A John D. Salamone, a Mercè Correa
Neuron - 8 Novembala 2012 (Vol. 76, Nkhani 3, mas. 470-485)
Chidule
Nucleus accumbens dopamine imadziwika kuti imathandizira njira zotsitsimutsa, ndipo kuwonongeka kwa masolimbic dopamine kungapangitse zizindikiro zowonongeka za kuvutika maganizo ndi mavuto ena, komanso zida za mankhwala osokoneza bongo. Ngakhale kuti zakhala zachizolowezi kuti dopamine neurons ndi "mphotho" ya neurons, izi ndizopangidwira, ndipo ndikofunikira kusiyanitsa pakati pa zifukwa zomwe zimakhudzidwa kwambiri ndi dopaminergic manipulations. Mwachitsanzo, kugwilitsila nchito dopamine sikukambilana ndi cakudya cacikulu ca chakudya kapena chilakolako, koma kumaphatikizapo njira zokhutiritsa ndi zosokoneza, kuphatikizapo kuyesayesa khalidwe, kuyesayesa, kuyesayesa, kuyendetsa ntchito, mapulogalamu a Pavlovia, ndi maphunziro ophunzirira. M'mbuyomuyi, timakambirana ntchito zovuta za dopamine muzochita zokhudzana ndi chikhalidwe.
Mfundo yaikulu
Nucleus accumbens dopamine (DA) yakhala ikukhudzidwa ndi ntchito zosiyanasiyana zomwe zimakhudzana ndi zifukwa. Komabe zenizeni zokhudzana ndi izi ndi zovuta ndipo nthawi zina zingakhale zovuta kuti zisokoneze. Chofunika kwambiri potanthauzira zotsatirazi ndizokhoza kusiyanitsa pakati pa zinthu zosiyanasiyana zolimbikitsana zomwe zimakhudzidwa ndi dopaminergic manipulations. Ngakhale kuti ventral tegmental neurons kawirikawiri imatchedwa "mphotho" ya neurons ndi mesolimbic DA yotchedwa "mphotho" kachitidwe kameneka, izi sizinagwirizane ndi zomwe zakhala zikuchitika. Tanthauzo la sayansi la "mphotho" silimveka, ndipo chiyanjano chake ndi malingaliro monga kulimbikitsa ndi kutsitsimodzinso nthawi zambiri amalembedwa. Maphunziro a zachipatala ndi a DA omwe amatsitsimula akuwonetsa kuti DA yowoneka kuti ndi yofunika kwambiri pazinthu zina zolimbikitsa, koma zazing'ono kapena zopanda phindu kwa ena. Zina mwa zomwe zimagwira ntchito zozizwitsa za DAlimbic DA zimayimira mbali zomwe zimagwirizanitsa ndi zida zoyendetsa magalimoto, zomwe zimagwirizana ndi kugwirizanitsidwa bwino kwa phokoso lomwe limagwiritsidwa ntchito pazinthu zowonongeka. Kuwonjezera apo, ngakhale mabuku ochuluka omwe akugwirizanitsa DAlimbic DA kuzinthu zotsutsa zolinga ndi kuphunzira, mabuku omwe amabwerera mmbuyo zaka makumi angapo (mwachitsanzo, Salamone et al., 1994), chizoloŵezi chokhazikitsidwa chakhala chotsindika kugwirizana kwa dopaminergic mu mphotho, chisangalalo, chizolowezi, ndi maphunziro okhudzana ndi mphoto, popanda kulingalira mochepa za kugawana kwa DAlimbic DA mu njira zowonongeka. Phunziroli lidzakambilana za kugwirizanitsidwa kwa DAlimbic DA muzosiyana zolimbikitsa, ndikugogomezera zowonongeka zomwe zimalepheretsa kulumikizana kwa DA, makamaka mu nkhono accumbens.
Mesolimbic DA ndi Chilimbikitso: Kusintha Kwachilengedwe
Ngati palibenso china, anthu amangofotokozera nkhani; Kupatula apo, ndife mbadwa za anthu omwe adakhala mozungulira moto usiku tikumasulidwa ndi nthano zowoneka bwino, nthano, komanso mbiri zamkamwa. Kukumbukira kwaumunthu kumakhala kotheka kwambiri ngati zowona kapena zochitika zosawerengeka zitha kulumikizidwa mozama mu nkhani yogwirizana. Asayansi ndiosiyana. Maphunziro ogwira ntchito kuyunivesite, kapena seminare yasayansi, nthawi zambiri amatchedwa "nkhani yabwino." Ndi mmenenso zilili ndi malingaliro asayansi. Ubongo wathu ukuwoneka kuti umalakalaka dongosolo ndi mgwirizano wamaganizidwe operekedwa ndi lingaliro losavuta komanso lomveka bwino la sayansi, lochirikizidwa ndi umboni wokwanira kuti likhale lomveka. Vuto ndilo-bwanji ngati nkhani ikugwirizana chifukwa cha kutanthauzira mopitirira muyeso zomwe zapezedwa, ndikunyalanyaza zina? Pang'ono ndi pang'ono, zidutswa zosanjana zomwe sizikukwanira zimapitiliza kuwononga zonse, ndikupangitsa kuti nkhani yonse ikhale yosakwanira.
Wina anganene kuti chisinthiko chotere chachitika pokhudzana ndi lingaliro la DA la "mphotho." "Nkhani" itha kupangidwa, yomwe ipitirire motere: Chizindikiro chachikulu cha kukhumudwa ndi anhedonia, ndipo popeza DA ndi "wopereka mphotho" yemwe amalumikizana ndi machitidwe am'mimba, kukhumudwa kumachitika chifukwa chochepetsa chisangalalo chokhazikitsidwa ndi DA . Chimodzimodzinso, akuti kugwiritsa ntchito mankhwala osokoneza bongo kumadalira momwe munthu amasangalalira ndi mankhwala osokoneza bongo omwe amalanda "mphotho" yaubongo, yomwe imalumikizidwa ndi kufalitsa kwa DA ndikusintha kuti ipereke chisangalalo chopangidwa ndi zinthu zachilengedwe monga chakudya. Izi zitha kunenanso kuti kuletsa ma receptors a DA atha kupereka chithandizo chothana ndi vuto losuta. Pomaliza, munthu atha kuperekanso "nkhani" yomangidwa poganiza kuti ma DA neurons amangoyankha zokondweretsa monga chakudya komanso kuti ntchitoyi imathandizira kuthana ndi izi, zomwe zimapangitsa kuti anthu azidya chakudya. Nthano zotere si "anthu a udzu" omwe adapangidwira ndendende. Koma mwatsoka, ngakhale adatchuka, palibe malingaliro awa omwe amathandizidwa kwathunthu ndikuwunika mosamala mabukuwo.
Kuti titenge chitsanzo cha dopaminergic kutenga nawo maganizo, wina akhoza kuyamba kumangomanga lingaliro limeneli pofotokoza kuti "anhedonia" mu kuvutika maganizo nthawi zambiri amatanthauziridwa kapena kusokonezedwa ndi odwala (Treadway ndi Zald, 2011). Kafukufuku wambiri amasonyeza kuti anthu ovutika maganizo amakhala ndi chizoloŵezi chodzimana chokha chokhudzana ndi zosangalatsa zokondweretsa komanso kuti, pambali pa mavuto alionse ndi zosangalatsa, anthu ovutika maganizo amawoneka kuti ali ndi zofooka pa kuyendetsa khalidwe, kupempha mphoto, ndi khama (Treadway ndi Zald, 2011). Inde, anthu ambiri opsinjika maganizo amavutika ndi magulu olumala omwe amachititsa kuti anthu azivutika maganizo, zomwe zimaphatikizapo kuchepetsa vutoli, matenda a anergia, ndi kutopa.Demyttenaere et al., 2005; Salamone et al., 2006), ndipo umboni wochuluka umakhudza DA mu zizindikiro izi (Salamone et al., 2006, Salamone et al., 2007). Zolembazi, kuphatikizapo mabuku omwe akusonyeza kuti palibe zolemba zosavuta pakati pa ntchito ya DA ndi chiwonetsero cha hedonic (mwachitsanzo, Smith et al., 2011) ndipo maphunzirowa akugwirizanitsa DA ndi kuwongolera khalidwe ndi kuyesetsa (Salamone et al., 2007; onani zokambirana pansipa), atsogolereni kuti kugwirizana kwa dopaminergic kuvutika maganizo kukuwoneka kovuta kwambiri kusiyana ndi nkhani yosavuta yomwe ingalole.
Mofananamo, zikuonekeratu kuti kafukufuku wochuluka wokhudzana ndi mankhwala osokoneza bongo ndi chizoloŵezi cha mankhwala osokoneza bongo sagwirizana ndi miyambo ya DA yomwe imaganizira za mphotho. Kafukufuku wambiri wasonyeza kuti kutsekedwa kwa DA zopuma kapena kuletsedwa kwa DA kaphatikizidwe kawiri kawiri sikungosinthasintha zachipongwe kapena "mkulu"Gawin, 1986; Brauer ndi De Wit, 1997; Haney et al., 2001; Nann-Vernotica et al., 2001; Wachtel et al., 2002; Leyton et al., 2005; Venugopalan et al., 2011). Kafukufuku waposachedwapa amadziwika kusiyana kwa makhalidwe omwe amasonyezedwa ndi makoswe panthawi ya Pavlovian approach, yomwe imakhudzana ndi kuyendetsa mankhwala osokoneza bongo. Makoswe omwe amasonyeza kuchitidwa kwakukulu kwa zizindikiro zowonongeka (owona chizindikiro) amasonyeza njira zosiyana za kusintha kwa dopaminergic kuti azindikire poyerekeza ndi zinyama zomwe zimamvetsera kwambiri kwa rein reincer (okonda zolinga; Flagel et al., 2007). Chochititsa chidwi n'chakuti, makoswe omwe amasonyeza kuti wamkulu wa Pavlovian amakhala pafupi ndi zovuta zowonongeka ndipo amasonyeza kuti alimbikitsana kwambiri ndi mankhwala osokoneza bongo, amasonyezanso kuti akuwopa kwambiri chifukwa cha mantha omwe amachititsa mantha komanso vuto lalikulu la mantha (Morrow et al., 2011). Kafukufuku wowonjezereka watsutsana ndi malingaliro ena omwe akhalapo kwa nthawi yaitali ponena za njira zowonongeka zomwe zimayambitsa kusokoneza bongo, mosiyana ndi zomwe zimayambitsanso mankhwala osokoneza bongo. Zakhala zowonongeka kwambiri kuona kuledzera pogwiritsa ntchito njira zochiritsira matenda osokoneza bongo, zomwe zimagwiritsidwa ntchito pazinthu zowononga mankhwala, zomwe zingakhale zosiyana ndi zida zothandizira zida kapena zochitika zoyambirira zokhuza mankhwala osokoneza bongo (Kalivas, 2008; Belin et al., 2009). Maganizo awa omwe akukamba za nkhanza za mankhwala osokoneza bongo, komanso mankhwala omwe angakhalepo, athandizidwa kwambiri kuposa nkhani yapachiyambi yoperekedwa ndi DA kulingalira kwa "mphotho."
Pambuyo pazaka zambiri zafukufuku, ndi kupitiliza zochitika zongopeka, pakhala pali kukonzanso kwakukulu kwa chidziwitso cha DA. Umboni wochuluka umasonyeza kuti kusokonezeka kwa kuyambitsidwa kwa DNA kumawonekedwe kumayambira pambali zolimbikitsa komanso zosankha za hedonic ku chakudya choyenera (Berridge, 2007; Berridge ndi Kringelbach, 2008; Salamone et al., 2007). Zotsatira za makhalidwe monga kupita patsogolo kwa chiŵerengero cha mapulogalamu okhudzidwa ndi zozizwitsa, zomwe poyamba zinagwiritsidwa ntchito ngati zizindikiro za ntchito za "mphoto" kapena "hedonia" za DA, tsopano zikuganiziridwa kuti zikuwonetsa ndondomeko zokhuza khama, kulingalira kwa khama -kulipira kapena kutengera mwayi, ndi kupanga chisankho (Salamone, 2006; Hernandez et al., 2010). Mapepala angapo a posachedwapa a electrophysiology asonyeza kuwonetseratu kwa zidziwitso zomwe zimaganiziridwa kapena zodziwika kuti DA neurons ndizochita zowonongeka (Anstrom ndi Woodward, 2005; Brischoux et al., 2009; Matsumoto ndi Hikosaka, 2009; Bromberg-Martin et al., 2010; Schultz, 2010; Lammel et al., 2011). Ofufuza ambiri tsopano akutsindika kuchitika kwa masolimbic ndi nigrostriatal DA mu maphunziro othandizira kapena kupanga mapangidwe (Wanzeru, 2004; Yin et al., 2008; Belin et al., 2009), m'malo mwa hedonia pa se. Zomwe zachitikazi zakhala zikuthandizira kubwereza kwakukulu kwa nkhani ya dopaminergic kutenga nawo mbali pamalimbikitsa.
Njira Zotsitsimula: Mbiri Yakale ndi Chikhalidwe
Mawu otanthauzira amatanthauza kumanga komwe kumagwiritsidwa ntchito kwambiri m'maganizo, m'maganizo, ndi m'maganizo. Monga momwe ziliri ndi malingaliro ambiri a maganizo, kukambitsirana zolimbikitsa kunachokera ku filosofi. Pofotokoza zinthu zomwe zimayambitsa khalidwe, wophunzira wa ku Germany Schopenhauer, 1999 analongosola lingaliro la chikhumbo chokhudzana ndi momwe zamoyo ziyenera kukhalira ndi "mwayi wosankha, kulanda, ngakhale kufunafuna njira zokhutira." Chilimbikitso chinalichonso chofunika kwambiri chokhudzidwa panthawi yopititsa patsogolo maphunziro a maganizo. Akatswiri odziwa zamaganizo a sayansi, kuphatikizapo Wundt ndi James, anaphatikizapo zolimbikitsa monga zolemba m'mabuku awo. Neobehaviorists monga Hull ndi Spence kawirikawiri amagwiritsa ntchito mfundo zolimbikitsa monga chisonkhezero ndi galimoto. Achinyamata, 1961 malingaliro otanthauzira monga "ndondomeko yowutsa, kuchita zinthu zomwe zikuchitika, ndikusintha ndondomeko ya ntchito." Malingana ndi tanthauzo laposachedwapa, cholinga ndi "njira zomwe zimayambitsa zamoyo, kuyandikira ndi kupezeka kwa zovuta. "(Salamone, 1992). Kawirikawiri, malingaliro amakono amalingaliro amatanthauza njira zomwe zimathandiza kuti zamoyo zizilamulira malo awo akunja ndi amkati (Salamone, 2010).
Mwinamwake chinthu chofunikira kwambiri cholimbikitsana ndi chakuti chimapereka mwachidule ndi makonzedwe apangidwe ka zochitika zomwe zimaoneka (Salamone, 2010). Chikhalidwe chimayang'anitsitsa kapena kuchoka ku zovuta zina, komanso ntchito zomwe zimaphatikizapo kugwirizana ndi zovutazo. Zamoyo zimapempha kupeza zowonjezereka (ie, chakudya, madzi, kugonana) ndi kupewa ena (mwachitsanzo, ululu, zovuta), mwa njira zonse zokhudzidwa ndi zovuta. Komanso, khalidwe lolimbikitsana limapezeka pamagulu (Table 1). Gawo lotsiriza la khalidwe lolimbikitsa, lomwe likuwonetseratu kulumikizana mwachindunji ndi cholinga chotsitsimutsa, chimatchulidwa kuti chimangoyamba. Mawu oti "owonongeka" (Craig, 1918) sichikutanthauza "kugwiritsidwa ntchito," m'malo mwake kuti "kutsirizira," kutanthawuza kuti "kukwaniritsa" kapena "kutsirizitsa." Poona kuti zolimbikitsa zomwe zimakhalapo nthawi zambiri zimapezeka pamtunda kapena m'maganizo kuchokera ku zamoyo, Njira yokhayo yopezeramo zokondweretsa izi ndi kukhala ndi khalidwe lomwe limawabweretsa pafupi, kapena kumachititsa kuti zichitike. Chikhalidwe ichi cha khalidwe lolimbikitsidwa nthawi zambiri chimatchedwa "zokondweretsa," "kukonzekera," "kuthandizira," "kuyandikira," kapena "kufunafuna." Motero, kafukufuku nthawi zina amasiyanitsa pakati pa "kutenga" ndi "kufuna" za chilengedwe monga chakudya (mwachitsanzo, Foltin, 2001), kapena wa reinforcer mankhwala; Inde, mawu oti "chichitidwe chofuna mankhwala" akhala mchilankhulo chofala m'chinenero cha psychopharmacology. Monga momwe tafotokozera m'munsimu, izi zidawoneka bwino (mwachitsanzo, zotsutsana ndi zofuna zowonongeka kapena zofunira) ndizofunika kumvetsetsa zotsatira za dopaminergic manipulations chifukwa cha zochitika zachilengedwe monga chakudya.
Kuphatikiza pa "kutsogolera" mbali zolimbikitsa (mwachitsanzo, khalidwelo likuyang'ana kapena kuchoka ku zokopa), khalidwe lolimbikitsanso limanenedwanso kukhala "zokakamiza" mbali (Cofer ndi Appley, 1964; Salamone, 1988, Salamone, 2010; Parkinson et al., 2002; Table 1). Chifukwa chakuti zamoyo nthawi zambiri zimasiyanitsidwa ndi zokakamiza zokakamiza ndi mtunda wautali, kapena ndi zolepheretsa zosiyanasiyana kapena ndalama zowonongeka, kuchita zinthu zothandizira nthawi zambiri kumaphatikizapo ntchito (mwachitsanzo, kubwezera, kuthamanga, kuthamanga kwa levu). Nyama ziyenera kupereka ndalama zambiri kuti zikhale ndi zofuna zowonjezera, zomwe zikhoza kuzindikiritsidwa ndi khama lalikulu, mwachitsanzo, liwiro, kupitiriza, ndi kuchuluka kwa ntchito zogwira ntchito. Ngakhale kuti kuyesetsa kwa khamali nthawi zina kungakhale kochepa (mwachitsanzo, nyama yolanda nyama ikuwombera nyama), pansi pa zochitika zambiri ziyenera kukhala zotsimikizika kwa nthawi yaitali. Zolinga zokhudzana ndi khama zimakhala zogwirizana kwambiri, chifukwa chilengedwe chikhoza kudalira momwe thupi limagonjera nthawi-kapena ndalama zokhudzana ndi kuyankhidwa. Pazifukwa izi, kuyambitsa khalidwe kumaonedwa kuti ndi chinthu chofunikira kwambiri cholimbikitsa kwa zaka zambiri. Akatswiri a zamaganizo akhala akugwiritsira ntchito mfundo za galimoto komanso zolimbikitsa kuti agogomeze zotsatira zolimbikitsa zomwe zimachititsa kuti anthu azichita zinthu, monga kuthamanga mofulumira. Cofer ndi Appley, 1964 anandiuza kuti panali njira yokonzekera yosinthidwa yomwe ingasinthidwe ndi kukakamiza, komanso zomwe zimayambitsa kulimbikitsa khalidwe lachida. Chiwonetsero chosasinthika cha zochitika zoyambitsa zolimbikitsa monga chakudya chokhazikitsa chakudya chingapangitse ntchito zosiyanasiyana, kuphatikizapo kumwa, kutayika, ndi magudumu (Ma Robbins ndi Koob, 1980; Salamone, 1988). Akatswiri ambiri ofufuza aphunzira momwe ntchito ikufunira pa ntchito, zomwe zathandiza kuti pakhale maziko a zochitika zachuma (monga, Hursh et al., 1988). Akatswiri a Ethologists amagwiritsanso ntchito mfundo zofananamo. Nyama zoweta ziyenera kugwiritsa ntchito mphamvu kuti zipeze chakudya, madzi, kapena zodyetsa, komanso mfundo zabwino zogwiritsira ntchito ponena za momwe kuchuluka kwa khama kapena nthawi yomwe ikugwiritsidwa ntchito kuti zithe kupeza izi ndizofunikira kwambiri pa khalidwe labwino.
Pali kulingalira kwakanthawi pakati pamachitidwe oyendetsa magalimoto ndi zochitika zina zolimbikitsira. Mwachitsanzo, kusowa kwa chakudya kumatha kuthamangitsa kuthamanga kwazitsulo. Kodi izi zikuwonetsa mikhalidwe yolimbikitsa, yamagalimoto, kapena kuphatikiza kwina? Zochita za locomotor zikuwongoleredwa ndi ma neural system omwe amayendetsa kayendedwe. Komabe, zochitika zogwirira ntchito mu makoswe zimakhudzanso zovuta zomwe zimayambitsa monga zachilendo, kusowa kwa chakudya, kapena kuwonetsa kanthawi kochepa pellets zazakudya. Kuphatikiza apo, ngati chamoyo chimaperekedwa ndi zovuta zokhudzana ndi ntchito panthawi yogwiritsa ntchito chida, nthawi zambiri chimayankha vutoli mwa kuyesetsa kwambiri. Kuwonjezeka kwa ziwopsezo pamachitidwe ogwirira ntchito, mpaka kufika poti, zitha kupanga zovuta zakukwera pamitengo yoyankha. Kukumana ndi chopinga, monga chotchinga mumizere, kumatha kuyambitsa makoswe kuti aziwonjezera kuyesetsa kwawo ndikudumpha chopingacho. Kuphatikiza apo, kuwonetsa kwamphamvu kwa Pavlovian komwe kumalumikizidwa ndi chinthu choyambitsa monga chakudya chitha kupangitsa kuyandikira kapena kukulitsa zochitika zankhondo, zomwe zimadziwika kuti Pavlovian kusinthira chida (Colwill ndi Rescorla, 1988). Choncho, machitidwe a neural omwe amayendetsa magalimoto amaoneka ngati akugwiritsidwa ntchito poyang'ana machitidwe a neural omwe amatsogoleredwa kapena kusiya njira zina (Salamone, 2010). Inde, mawu akuti "motor control" ndi "zifukwa" sizikutanthawuza chinthu chimodzimodzi, ndipo wina angapeze mfundo za nonoverlap. Komabe, zikuonekeratu kuti palinso chiyanjano chachikulu (Salamone, 1992, Salamone, 2010). Malingaliro awa, ndizofunikira kulingalira kuti mawu a Chingerezi olimbikitsa ndi kayendetsedwe kawiri onse amachokera ku mawu achilatini wosasamala, kusuntha (ie, kuti ndi gawo lapitalo la wosasamala). Mosiyana ndi kusiyana pakati pa zotsutsana ndi chizoloŵezi choipa (kapena kufunafuna kutengera), kusiyana pakati pa zokakamiza ndi zovuta zomwe zimagwiritsidwa ntchito pogwiritsira ntchito kufotokozera zotsatira za dopaminergic manipulations (Table 1). Njira zosiyanasiyana zolimbikitsana ndizofunikira kwambiri pazinthu zomwe zikufotokoza za khalidwe la dopaminergic manipulations, komanso kuganizira ntchito yovuta ya DA neurons.
Mitundu ya Dissociative ya Mitengo ya Kufikira ndi Nucleus Accumbens DA Transmission
Poyesera kumvetsetsa mabukuwa pa ntchito yogwira ntchito ya accumbens DA, tiyenera kulingalira mfundo zingapo zomwe zili pamwambapa. Ku mbali imodzi, tifunika kuzindikira kuti njira zothandizira ena zimakhala zosasokonezeka kukhala zigawo zina, ndipo njira zomwe zimagwiritsidwa ntchito pophatikizapo kachilombo ka DA nthawi zina zimatha kugwirizanitsa zigawozi monga kugwiritsa ntchito dothi la diamondi, kusintha kwenikweni pamene ena asiya kusakhudzidwa (Salamone ndi Correa, 2002; Berridge ndi Robinson, 2003; Smith et al., 2011). Kumbali inayi, tiyeneranso kuzindikira kuti njira zolimbikitsira zimayenderana ndi njira zokhudzana ndi kutengeka, kuphunzira, ndi ntchito zina, ndikuti palibe mapu oyenera pakati pa machitidwe ndi machitidwe a neural. Chifukwa chake, zina mwazovuta zamankhwala osokoneza bongo a dopaminergic zitha kumveka bwino pokhudzana ndi zomwe zimachitika pazomwe zimapangitsa, kuyendetsa galimoto kapena kuphunzira, pomwe zovuta zina zitha kukhala zowonekera kwambiri pakakhala kulumikizana pakati pa ntchitoyi. Pomaliza, wina akuyeneranso kuganizira kuti ndizokayikitsa kwambiri kuti kudzikundikira DA kumangogwira ntchito imodzi yokha; ndizovuta kutenga makina ovuta ngati ubongo wa mammalia womwe ukugwira ntchito mophweka chonchi. Chifukwa chake, kusungunula DA mwina kumagwira ntchito zingapo, ndipo njira iliyonse yamakhalidwe kapena njira ya neuroscience itha kukhala yoyenererana ndi ntchito zina, koma zosayenera ena. Poganizira izi, zingakhale zovuta kuti mupange mawonekedwe ogwirizana.
Kugwiritsa ntchito ubongo kungasinthe kagwiridwe kake kachitidwe kachitidwe mwachindunji. Mfundo imeneyi yakhala yothandiza kwambiri pa chidziwitso cha ubongo ndipo yachititsa kuti zikhale zofunikira kwambiri pazinthu zosiyana siyana zazinthu zosiyana siyana (ie, kufotokoza motsutsana ndi procedural memory, kugwira ntchito motsatira ndondomeko ya chikumbukiro, machitidwe a hippocampal-odalira - osakwanira). Mosiyana ndi zimenezi, chizoloŵezi cha mabuku omwe akukambirana za ntchito za accumubs DA chimalimbikitsa kugwiritsa ntchito zida zowonongeka monga "mphotho," kuti afotokoze mwachidule zochita za mankhwala kapena mankhwala ena. Inde, mawu akuti "mphotho" adatsutsidwa mwatsatanetsatane kwina (Cannon ndi Bseikri, 2004; Salamone, 2006; Yin et al., 2008; Salamone et al., 2012). Ngakhale kuti malipiro a mphotho ali ndi tanthawuzo lofanana ndi liwu loti "kulimbitsa mtima," palibe tanthawuzo losasinthika la sayansi la "mphotho" pamene limagwiritsidwa ntchito pofotokoza njira yokhala ndi ubongo; Ena amagwiritsa ntchito mawuwa kuti "kulimbikitsa," pamene ena amagwiritsa ntchito kutanthauzira kuti "choyambitsa" kapena "chilakolako," kapena ngati chiwonetsero chophatikizapo "zosangalatsa" kapena "hedonia" (chifukwa cha mbiri yakale ya "anhedonia hypothesis" , "Onani Wanzeru, 2008). Nthawi zambiri, mawu oti "mphotho" amawoneka kuti amagwiritsidwa ntchito ngati mawu omwe amasonyeza za zovuta, kuphunzira, ndi kukhudzidwa, kuphatikizapo zikhalidwe ndi zosavomerezeka; Kugwiritsiridwa ntchito uku ndiko kwakukulu kukhala kopanda phindu. Wina anganene kuti kugwiritsira ntchito mawu akuti "mphotho" ndizochititsa kuti anthu asokonezeke kwambiri. Ngakhale nkhani imodzi ingagwiritse ntchito mphotho kuti ikhale yosangalatsa, wina angagwiritse ntchito liwu kuti liwone za kuwonjezera maphunziro koma osati zosangalatsa, ndipo gawo lachitatu likutanthauza zofuna zokhutiritsa mwanjira yeniyeni. Izi ndizitanthawuzo zitatu zosiyana kwambiri za mawu, zomwe zimapangitsa kuti kukambirana kwa ntchito za mesolimbic DA zisakwaniritsidwe. Kuwonjezera apo, kutchula DA zowoneka ngati "mphotho" kumatanthauzira kuchitapo kanthu mwachangu. Mwina vuto lalikulu ndilo "mphotho" ndilokuti limatulutsa lingaliro la chisangalalo kapena hedonia mwa owerenga ambiri, ngakhale izi sizikukhudzidwa ndi wolemba.
Kuwongolera kwaposachedwapa kukugogomezedwa ndi kukhudzidwa kwa accum accums DA mu zifukwa zolimbikitsa zowonjezera zachilengedwe monga chakudya. Mwachidziwikire, palibe kukayikira kuti kudzikundikira DA kumaphatikizapo mbali zina za zifukwa za chakudya; koma ndi mbali ziti? Monga momwe tionere m'munsimu, zotsatira za kusokonezeka ndi kulumikizidwa kwa DA ndizomwe zimasankha kapena kusokoneza chilengedwe, zimawononga zinthu zina zomwe zimakhudza anthu ena. Zotsala za gawo lino zidzakumbukira zotsatira za zowonongeka zomwe mankhwala ophera dopaminergic kapena othandizira pa matendawa amagwiritsidwa ntchito kusintha khalidwe labwino.
Ngakhale kuti kawirikawiri amadziŵa kuti DA yotsekemera imatha kuchepetsa kudya, zotsatirazi zimagwirizanitsidwa kwambiri ndi kuponderezedwa kapena kutsutsana kwa DA m'magetsi kapena malo ogwiritsira ntchito magalimoto omwe amatha kutsogoloza kapena kuthamanga, koma osati nucleus accumbens (Dunnett ndi Iversen, 1982; Salamone et al., 1993). Kafukufuku wamakono optogenetics anasonyeza kuti kulimbikitsana kwa GABA mkodzo, zomwe zimabweretsa chiletso cha DA neurons, zomwe zimaletsa kuthetsa chakudya (van Zessen et al., 2012). Komabe, sizikuwonekeratu ngati zotsatirazi zikuchitika chifukwa cha zochita za dopaminergic, kapena ngati zimadalira zotsatira zowononga zomwe zimapangidwanso ndi kugwiritsidwa ntchito (Tan et al., 2012). Ndipotu, kuwonjezereka kwa kudetsedwa kwa DA ndi kutsutsana kwakhala kukusonyezedwa mobwerezabwereza kuti sichidetsa kwambiri kudya chakudya (Ungerstedt, 1971; Koob et al., 1978; Salamone et al., 1993; Baldo et al., 2002; Baldo ndi Kelley, 2007). Malingana ndi zomwe apeza kuti majekeseni a D1 kapena D2 amtundu wa banja ku accumbens pachimake kapena chipolopolo chosokonezeka motengera ntchito, koma sanalepheretse kudya, Baldo et al., 2002 adanena kuti kudzimphana ndi chilakolako cha DA "sikunathetse cholinga chachikulu chodyera." Kugwiritsidwa ntchito kwa DA kunaperewera kuchepetsa chakudya chokwanira kapena kudyetsa chakudya, ndipo sikunapangitse kuti zakudya zisawonongeke,Salamone et al., 1993). Kuonjezera apo, zotsatira za otsutsana ndi DA kapena kuwonetsa madandaulo a DA pazinthu zolimbitsa chakudya sizikufanana ndi zotsatira za mankhwala osokoneza bongo (Salamone et al., 2002; Sink et al., 2008), kapena chiwerengero cha reinforcer choperekedwa ndi prefeeding (Salamone et al., 1991; Aberman ndi Salamone, 1999; Pardo et al., 2012). Lex ndi Hauber, 2010 adawonetsa kuti makoswe omwe adakalipidwa ndi DA omwe anali ndi vutoli anali ozindikira kufunika kwa kulimbikitsa chakudya pa ntchito yovuta. Komanso, Wassum et al., 2011 adawonetsa kuti mdani wa DA flupenthixol sanakhudze mgwirizano wa chakudya cha mphotho kapena kuwonjezeka kwa malipiro okhudzidwa chifukwa cha kukakamizika kwapakati pazimene zimapangitsa kuti phindu la chakudya liwonjezeke.
Umboni wochuluka umasonyezanso kuti nucleus accumbens DA sizimagwirizana mwachindunji ndi reactivity kwa chakudya. Ntchito yaikulu kuchokera ku Berridge ndi ogwira nawo ntchito yasonyeza kuti kayendetsedwe ka kayendedwe kotsutsa a DA, komanso kuwonongeka kwa DA m'thupi lonse kapena nucleus accumbens, sichimveka bwino kugwiritsira ntchito kukoma mtima kwa chakudya, chomwe ndi chiyeso chovomerezeka cha hedonic reactivity to solutions solutions (Berridge ndi Robinson, 1998, Berridge ndi Robinson, 2003; Berridge, 2007). Komanso, kugogoda kwa DA wotumiza (Peciña et al., 2003), komanso ma microinjections a amphetamine mu ma nucleus accumbens (Smith et al., 2011), zomwe zonse zimakweza DA extracellular, sizinapangitse kukondweretsa kukoma reactivity kwa sucrose. Sederholm et al., 2002 adafotokoza kuti D2 receptors mu nucleus accumbens shell amachititsa chidwi kwambiri reactivity, ndipo ubongo D2 kulandira chotsitsimula analetsa sucrose kumwa, koma ngakhale anthu of receptors ankatsutsana pa hedonic kukoma kukoma.
Ngati ma nyukiliya amadziphatika ndi DA osagwirizana ndi chidwi chodyera pa se, kapena mayankho a hedonic omwe amachititsa chakudya, ndiye kuti akutenga nawo gawo lotani pakulimbikitsa chakudya? Pali mgwirizano wambiri womwe umapangitsa kuwonongeka kwa DA kapena kutsutsana kumasiya mbali zoyambira za hedonia, njala, kapena chakudya choyambirira, koma zimakhudzanso machitidwe azinthu zofunikira (kutanthauza kufunafuna chakudya) (Gulu 1; Chithunzi 1) . Ofufuzawo akuti nucleus accumbens DA ndiyofunikira kwambiri pakukhazikitsa machitidwe (Koob et al., 1978; Ma Robbins ndi Koob, 1980; Salamone, 1988, Salamone, 1992; Salamone et al., 1991, Salamone et al., 2005, Salamone et al., 2007; Calaminus ndi Hauber, 2007; Lex ndi Hauber, 2010), kuyesayesa mwakhama nthawi yamaganizo (Salamone et al., 1994, Salamone et al., 2007, Salamone et al., 2012; Mai et al., 2012), Pavlovian kupititsa patsogolo (Parkinson et al., 2002; Everitt ndi Robbins, 2005; Lex ndi Hauber, 2008), njira yochepetsera njira (Nicola, 2010), kugwiritsa ntchito mphamvu ndi mphamvu (Salamone, 1987; Beeler et al., 2012), ndikugwiritsa ntchito mphoto kuphunzira (Beeler et al., 2010). Kugwirizanitsa ziphuphu za DA ndi kutsutsana kumachepetsa ntchito zodzikongoletsera komanso zosangalatsa zomwe zimapangitsa anthu kupanga ntchito komanso kulera, komanso zochitika zolimbikitsa (Koob et al., 1978; Abale ndi al., 1993; Baldo et al., 2002). Zochitika monga kumwa kwambiri, kuyendetsa magudumu, kapena zoyendetsa ndege zomwe zimachitika chifukwa chakuwonekera kwakanthawi kwa zakudya zazinyama zomwe zimadya chakudya zimachepetsedwa ndikuchepetsa ma DA (Ma Robbins ndi Koob, 1980; McCullough ndi Salamone, 1992). Kuonjezera apo, kuchepa kwa madokotala a DA, komanso kuphatikizapo kutsutsana kwa DA kapena kuchepa, kuchepetsa kuchitapo kanthu kwa zakudya zokhudzana ndi ntchito zina ngakhale kuti chakudya chokhala ndi chakudya chimasungidwa pansi pazimenezo (Salamone et al., 1991, Salamone et al., 2002; Ikemoto ndi Panksepp, 1996; Koch et al., 2000). Zotsatira za kusungunuka kwapadera kwa DA pazinthu zowonjezera chakudya zimasiyanasiyana kwambiri malinga ndi ntchito zofunika kapena nthawi yowonjezera. Ngati zotsatira zowonongeka kwa DA zokhudzana ndi kuchepa kwa njala, ndiye kuti wina angayembekezere kuti ndandanda ya 1 (FR1) yomwe iyenera kukhala yofunika kwambiri ikhale yovuta kwambiri. Komabe, ndondomekoyi ndi yosasamala za zotsatira za kusintha kwa DA mu accumcums (Aberman ndi Salamone, 1999; Salamone et al., 2007; Nicola, 2010). Chimodzi mwa zifukwa zovuta zomwe zimapereka mphamvu zokhudzana ndi zotsatira zowonongeka kwa DA pazinthu zowonjezera chakudya ndi kukula kwa chiŵerengero chofunikira (mwachitsanzo, chiwerengero cha makina oyendetsa nkhumba amafunikanso kuwonjezera; Aberman ndi Salamone, 1999; Mingote et al., 2005). Kuphatikiza apo, kutsekedwa kwa ma accumbens DA receptors kumalepheretsa magwiridwe antchito amachitidwe chifukwa chofotokozera ((Wakabayashi et al., 2004; Nicola, 2010).
Kukhoza kwa antchito a DA kapena kubweretsa mavuto a DA kuti asokoneze pakati pa zakudya ndi zakudya zothandizira chakudya, kapena pakati pa ntchito zosiyanasiyana, sizomwe zimakhala zochepa kapena zotsatira zapiphenomenal. M'malo mwake, zikuwonetsa kuti pansi pa mikhalidwe yomwe khalidwe lothandizira chakudya likhoza kusokonezedwa, mbali zofunikira zokhutira chakudya zilibe zoyenera. Ofufuza ambiri omwe alemba za makhalidwe ofunika kwambiri a kulimbitsa mtima adatsimikiza kuti kukakamiza anthu kukhala olimbikitsana kumakhala kosavomerezeka, kapena kuyesetsa njira, zolinga zolingalira, kapena khalidwe lachiwonongeko, kapena kupanga chiwopsezo chokwanira, ndi kuti zotsatirazi ndizofunikira kwambiri polimbikitsa (Dickinson ndi Balleine, 1994; Salamone ndi Correa, 2002; Salamone et al., 2012). Monga tafotokozera mu kusanthula kwa kayendetsedwe ka zachuma komwe kunaperekedwa ndi Kutha, 1993: "Kuyankha kumawerengedwa kuti ndi njira yachiwiri yodalira yomwe ndi yofunika chifukwa imathandizira kuwongolera kugwiritsidwa ntchito." Chifukwa chake, zotsatira zomwe zafotokozedwa pamwambapa zikuwonetsa kuti kuchepa kwa omwe amatsutsana ndi DA ndikuchulukitsa kuchepa kwa DA sikuwononga zofunikira pakulimbikitsa kapena kulimbitsa chakudya koma kumapangitsa kuti nyama zizindikire zina mwazofunikira pakuyankha, kuyankha molakwika pazoyenera, ndikuchepetsa chizolowezi cha nyama zogwirira ntchito yolimbitsa chakudya.
Chimodzi mwa mawonetseredwe amachitidwe osiyanitsa amachitidwe chifukwa cha kuchepa kwamachitidwe a omwe amatsutsana ndi DA, ndikuchepetsa kapena kutsutsana kwa accumbens DA, ndikuti izi zimakhudza magawidwe amomwe nyama zimayankhira pantchito zomwe zimayesa kupanga zisankho mozama (Salamone et al., 2007; Floresco et al., 2008; Mai et al., 2012). Ntchito imodzi yomwe yakhala ikugwiritsidwa ntchito kuwunika momwe dopaminergic imagwirira ntchito pakugawana mayankho imapatsa makoswe chisankho pakati pa kukanikiza kwa lever komwe kumalimbikitsidwa ndikupereka chakudya chomwe amakonda, poyerekeza ndi kudya chakudya chomwe chilipo koma chosakondedwa kwenikweni (Salamone et al., 1991, Salamone et al., 2007). Pansi pa zochitika zoyambira kapena zowonongeka, makoswe ophunzitsidwa amapeza chakudya chochuluka ndi chiwindi chokakamiza, ndi kudya zochepa za chow. Mlingo wochepa kwambiri wa otsutsana ndi DA omwe amalepheretsa D1 kapena D2 magawo am'magazi olandirira mabanja amatulutsa mayankhidwe akulu mu makoswe omwe akugwira ntchitoyi, amachepetsa kukanikiza kwa wolimbikitsira chakudya koma akuwonjezera chow (Salamone et al., 1991; Koch et al., 2000; Sink et al., 2008). Ntchitoyi yatsimikiziridwa mu mayesero angapo. Mankhwala omwe amatsutsana ndi DA omwe amachititsa kusintha kuchoka ku lever akukakamiza kuti adye chakudya samakhudza chakudya chokwanira kapena kusintha zosakaniza pakati pa zakudya ziwirizi muzitsulo zosankha zaulere (Salamone et al., 1991; Koch et al., 2000). Mosiyana ndi zimenezi, zilakolako zokhumba zokhudzana ndi magulu osiyanasiyana, kuphatikizapo fenfluramine ndi antioxinid CB1 antagonists (Salamone et al., 2007; Sink et al., 2008), adalephera kuwonjezera kuwonjezera pa mankhwala omwe amachititsa kuti chiwindi chisavutike. Mosiyana ndi zotsatira za kutsutsana kwa DA, kudyetsa chakudya, chomwe ndi mtundu wa kuyimilira, kumachepetsanso kupweteka kwa chiwindi ndi chow (Salamone et al., 1991). Zotsatira izi zikuwonetsa kuti kusokonezeka ndi kutumiza kwa DA sikungowononga chakudya choyambirira cha chakudya kapena kudya koma m'malo mwake kumawongolera kuyankhulana pakati pa zakudya zina zomwe zimapezeka mwa mayankho osiyanasiyana. Zotsatira za khalidweli zimadalira kuwonjezereka kwa DA, ndipo zimapangidwa ndi kusungidwa kwa DA ndi zida za D1 kapena D2 Otsutsa a m'banja mwa accum accums core kapena shell (Salamone et al., 1991; Koch et al., 2000; Tsopanoend et al., 2001; Farrar et al., 2010; Mai et al., 2012).
Ndondomeko ya T-maze yakhazikitsidwa kuti iphunzire zoyenera zokhudzana ndi khama. Chifukwa cha ntchitoyi, manja awiri osankhidwa mcherewo amachititsa zinthu zosiyana siyana (monga, 4 motsutsana ndi 2 chakudya cha pellets, kapena 4 motsutsana ndi 0), ndipo pansi pa zochitika zina, choletsedwa chimayikidwa mu mkono ndi msinkhu wochulukitsa chakudya kukakamiza zovuta zokhudzana ndi khama (Salamone et al., 1994). Pamene mkono wochulukitsitsa uli ndi chilephereko, ndipo mkono wopanda chotchinga uli ndi zochepa zolimbitsa thupi, zowonjezera kuwononga kwa DA kapena kutsutsana kukuchepetsani chisankho cha mtengo wapatali / mphotho yapamwamba, komanso kuonjezera chisankho chochepa /Salamone et al., 1994; Denk et al., 2005; Pardo et al., 2012; Mai et al., 2012). Pamene panalibe cholepheretsa mu maze, makoswe ankakonda kuthamanga kwapamwamba mkono, ndipo ngakhale kutsutsana kwa DA sikunakwaniritsidwe kapena kudalitsidwa kwa DA kunasintha chisankho chawo (Salamone et al., 1994). Pamene mkono uli ndi cholepheretsa uli ndi mapaleteni a 4, koma mkono winanso ulibe pellets, makoswe omwe amatha kusungunula zida za DA adasankha dzanja lopambanitsa, anakwera chotchinga, nanyeketsa pellets. Mu kafukufuku wam'mbuyo wa T-makedwe ndi mbewa, pamene haloperidol inachepetsera kusankha kwa mkono ndi cholepheretsa, mankhwalawa sanagwire ntchito posankha pamene mikono yonse idalephereka (Pardo et al., 2012). Choncho, dopaminergic manipulations sizinasinthe malingana ndi mphamvu zowonjezera, ndipo sizinakhudze kusankhana, kukumbukira kapena njira zophunzirira zophatikizapo zokhudzana ndi mkono. Bardgett et al., 2009 anakhazikitsa ntchito yothetsera ntchito ya T-maze, yomwe chakudya chokwanira chazitalicho chinachepetsa chiyeso chilichonse chimene makoswe anasankha mkonowo. Kuwonetsa khama kunasinthidwa ndi kuyang'anira D1 ndi D2 Otsutsa amtundu wa banja, zomwe zinapangitsa kuti makoswe angasankhe kutsika / kutsika mtengo. Kuchulukitsa kupititsa patsogolo kwa DA poyendetsa amphetamine kunaletsanso zotsatira za SCH23390 ndi haloperidol komanso makoswe osankhidwa pofuna kusankha mkono wopambana / wotsika mtengo, womwe umagwirizana ndi maphunziro osankhidwa pogwiritsa ntchito makompyuta a DA opanga kugwedeza (Cagniard et al., 2006).
Chinthu chimodzi chofunika kwambiri m'derali ndi momwe nyama zoperewera zopatsirana pogwiritsa ntchito DA zogwirira ntchito zimakhudzidwa ndi ntchito zogwira ntchito, kapena zinthu zina monga kuchedwa kwa nthawi (mwachitsanzo, Denk et al., 2005; Wanat et al., 2010). Zonsezi, zotsatira za kutsutsana kwa DA pa kuchepetsa kuchepetsa kuwonetsa kuti zakhala zosakanikirana (Wade et al., 2000; Koffarnus et al., 2011), Ndi Winstanley et al., 2005 adanena kuti kusungunuka kwa madandaulo a DA sikulepheretse kuchepetsa kuchepetsa. Floresco et al., 2008 adawonetsa kuti mdani wa DA wolemba haloperidol adasintha kagwiritsidwe kabwino kake ngakhale atayang'anira zotsatira za mankhwalawa poyankha kuchedwa. Wakabayashi et al., 2004 anapeza kuti blockade ya nucleus accumbens D1 kapena D2 zolandilira sizinalepheretse magwiridwe antchito pang'onopang'ono, zomwe zimaphatikizapo kudikirira kwakanthawi komanso nthawi yayitali kuti mulimbikitsidwe. Kuphatikiza apo, maphunziro omwe ali ndi magawo olimbikitsira omwe ali ndi ziwerengero zomwe zimafunikira pakadutsa nthawi akuwonetsa kuti kuwonjezeka kwa kuwonongeka kwa DA kumapangitsa kuti nyama zizimvera zowonjezerapo koma sizipangitsa kuti nyama zizindikire nthawi yayitali kuyambira 30-120 s (Correa et al., 2002; Mingote et al., 2005).
Mwachidule, zotsatira za kafukufuku wa T ndi maphunziro opindulitsa mwa makoswe zimagwirizana ndi lingaliro lakuti kuchepetsa kuchepa kwa antchito a DA ndikumabweretsa mavuto a DA kusiya maziko ofunikira ndi kulimbitsa bwino, komabe kumachepetsa kusintha kwa khalidwe ndi kuyambitsa ziweto zawo Kusankhidwa kwayankhidwe pogwiritsa ntchito zoyenera kuchita pa ntchitoyo ndi kusankha njira zochepetsera ndalama kuti mupeze othandizira (Salamone et al., 2007, Salamone et al., 2012). Umboni wochuluka umasonyeza kuti DA yodalirika ndi mbali ya maulendo akuluakulu oyendetsera khalidwe ndi ntchito zomwe zimagwira ntchito, zomwe zimaphatikizapo ena othandizira (adenosine, GABA; Mingote et al., 2008; Farrar et al., 2008, Farrar et al., 2010; Nunes et al., 2010; Salamone et al., 2012) ndi malo a ubongo (basolateral amygdala, kansalu kakang'ono kamene kalikonse, ventral pallidum; Walton et al., 2003; Floresco ndi Ghods-Sharifi, 2007; Mingote et al., 2008; Farrar et al., 2008; Hauber ndi Sommer, 2009).
Kuphatikizidwa kwa Mesolimbic DA mu Chikhumbo Chokhutiritsa: Ntchito Yamphamvu ya DA Systems
Ngakhale kuti nthawi zina zimanenedwa kuti nucleus accumbens DA kumasulidwa kapena ntchito ya ventral tegmental DA neurons imayambitsidwa ndi kuwonetsa anthu olimbitsa mtima monga chakudya, mabuku omwe akufotokoza kuyanjidwa kwa DAlimbic DA ku zowonongeka ndizovuta kwambiri (Hauber, 2010). Mwachidziwitso, kodi chakudya chimapanga ntchito ya DA neuron kapena kubweretsa DA kumasulidwa? Pakati pa zochitika zambiri, ndi kupyolera muzigawo zosiyana za khalidwe lolimbikitsidwa, lomwe limagwirizanitsa kapena mbali zina zolimbikitsa zimagwirizanitsidwa kwambiri ndi kuchitidwa kwa ntchito ya dopaminergic? Yankho la mafunso awa limadalira pa nthawi yeniyeni ya chiyeso, ndi momwe zikhalidwe zenizeni zimayambira. Kusiyanitsa kwa ntchito za DA kungathe kuchitika pafupipafupi, ndipo kusiyana komwe kumachitika kawirikawiri pakati pa "phasic" ndi "tonic" ntchito (Chisomo, 2000; Floresco et al., 2003; Goto ndi Grace, 2005). Njira zamakono zojambula zamagetsi zimatha kuyeza zochitika zapadera za DA neuroni (mwachitsanzo, Schultz, 2010), ndi njira zowonongeka (mwachitsanzo, kuthamanga kwapadera kwapamwamba) zolemba za DA "zochepa" zomwe zimasintha mwatsatanetsatane mu DA, yomwe imaganiziridwa kuti ikuimira kutuluka kwa ntchito ya DA neuron (mwachitsanzo, Roitman et al., 2004; Sombers et al., 2009; Brown ndi al., 2011). Zanenanso kuti kusintha kwapadera kwa DA kumasulidwa kungakhale kosasunthika ndi kuwombera kwa DA neuron, ndipo pamalo mwake kungasonyeze kuwombera kosakanikirana kwa njira zothamanga zowonongeka zomwe zimalimbikitsa DA kumasulidwa kudzera mu njira ya presynaptic nicotinic receptor (Mpunga et al., 2011; Threlfell et al., 2012; Surmeier ndi Graybiel, 2012). Njira zina za microdialysis, imayeza DA extracellular m'njira yomwe ikuimira zotsatira zowonongeka ndi kutsegula njira zowonjezera pazigawo zazikulu za nthawi ndi malo pa electrophysiology kapena voltammetry (mwachitsanzo, Hauber, 2010). Choncho, kawirikawiri zimatchulidwa kuti njira za microdialysis zimapanga DA level "tonic". Komabe, chifukwa chakuti microdialysis ikhoza kuyesa kusintha kwa khalidwe-kapena kusintha kwa mankhwala (mwachitsanzo, kuwonjezeka kumatsata ndi kuchepa) mu DA ya extracellular yomwe imachitika maminiti pang'ono, mwina ndi othandiza kwambiri kugwiritsa ntchito mawu oti "fast phasic" kulankhula za kusintha kofulumira kwa ntchito yokhudzana ndi DA yomwe ingakhoze kuyesedwa ndi electrophysiology kapena voltammetery, ndi "kupuma pang'ono" ponena za kusintha komwe kumachitika pang'onopang'ono poyerekeza ndi njira za microdialysis (mwachitsanzo, Hauber, 2010; Segovia et al., 2011).
Maphunziro a Electrophysiology awonetsa kuti kuwonetsera kwa buku lachilendo kapena chakudya chosayembekezereka kumaphatikizapo kuwonjezeka kwapadera pa ntchito ya kuika maganizo kwa DA neurons, koma kuti zotsatirazi zimachokapo ndi kuwonetsera nthawi zonse, kapena kuwonetsedwa mobwerezabwereza kupyolera mu maphunziro (Schultz et al., 1993; Schultz, 2010). Kugwiritsa ntchito njira za voltammetry kuti athe kuyeza kusintha kwapadera pa DA kuchoka, Roitman et al., 2004 anawonetsa kuti, pamaphunziro ophunzitsidwa bwino, kuwonetsa kuti chiwombankhanga chimapangitsa kuti sucrose yobweretsedwe ikhale limodzi ndi kuwonjezeka kwa madera a DA, komabe, kuwonetsera kwenikweni kwa sucrose reinforcer sikunali. Kufufuza komweku kunanenedwa zaka zapitazo Nishino et al., 1987, yemwe anaphunzira zaulere wothandizana ndi azimayi omwe akugwira ntchito mosakanikirana ndi nyani ndipo adawona kuti ntchito zapadera za DAA zowonjezereka zowonjezereka zinkawonjezeka panthawi ya chiwombankhanga zomwe zinkakakamiza ziweto zomwe zinkaphunzitsidwa koma zinkatsika panthawi yopereka mphamvu. Kusanenedweratu kwa chakudya, komanso kufotokozera zizindikiro zomwe zinaneneratu kuti chakudya chidzatulukidwe, kuwonjezeka kwachidziwitso mofulumira monga momwe chiyamikiridwa ndi kutsika kwapakati pa nucleus accumbens core (Brown ndi al., 2011). DiChiara ndi anzake adasonyezeratu kuti kudya zakudya zopatsa thanzi kuwonjezereka kwawonjezeka DA choonjezera mu nucleus accumbens shell monga kuyesedwa ndi microdialysis, koma kuti yankholi lidayenda mofulumira (mwachitsanzo, Bassareo et al., 2002). Kapepala kakang'ono kamene kakang'ono kakang'ono ka microdialysis kanasonyeza kuti kuwonetsa makapu apamwamba kwambiri a zakudya zamagulu ku makoswe omwe sanawonepo kale sanapange kusintha kulikonse kwa DA extracellular mu accumcums core kapena shell (Segovia et al., 2011). Mosiyana ndi zonse, kupeza ndi kukonzanso zofunikira zogwiritsira ntchito chiŵerengero chowongolera zidawonjezeredwa ndi kuwonjezeka kwa DA kumasulidwa (Segovia et al., 2011). Chitsanzo chomwecho chinasonyezedwa pamene zizindikiro za kusintha kwa chizindikiro cha DA (c-Fos ndi DARPP-32) zinayesedwa (Segovia et al., 2012). Kuphatikizidwa pamodzi, maphunzirowa sagwirizana ndi lingaliro lakuti chakudya chapafupi, kuphatikizapo chakudya chokoma, chikuwonjezereka kwambiri chikuwonjezereka DA kumasulidwa pamtundu wambiri.
Komabe, umboni wochuluka umasonyeza kuti kuwonjezeka kwa kulumikizana kwa DA kumayanjananso ndi kuwonetsa zokondweretsa zomwe zimagwirizanitsidwa ndi zowonjezera zachilengedwe monga chakudya, kapena ntchito ya chida; izi zawonetsedwa mu maphunziro okhudza microdialysis (Sokolowski ndi Salamone, 1998; Ostlund et al., 2011; Hauber, 2010; Segovia et al., 2011), voltammetry (Roitman et al., 2004; Brown ndi al., 2011; Cacciapaglia et al., 2011), ndi ma electrophysiological panthawi yopereka maofesi aulere (Nishino et al., 1987; Kosobud et al., 1994). Cacciapaglia et al., 2011 adanena kuti kuthamanga kwapadera kwa DA kudutsa mu nucleus accumbens komwe kunayesedwa ndi kuyendetsa ndege kunachitika panthawi yomwe inayamba kufotokoza reinforcer kupezeka, komanso nyuzipepala yotsutsa, komanso kuti zotsatira zowonongeka kwa pulojekitiyi zinkasokonezeka chifukwa cha kutsekedwa kwa mphepo mu ventral tegmental DA neurons. Kuwonjezera apo, kafukufuku wambiri wamagetsi amadziwitsa zinthu zina zomwe zimapangitsa kuti anthu asagwiritsidwe ntchito pochita zida zowonjezereka, kuphatikizapo kufotokozera zizindikiro zomwe zimagwirizanitsidwa ndi primary reinforcer, komanso zinthu zomwe zili ndi mphamvu zowonjezera Chiyembekezero chochitidwa ndi zochitika zammbuyomu (Schultz et al., 1997). Zotsatira zomwe zachitika pambuyo pake zachititsa kuti lingaliro lakuti DA neuron ntchito ingayimire mtundu wa chisonyezo cholakwika cholosera chomwe chafotokozedwa ndi mitundu ina ya maphunziro (mwachitsanzo, Rescorla ndi Wagner, 1972). Mchitidwe uwu mu DA neurons wotsitsika wapereka maziko ovomerezeka a kuchitapo kanthu kofulumira kwa DA kuwonetsera muzitsulo zophunzitsira zolimbikitsa (Schultz et al., 1997; Bayer ndi Glimcher, 2005; Niv, 2009; Schultz, 2010).
Ngakhale kuti cholinga chachikulu cha pepala lino ndi zotsatira za dopaminergic manipulations pa zosiyana ndi zolimbikitsa, ndibwino kuganizira kufunika kwa nthawi yofulumizitsa komanso kutsika pang'ono (mwachitsanzo, "tonic") chizindikiro chomasulira zotsatira za mikhalidwe yomwe imasokoneza ndi kulengeza kwa DA. Zochitika zosiyana za ntchito za dopaminergic zingagwire ntchito zosiyana kwambiri, choncho, zotsatira za kugwiritsidwa ntchito kokha zimadalira kwambiri ngati zikusintha ntchito yofulumira kapena yocheperapo kayendedwe ka DA. Ochita kafukufuku agwiritsira ntchito njira zosiyanasiyana zamagetsi kapena zam'mimba zosiyana kwambiri ndi zomwe zimachititsa kuti ntchito ya DA ikwaniritsidwe poyerekeza ndi DA pang'onopang'ono.Zweifel et al., 2009; Parker et al., 2010; Grieder et al., 2012) ndipo awonetsa kuti njira izi zingathe kukhala ndi zotsatira zosiyana za khalidwe. Mwachitsanzo, Grieder et al., 2012 anawonetsa kuti kusokonezeka kwadongosolo la ntchito ya DA kunachititsa kuti malo osokoneza bongo asatengedwe ndi chikonga chimodzi chokha, koma kuti asachoke ku chikonga chosatha. Mosiyana ndi zimenezi, kutsekedwa kwa mabungwe a D2 obwera chifukwa cha kusokonezeka kwa nthawi yaitali, koma osati kuchoka kovuta. Zweifel et al., 2009 adanena kuti anthu omwe ali ndi kachilombo koyambitsa matenda a NMDA, omwe sanagwiritse ntchito mankhwalawa, adasokoneza kwambiri ma V11 DA neurons, omwe sagwiritsidwa ntchito pofuna kupeza chilakolako chofuna kuphunzira koma sanasokoneze khalidwe la ntchito yokonza chakudya pa nthawi yowerengera. Ndipotu, ntchito zosiyanasiyana zokhudzana ndi khalidwe la DA zimasungidwa ku zinyama zopanda mphamvu zochitika za DA (Zweifel et al., 2009; Wall et al., 2011; Parker et al., 2010). Zochitika izi zimatanthawuza kuphatikiza mfundo kuchokera ku zochitika zapadera zochitika ndi zomwe zikuwonekera pa zotsatira za kutsutsana ndi DA kapena kupasuka. Choyamba, amasonyeza kuti munthu ayenera kukhala wochenjera pochita zinthu kuchokera kuzinthu zopangidwa ndi electrophysiology kapena kuyendayenda (mwachitsanzo, kuti kumasulidwa kwa DA kumakhala "chizindikiro chophunzitsira") kuntchito zomwe zilibe vuto pamene mankhwala osokoneza bongo kapena madontho a DA akugwiritsidwa ntchito kuti asokoneze kulengeza kwa DA. Kuwonjezera pamenepo, amasonyeza kuti kufufuza kwa ntchito yofulumira ya mazira a DA neurons kungapangitse zochitika zomwe zikuwonjezereka kapena kuchepetsa ntchito ya DA kapena kupereka chizindikiro cha DA koma sikutidziwitsa ife za ntchito zambiri zomwe zimachitika ndi DA pa maulendo angapo timescales kapena osokonezeka ndi kusokonezeka kwa kufalitsa kwa DA.
Kuphatikizidwa kwa Mesolimbic ndi Neostriatal Njira mu Kugwiritsa Ntchito Zogwiritsa Ntchito
Ngakhale kuti wina angathe kufotokozera zifukwa zomwe zimapangitsa kuti zikhale zosiyana ndi zomangidwe zina, ziyenera kuzindikira kuti, pokambirana momveka bwino za makhalidwe omwe amachititsa kapena khalidwe lachilengedwe lachangu, wina ayenera kulingalira ntchito zogwirizana. Ubongo ulibe mizere kapena mzere wotsitsi-ndi-mzere kapena mizere yomwe imasiyanitsa bwino maganizo apadera a maganizo m'maganizo osasunthika, osagwiritsidwa ntchito ndi neural. Choncho, ndikofunikira kumvetsetsa mgwirizano pakati pa zokakamiza ndi ntchito zina monga homeostasis, allostasis, kutengeka, kuzindikira, kuphunzira, kulimbitsa, kumva, ndi magalimoto (Salamone, 2010). Mwachitsanzo, Panksepp, 2011 Anagogomezera momwe maubwenzi apakati muubongo amawongolera mwachidwi ndi machitidwe olimbikitsa omwe amagwira ntchito monga kufuna, kukwiya kapena mantha. Kuwonjezera pamenepo, kufunafuna / kuthandizira sikuti kumangokhala ndi maganizo kapena zolimbikitsa zokhazokha, koma, komanso, njira zophunzirira. Nyama zimaphunzira kuchita zenizeni zomwe zimayambitsa zokhudzana ndi zotsatira zowonjezera. Monga mbali yovuta ya mgwirizano wothandizira, zirombo zimayenera kudziwa zomwe amachita zomwe zimatsogolera (mwachitsanzo, mayina a zotsatira-zoyenera). Choncho, ntchito zothandizira zimayendetsedwa ndi magalimoto, malingaliro, maganizo, ndi ntchito zina (Mogenson et al., 1980). Ngakhale kuti zomwe zikuchitika panopa zikugwiritsidwa ntchito pokhudzana ndi kuwonetseratu za DAlimbic DA mothandizira anthu olimbitsa thupi, zimathandizanso kuti mukambirane mwachidule za kugwirizanitsa ntchito ya mesolimbic DA muphunziro lachida.
Wina angaganize kuti kungakhale kosavuta kusonyeza kuti nucleus accumbens DA amaphatikizapo kulimbikitsa kuphunzira kapena amagwirizana kwambiri ndi njira zopangira mapulasitiki zomwe zimayambitsa mgwirizanowu ndi magulu othandizira anthu omwe akugwira ntchito. Koma kafukufukuyu ndi ovuta komanso ovuta kutanthauzira monga kufufuza komwe kumakambidwa pamwambapa. Mwachitsanzo, Smith-Roe ndi Kelley, 2000 adawonetsa kuti kubwezeretsedwa kwa DA Dulendo kamodzi1 ndipo obwera NMDA mu nucleus accumbens pachimake analepheretsa kupeza chida chowongolera. Kuonjezera apo, zochitika zomwe zimakhudza kugwirizanitsa kukumbukira kukumbukiranso zomwe zimagwiritsidwa ntchito popanga chida chamagetsi (Hernandez et al., 2002). Komabe, powerenga mabuku pa nucleus accumbens ndi kuphunzira, Yin et al., 2008 anapeza kuti "accumcums sichifunikira kapena sitingakwanitse kuphunzira chida." Mofananamo, Belin et al., 2009 adanenanso kuti kuwonongeka kwa zotupa ndi mankhwala osokoneza bongo komwe kumafikira pachimake kumatha kukhudza kupezeka kwa zida zolimbikitsidwa ndi zoyambitsa zachilengedwe, koma adati "zopereka zenizeni zamaganizidwe" am'magulu am'magulu am'magulu amtundu waubongo sizikudziwikabe. Ngakhale pali maphunziro ambiri omwe akuwonetsa kuti zotupa zam'maselo, otsutsana ndi DA, kapena kufooka kwa DA kumatha kukhudza zotsatira zokhudzana ndi kuphunzira m'njira monga kukonda malo, kupeza kwa lever pressing, kapena njira zina, izi sizomwe zikuwonetsera zokha kuti ma nyukiliya amasonkhanitsa ma neuron kapena kufalitsa kwa mesolimbic DA ndikofunikira pamayanjano omwe amapanga kuphunzira kwambiri (Yin et al., 2008). Zotsatira zenizeni zokhudzana ndi kuphunzira kwachinthu zingathe kuwonetsedwa mwa kuwonetsa zotsatira za kulimbikitsitsa kudzichepetsa kapena kuwonongeka kwapadera, zomwe nthawi zambiri sizikuchitidwa mu maphunziro apamtima kapena mankhwala osokoneza bongo. Poganizira izi, ndikofunikira kuzindikira kuti zilonda zam'thupi mumtundu uliwonse kapena chipolopolo cha accumbens sizinasinthe kukhumudwa kwachinyengo (Corbit et al., 2001). Lex ndi Hauber, 2010 anapeza kuti makoswe okhala ndi nucleus accumbens DA adakali ofunitsitsa kugwirizanitsa chiwerengero, ndipo adalonjeza kuti kusonkhanitsa dera lalikulu DA kungakhale kosafunikira kuti tiyambe kusonkhana ndi mayanjano a zotsatira. Ngakhale sizikudziwikiratu kuti ngati DA imagwiritsidwa ntchito ndizofunikira kwa mayanjano pakati pa mayankho ndi mphamvu zowonjezera, umboni wochuluka ukuwonetsa kuti nucleus accumbens DA ndi yofunika kuti apite ku Pavlovian ndi Pavlovian kuti apereke njira zothandizira (Parkinson et al., 2002; Wyvell ndi Berridge, 2000; Dalley et al., 2005; Lex ndi Hauber, 2008, Lex ndi Hauber, 2010; Yin et al., 2008). Zotsatira zoterezi zingapangitse njira zomwe zimakhalira zowonongeka zingayambitse zotsatira zowonjezera (Robbins ndi Everitt, 2007; Salamone et al., 2007), monga tafotokozera pamwambapa. Zomwe zimayambitsa kapena kukondweretsa zotsatira zowonongeka zikhoza kukhala zolimbikitsira kuyanjanitsa kwa kalembedwe kake komwenso zingathe kuchitapo kanthu pofuna kulimbikitsa kupeza mwa kuonjezera kuyanjananso ndi kusiyana kwa khalidwe, motero kuyika mpata woti akhale ndi mipata yambiri yogwirizanitsa yankho ndi kulimbitsa. Mapepala atsopano awonetsa kuti zokopa za optogenetic za ventral tegmental DA neurons sizinapangitse kuti chiwongolero chowongolera chokhacho chikhale cholimba komanso chosakhudza chakudya, komabe chinapangitsa kuti kuyambika kwa chakudya kumangirire pamutu pachithunzi Zotsatira za zida zoyamba kuzimitsidwa (Adamantidis et al., 2011).
Chochititsa chidwi, ngakhale kuti kugogoda kwa DA D1 mapulogalamu ovomerezekawa anaphatikizapo kugwiritsidwa ntchito kwa njira ya Pavlovian, kugogoda kwa mapulogalamu a NMDA, zomwe zinapangitsa kuti 3 ichepetse pang'onopang'ono kutulutsidwa kwa DA kuchitidwa ndi kupereka chakudya chogwirizana, osati kubwezeretsa kupeza njira ya Pavlovian (Parker et al., 2010). Izi zikuwonetsa kuti ubale wapakati pa DA kutuluka ndi kuphunzira sikutsimikizika. Kafukufuku wamtsogolo akuyenera kuwunika momwe zinthu zimakhudzira zomwe zimakhudza kuwonetsa kwa DA mwachangu pogwiritsa ntchito njira zomwe zimawunikira kulimbikitsidwa kwa kuphunzira (mwachitsanzo, kulimbikitsa kutsika kwa zinthu ndi kuwonongeka kwadzidzidzi). Kuphatikiza apo, njira zamankhwala ndi zamankhwala zomwe zimayambitsa kupondereza zochitika za DA mwachangu ziyenera kuwunikidwanso pazomwe amachita pakuwongolera machitidwe ndi zina zokhudzana ndi zoyeserera.
Kuphatikizidwa kwa Mesolimbic DA mu Chidziwitso Chotsutsa ndi Kuphunzira: Ntchito Yopambana ya DA Systems
Kuwerenga mwatsatanetsatane za zolemba zina za DA zomwe zimachoka m'modzi ndi lingaliro lakuti DAlimbic DA imagwira ntchito mwachangu, njira zokhutiritsa, ndi maphunziro okhudzana ndi kulimbikitsana, kuti asatengere mbali zina za maphunziro ndi zolinga. Komabe, lingaliro limeneli likanakhala losiyana ndi mabuku. Monga tafotokozera pamwambapa, umboni wochuluka ukuwonetsa kuti kusungunula mauthenga a DA sikutanthauza mwachindunji machitidwe a hedonic kuti akhudzidwe. Komanso, pali mabuku akuluakulu omwe amasonyeza kuti DA imagwira ntchito molimbika ndipo ingakhudze makhalidwe mu njira zophunzirira. Zinthu zosiyanasiyana zosiyana siyana (mwachitsanzo, mantha, mchira, kusokoneza maganizo, mankhwala osokoneza bongo, mankhwala osokoneza bongo, kusagwirizana pakati pa anthu) akhoza kuonjezera kutulutsidwa kwa DA monga momwe zilili ndi njira za microdialysis (McCullough et al., 1993; Salamone et al., 1994; Tidey ndi Miczek, 1996; Achinyamata, 2004). Kwa zaka zambiri, ankaganiziridwa kuti ntchito yothandizira boma la DA neuron siidapangidwe ndi zosokoneza; Komabe, kafukufuku waposachedwapa wawonetsa kuti ntchito ya electrophysiological ya DA neurons yodziwika kapena yowonjezera ikuwonjezeka ndi zovuta kapena zovuta (Anstrom ndi Woodward, 2005; Brischoux et al., 2009; Matsumoto ndi Hikosaka, 2009; Bromberg-Martin et al., 2010; Schultz, 2010; Lammel et al., 2011). Ngakhale Roitman et al., 2008 adanena kuti chochititsa chidwi chochuluka (quinine) chinachepetsa chiwerengero cha DA mu nucleus accumbens, Anstrom et al., 2009 adawona kuti kugonjetsedwa pakati pa chikhalidwe cha anthu kunkaphatikizidwa ndi kuwonjezeka kwa ntchito ya DA yofulumira monga momwe anayendera ndi electrophysiology ndi voltammetry. Kusatsimikizika kumakhalapobe ngati pali DA neuron yodzipatula yomwe imayankha mosiyana ndi zowonongeka ndi zowopsya, ndipo zimakhala zotani kwa aliyense, koma zikuwoneka kuti palibe kukayikira kuti ntchito ya DAlimbic yowonjezera ingathe kuwonjezeredwa ndi zinthu zina zovuta, choncho sichimangiriridwa ku hedonia kapena kulimbitsa bwino.
Umboni wambiri womwe ukubwerera mmbuyo zaka makumi angapo (Salamone et al., 1994) ndikupitirizabe mabuku atsopano (Faure et al., 2008; Zweifel et al., 2011) amasonyeza kuti kusokoneza ndi kutumiza kwa DA kungawononge kupeza kapena kuchitapo kanthu kwa khalidwe loipa. Ndipotu, kwa zaka zambiri, otsutsa a DA ankayang'anitsitsa njira zowononga matenda opatsirana pogwiritsa ntchito mphamvu zawo zowonongeka (Salamone et al., 1994). Kukumana ndi DA kukhumudwa kumapangitsa kuti munthu asamasunthike.McCullough et al., 1993). Majekeseni ovomerezeka kapena intra-accumbens a DA otsutsa amachititsanso kusokoneza kupeza malo a chiwonongeko ndi kulawa chisokonezo (Acquas ndi Di Chiara, 1994; Fenu et al., 2001), komanso mantha (Inoue et al., 2000; Pezze ndi Feldon, 2004). Zweifel et al., 2011 adanena kuti kugogoda kwa a NMDA receptors, omwe amachepetsa kuchepetsa kutuluka kwa DA, kusokonezeka kwa chiwerengero cha mantha.
Kafukufuku waumunthu awonetsanso mbali yothandizana ndi intaneti muzinthu zotsitsimula komanso kuphunzira. Ankhondo a nkhondo omwe anali ndi matenda ovutika maganizo pambuyo pake anawonetsa kuwonjezeka kwa magazi mu ventral striatum / nucleus accumbens poyankha kuwonetsa zosokoneza (ie, kumveka kwa nkhondo; Liberzon et al., 1999). Kafukufuku waumunthu wa anthu amasonyeza kuti mayankho a BOLD oyenda pansi, monga momwe amawerengeredwera ndi fMRI, akuwonjezeka poyankhidwa ndi zolakwika zowonetsera mosasamala kanthu kuti zochitikazo zinaneneratu zochitika zopindulitsa kapena zotsutsa (Jensen et al., 2007), ndipo kuti zolakwitsa zowonongeka zoletsedwa zinatsekedwa ndi mdani wa DA haloperidol (Menon et al., 2007). Baliki et al., 2010 adanenanso kuti m'maphunziro abwinobwino, mayankho a BOLD a phasic adachitika poyambira komanso poyambitsa chopweteka champhamvu. Delgado et al., 2011 adawonetsa kuti mayankho a BOLD oyenda mwamphamvu adakulirakulira panthawi yosinthasintha ndikuyamba kukondoweza (mantha) komanso kutayika kwachuma. Kafukufuku wa PET yemwe adapeza mayendedwe a vivo raclopride kusamutsidwa kuti athe kuyesa kutulutsidwa kwa DA mwa anthu akuti kuwonekera pamavuto amisala kumawonjezera madera a DA akunja mu ventral striatum m'njira yomwe imalumikizidwa ndi kuchuluka kwa cortisol kumasulidwa (Pruessner et al., 2004). Motero, kufufuza kwaumunthu kwa anthu kumasonyezanso kuti ventral striatum ndi masolimbic DA innervation zimakhudzidwa ndi zowopsya komanso zosokoneza.
Chidule ndi Mapeto
Mwachidule, malingaliro achikhalidwe onena za DA ngati mkhalapakati wa "hedonia," komanso chizolowezi chofanizira kufalitsa kwa DA ndi "mphotho" (ndi "mphotho" ndi "hedonia") zikutsindika kulowererapo kwa dopaminergic pazinthu zina zolimbikitsa ndi njira zokhudzana ndi kuphunzira (Chithunzi 2), kuphatikiza kuyambitsa machitidwe, kuyesetsa, kuyeserera kolimbikitsa, kulosera zamtsogolo, ndi njira za Pavlovian. Kutumiza kwa DA mu ma nucleus accumbens sikukhala ndi mphamvu yayikulu pakuyambiranso kwa hedonic kuzokonda, komanso sikuwoneka ngati kukuyanjanitsa chakudya kapena njala (Berridge ndi Robinson, 1998; Salamone ndi Correa, 2002; Kelley et al., 2005; Barbano et al., 2009). Komanso, ngakhale kuti dopaminergic manipulations ingasokoneze zotsatira za khalidwe pa zinyama zophunzitsidwa pa maphunziro, palibe umboni wamphamvu wakuti kudzikweza DA ndizofunikira kwambiri pa mbali yeniyeni yophunzirira zinthu zomwe zimaphatikizapo mgwirizano pakati pa zomwe zimagwira ntchito ndi zotsatira zowonjezera (Yin et al., 2008). Komabe, kudzikundikiritsa DA n'kofunika kwambiri pazinthu zokhutiritsa komanso zowonongeka (Salamone et al., 2007; Cabib ndi Puglisi-Allegra, 2012) ndipo amapita nawo mu njira zophunzirira, makamaka mwa mbali mwa njira zomwe zimaphatikizapo njira ya Pavlovian ndi Pavlovian kupititsa patsogolo ntchito (Yin et al., 2008; Belin et al., 2009). Kusamvana ndi accumbens DA kutumiza kuyanjanitsa kupeza njira za Pavlovian zoyankha zomwe zimayesedwa ndi zizindikiro zomwe zimalosera kubweretsa chakudya ndi kusokoneza mayankho okhudzidwa omwe amachititsa kuti ziwonongeke zowonongeka. Kugwirizanitsa ziphuphu za DA kapena zotsutsana zimachepetsa zotsatira zowonongeka komanso zimapangitsa nyama kukhala yovuta kwambiri kuntchito zothandizira kuthandizira (mwachitsanzo, kutuluka kwa ndondomeko ya chiŵerengero chokhala ndi chiŵerengero chokwanira, kukwera; Salamone et al., 2007, Salamone et al., 2012; Barbano et al., 2009). Chifukwa chake, ma nucleus accumbens DA amatenga nawo gawo pazolimbikitsa, ndikuwongolera zomwe zikuwongoleredwa ndi zolinga, koma m'njira yeniyeni komanso yovuta yomwe sinafotokozedwe ndi mawu oti "mphotho." Ntchito zina zothandizirana zimagwira ntchito zomwe mesolimbic DA (mwachitsanzo, zoyeserera zolimbikitsira, kuyesetsa mwamphamvu), motero kuwonongeka kwa mesolimbic DA kumakhudza mosavuta magwiridwe antchito, poyankha ntchito zina zolimbikitsidwa, kapena magawo a chakudya choyambirira chilimbikitso, zimasiyidwa.
M'zaka zingapo zapitazi, chithunzi chomwe chatuluka ndikuti neostriatum (mwachitsanzo, dorsal striatum) ndi kusungidwa kwake kwa DA kumawoneka kuti kukugwirizana bwino ndi momwe mabungwe azida amagwirira ntchito kuposa momwe ma nyukiliya amathandizira (Yin et al., 2008). Zilonda za dorsomedial neostriatum zinapangitsa nyama kusamvetsetsa zonsezi kuti zikhazikitse chiwonongeko ndi kuwonongeka kwa zinthu (Yin et al., 2005). Zilonda za thupi la maselo ndi zida za DA zomwe zimagwiritsidwa ntchito pochita zinthu zowonongeka zimasonyezedwa kuti zimapangitsa kupanga mapangidwe a zisudzo (Yin et al., 2004; Faure et al., 2005). Kuphatikizidwa kwa neostriatum mu mapangidwe a zizolowezi kungagwirizane ndi ntchito yoganizira za gulu lachilengedwe lokhazikitsa zochitika zotsatizana kapena "kuthandizana" kwa zigawo zikuluzikulu za khalidwe (Graybiel, 1998; Matsumoto et al., 1999). Lingaliro loti pali kusintha kuchoka pamalamulo oyenda mozungulira a zida zothandizila kuyankha njira za neostriatal zomwe zimayang'anira kapangidwe ka zizolowezi zagwiritsidwa ntchito kwambiri kuti afotokoze za zinthu zingapo zomwe zimachitika pakumwa mankhwala osokoneza bongo (onani ndemanga ndi Belin et al., 2009), ndiyofunikiranso pakumvetsetsa zovuta za othandizira mwachilengedwe (Segovia et al., 2012). Komabe, m'nkhaniyi, ndibwino kutsimikizira kuti kugwira ntchito kwa nucleus accumbens DA m'zinthu zophunzitsira kapena kugwira ntchito, kapena kuchitapo kanthu kwa neostriatal DA poyendetsa kukodola kwa mayanjano-zotsatira kapena kupanga zizoloŵezi, sizikutanthauza kuti izi Zotsatira zake zimagwirizanitsidwa ndi zochita pazomwe zimayambitsa zilakolako kapena chilakolako cha anthu olimbitsa thupi monga chakudya. Mwachitsanzo, Smith-Roe ndi Kelley, 2000 adawonetsa kuti jakisoni wophatikizidwa wa D1 Wotsutsa ndi NMDA omwe amatsutsana ndi mankhwala omwe amalephera kupeza chakudya chowongolera chakudya sanagwilitsile nchito kudya ndikutanthauzira zotsatirazi monga kusonyeza kuti palibe chifukwa chachikulu chokhudzidwa. Komanso, kusokonezeka ndi kulumikizana kwa DA m'ndandanda wazitsulo zowonongeka, kunawonetseratu kuti zimapangitsa kuti chizoloŵezi chisachitidwe, koma musiye zolinga zamtunduwu (mwachitsanzo, mothandizidwa)Faure et al., 2005). Chifukwa chake, kutenga nawo gawo kwa DA posakhazikika pakupanga zizolowezi sikupereka umboni wothandizirana ndi dopaminergic wazomwe zimalimbikitsa chakudya kapena njala. M'malo mwake, kudya komwe kumakhudzidwa kumakhudzidwa kwambiri ndi kuchepa kwa DA mu ventrolateral neostriatum, ndipo kuwonongeka kumeneku kumakhudzana ndi zovuta zamagalimoto zomwe zimakhudza kuchuluka kwa chakudya ndi kugwiritsiridwa ntchito kwa nthawi yopatsa chakudya, ndipo zimachitika mofananira ndi kuponyedwa kwa kunjenjemera kwa pakamwa komwe kumatha kupumula kwa Parkinsonia kunjenjemera (Jicha ndi Salamone, 1991; Salamone et al., 1993; Collins-Praino et al., 2011).
Ngakhale sichizindikiro chophweka cha hedonia kapena chakudya choyambirira komanso chilakolako chofuna kudya, DA mu ma nucleus accumbens akuwoneka kuti amayang'anira njira zingapo zidziwitso zomwe zimadutsa pamutuwu ndipo amatenga nawo gawo pamachitidwe osiyanasiyana okhudzana ndi zomwe zimapangitsa. Kwa zaka makumi ambiri, ofufuza akuti mabungwe oyambira pamagalasi amakhala ngati oyang'anira magwiridwe antchito, zomwe sizitanthauza kuti kusokonekera kwa basal ganglia kumabweretsa ziwalo zosavuta kapena kulephera kwa magalimoto, koma m'malo mwake kumatanthawuza lingaliro loti nyumbazi, kuphatikiza ma accumbens, amatenga nawo mbali mukumangirira (mwachitsanzo, kutsekereza) pazomwe zimakhudzidwa ndikulowerera pamachitidwe. Mofananamo, Mogenson et al., 1980 ndi anzawo adanenanso zaka zapitazo kuti maukosi ophatikizika amakhala ngati "limbic-motor" mawonekedwe, opereka ulalo pakati pamiyendo yamiyendo yomwe imakhudzidwa ndikumverera komanso kuzindikira komanso mabwalo amitsempha owongolera momwe zimakhalira. Umboni wowoneka kuchokera kuzinthu zingapo ukuwonetsa kuti ma nucleus accumbens amakhala ngati chipata, zosefera, kapena zokulitsira, zidziwitso zomwe zimadutsa m'malo osiyanasiyana am'mimba kapena amiyendo popita kumadera osiyanasiyana am'magazi (mwachitsanzo, Roesch et al., 2009). Kafukufuku wa electrophysiological ndi voltammetry amasonyeza kuti nucleus accumbens imapangidwira kuti ikhale yokhala ndi tizilombo toyambitsa matenda omwe amadziwika ndi DA (O'Donnell, 2003; Carelli ndi Wondolowski, 2003; Cacciapaglia et al., 2011). Roesch et al., 2009 adanena kuti nucleus accumbens neurons akuphatikizira zambiri za mtengo wa malingaliro omwe amayembekezerapo ndi zida za motor (zotsatira, liwiro kapena kusankha) zomwe zimachitika panthawi yopanga zisankho. DA atamasulidwa akhoza kuika malipiro a mtengo wapatali, ndipo m'madera ena angapereke galimoto yopindulitsa yogwiritsira ntchito chuma (Masewera ndi al., 2007; Gan et al., 2010; Beeler et al., 2012). Izi zikugwirizana ndi kugwirizanitsidwa komwekukokedwa kwa DA kuphatikizapo DA muzochita zamakhalidwe abwino, makamaka potsata ndondomeko ya mtengo / zopindulitsa (Salamone et al., 2007, Salamone et al., 2009).
Monga tafotokozera pamwambapa, zamoyo nthawi zambiri zimasiyanitsidwa ndi zolinga kapena zolinga zoyambitsa zokakamiza ndi zolepheretsa kapena zovuta. Njira inanso yonena izi ndikuti njira yogwirira ntchito yolimbikitsa imafuna kuti zamoyo zigonjetse "mtunda wamalingaliro" pakati pawo ndi zolimbikitsa zomwe zimakhudza. Lingaliro la mtunda wamaganizo ndi lingaliro lakale mu maganizo (monga, Lewin, 1935; Shepard, 1957; Liberman ndi Forster, 2008) ndipo watenga ziphunzitso zosiyanasiyana zosiyana siyana m'maganizo osiyanasiyana (mwachitsanzo, kuyesera, chikhalidwe, umunthu, ndi zina). M'nkhani yomweyi, imagwiritsidwa ntchito mobwerezabwereza kuti lingaliro loti zinthu kapena zochitika sizipezeka mwachindunji kapena zodziwa bwino, choncho zamoyo zimagawanika pambali yosiyanasiyana (mwachitsanzo, kutalika kwa thupi, nthawi, mwinamwake, zofunikira zamagulu) kuchokera zinthu izi kapena zochitika. Mu njira zosiyanasiyana, DA imagwilitsila nchito ngati mlatho umene umathandiza kuti nyama zithetse mtunda wamaganizo zomwe zimasiyanitsa iwo ndi zinthu zolinga kapena zochitika. Ofufuza ambiri amalembera izi m'njira zosiyanasiyana kapena amatsindika mbali zosiyanasiyana za ndondomekoyi (Everitt ndi Robbins, 2005; Kelley et al., 2005; Salamone et al., 2005, Salamone et al., 2007, Salamone et al., 2009; Phillips et al., 2007; Nicola, 2010; Lex ndi Hauber, 2010; Panksepp, 2011; Beeler et al., 2012; onani Chithunzi 2), koma ntchito zambiri zomwe zimaphatikizira DA zakhala zikuphatikizidwa, kuphatikiza kuyambitsa machitidwe, kuyesetsa mwamphamvu pakugwiritsa ntchito chida, Pavlovian kusinthira chida, kuyankha pazokopa, kuneneratu zochitika, njira zosinthira, kufunafuna, ndi mphamvu Kugwiritsa ntchito ndalama ndi kuwongolera, zonse ndizofunikira pothandiza kuthekera kwa ziweto kuthana ndi zopinga ndipo, mwanjira ina, zimadutsa mtunda wamaganizidwe. Ponseponse, ma nyukiliya amasonkhanitsa DA ndikofunikira pakuchita mayankho ogwira ntchito omwe amafunsidwa kapena kusungidwa ndi zoyambitsa ((Salamone, 1992), chifukwa choyesetsa khama poyankha nthawi yopanda chidziwitso chachikulu (Salamone et al., 2001; Salamone ndi Correa, 2002), komanso poyang'anira kugawidwa kwa zikhalidwe zamakhalidwe mwa kukhazikitsa zovuta pamayankho omwe amasankhidwa kuti athandizidwe pogwiritsa ntchito ndondomeko ya ndalama / zopindulitsa (Salamone et al., 2007, Salamone et al., 2012; Hernandez et al., 2010).
Kutanthauzira ndi Kutanthawuzira kwachipatala
Mofananamo ndi kufufuza kwa nyama zomwe tawunikiridwa pamwambapa, maphunziro a kuyesa ndi zachipatala ndi anthu ayambanso kufotokozera ntchito zina zomwe zimalimbikitsa anthu kuti ayambe kuchita zinthu zowonongeka. Kafukufuku amene akufalikira pa anthu, pogwiritsa ntchito mafanizo komanso njira zamagetsi, wapanga zotsatira zogwirizana ndi lingaliro lakuti maseŵera otha msinkhu, komanso DA makamaka, akuphatikizidwa m'zinthu zamaganizo, kuyembekezera kulimbitsa, kuwongolera khalidwe, njira zokhudzana nazo. Knutson et al., 2001 adanenanso kuti kuwonjezeka kwa fMRI kumawonekera mwa anthu omwe akuchita njuga, koma kuti zomwe zikuwonjezeka zimalumikizidwa ndi kuneneratu za mphotho kapena kuyembekezera m'malo mofotokozera zenizeni za mphotho ya ndalama. O'Doherty et al., 2002 adawonetsa kuti kuyembekezera kutuluka kwa shuga kunakhudzidwa ndi kuwonjezereka kwa fMRI m'katikati mwa midzi ndi madera a DA omwe akupha koma malowa sankayankhidwa. Kafukufuku wam'mbuyomu posachedwapa wagwira ntchito yopanga ndondomeko ya mtengo / zopindulitsa (Croxson et al., 2009; Botvinick et al., 2009; Kurniawan et al., 2011). Pewani et al., 2012 anapeza kuti kusiyana kwakukulu pakati pa anthu kunayanjanitsidwa ndi chizindikiro cha kujambula kwa ma ARV. Kuphatikiza apo, Wardle et al., 2011 adawonetsa kuti amphetamine imalimbikitsa chidwi cha anthu kuti achite khama kuti alandire mphotho, makamaka pomwe mwayi wamalipiro unali wochepa koma sizinasinthe zotsatira za mphotho yayikulu pakufunitsitsa kuchita khama. Pepala laposachedwa lowonetsa kuti milingo ya L-DOPA yomwe idakulitsa chiwonetsero chazomwe zimakhutiritsa sizinakhudze kuyimilira kwa mphamvu yakulimbikitsira (Guitart-Masip et al., 2012). Lipoti lina laposachedwapa linalongosola kuti mphamvu za catecholamine zimagwiritsidwa ntchito kuti zisiyanitse pakati pa zinthu zosiyana ndi zomwe zimakhudzanso anthu (Venugopalan et al., 2011). Mu phunziro ili, kupeza kwa kusuta fodya kunagwiritsidwa ntchito monga reinforcer, ndipo ofufuzawo anagwiritsa ntchito njira yotumizira DNA kudzera mwachangu kuopseza catecholamine kaphatikizidwe ndi phenylalanine / tyrosine kutha. Kuletsedwa kwa kapecholamine kaphatikizidwe sizinatanthauze kudzikonda kwina komwe kunkafuna kusuta ndudu, kapena mayankho okhudza kusuta fodya. Ngakhale zili choncho, izi zinapangitsa kuti anthu asagwiritse ntchito mankhwala osuta fodya. Kuwonjezera apo, kufotokoza zofukufuku kwawonetsa kuti nucleus accumbens / ventral striatum sichimangokhulupirira zokhazokha, koma imayankha kupsinjika, kuthamangitsidwa, ndi kukhumudwa / kukhumudwa (Liberzon et al., 1999; Pavic et al., 2003; Phan et al., 2004; Pruessner et al., 2004; Levita et al., 2009; Delgado et al., 2011). Kuphatikizidwa pamodzi, maphunzirowa akusonyeza kuti pali kusiyana kwakukulu pakati pa kafukufuku wopangidwa kuchokera ku zitsanzo za zinyama ndi zomwe zapezeka kuchokera kufukufuku waumunthu, mwazinthu zambiri zomwe zimakhudza ntchito za mesostriatal DA.
Malingaliro onena za DA akupitirizabe kusintha, kufufuza za ntchito za DA kudzakhala ndi zofunikira kwambiri pa kufufuza kwachipatala za zovuta zomwe zimachititsa anthu omwe ali ndi vuto la maganizo, schizophrenia, kugwiritsa ntchito mankhwala osokoneza bongo, ndi mavuto ena. Kwa anthu, zovuta zokhudzana ndi kusintha kwa khalidwe ndizofunika kwambiri. Kutopa, kusayanjanitsika, kutulutsa mphamvu (ie, kudzidzimva mopanda mphamvu), ndi kuchepetsa maganizo ndizofala zowonongeka (Marin et al., 1993; Stahl, 2002; Demyttenaere et al., 2005; Salamone et al., 2006), ndi zizindikiro zofanana zokhudzana ndi zizindikiro zokhudzana ndi matenda a m'maganizo komanso zokhudzana ndi ubongo monga schizophrenia (kutanthauza, "kubwezeretsa"), kuchotsa mwachangu (Volkow et al., 2001), Parkinsonism (Friedman et al., 2007; Shore et al., 2011), multiple sclerosis (Lapierre ndi Hum, 2007), ndi matenda opatsirana kapena otupa (Dantzer et al., 2008; Miller, 2009). Umboni wochuluka wochokera ku zinyama ndi maphunziro aumunthu umasonyeza kuti DA osolimbic ndi ovulaza akuphatikizidwa m'zinthu zovuta zomwe zimakhudzidwa (Schmidt et al., 2001; Volkow et al., 2001; Salamone et al., 2006, Salamone et al., 2007, Salamone et al., 2012; Miller, 2009; Treadway ndi Zald, 2011). Kafukufuku waposachedwapa wa kafukufuku wa zaumoyo wakhala akuthandizira kuchepetsa chidziwitso cha zizindikiro za chikhalidwe, ndipo m'malo mwake amayang'ana maulendo a neural omwe amatsutsana ndi zizindikiro zina zomwe zimapangitsa kuti zikhale zovuta. Morris ndi Cuthbert, 2012). Ndizotheka kuti kupitiliza kafukufuku pazantchito zothandizirana ndi DA kudzawunikira mayendedwe amitsempha omwe ali ndi zina mwazomwe zimayambitsa matenda a psychopathology, ndipo zithandizira kukulitsa njira zochiritsira zatsopano pazizindikirozi zomwe zimathandizira pamavuto angapo.
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