MAFUNSO: Kuphunzira koyamba kusonyeza kuti kugwiritsa ntchito mankhwala osokoneza bongo kumayambitsa kuchepa kwa dopamine (D2) receptors. Chofunika chifukwa chakuti oledzeretsa ali ndi chiwerengero chochepa cha mapepala oterewa, omwe angapangitse kuledzera. Zimasonyezanso kuti mapulogalamu amatha kubwereranso, koma mlingo ndi wotheka kwambiri komanso wosagwirizana ndi ovomerezeka a D2.
Kuzunzidwa kwa Cocaine ndi Mipangidwe ya Pulogalamu: PET Imaging Imatsimikizira Chizindikiro
14 Jul 2006
Pogwiritsa ntchito positron emission tomography (PET), ofufuza apeza mgwirizano pakati pa khalidwe la ubongo ndi chizoloŵezi cha munthu kugwiritsa ntchito mowa wa cocaine ndipo mwinamwake amakhala wosokonezeka, posonyeza njira zomwe angathe kusankha mankhwala.
Kafukufukuyu, wazinyama, akuwonetsa kulumikizana kwakukulu pakati pa kuchuluka kwa zolandirira m'mbali yaubongo kwa neurotransmitter dopamine - yomwe imayesedwa ntchito ya cocaine isanayambe - komanso kuchuluka komwe nyamayo idzadziperekere mankhwalawo. Kafukufukuyu adachitika mu anyani a rhesus, omwe amadziwika kuti ndi chitsanzo chabwino kwambiri cha ogwiritsa ntchito mankhwala osokoneza bongo.
Kawirikawiri m'munsimu chiwerengero choyamba cha dopamine receptors, chomwe chimakhala chokwanira cha ntchito ya cocaine, ofufuza apeza. Kafukufukuyo anatsogoleredwa ndi Michael A. Nader, Ph.D., pulofesa wa zaumulungu ndi mankhwala a pharmacology ku Wake Forest University School of Medicine.
Zinali kudziwika kale kuti olakwira mankhwala a cocaine anali ndi zochepa zochepa za dopamine receptor yotchedwa D2, mu nkhani zonse za anthu ndi zinyama, poyerekeza ndi osagwiritsa ntchito. Koma sichidziwika ngati icho chinali chikhalidwe chomwe chinalipo kale chomwe chinapangidwira anthu kuti azigwiritsa ntchito mankhwala osokoneza bongo kapena chinali chifukwa cha ntchito ya cocaine.
"Zomwe anyani apeza pano zikusonyeza kuti mwina zonsezi ndi zoona,"
Nader ndi anzawo alemba mu kafukufuku wofalitsidwa pa intaneti sabata ino munyuzipepala ya Nature Neuroscience. "Zomwe apezazi zikusonyezanso kuti anthu omwe ali pachiwopsezo atha kugwiritsa ntchito mankhwala osokoneza bongo a cocaine chifukwa cha kuchepa kwa mankhwala osokoneza bongo a cocaine m'magazi a D2 receptor."
Umenewu unali phunziro loyambirira lomwe nthawi zonse linkayezetsa zinyama zoyamba za D2 zomwe sizinagwiritsepo ntchito cocaine ndi kuyerekeza miyeso imeneyo kusintha kwa ovomerezeka a D2 ziweto zitayamba kugwiritsa ntchito. Kuyerekezera kotere sikutheka ndi maphunziro a anthu, ndipo m'kafukufuku wakale wa nyani, kuchuluka kwa nyama zomwe zidagwiritsidwa ntchito ndi cocaine zimafaniziridwa kokha ndi "njira zowongolera" zosagwiritsa ntchito.
Kafukufukuyu wasonyeza kuti kuyamba kugwiritsa ntchito cocaine inachititsa kuti D2 izigwetseratu kwambiri ndipo kuti apitirize kugwiritsa ntchito mankhwalawa adasunga miyezo ya D2 pansi pazomwezo.
"Pazonse, zomwe apezazi zimapereka umboni wosatsutsika wokhudza gawo la [dopamine] D2 zolandilira pakugwiritsa ntchito mankhwala osokoneza bongo a cocaine ndikuwonetsa kuti mankhwala omwe cholinga chake ndikukula kwamilingo a D2 atha kukhala ndi lonjezo lakuchepetsa kuwonjezera kwa mankhwala," ofufuzawo alemba.
Kafukufukuyu akuwonetsa kuti kuwonjezeka kwa ma D2 receptors atha kuchitidwa "mankhwala" kapena kusintha zinthu zachilengedwe, monga kuchepetsa kupsinjika. Koma kafukufukuyu akuti, "pakadali pano palibe mankhwala othandiza pakumwa mankhwala osokoneza bongo a cocaine, ndipo kumvetsetsa kwa oyimira chilengedwe ndi zachilengedwe omwe ali pachiwopsezo chogwiritsa ntchito mankhwala osokoneza bongo a cocaine sikungakhale kovuta."
Dopamine, monga ma neurotransmitters ena, amasuntha pakati pa maselo amitsempha muubongo kuti apereke "mauthenga" ena. Amatulutsidwa ndi khungu limodzi lamitsempha ndipo amalowetsedwa ndi zolandilira pa cell yotsatira yamitsempha, ina mwa iyo ndi D2. Dopamine yosagwiritsidwa ntchito imasonkhanitsidwa mwa "onyamula" omwe amaibweza ku selo yotumiza.
Cocaine imagwira ntchito polowetsa wonyamula, kutsekereza "kubwezeretsanso" kwa dopamine ndikusiya zochulukirapo pakati pamaselo. Akuganiza kuti kuchuluka kwa dopamine kumapangitsa wogwiritsa ntchito mankhwala osokoneza bongo a "mkulu".
Koma dopamine iyi imadzaziranso imalandiranso ma D2 receptors pamaselo omwe amalandila, ndipo ma cell amenewo pamapeto pake amachitapo kanthu pochepetsa kuchuluka kwa ma D2 receptors. Ofufuza za mankhwala osokoneza bongo amaganiza kuti ndikusintha kumeneku komwe kumapangitsa chidwi cha cocaine: mulingo wolandila ukatsika, dopamine yambiri imafunika kuti wogwiritsa ntchito azimva "wabwinobwino."
Monga kugwiritsa ntchito cocaine, kupsinjika kumathandizanso kukulitsa kuchuluka kwa dopamine ndipo zikuwoneka kuti kumapangitsa kuchepa kwa ma D2 receptors. Kafukufuku woyambirira wa gulu la Nader ku Wake Forest adawonetsa kulumikizana pakati pamavuto ndi chizolowezi chogwiritsa ntchito mankhwala osokoneza bongo a cocaine.
Kafukufuku wamakono akuwonanso kusiyana pakati pa nthawi yomwe zidatengera kuti obwera D2 abwerere kuzinthu zoyenera kugwiritsa ntchito kamodzi ka cocaine. Ng'ombe zomwe zinagwiritsidwa ntchito kwa sabata imodzi yokha zinali ndi kuchepa kwa 15 peresenti muzipatala za D2 ndipo zinapezedwa kwathunthu mkati mwa masabata atatu.
Koma nyani zomwe zimagwiritsidwa ntchito kwa chaka zinali ndi kuchepetsa kwa 21 peresenti muzipatala za D2. Zitatu mwa anyaniwa adatulukira miyezi itatu, koma awiri a abuluwo sanabwerere ku miyeso yawo yoyamba D2 pambuyo pa chaka chimodzi chodziletsa.
Kulephera kuchira sikunali kofanana ndi magawo oyambira a D2. Kafukufukuyu akuwonetsa kuti "zinthu zina, mwina zokhudzana ndi ma neurotransmitter, zimathandizira kuyambiranso kwa ntchito yolandirira ya D2."
PHUNZIRO: Zithunzi za PET za dopamine D2 receptors pa nthawi ya cocaine yokhala ndi ubwino wodziteteza.
Nader MA, Morgan D, Gage HD, Nader SH, Calhoun TL,
Buchheimer N, Ehrenkaufer R, Mach RH.
Nat Neurosci. 2006 Aug, 9 (8): 1050-6. Epub 2006 Jul 9.
Dipatimenti ya Physiology ndi Pharmacology, Wake Forest University School of Medicine, Medical
Centre Boulevard, Winston Salem, North Carolina 27157, USA. [imelo ndiotetezedwa]
Dopamine neurotransmission ikugwirizanitsidwa ndi kukwera kwamtundu wa mankhwala osokoneza bongo. Positron emission tomography anagwiritsidwa ntchito mu 12 rhesus macaques kudziwa ngati dopamine D2 receptor kupezeka ankagwirizana ndi mlingo wa cocaine kutsimikiziridwa, ndi kuphunzira kusintha mu ubongo dopaminergic ntchito pa kukonza ndi kupewa kupewa cocaine. Kupezeka kwadongosolo kwa Baseline D2 kunali kosagwirizana kwambiri ndi mitengo ya cocaine kudzilamulira. Kupezeka kwa D2 kupezeka kunachepetsedwa ndi 15-20% mkati mwa sabata la 1 loyambitsa kudzilamulira ndipo linachepetsedwa pafupifupi pafupifupi 20% panthawi ya 1 chaka chodziwika. Kuchepetsa kwa nthawi yaitali mu kupezeka kwa D2 kupezeka kunawonetsedwa, ndipo kumachepetsa kupitirizabe mpaka chaka cha 1 chodziletsa m'monke ena. Deta imeneyi imapereka umboni wokhala ndi chithandizo cha cocaine pogwiritsa ntchito D2 receptor kupezeka, ndipo amasonyeza kuti ubongo wa dopamine dongosolo amatsatira mofulumira kutsatira cocaine. Kusiyanitsa kwa aliyense pa mlingo wa kupulumutsidwa kwa ntchito ya D2 receptor pamene kudziletsa kunatchulidwa.
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