Kodi ndipadera bwanji vuto lakutchova njuga kapena vuto lakutchova njuga? (2013)

Front Behav Neurosci. 2013; 7: 206.

Idasindikizidwa pa intaneti Dec 23, 2013. do:  10.3389 / fnbeh.2013.00206
PMCID: PMC3870289

Kutchova njuga kwachidziwitso [PG - tsopano yotchedwa "vuto la kutchova njuga" ku DSM-5 (APA, 2013; Petry et al., 2013)] amadziwika ndi njira zoyipa za njuga zomwe zimagwirizanitsidwa ndi kusokonezeka kwakukulu pakugwira ntchito. Kwazaka khumi zapitazi, kupita patsogolo kwakukulu kwachitika pakumvetsetsa pathophysiology ya PG (Potenza, 2013). Kufanana pakati pa zovuta za PG ndi zovuta kugwiritsa ntchito mankhwala (Petry, 2006; Potenza, 2006; Leeman ndi Potenza, 2012) idalimbikitsa kukonzanso kwa PG ku DSM-5 ngati vuto losokoneza bongo (m'malo mopupuluma pakuwongolera, monganso momwe zinalili ndi DSM-IV).

Makina ambiri a neurotransmitter adakhudzidwa ndi PG kuphatikiza serotonergic, noradrenergic, dopaminergic, opioidergic, ndi glutamatergic (Potenza, 2013). Kuzindikira kwa machitidwewa momwe amagwirizanirana ndi PG ndikofunikira pakukonzekera kwa mankhwalawa chifukwa pakadali pano palibe mankhwala ovomerezeka a FDA omwe ali ndi zisonyezo za PG. Dopamine idakhudzidwa kalekale ndi zosokoneza bongo ndipo zolemba zoyambirira zidalemba gawo lofanana ndi dopamine ku PG (Potenza, 2001). Komabe, gawo lenileni la dopamine mu PG silidziwika bwinobwino. Kafukufuku wa zitsanzo zamadzimadzi a cerebrospinal adawonetsa kuchepa kwambiri kwa dopamine komanso kuchuluka kwambiri kwa dopamine metabolites ku PG, kukulitsa mwayi woti chiwonjezere cha dopamine (Bergh et al., 1997). Komabe, mankhwala omwe amayang'ana ntchito ya dopamine sanawonetse zovuta mu PG. Mwachitsanzo, mankhwala omwe amaletsa dopamine D2-like receptor function (mwachitsanzo, olanzapine) awonetsa zotsatira zoyipa m'mayeso ang'onoang'ono, osankhidwa mwatsatanetsatane (Fong et al., 2008; McElroy et al., 2008). Kuphatikiza apo, D2-ngati dopamine receptor antagonist wogwiritsidwa ntchito kwambiri pochiza matenda amisala (haloperidol) adapezeka kuti amawonjezera zolimbikitsa zokhudzana ndi juga ndi machitidwe mwa anthu omwe ali ndi PG (Zack ndi Poulos, 2007). Komabe, kuyang'anira kwa pro-dopaminergic (ndi pro-adrenergic) mankhwala amphetamine kunapangitsanso kuchuluka kwa malingaliro okhudzana ndi juga mu PG (Zack ndi Poulos, 2004).

Kafukufuku waposachedwa ayamba kugwiritsa ntchito ma radioligands ndi positron-emission tomography kuti afufuze ntchito ya dopamine mu PG. Mosiyana ndi zomwe zapezedwa pakudalira kwa cocaine pomwe kusiyana pakati pa gulu kunawonedwa [11C] raclopride-binding in striatum, milingo yofanana idawonedwa mu PG ndikufanizira maphunziro ndi magulu awiri ofufuza (Linnet et al., 2010, 2011; Clark et al., 2012). Mofananamo, palibe kusiyana pakati pa PG ndi zoyerekeza zomwe zinaonedwa zikugwiritsa ntchito [11C] raclopride kapena D3-yosankha agonist-radioligand [11C] - (+) - propyl-hexahydro-naphtho-oxazin (PHNO) (Boileau et al., 2013). Komabe, mmaphunzirowa, maubwenzi omwe amakhala okhudzana ndi kusokonekera kapena kusokonekera kwazomwe zimachitika, zosankha zoyipa kapena zovuta zamagetsi zidanenedwa, ndikuwonetsa kuti ntchito ya dopamine ikhoza kufanana ndi zina za PG (Potenza ndi Brody, 2013). Zotsatira izi zikugwirizana ndi lingaliro loti PG imayimira zovuta komanso kuti kuzindikira kusiyanasiyana koyenera kwa anthu kapena magulu ang'onoang'ono kungathandize kupititsa patsogolo chitukuko cha chithandizo chamankhwala kapena kutsata koyenera kwa njira zochizira.

Mgwirizano wodziwika bwino pakati pa dopamine ndi PG ulipo mu matenda a Parkinson (PD) (Leeman ndi Potenza, 2011). Makamaka, dopamine agonists (mwachitsanzo, pramipexole, ropinirole) adalumikizidwa ndi PG komanso machitidwe owononga kwambiri kapena ovuta m'magawo ena (okhudzana ndi kugonana, kudya, ndi kugula) mwa anthu omwe ali ndi PD (Weintraub et al., 2010). Kuphatikiza apo, levodopa dosing imagwirizananso ndi izi mu PD (Weintraub et al., 2010). Komabe, zinthu zomwe zimawoneka kuti sizigwirizana ndi dopamine (mwachitsanzo, msinkhu wa PD kumayambira, malo aukwati ndi malo omwe ali nawo) zalumikizananso ndi izi mu PD (Voon et al., 2006; Weintraub et al., 2006, 2010; Potenza et al., 2007), ndikuwonetsa zovuta zamtunduwu. Komabe, mu kafukufuku wogwiritsa ntchito [11C] raclopride, anthu omwe ali ndi PD ndi PG poyerekeza ndi omwe ali ndi PD yekhayo omwe akuwonetsedwa mu ventral (koma osati dorsal) striatum idatsika ngati D2-yomangiriza pamaziko oyambira ndi okulirapo [11C] raclopride kusamutsidwa pa njuga / ntchito yopanga chisankho (ndikuwonetsa kutulutsidwa kwakukulu kwa dopamine mu gulu la PG panthawi yogwira ntchito) (Steeves et al., 2009). Izi zakumbukira zomwe zikusonyeza kuti anthu omwe achoka ndi levodopa akhazikitsidwa chifukwa cha [11C] raclopride mu ventral koma osati dorsal striatum mu PD maphunziro omwe amadzichitira okha omwe amachititsa ma dopamine-m'malo olimbitsa thupi mopitirira muyeso (poyerekeza ndi omwe satero) (Evans et al., 2006). Zotsatira zina zawoneka pothandizana ndi zizolowezi za PD (motsutsana ndi omwe ali ndi PD yekha) kuchepetsedwa chizindikiritso mu ventral striatum pamsewu komanso panthawi yangozi (Rao et al., 2010), funso limabuka kuti dopamine ingafanane ndi njirazi mu PD. Mafunso omwewa alipo pokhudzana ndi zovuta zomwe zimapangitsa kuti pakhale ma PG osagwirizana ndi PD PG pamaganizidwe osagwirizana ndi ligand panthawi yamasewera a juga (Reuter et al., 2005) ndikukonzanso mphoto yazandalama (Balodis et al., 2012a; Choi et al., 2012). Ngakhale maphunziro angapo apeza kuti gawo la ndalama likuyendetsedwa bwino panthawi yolandila ndalama (makamaka panthawi yogwira ntchito ya Monetary Incentive Delay) pamavuto ambiri osokoneza bongo [mwachitsanzo, kugwiritsa ntchito mowa (Wrase et al., 2007; Beck et al., 2009) ndi kugwiritsa ntchito fodya (Peters et al., 2011) zovuta] ndi mikhalidwe ina yodziwika ndi kuwonongeka kwakanthawi kovutitsa [mwachitsanzo, vuto la kudya kwambiri (Balodis et al., 2013, muzolengeza)], maphunziro ena apeza kuchulukitsa kopitilira muyeso panthawi yogulitsa mphotho mwa anthu omwe ali ndi PG komanso omwe ali ndi ziwonetsero zina (Hommer et al., 2011; van Holst et al., 2012a), ndikuwonjezeranso mafunso okhudzana ndi momwe ntchito ya striatal imathandizira ndendende ndi PG komanso zowonjezera komanso momwe dopamine ingatengere nawo njirazi (Balodis et al., 2012b; Leyton ndi Vezina, 2012; van Holst et al., 2012b).

Ngakhale zambiri zokhudzana ndi radioligand zomwe zafotokozedwa pamwambapa zimafufuza ntchito ya D2 / D3 receptor, zina dopamine receptors zikuwonetsetsa ku PG. Mwachitsanzo, pamakina ogwiritsa ntchito makina ojambulira, D2-like receptor agonist quinpirole idakulitsa chiyembekezo cholakwika cha mphothozo pakayesedwe kopita, ndipo izi zidakwaniritsidwa ndi D4 yosankha (koma osati D3 kapena D2) dopamine receptor antagonist (Cocker et al., 2013). Zotsatira zoyambirira izi zimagwirizana ndi maphunziro a anthu omwe amalimbikitsa gawo la D4 dopamine receptor mu machitidwe a juga. Mwachitsanzo, kusiyanasiyana kwa gene coding kwa D4 dopamine recopor kwalumikizidwa ndi mayankho osiyanasiyana pakuwonjezeka kwokhudzana ndi levodopa pamakhalidwe achita njuga (Eisenegger et al., 2010). Zotsatirazi zimakwaniritsa zolemba zazikulu zomwe zimagwirizanitsa D4 dopamine receptor ndi zovuta zokhudzana ndi kukhudzidwa ndi kusokonezeka ngati chidwi-deficit / hyperactivity disorder, ngakhale zili zosagwirizana (Ebstein et al., 1996; Gelernter et al., 1997; DiMaio et al., 2003). Monga preclinical (Fairbanks et al., 2012) komanso umunthu (Sheese et al., 2012) deta ikuwonetsa kuyanjana kwa gene ndi chilengedwe komwe kumakhudzanso jini yomwe imalembera D4 dopamine receptor ndi mbali zamakhalidwe osalamulirika kapena olamulidwa bwino, kafukufuku wowonjezerapo amayenera kuyang'ana gawo la D4 dopamine receptor ku PG, makamaka mu maphunziro ogwiritsa ntchito zowunikira mosamala za chilengedwe ndi majini zinthu. Ngakhale ma D4 angapo posankha / makina osankhira agonist (mwachitsanzo, PD-168,077 ndi CP-226,269) adagwiritsidwa ntchito mu maphunziro oyamba kuti aphunzire ma D4 receptors, kafukufuku owonjezera amafunikira kuti aphunzire ma D4 dopamine receptors momwe angakwaniritsire kudzera positron-emission- maphunziro a tomography - izi zikuyimira mzere wofunikira kafukufuku wamtsogolo (Bernaert and Tirelli, 2003; Tarazi et al., 2004; Basso et al., 2005). Kuphatikiza apo, monga D1 dopamine receptor yayikiridwa pazowonjezera monga kudalira kwa cocaine (Martinez et al., 2009), udindo wa D1 dopaminergic system mu PG warriers kufufuza.

Zomwe zapezeka pamwambapa zikuwonetsa kuti momwe dopaminergic ntchito ingathandizire PG ndi zosokoneza zina pakadali pano poyambira kumvetsetsa. Zomwe zilipo pakadali pano zikuwonetsa kuti kusinthasintha kwa ntchito mu dopamine kumatha kubisa kusiyana pakati pa anthu a PG ndi omwe si a PG, mwatsatanetsatane kusiyana kwakukulu pakati pa gulu mpaka pano komwe kumawonedwa pagulu lomwe lili ndi dopaminergic pathology (PD). Makhalidwe ake (mwachitsanzo, kunyinyirika, kupanga zisankho ndi njira zokhudzana ndi juga) zolumikizidwa ndi ntchito ya dopamine mu PG ndi maphunziro omwe si a PG amafunikanso kuwunikira kuchokera pakuwona kwachipatala ndikuwonetsa kuti izi zitha kuyimira zofunikira zachipatala zomwe zimalumikizana kwambiri ndi kwachilengedwe ntchito [yokweza kuthekera kwakuti akhoza kukhala othandiza makamaka pakulimbana ndi mankhwala (Berlin et al., 2013)]. Kuphatikiza apo, endophenotypes ena otheka monga kukakamiza (Fineberg et al., 2010, muzolengeza) kuwunikira kolingana ndi kulumikizana kwawo koyambira pazotsatira za chithandizo cha PG (Grant et al., 2010). Kuphatikiza apo, machitidwe omwe angapangitse dopamine kugwira ntchito amathandizanso kuganiziridwanso pakukula kwa mankhwala. Mwachitsanzo, pamayeso azachipatala osasinthika, othandizira opioid ngati nalmefene ndi naltrexone adapezeka kuti apamwamba kuposa placebo pochiza PG (Grant et al., 2006, 2008b), makamaka pakati pa anthu omwe ali ndi chidwi chofuna kutchova juga kapena mbiri yakale ya anthu omwe amamwa mowa (Grant et al., 2008a). Mofananamo, machitidwe a glutamatergic amafunikira kuganizira pankhaniyi (Kalivas ndi Volkow, 2005), ndi deta yoyambirira yolumikiza neutraceutical n-acetyl cysteine ​​ndi zotsatira zabwino zamankhwala ku PG (Grant et al., 2007). Monga dissecting dopamine dongosolo ikupereka chidziwitso mu PG, njira zofananira ziyenera kugwiritsidwa ntchito pofufuza ntchito ya serotonin mu PG (Potenza et al., 2013), zoperekedwa makamaka zosagwirizana ndi mankhwala a serotonergic pochiza PG (Bullock and Potenza, 2012). Njira yofufuzira matenda a neurobiology ndi zamankhwala za PG ziyenera kuthandizira njira zopewera komanso zochizira PG.

Kulankhulidwa

Dr. Marc N. Potenza alibe mikangano pazachuma pazokhudza zomwe zalembedwazi ndipo walandila thandizo lazachuma kapena chipukuta misozi zotsatirazi: Dr. Marc N. Potenza adafunsira ndikulangiza Boehringer Ingelheim, Ironwood, ndi Lundbeck; adafunsira ndipo ali ndi zokonda zachuma ku Somaxon; walandila thandizo lofufuza kuchokera ku Mohegan Sun Casino, National Center for Responsible Gaming, Forest Laboratories, Ortho-McNeil, Oy-Control / Biotie, Psyadon, Glaxo-SmithKline, National Institutes of Health and Veteran's Administration; watenga nawo mbali pakufufuza, kutumiza makalata kapena kufunsa patelefoni zokhudzana ndi mankhwala osokoneza bongo, zovuta zowongolera kapena zina zamankhwala; yafunsira maofesi azamalamulo ndi ofesi ya federoli pamilandu yokhudzana ndi zovuta zowongolera; imapereka chithandizo chamankhwala ku Connecticut department of Mental Health and Addiction Services Vuto la Kutchova Njuga; yachita kuwunika kwa mabungwe a National Institutes of Health ndi mabungwe ena; ali ndi magawo azosinthidwa ndi alendo; wapereka zokambirana pamaphunziro akulu, zochitika za CME ndi malo ena azachipatala kapena asayansi; ndipo wapanga mabuku kapena mitu yamabuku ofalitsa amalemba azaumoyo.

Kuvomereza

Kafukufukuyu adathandizidwa ndi National Institute on the Abuse Abuse (NIDA) P20 DA027844, National Institute on Alcohol Abuse and Alcoholism RL1 AA017539, Connecticut department of Mental Health and Addiction Services, Connecticut Mental Health Center, ndi National Center for Responsible Gaming Center of Excellence mu Kutchova Njuga ku Yale University.

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