: tyrosine hydroxylase (TH) ndi zonunkhira L-amino acid decarboxylase (AAAD) (Lindblom et al. 2006). Choncho, nthawi ya kusala imatha kukonzekera VTA DA neurons kuti amasule DA ochulukirapo ku NAc pa kupereka chakudya chokoma. Kulepheretsa chakudya chamakono kumabweretsa kuwonjezeka kwakukulu m'mawu a DAT mu VTA (Lindblom et al. 2006). Komabe, ndikofunika kuzindikira kuti kuchepetsa chakudya ndi chimodzi chokha cha kusakhala kuyeretsa BN. Motero, kafufuzidwe ka mtsogolo kamayenera kuwonanso momwe kudalira zakudya ndi zoletsera za VTA TH, AAAD, ndi DAT. Matenda a cocaine ndi morphine amathandiza kwambiri kuwonjezera VTA TH immunoreactivity (Beitner-Johnson ndi Nestler 1991), koma methamphetamine maulamuliro samasintha kwambiri ma THRNA m'magulu a VTA (Shishido et al. 1997).

Mwachidule, zitsanzo za zinyama zomwe zimatsanzira kusakhala kuyeretsa BN ndi zigawo zina zazikulu za BN, monga kuchepetsa chakudya, zakhala zikugwiritsidwa ntchito kupeza kuwonjezeka kwa DAT mRNA, kutchulidwa kwa mapuloteni opangidwa ndi DA kaphatikizidwe (TH ndi AAAD), ndi kuwonjezeka kwa DA mu VTA. Zotsatirazi zikufanana ndi njira zomwe zimapezeka mobwerezabwereza amphetamine, morphine, ndi chikonga, koma zimatsutsana ndi zomwe zimapangidwa ndi cocaine yomwe siidali yongogonjetsa komanso yovomerezeka yokhayokha komanso ya methamphetamine. Zomwe zinagwiritsidwa ntchito, zowonjezera zomwe zasinthidwa m'gawo lino zimasonyeza kuti kusintha kwa VTA dopaminergic komwe kumapezeka m'zinthu zamtundu wa BN ndi ofanana ndi omwe alipo pambuyo powagwiritsa ntchito mankhwala osokoneza bongo.

Zotsatira za otsutsa a dopamine pa kudya mowa kwambiri ndi kufunafuna mankhwala osokoneza bongo

Chifukwa chakuti kumasulidwa kwa DA kumapezeka ku NAc pamene akudya, kafukufuku wochulukirapo adafufuza kuthekera kwa kayendedwe kake ka D1 ndi D2 omwe amatsutsana nawo kuti athetse khalidweli. Pogwiritsira ntchito pulojekiti yochepa yofikira ndi mafuta / sucrose mix mix, Wong ndi anzake (2009) anapeza kuti mdani wa D2 raclopride ali ndi kuchepetsa kuchepa kwa mlingo mu zakudya zowonjezera zokhala ndi zokwanira za sucrose. Phunziro lawo, makoswe analoledwa kupeza mwayi wa 100% wofupika ndi 3.2, 10, kapena 32% sucrose (w / w) kwa ola limodzi, mwachindunji (MWF) tsiku lililonse. Nthata zokha zomwe zinapatsidwa mwayi wopezera chakudya chokoma chokhala ndi 3.2 kapena 10% sucrose zinakhala ndi zofunikira zotsalira. Mu nyama izi, mlingo wa 0.1 mg / kg (IP) wa raclopride kuwonjezeka kumwa mowa panthawi ya 0.3 mg / kg (IP) mlingo kuchepa Kudya chakudya chokoma m'ma rats akudya 3.2% sucrose. Raclopride sanakhale ndi zotsatira za kudya pakati pa makoswe operekedwa tsiku ndi tsiku kapena kufika pakati pa msinkhu wambiri (32%) osakaniza mafuta / sucrose pa mlingo uliwonse, komanso sanakhudze kumwa makoswe opatsidwa tsiku ndi tsiku. Pa kafukufuku wofanana ndi gulu lomweli, mlingo womwewo wa raclopride unayesedwa kuti athetse kuchepetsa kumwa mowa mwina mafuta (kuchepetsa) kapena sucrose-containing (3.2, 10, ndi 32%) zakudya zinyama zitaperekedwa nyama tsiku ndi tsiku kapena mwachindunji kupeza zakudya izi (Corwin ndi Wojnicki 2009). Zofanana ndi zotsatira za Wong et al. (2009) Kuphunzira, chiwerengero cha 0.1 mg / kg cha raclopride chiwonjezeredwa kwambiri kuti chichepetse pakati pa makoswe omwe amapezeka pafupipafupi -wowonjezera mauthenga ndipo amapatsidwa maola ochepa a 1 maola a 100% mafuta, koma zotsatirazi sizinawonedwe pakati pa makoswe omwe amapatsidwa mafuta tsiku ndi tsiku (Corwin ndi Wojnicki 2009). Mlingo wokwanira kwambiri wa raclopride (0.3 mg / kg) unachepetsa kudya kwa sucrose onse Mkhalidwe wa sucrose kudya. Phunziro lina, makoswe ogwidwa ndi 0.3 mg / kg (IP) raclopride ndipo anapatsidwa mafupipafupi a 4 maola ochepa kwa 56% mafuta okhwima olimbitsa thupi kapena tsiku lililonse kwa 4 maola a 18%, 32%, kapena 56% emulsions ofooka kwambiri kudya kwawo (Rao et al. 2008). Raclopride samasintha chakudya cha chow nthawi zonse (Corwin ndi Wojnicki 2009; Rao et al. 2008; Wong et al. 2009), kusonyeza kuti raclopride makamaka imakhudza kudya zakudya zokometsetsa komanso zimatero pa zinyama zomwe zimadya zakudya izi.

Pokhudzana ndi mankhwala osokoneza bongo, 0.1 mg / kg raclopride amalepheretsa kubwezeretsedwa kwa cocaine pamutuCrombag et al. 2002) ndipo 0.25 mg / kg raclopride amachepetsa kubwerera kwa heroin.Shaham ndi Stewart 1996). Mankhwala a moderate (0.1 mg / kg) ndi mkulu (0.3 mg / kg) Mlingo wa raclopride kwa masiku asanu otsatizana amachititsa kuti mankhwalawa asamangidwe kwambiri.Alen et al. 2008). Kuchuluka kwa mankhwala a rapafini kumapangitsa kuti munthu asamangokhalira kufunafuna mankhwala a cocaine zomwe zimayambitsa zotsatira zake pa kudya zakudya zolimbitsa thupi: mlingo wochepa umayambitsa kubwezeretsa pamene chiwerengero chapamwamba chimasokoneza (Berglind ndi al. 2006). Kuphatikizana, kuchepa kwakukulu kwa raclopride kuchepa, pamene kuchepa kwa mlingo kumawonjezeka, mafuta ndi sucrose mowa mwakumwa makoswe, koma osati mu makoswe osakanizidwa opatsidwa tsiku lililonse chakudya chokoma. Malinga ndi kubwezeretsedwa kwa mankhwala osokoneza bongo, zotsatira za raclopride pa sucrose zoledzera zimakhala zofanana ndi zomwe zimapangidwa ndi intra-amygdala infusions koma osati majekeseni.

Wotsutsa D1 SCH 23390 amachepetsa kudya chakudya chokoma. Kupereka makoswe ndi 0.1 kapena 0.3 mg / kg (IP) SCH 23390 imachepetsa kudya kwa 3.2%, 10%, ndi 32% madzi a sucrose njira mu makoswe omwe amapatsidwa mwayi wochepa (ora limodzi / tsiku) kuti apatsidwe tsiku lililonse kapena mwachindunji, ndi zotsatira zambiri Amatchulidwa kuti makoswe anapatsidwa mwayi wolowera (Corwin ndi Wojnicki 2009). Kuwonjezera pamenepo, mlingo wa 0.3 mg / kg SCH 23390 imachepetsanso kuchepetsa kudya kwa makoswe omwe amapatsidwa maola ochepa tsiku ndi tsiku komanso mafuta omwe ali ndi 1 mg / kg. Zowoneka kuti, SCH 0.3 sichimakhudza chakudya cha chow nthawi zonse (Corwin ndi Wojnicki 2009; Rao et al. 2008; Wong et al. 2009). Mofananamo, kukonza makoswe ndi SCH 23390 kumapangitsa kuti anthu asamayesere kuyankha moyenera kuti athe kupeza mankhwala osokoneza bongo.Weissenborn et al. 1996). SCH 22390 imayesetsanso kukonzanso za cocaine zokhazokha (Crombag et al. 2002), kubwezeretsedwa kwa heroin (Shaham ndi Stewart 1996), kubwezeretsa mafuta m'thupi (Liu & Weiss, 2002) komanso heroin reinstatement (omwe amalephera kudya chakudya)Tobin et al. 2009) mu makoswe. SCH 22390 imachepetsa chikonga chodzilamulira (Sorge & Clarke, 2009; Masitepe, Neugebauer, & Bardo, 2010) ndi cocaine kudziyang'anira (Sorge & Clarke, 2009). Ngakhale SCH 22390 imaletsa kwambiri kukakamizidwa kwa cocaine patatha nthawi yochotsa pakati pa amuna ndi akazi omwe amapatsidwa mwayi wochepa wa mankhwalawa,Ramoa, Doyle, Lycas, Chernau, & Lynch, 2013), mogwirizana ndi kuchepetsedwa kwa DA kumasulidwa kumene kumapezeka zotsatirazi zowonjezera (zomwe takambirana pamwambapa). Mwachidule, wotsutsa D1 SCH 22390 amaletsa kudya zakudya zokoma ndipo amaletsa kubwezeretsedwa kwa mankhwala osokoneza bongo.

Chifukwa chakuti DA yowonjezera ikuwonekera mu NAC pamene mukudya mowa, zimayesa kunena kuti zotsatira za machitidwe a D1 ndi a D2 omwe amatsutsana nawo ndi oyenerera ndi a NAc. Kuyesera kuthekera kwa kulowetsedwa kwa agonist ndi otsutsa ku NAC kuchepetsa kuledzera ndikofunikira. Wopikisana ndi D2 raclopride ali ndi biphasic m'kudyera zakudya zokoma; izi zikhoza kuchitika chifukwa cha mtundu wosiyana wa anthu awiri a D2 receptors (chisanadze ndi post-synaptic). Mankhwala otsika a agonists amakonda kwambiri amachititsa kuti asamapangitse kuti D2 isamangidwe, motero kuchepetsa DA kumasulidwa (Henry et al. 1998). Zingaganizedwe kuti kuchepa kwa mlingo wotsutsana ndizomwe kumakhala ndi zotsatira zabwino pa autoreceptors, motero kumawonjezera DA efflux (mwachitsanzo, Onani ndi al. 1991) ndi kuyendetsa zakudya zopatsa thanzi. Mlingo waukulu ukhoza kulepheretsa positi-synaptic receptors, motero kuchepetsa kudya zakudya zokoma. Zotsatira izi zikuwonetsa kuti DA kumasulidwa ndi kumangiriza D1, ndipo mwina D2, mapulogalamu amalandira kudya kwambiri. Kuwonjezeka kwa DA kumasulidwa kupyolera kutsutsana ndi ovomerezeka a D2 kumapangitsanso kuwonjezereka. Izi zimapeza zotsatira zofanana za kuwonjezereka kwa D1 ndi kuchepetsa kukakamizidwa kwa D2 ku NAC mu makoswe ndi mbiri yakudya chakudya chokoma. Kuphatikizidwa pamodzi, zikutheka kuti kuchepa kwa mawu a NAC D2 kumabweretsa kuonjezeredwa kwa DA panthawi yomwe akugwiritsanso ntchito maulendo apakati pomwe ma D1 amawotcha ma post-synaptic neurons kuti athe kuyankha mwatsatanetsatane kwa DA atatulutsidwa pakamwa.

Glutamatergic neurotransmission ku BN

Kusintha kwa malingaliro a glutamate ndi ma subunit receptor akuyesedwa kwambiri potsatira kudzikonda kwa mankhwala osokoneza bongo ndi makoswe. Glutamate ili ndi mitundu yambiri yolandirira yomwe ili yoyamba komanso yotsatizana. Pano tikukambirana mauthenga ofunikira omwe amadziwika kuti amatha kusokoneza ubongo: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-d-aspartate (NMDA), ndi metabotropic glutamate receptor 5 (mGluR5).

Pambuyo posiya kudziwika kwa cocaine kudziyang'anira, pali kuwonjezeka kwa NAc pamwamba pa mawonekedwe a GluA1 subunit ya tetrameric AMPA receptor, koma palibe kusintha kwa mawu a GluA2 subunit (Conrad et al. 2008). Zotsatirazi zimapangitsa kuwonjezereka kwa calcium-permmeable, GluA2-yopanda AMPA receptors (CP-AMPA), yomwe imathandizira kuwonjezereka kwa ma synaptic neurons, motero kumalimbitsa mgwirizano wa synaptic (Conrad et al. 2008). Kuwonjezeka kwa CP-AMPAs kwakhala kukuchitika pambuyo pa 30, 45, ndi masiku a 70 atachotsedwa, koma patapita tsiku limodzi lokha (Conrad et al., 2008; Ferrario et al., 2011; Wolf & Tseng, 2012) kapena mutangotsala pang'ono kupeza cocaine self administration (Purgianto et al. 2013). Nthiti zoletsedwa pa zakudya zimasonyeza kuwonjezeka kwakukulu kwa mawu a post-synaptic ochuluka a GluA1 mu NAc poyerekeza ndi machitidwe pamene GluA2 mawu samasintha (Peng et al. 2011). Choncho, n'zotheka kuti nthawi ya chakudya chimene chimachitika panthawi ya BN imayambitsa kulembedwa kwa CP-AMPAs komwe kumasintha kuthamanga kwa mankhwala osokoneza bongo mumtundu wa NAc kupita ku mchere wambiri. Kudzisamalira kwa mankhwala osokoneza bongo kumabweretsa kuwonjezereka kwa glutamate yotulutsidwa ndi synaptically mu NAc, yomwe imayambanso kubwerera pambuyo pa nthawi yopanda mankhwala; Kuwonjezeka kumeneku kwasonyezedwa kuti kumachitika ngati abwererenso mowa (Gass et al. 2011), cocaine (McFarland et al. 2003), ndi heroin (LaLumiere ndi Kalivas 2008). Kutulutsidwa kwawotchedwa glutamate kumasulidwa pamodzi ndi mapuloteni othamanga kwambiri omwe amatha kukhala ndi CP-AMPAs m'dera limene limayendetsa kuyendetsa khalidwe lofunafuna mankhwala (pogwiritsa ntchito majekiti a NAc ku malo opitikitsa ubongo). Mpaka lero, palibe maphunziro omwe akugwiritsa ntchito zitsanzo za nyama za BN kapena kudya mowa mwauchidakwa tafufuza ma glutamate mu NAC kapena m'madera ena a ubongo atatha kudya chakudya chokoma pambuyo pa kudziletsa. Komabe, ngati kuwonjezeka kotereku kudzachitika, zikanatsimikizira lingaliro lakuti kuwonongeka kwa kayendetsedwe ka zakudya zopatsa thanzi komanso mankhwala osokoneza bongo pambuyo pa nthawi ya kudziletsa kumadalira njira zofanana zogwiritsira ntchito mankhwalawa.

Pogwirizana ndi lingaliro loti kutulutsidwa kwa glutamate kumaphatikizidwa ku BN, mtsogoleri wothandizana ndi NMDA amatha kuchepetsa kudya mowa ngati mafuta amphongo osaloledwa ndipo amachititsa kuwonjezereka kokwanira kwa chakudya choyenera cha laboratory chow (Popik et al. 2011). Phunziro lomwelo linasonyeza kuti MTEP (3- (2-Methyl-4-thiazolyl-ethynyl) pyridine), woyendetsa bwino mankhwala a mGluR5, adawathandiza kuti achepetse zakudya zamagazi. Pogwiritsa ntchito chitsanzo chamapanga cha matenda odyera zakudya omwe abambo amapatsidwa mwayi wapakati pa shuga ndi ad adum access to chow standard, Bisaga ndi anzanu (2008) anapeza kuti mememine ndi MTEP zimachepetsanso kuchepa kwa shuga. Zotsatira zofanana za mementine pafupipafupi za kudya mowa mwauchidakwa zinkawonedwa mu mayesero a zachipatala (Brennan et al. 2008).

Ngakhale kuti pulogalamu ya glutamate microdialysis iyenera kuyendetsedwa pogwiritsira ntchito zitsanzo za nyama za BN, kuti odwala omwe amamwa mankhwala a glutamate amatha kukumbukira ndipo MTEP imachepetsanso kudya zakudya zolimbitsa thupi kuti kuganiza kuti kudya chakudya kumadalira kutumizira kwa glutamatergic, ngakhale kuti kumapezeka m'dera la ubongo kunja kwa NAc. Mu makoswe, MTEP yatsimikiziridwa moona kuti kuchepetsa kufunafuna cocaine (Bäckström ndi Hyytiä 2006; Knackstedt et al. 2013; Kumaresan et al. 2009; Martin-Fardon et al. 2009), mowa (Sidhpura et al. 2010), methamphetamine (Osborne ndi Olive 2008), ndi opioids (Brown ndi al. 2012). Maselo angapo ochepa a kachipatala apeza kuti kuchepetsa kuchepa kumachepetsanso zotsatira za mankhwala a chikonga (Jackson et al. 2009) ndi heroin (Bwerani ndi Sullivan 2007) ndipo amachepetsa kuchotsa zizindikiro kuchokera ku mowa (Krupitsky et al. 2007) ndi opioids (Bisaga et al. 2001). Komabe, kufufuza kwakukulu, komwe kunayikidwa pa malobo kunasonyeza kuti kumapeto sikulepheretsa kumwa mowa wodwala mowa (Evans et al. 2007). Chochititsa chidwi n'chakuti mu phunziro la oyendetsa odwala la odwala la 29, nthawi yowonjezera yomwe inachepera kutchova njuga ndi kuwonjezeka kwa chidziwitso (Grant et al. 2010), kuwonetsa kuti kukumbukira kungakhale kothandiza kwa odwala omwe amakhala ndi chizoloŵezi chokhala ndi zizoloŵezi zokhudzana ndi makhalidwe monga kutchova juga ndi kudya mowa koma osati mankhwala osokoneza bongo. Mwachidule, ngakhale kuti pali zovuta za kafukufuku wogwiritsa ntchito zinyama za BN kuti zithetse kusintha kwa kulumikiza kwa glutamate, kufufuza koyambirira kotchulidwa m'gawo lino kukuwonetsanso kuti kusintha kofananako mu njira ya glutamate yokhudzana ndi matenda a ubongo kungayang'anire BN ndi kufunafuna mankhwala.

Kutaya ulamuliro

Kugwiritsa ntchito mankhwala osokoneza bongo kumaphatikizapo kusinthika kuchoka ku ntchito zowonetsera, zoyendetsera ntchito kuzochita zachizoloŵezi komanso kusayendetsa kugwiritsira ntchito mankhwala osokoneza bongo zomwe zimabweretsa chisokonezo cha ntchito ya PFC (Kalivas ndi O'rien 2008; Koob ndi Le Moal 2001). Monga tanenera kale, chimodzi mwa zinthu zofunika kwambiri za BN ndikumverera kosalamulirika pa kudya, ndi kulephera kuletsa kudya kapena kuchepetsa kuti ndiyani kapena kudya kotani (Association of Psychiatric Association 2013). Kafukufuku wogwiritsidwa ntchito pogwiritsa ntchito maginito (fmRI) apeza kuti, pokhudzana ndi kulamulira bwino, BN-anthu amawonetsa ntchito yochepa ya PFC pazochita zogwira ntchito monga kugonjetsa mphamvu (Marsh et al. 2011; Marsh et al. 2009). Zochepa zomwe zimachitika pa frontostriatal njira, kuphatikizapo kumanzere kwa inferolateral PFC, zimagwirizana ndi kuyankha mwachidwi (Marsh et al. 2009), kuwonetsa ogwira ntchito akuluakulu ogwira ntchito pakati pa BN-individuals. Zokhudzana ndi maulamuliro, BN-anthu amasonyeza ntchito zapamwamba mu PFC pamene aperekedwa ndi zithunzi za chakudya (Uher et al. 2004), wophimbidwa ndi mawu opanda pake okhudza chithunzi cha thupi (Miyake et al. 2010), kapena akuwonetsa matupi olemera kwambiri (Spangler ndi Allen 2012).

Kuphatikizidwa pamodzi, BN aliyense amasonyeza chisangalalo pamene akufotokozedwa ndi zinthu zosagwirizana ndi chakudya komanso ntchito yochulukirapo pamene amaperekedwa ndi zovuta zokhudzana ndi matenda. Ntchito imeneyi ikuwonetsanso pakati pa oledzera. Mwachindunji, kusakhulupirika kwa PFC chifukwa cha zomwe sizikugwirizana ndi mankhwala osokoneza bongo ndizodziwika pakati pa ogwiritsira ntchito mankhwala osokoneza bongo a cocaine (Goldstein et al. 2007), methamphetamine (Kim et al. 2011; Nestor et al. 2011; Salo et al. 2009), ndi mowa (Crego et al. 2010; Maurage et al. 2012). Kupereka mankhwala osokoneza bongo ndi zithunzi za mankhwala osokoneza bongo kumawonjezera PFC ntchito pakati pa zidakwa (George et al. 2001; Grusser et al. 2004; Tapert et al. 2004), cocaine (Wilcox et al. 2011), ndi anthu enieni (nicotie)Lee et al. 2005). Choncho, BN-anthu amasonyeza zochitika za PFC zofanana ndi mankhwala osokoneza bongo.

 

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