John D. Salamone, Mercè Correa
Neuron - 8 Mbudzi 2012 (Vol. 76, Nyaya 3, mapeji 470-485)
pfupiso
Nucleus accumbens dopamine inozivikanwa kuti inobatsira pakuita zvinokurudzira, uye zvinokonzera mesolimbic dopamine zvinogona kuita kuti zviratidzo zvinokurudzira zvekuora mwoyo uye zvimwe zvinetso, uyewo zvinoshandiswa pakushandisa zvinodhaka. Kunyangwe zvave zvisiri tsika zvekureva dopamine neurons se "mubairo" neurons, uku ndiko kuwedzerwa, uye zvakakosha kusiyanisa pakati pezvinhu zvinokurudzirwa zvakasiyana-siyana zvakakanganiswa nedopaminergic manipulations. Semuenzaniso, accumbens dopamine haibvumiri chivako chekudya chekudya kana chido, asi inobatanidzwa mukushushikana uye kupesana kwekukurudzira zvinosanganisira kushandiswa kwekuita, kushanda nesimba, nzira yekuita, kushandiswa kwekuita basa, mapurogiramu ePavlovian, nekudzidza kwechikoro. Muchidzidzo ichi, tinokurukura basa rakaoma re dopamine mumabasa ekutevedzera ane chokuita nekukurudzira.
Main Text
Nucleus accumbens dopamine (DA) yakabatanidzwa mumabasa akawanda ehupenyu ane chokuita nekukurudzira. Asi zvakananga zvekubatanidzwa uku kwakaoma uye pane dzimwe nguva zvinogona kuva zvakaoma kudzivisa. Chimwe chinhu chinonyanya kukoshesa mukududzira zvitsva izvi ndiko kukwanisa kusiyanisa pakati pezvinhu zvakasiyana-siyana zvekukurudzira basa izvo zvakasiyana-siyana zvakakanganiswa nedopaminergic manipulations. Kunyange zvazvo ventral tegmental neurons yakagara ichinzi "mubayiro" neurons uye mesolimbic DA inonzi "mubairo" system, izvi zvisizvo zvisingaenzaniswi nezvakawanikwa zvinowanikwa. Shanduro yesayenzi yezwi rokuti "mubairo" haisi pachena, uye ukama hwayo nemafungiro akadai sekusimbisa nekukurudzira kunowanzorwara kunotsanangurwa. Zvidzidzo zveAppmacological uye zveDA zvinoratidzira kuti DAlimbic DA inonyanya kukosha kune zvimwe zvikonzero zvekusimudzira basa, asi zvishoma kana zvisingabatsiri kune vamwe. Zvimwe zvemashoko anoshingaira e-mesolimbic DA zvinomiririra nzvimbo dzinopindirana pakati pezvinhu zvinokurudzirwa uye zvinoshandiswa nemotokari yekudzivirira, iyo inopindirana nekubatanidzwa kwakanyatsozivikanwa kwekisikiti kunowanikwa mumagetsi uye nemamwe maitiro akafanana. Uyezve, pasinei nemabhuku makuru anobatanidza DA inobata maziso kune zvimwe zvekuvhiringidza uye kudzidza, mabhuku anodzokera kumashure makumi emakore (eg, Salamone et al., 1994), tsika yakagadziriswa yave iri yekusimbisa dopaminergic kubatanidzwa mukubhadhara, kufara, kukanganisa, uye kupiwa mubairo, uye zvisingambofungi nezvekubatanidzwa kweAlsolimbic DA mumagetsi. Iko kuongorora ikozvino kuchakurukura kusabatanidzwa kweAlsolimbic DA muzvinhu zvakasiyana-siyana zvekukurudzira, nekusimbiswa kune miedzo inopesana nekutapurirwa kweDA, kunyanya mu nucleus accumbens.
Mesolimbic DA nekukurudzira: The Changing Theoretical Landscape
Kana pasina chimwe chinhu, vanhu inveterate nyaya vanotaura; isu tiri, shure kwezvose, vazukuru vevanhu vakagara vakakomberedza moto husiku vachigadziriswa nezvakajeka ngano, ngano, uye nhoroondo dzemumuromo. Ndangariro dzevanhu dzinonyanya kushanda kana zvisina kujairika chokwadi kana zviitiko zvinogona kuvezwa mukati mechidzitiro chine musoro chenyaya yakabatana. Masayendisiti haana kusiyana. Hurukuro inobudirira yeyunivhesiti, kana seminari yesainzi, inowanzonzi "nyaya yakanaka." Saka ndozvazvakaita nepfungwa dzesainzi nedzidziso. Uropi hwedu hunoratidzika kunge hunoshuva kurongeka uye kubatana kwepfungwa kunopihwa neyakareruka uye yakajeka sainzi yekufungidzira, yakatsigirwa nehumwe humbowo hwakakwana kuti iite kuti inzwike. Dambudziko ndere- ko kana kubatana kwenyaya kuri kuwedzerwa nekunyanyisa kududzira zvimwe zvakawanikwa, nekuregeredza zvimwe? Zvishoma nezvishoma, zvidimbu zvepikicha zvisina kukodzera zvinoramba zvichidya zvachose, zvichizopedzisira zvichipa nyaya yese nhamo zvisina kukwana.
Mumwe anogona kupokana kuti mhando iyi yeshanduko yakaitika maererano nepfungwa yeDA ye "mubairo." "Nyaya" inogona kuvakwa, iyo yaizoenderera seinotevera: chiratidzo chikuru chekushushikana ndeye anhedonia, uye sezvo DA iri "mubairo wekutepfenyura" uyo unopindirana nemahedonic reaction, saka kushushikana kunokonzerwa nekudzikiswa kweDA-inodzorwa ruzivo rwekunakidzwa . Saizvozvowo, zvakataurwa kuti kupindwa muropa nezvinodhaka kunoenderana neruzivo rwekunakidzwa nemishonga inobira huropi "mubairo wehurongwa," iyo inopindirana nekutapurirana kweDA uye yakashanduka kuratidza mufaro unogadzirwa nehunhu hwepanyama senge chikafu. Izvi zvaigona kutoratidza kuti kuvharira maDA receptors kunogona kupa kurapwa kuri nyore kupindwa muropa. Chekupedzisira, mumwe anogona zvakare kupa "nyaya" yakavakirwa pane fungidziro yekuti DA neurons inongopindura chete kune zvinonakidza zvinokurudzira senge chikafu uye kuti chiitiko ichi chinopindirana nemanzwiro ekupindura kune izvi zvinokonzeresa, izvo zvinokonzeresa chishuwo chekudya chikafu. Nyaya dzakadai hadzisi "varume vemashanga" dzakagadzirwa nenzira dzeidzi ndima. Asi zvinosuruvarisa, kunyangwe paine mukurumbira, hapana kana imwe yemazano aya inotsigirwa zvizere nekunyatsoongorora zvinyorwa.
Kutora muenzaniso wekuita dopaminergic mukuora mwoyo, mumwe angatanga kudonongodza pfungwa iyi nekuratidza kuti "anhedonia" mukuderera kunowanzosanzwisiswa kana kushorwa nemakiriniki (Treadway naZald, 2011). Kuongorora kwakasiyana-siyana kunoratidza kuti vanhu vakaora mwoyo vanowanzova nemafungiro ezvakaitika pakuzvimiririra okusangana nemafaro anonakidza uye kuti, pamusoro pematambudziko chero ose ane ruzivo rwemufaro, vanhu vanoora mwoyo vanoita sevanopererwa muhutano hwekuita, maitiro ekutsvaga mubayiro, uye kushanda nesimba (Treadway naZald, 2011). Zvechokwadi, vanhu vane mwoyo yakaora mwoyo vanotambura neboka rekuremara rekuvhiringidzika kunovhiringidza kunosanganisira kuora mwoyo kwepfungwa, anergia, uye kuneta (Demyttenaere et al., 2005; Salamone et al., 2006), uye uchapupu hwakawanda hunobatsira DA mune zviratidzo izvi (Salamone et al., 2006, Salamone et al., 2007). Aya maonero, pamwe nemabhuku anoratidza kuti hapana mutsara unyore pakati pebasa reDAD uye hedonic chiitiko (semuenzaniso, Smith et al., 2011) uye zvidzidzo zvakabatanidza DA kudhidzira kushanda uye kushanda nesimba (Salamone et al., 2007; ona kukurukurirana pasi apa), tungamira mumwe kugumisa kuti dopaminergic kupinda mukutambudzika kunoratidzika kunge kwakaoma kupfuura iyo nyaya isina nyore ingadai yakabvumira.
Saizvozvowo, zvakajeka kuti chikwata chikuru chekutsvakurudza pamishonga yekushandisa zvinodhaka uye kusagadzikana hazvibvumirwi nemitemo yakatarwa yeDA hypothesis yemubairo. Tsvakurudzo dzinoverengeka dzakaratidza kuti kudzivirirwa kweDA receptors kana kuvharwa kweDNA synthesis hakusi kusinganzwisisi kuzvirumbidza kwehupenzi kana kuti "kukwirira" kunokonzerwa nemishonga yekudzvinyirirwa (Gawin, 1986; Brauer na De Wit, 1997; Haney et al., 2001; Nann-Vernotica et al., 2001; Wachtel et al., 2002; Leyton et al., 2005; Venugopalan et al., 2011). Ongororo ichangobva kuitika yave ichinyatsosiyanisa maitiro ehutsika anoratidzwa nemakonzo munguva yePavlovian yekugadzirisa, iyo inofananidzwa nehuwandu hwekuzvipa mishonga. Rats inoratidza kukurira kukuru kune zvakagadziriswa (zviratidzo zvekucherechedza) zvinoratidza maitiro akaenzana ekugadzirisa dopaminergic kudzidziswa kana ichifananidzwa nemhuka dzinowedzera kugamuchira kune chinonyanya kusimbisa (chinangwa chevateereri; Flagel et al., 2007). Zvinofadza kuti makonzo anoratidza maPavlovian zvakanyanya kufanana nekusvika kune chinetso chekuvhiringidza uye kuratidzira kukurudzirwa kwakanyanya kune mishonga yekushandisa zvinodhaka, uyewo anowanzoratidza kuratidza kutya kukuru mukupindurwa kwezvinyorwa zvichitarisa kushamisika uye kuwedzera kwekutya kwemaitiro (Morrow et al., 2011). Kutsvakurudza kwakawedzerwa kwakapesana nedzimwe pfungwa dzakareba dzakatarisana pamusoro pezvinonzi neural nenzira inokonzera kusagadzikana, kusiyana nekutanga kusimbisa maitiro emishonga. Yakava yakajairika pakuona kusagadzikana maererano neostriatal tsika-kugadzira nzira dzakagadzirirwa pane zvakanyanya kutengesa zvinodhaka, izvo zvinogona kunge zvisingabatsiri nezvibatsiro zvekugadzirisa zvigadzirwa kana kuti maitiro ekutanga anokurudzira emishonga ekusimbisa zvinodhaka (Kalivas, 2008; Belin et al., 2009). Aya maonero anobuda pamusoro pehutano hwemishonga yezvinodhaka, pamwe nehutano hwahwo huripo, wakatamira mberi kupfuura nyaya yepakutanga inopiwa neDA hypothesis ye "mubayiro."
Mushure memazana makumi emakore ekutsvakurudza, uye nekuenderera mberi kwezvakaitika, zvakakonzerwa nekugadziriswa kwepfungwa mumunda weDAD tsvakurudzo. Uchapupu huzhinji hunoratidza kuti kupindira kwekutsvaira maziso DAlimbic kunoita kuti zvive zvakakosha zvekukurudzira uye hedonic yezvokudya zvakasimba (Berridge, 2007; Berridge uye Kringelbach, 2008; Salamone et al., 2007). Zviratidzo zvekuita sekufambira mberi kwemazana ekuputika kwepakati uye kukanganisa kuzvidzora, izvo zvakambofungidzirwa kuti zvinobatsira sezviratidzo zve "mubayiro" kana "hedonia" mabasa eDA, iko zvino inofungidzirwa kuratidza nzira dzinosanganisira kushanda nesimba, kunzwisisa kwekuedza -kubatanidzwa kana kuti mukana wekuwana, uye kugadzira chisarudzo (Salamone, 2006; Hernandez et al., 2010). Mune mapepa emapepanhau emagetsi ekupedzisira anoratidza kusateerera kwezvingafungidzirwa kana kuti zvakatsanangurwa zvekutsvaga maDA neurons kune zvinokonzera kushushikana (Anstrom na Woodward, 2005; Brischoux et al., 2009; Matsumoto naHikosaka, 2009; Bromberg-Martin et al., 2010; Schultz, 2010; Lammel et al., 2011). Vatsvakurudzi vazhinji zvino vanosimbisa kusabatanidzwa kwemazisolimbic uye nigrostriatal DA mukudzidzira kusimbisa kana kugadzira tsika (Akachenjera, 2004; Yin et al., 2008; Belin et al., 2009), panzvimbo yeHedonia nega. Izvo zviito zvose zvakabatanidzwa mukunyora kunyoresa kwenyaya yekuita dopaminergic mukukurudzira.
Zvinokurudzirwa Nzira: Nhoroondo uye Nheyo
Izwi rinokurudzira rinoreva chivakwa chinowanzoshandiswa mune zvepfungwa, masayendisiti, uye neuroscience. Sezvakangoita nemafungiro mazhinji epfungwa, kukurukurirana kwekukurudzira kwakave kwakabva mufilosofi. Mukutsanangura zvikonzero zvinodzora maitiro, muzivi wechiGermany Schopenhauer, 1999 akakurukura pfungwa yekukurudzira maererano nenzira iyo zvipenyu zvinogona kunge zviri mukana we "kusarudza, kubata, uye kunyange kutsvaka nzira yekugutsikana." Kukurudzirwa zvakare kwaive nzvimbo inokosha yekufarira munguva yekutanga kukura kwepfungwa. Masayendisiti ezvepfungwa dzekutanga, kusanganisira Wundt naJames, dzaisanganisira kushingaira sehurukuro mumabhuku avo. Neobehaviorists dzakadai seHull neSpence zvinowanzoshandiswa zvinokurudzira pfungwa dzakadai sokukurudzira uye kutyaira. Muduku, 1961 tsananguro inotsanangurwa se "nzira yekusimudzira zviito, kusimbisa basa iri riri mberi, uye kuronga maitiro emabasa." Maererano nekutsanangurwa kwemazuva ano, zvinokurudzira "mararamiro emitemo kuburikidza nezvisikwa zvipenyu zvinotungamirira mukana, kuswedera pedyo nekuwanikidzwa kwezvinhu zvinokurudzira "(Salamone, 1992). Kazhinji kutaura, kugadzirwa kwepfungwa kwemazuva ano kunoreva maitiro anoenderana-kuita zvinoita kuti zvipenyu zvironge zvose zviri mukati uye mukati memo (Salamone, 2010).
Zvichida kushandiswa kukuru kwekuvaka kwekukurudzira ndekuti kunopa chidimbu chakanaka uye sangano rehurongwa kwezvinhu zvinoonekwa zvekuita (Salamone, 2010). Unhu hunoendeswa mberi kana kure pane zvimwe zvinhu, pamwe nemabasa anosanganisira kuwirirana neavo vanoita. Nhengo dzinotsvaka kuwana zvimwe zvinokonzerwa nemamiriro ezvinhu (kureva, zvokudya, mvura, zvepabonde) uye kudzivisa vamwe (kureva, kurwadziwa, kusagadzikana), mune zvose zviri zviviri uye zvisingatauriki. Uyezve, mufambiro unokurudzira unowanzoitika muzvikamu (Tafura 1). Icho chigarire chiitiko chekuzvibata, icho chinoratidza kushamwaridzana zvakananga nechinangwa chinokurudzira, chinowanzotaurwa sechikamu chinopedza. Izwi rokuti "kupedza" (Craig, 1918) haisi kureva "kushandiswa," asi kunoreva "kupedza," zvinoreva kuti "kupedzisa" kana kuti "kupedzisa." Mukuona kwekuti chikonzero chinokurudzira chinowanzowanikwa pane imwe nzvimbo yepanyama kana yepfungwa kubva kumhuka, Nzira chete yekuwana nayo izvi zvinokurudzira ndeyekuita mufambiro unovaunza pedo, kana kuita kuti zviitiko zvavo zvive nyore. Ichi chikamu chekuzvibata kwakakurudzirwa kazhinji kunonzi "kunetseka," "kugadzirira," "kushanda," "kuswedera," kana "kutsvaka." Nokudaro, vatsvakurudzi dzimwe nguva vanosiyanisa pakati pe "kutora" ne "kutsvaga" kwezvinhu zvakasikwa zvakadai se zvokudya (semuenzaniso, Foltin, 2001), kana kuti zvekusimbisa zvinodhaka; zvirokwazvo, izwi rokuti "kutsvaga zvinodhaka" rave mutsara unowanikwa mumutauro we psychopharmacology. Sezvakakurukurwa pasi apa, izvi zvakasarudzwa (semuenzaniso, zvinopesana nezvinopisa kana kutsvaga kana kutora) zvinokosha pakunzwisisa migumisiro ye dopaminergic manipulations pamusana pekukurudzira kwezvinhu zvakasikwa zvakadai sekudya.
Mukuwedzera kune "kutungamira" zvinhu zvinokurudzira (kureva, kuti mufambiro unotungamirirwa kana kure kure nekukurudzira), unhu hunosimbisa zvakare hunonzi "huchiita" zvinhu (Cofer naAppley, 1964; Salamone, 1988, Salamone, 2010; Parkinson et al., 2002; Tafura 1). Nemhaka yokuti zvipenyu zvinowanzoparadzana kubva pakukurudzira kunofambisa nerwendo rurefu, kana nezvipingamupinyi zvakasiyana-siyana kana kuti zvinopindura, kuitisa muzviito zvinowanzosanganisira kushanda (semuenzaniso, kubata, maze kushanda, lever kushivirira). Mhuka dzinofanira kugovera zviwanikwa zvakanyanya pakuita unhu hwekutsvaga, izvo zvinogona kuratidzirwa nekuedza kukuru, kureva, kukurumidza, kushivirira, uye kukwirira kwebasa rinobuda. Kunyange zvazvo kuedza kweizvi kuedza dzimwe nguva kungave kwenguva pfupi (semuenzaniso, mhuka inoparadza pangozi yayo), pasi pemamiriro mazhinji ezvinhu inofanira kusimbiswa kwenguva refu. Simba-rine simba rakakosha rinonyatsopindirana, nokuti mune zvakasikwa zvakasikwa zvinogona kutarisana nekukwirira kwokuti muviri unopedza nguva-kana yehupfumi yekuita basa. Nokuda kwezvikonzero izvi, kushandura mafambiro kwakaonekwa sechinhu chinokosha chekukurudzira kwemakumi emakumi emakore. Nyanzvi dzezvepfungwa dzakashandisa kwenguva refu pfungwa dzekutya uye zvinokurudzira kusimudzira migumisiro inokurudzira yezvinosimudzira mamiriro ekugadzirisa maitiro, sezvinoita kumhanyisa kukurumidza mu maze. Cofer naAppley, 1964 vakaratidza kuti paiva nekutarisira-kushandiswa kwekugadzirisa nzira iyo inogona kushandiswa nemaitiro anogadziriswa, uye iyo inoshandiswa kusimbisa mafambiro emhando. Chirongwa chisingadikanwi mharidzo yezvinonyanya kukurudzira zvinokurudzira zvakadai sekusimudzira kudya kwepellets zvinogona kuita mabasa akasiyana-siyana, kusanganisira kunwa, kuputika, uye kufamba-ngoro (Robbins naKoob, 1980; Salamone, 1988). Vanotsvakurudza vanoverengeka vakaongorora kukosha kwebasa rinodiwa pakushanda kwebasa rekushandisa, iro rakazobatsira pakuisa hwaro hwekuvandudza mararamiro ehupfumi hwekuita basa (semuenzaniso, Hursh et al., 1988). Ethologists zvakare akashandisa pfungwa dzakafanana. Mhuka dzinoshandisa mhuka dzinoda kushandisa simba kuti dziwane zvokudya, mvura, kana nyuchi, uye inyanzvi yekugadzira mhando yezvinyorwa inotsanangura kuti yakawanda sei simba kana nguva inoshandiswa kuti zviwane izvi zvinokonzera kukosha kunokosha kwekuita sarudzo.
Pane huwandu hwakati wandei hwepfungwa hunowirirana pakati pemabatirwo emagetsi ekudzora uye nekumisikidza maficha ekukurudzira. Semuenzaniso, kushomeka kwechikafu kunogona kumhanyisa kumhanya kumhanya mumaze. Izvi zvinoratidza mamiriro ari kukurudzira, mota, kana kumwe kusanganisa kwevaviri? Locomotor chiitiko zvakajeka chiri pasi pekutonga kweiyo neural masisitimu ayo anodzora kufamba. Zvakangodaro, chiitiko chema locomotor mumakonzo zvakare chine hanya zvakanyanya nemhedzisiro yemamiriro ekukurudzira senge utsva, kushomeka kwechikafu, kana kuratidzwa kwapanhambo nenhambo kwezvipikiri zvidiki zvekudya. Pamusoro pezvo, kana muviri ukapihwa chinetso chine chekuita nebasa panguva yekuita chiridzwa, chinowanzo pindura kudambudziko iri nekuedza nesimba. Kuwedzera zviyero zvinodiwa paanoshanda mashedhiyo, kusvika padanho, zvinogona kuumba zvakakura kumusoro kumanikidza pamitengo yemhinduro. Kutarisana nechipingamupinyi, senge chipingamupinyi mumazeya, kunogona kutungamira makonzo kuti awedzere kuedza kwavo kwekuyedza uye kusvetuka pamusoro pechipingamupinyi. Kupfuurirazve, kuratidzwa kwePavlovian yakagadziriswa inosimudzira inosanganisirwa neyekutanga yekukurudzira inosimudzira senge chikafu inogona kushandira kukurudzira nzira kana kuwedzera chiitwa chevaridzi, chiitiko chinozivikanwa sePavlovian kuchinjisa kuchishandiswa (Colwill uye Rescorla, 1988). Nokudaro, neural systems dzinodzora motokari dzinowanzoshanda pane zvinyorwa zvevaneural systems iyo inoratidzira maitiro kana kuti kure nezvimwe zvinokonzera (Salamone, 2010). Zvechokwadi, mazwi "motokari yekudzora" uye "kukurudzira" hazvirevi chaizvoizvo chinhu chimwe chete, uye munhu anogona nyore nyore kuwana nonoverlap. Kunyange zvakadaro, zvakajeka kuti kune humwe hutano hwakakosha pamwe chete (Salamone, 1992, Salamone, 2010). Muchirevo chekucherechedza uku, zvinodzidza kufunga kuti mazwi echiChirungu anokurudzirwa uye kufambisa zvose zviri pakupedzisira anobva muzwi rechiLatini movere, kuenda (kureva, chinangwa ndiyo yakatora chikamu che movere). Sezvo nekuparadzaniswa pakati pekugadzirisa zvinopesana nemafambiro ekutsvaira (kana kutsvaga zvichienderana nekutora), kusiyana pakati pekushanda pamwe nekutungamirirwa kwezvinhu zvinokurudzira zvinoshandiswa zvakanyanya kurondedzera migumisiro ye dopaminergic manipulations (Tafura 1). Izvo zvakasiyana-siyana zvekukurudzira nzira ndeyekukosha kwebhuku rinokurukura maitiro ekubata kwe dopaminergic manipulations, uyewo iyo inotarisa pamabasa ekugadzirisa maziso aD DA neurons.
Dissociative Nature yemigumisiro yekupinda neNucleus Accumbens DA Transmission
Mukuedza kunzwisisa mabhuku pamusoro pemabasa anokurudzira ekugadzirisa DA, tinofanirwa kuongorora mitemo yakawanda inoratidzwa pamusoro apa. Kune rumwe rutivi, tinofanirwa kuziva kuti zvinokurudzira zvinoshandiswa zvakasununguka kuva zvikamu zvezvikamu, uye kuti kushandiswa kwekutengesa kudhindwa kweDA dzimwe nguva kunokwanisa kubatanidza zvinhu izvi sekushandiswa kwemukati wedhaimani, kuchinja zvikuru dzimwe nguva pavanenge vachisiya vamwe zvikuru vasingabatsiri (Salamone uye Correa, 2002; Berridge naRobinson, 2003; Smith et al., 2011). Kune rimwe divi, isu zvakare tinofanirwa kuona kuti zvinokurudzira zvinowirirana nenzira dzinoenderana nemanzwiro, kudzidza, uye mamwe mabasa, uye kuti hapana chaiyo mapoinzi-kunongedzera mepu pakati pehunhu maitiro uye neural masisitimu. Nekudaro, mimwe yemhedzisiro yedopaminergic manejimendi inogona kunyatsonzwisiswa maererano nezviito pane chaiwo maficha ekukurudzira, mota mashandiro kana kudzidza, nepo mimwe mhedzisiro inogona kunge yakanyanyisa munzvimbo dzekupindirana pakati peaya mabasa. Chekupedzisira, mumwe zvakare anofanirwa kufunga kuti hazviite zvakanyanya kuti kuunganidza DA kunoita basa rimwe chete chairo; Zvakaoma kubata pamushini wakaomesesa senge mammalian uropi hunoshanda nenzira yakapfava kudaro. Nekudaro, kuunganidza DA pamwe kunoita mabasa akati wandei, uye chero maitiro kana maitiro euroscience anogona kunge akakodzera kuratidza mamwe emabasa aya, asi asina kukodzera vamwe. Mukuona kweizvi, zvinogona kuve zvinonetsa kuunganidza kuwirirana maonero.
Ubongo huripo hunogona kuchinja zvikamu zvekuita nenzira nenzira yakananga. Iyi nhungamiro yakave yakakosha mukufungisisa neuroscience uye yakatungamirira kukakosha kunokosha maererano nemasikirwo emasikirwo emasikirwo (kureva, declarative versus procedural memory, kushanda zvichienderana neshoko rekuyeuchidza, hippocampal-inotenderera kune-inotenderera nzira). Kusiyana neizvi, kufarira mune zvakawanda zvebhuku rinotaura nezvemabasa ekugadzirisa DA inoshandiswa kushandisa pane zvinyararire zvishandiso zveshoko, kureva, mazwi akajeka uye asinganzwisisiki akadai se "mubairo," kuisa muchidimbu zviito zvemishonga kana zvimwe zvinogadziriswa. Zvechokwadi, izwi rokuti "mubairo" rakatsoropodzwa zvakanyanyiswa mune imwe nzvimbo (Cannon uye Bseikri, 2004; Salamone, 2006; Yin et al., 2008; Salamone et al., 2012). Kunyange zvazvo shoko rokuti mubairo rinoreva sezwi rinoreva "kusimbisa," hapana shanduro isingagumi yesayenzi ye "mubairo" iyo inoshandiswa kutsanangura nzira yeurourobehavior; vamwe vanorishandisa sechirevo chezwi rokuti "kusimbiswa," asi vamwe vanoshandisa iro kureva "chinangwa chekutanga" kana "chido," kana sechinyorwa chisinganzwisisiki che "mufaro" kana "hedonia" (nokuda kwezvakaitika kare zve "anhedonia hypothesis" , "Ona Akachenjera, 2008). Muzviitiko zvakawanda, izwi rokuti "mubairo" rinoratidzika seiri kushandiswa sezwi rinowanzoreva zvinoreva zvose zvinokonzera kushaya simba, kudzidza, uye manzwiro, kusanganisira zvose zvakagadziriswa uye zvisingaverengeki; kushandiswa uku kwakazara zvokuti hazvirevi. Mumwe anogona kutaura kuti kushandiswa kweshoko rokuti "mubairo" ndiko kunokonzera kuvhiringidzika kukuru munharaunda iyi. Kunyange imwe nyaya ingashandisa mubairo kunoreva kufara, mumwe angashandisa izwi kuti ataure nezvekusimudzira kudzidza asi kwete kufara, uye chetatu inogona kunge ichireva kushuva kwechishuwo nenzira yakawanda. Izvi ndezvirevo zvitatu zvakasiyana zvakasiyana zvezwi, izvo zvinokonzera kukurukurirana kwemaitiro ekuita mabasa e-mesolimbic DA. Uyezve, kutaura kuti DA's mesolimbic se "mubayiro system" inoshandisa kuderedza basa rayo mukudzivirira mafungiro. Pamwe dambudziko guru pane izwi rokuti "mubairo" nderokuti rinovhiringidza pfungwa yekufadza kana hedonia muverengi vakawanda, kunyange kana izvi zvisingadikanwi nemunyori.
Kuongorora kwemazuva ano kunotarisa kuve nekubatanidzwa kwekuunganidza DA mune zvimwe zvikonzero zvekusimudzirwa kwezvisikwa zvakadai sekudya. Pakati pese, pane kusava nechokwadi kudarika kunobatanidza DA kunobatanidzwa mune zvimwe zvikamu zvekudya zvinokurudzira; asi izvo zvipi? Sezvatichaona pasi apa, migumisiro yekupindira nekutengesa DA yakagadzirwa neve DA inonyanya kusarura kana kuti kusiyanisa muzvisikwa, kuora mwoyo zvimwe zvezvinhu zvinokurudzira apo vamwe vachisiya vamwe. Zvasara zvechikamu chino zvichakurukura pamigumisiro yezviongorori umo dopaminergic zvinodhaka kana neurotoxic agents zvinoshandiswa kugadzirisa unhu hwekuita.
Kunyange zvazvo inowanzozivikanwa kuti forebrain DA inopedzisira inogona kukanganisa kudya, izvi zvinoitika zvakabatana nekuderedza kana kupesana kweDA mumagetsi kana nzvimbo dzinofambisa motokari dzenharaal or ventrolateral neostriatum, asi kwete nucleus accumbens (Dunnett naIversen, 1982; Salamone et al., 1993). Chiitiko chekupedzisira chinonzi optogenetics chakaratidza kuti kukurudzira chirongwa cheGABA neurons, chinoguma nekudzivirira kweA DA neurons, yakagadzirisa kubvisa kudya kwekudya (van Zessen et al., 2012). Zvisinei, hazvisi pachena kana izvi zvichinyanya kukosha nokuda kwezviito zveDopaminergic, kana kana zvichienderana nezvisingaiti zvinokonzerwawo nekugadzirisa (Tan et al., 2012). Ichokwadi, kuunganidza DA kuderedza uye kupesana kwakaratidzwa kakawanda kwete kunyanya kukanganisa kudya zvokudya (Ungerstedt, 1971; Koob et al., 1978; Salamone et al., 1993; Baldo et al., 2002; Baldo naKelley, 2007). Kubva pane zvavakawana kuti majekesiti eD1 kana D2 vanopikisana nevemumhuri kuti vawane hutanda kana hutachiona husina kusimba motokari, asi haana kubvisa kudya kudya, Baldo et al., 2002 vakataura kuti vanobatanidza kudzvinyirira kweDA "havana kubvisa chinangwa chekudya." Kubatana kwaD DA kukanganiswa kwakakundikana kuderedza kudya kwekudya kana kudyidzana kwekudya, uye hazvina kukanganisa kudya kwekudya, kunyange zvazvo kuderera kwakafanana kwekutsvaga neostriatum kwakakanganisa matanho aya (Salamone et al., 1993). Mukuwedzera, migumisiro yevanopikisana neDA kana kuunganidza dambudziko reDA pamusoro pekudya-kusimbiswa kwechimiro chekuita hakuiti zvakafanana nemigumisiro yezvokudya zvinodhaka zvinodhaka (Salamone et al., 2002; Sink et al., 2008), kana kukurudzirwa kwekusimudzira kwakapiwa nekufananidza (Salamone et al., 1991; Aberman naSalamone, 1999; Pardo et al., 2012). Lex naHuber, 2010 yakaratidza kuti makonzo ane accumbens DA akange achinetseka kuongorora kuwedzerwa kwezvokudya panguva yebasa rinoitwa. Uyezve, Wassum et al., 2011 yakaratidza kuti Dhigirii anopikisa flupenthixol haana kukanganisa kugadzikana kwekupa mubairo wezvokudya kana kuwedzerwa mubairo kunogadziriswa nekusimudzirwa mune zvekusimudzira nyika yakabudiswa nekuwedzera kwekudya kwekudya.
Uchapupu hwakajeka hunoratidzawo kuti nucleus accumbens DA haina kurongedza zvakananga hedonic reactivity kune zvokudya. Bhuku guru rebasa rinobva kuBerridge uye vashandi pamwe navo vakaratidza kuti maitiro ekugadzirisa kwevanopikisana neDA, pamwe chete neDA zvinyorwa muhuwandu we forebrain kana nucleus accumbens, hazvirevi kushushikana kwechingwa reactivity yezvokudya, iyo inyanzvi yakawanda inogamuchirwa ye hedonic reactivity kusvika kunhu rakanaka (Berridge naRobinson, 1998, Berridge naRobinson, 2003; Berridge, 2007). Uyezve, kugogodza kweDA transporter (Peciña et al., 2003), pamwe nema microinjections eamphetamine mu nucleus accumbens (Smith et al., 2011), iyo yose inokwidziridza DA inonzi extracellular, yakakundikana kuwedzera kudhavira kugona reactivity ye sucrose. Sederholm et al., 2002 yakashuma kuti D2 receptors mu nucleus accumbens shell inodzora kushandura kunakidza reactivity, uye kuti braininess yakagadziriswa D2 kukurudzira yakaderedza kushandiswa kwezvinoshandiswa, asi hapana vanhu vanogamuchira zvakagadzirisa zviratidzo zveheonic.
Kana nucleus inounganidza DA isingabatanidzi chishuwo chekudya pane yega, kana chikafu-chinokonzeresa kuita kwehedonic, saka iko kubatanidzwa kupi mukukurudzira kwekudya? Pane chibvumirano chakakura chinogumbura kudonha kweDA kana kupokana kunosiya zvakakosha zvechikafu-chinokonzeresa hedonia, chishuwo, kana chekutanga chikafu chinokurudzira, asi zvakadaro zvinokanganisa maficha akakosha ehunhu (kureva, kutsvaga chikafu) maitiro (Tafura 1; Mufananidzo 1) . Vatsvakurudzi vakaratidza kuti nucleus inounganidza DA inonyanya kukosha pakuita maitiro (Koob et al., 1978; Robbins naKoob, 1980; Salamone, 1988, Salamone, 1992; Salamone et al., 1991, Salamone et al., 2005, Salamone et al., 2007; Calaminus naHuber, 2007; Lex naHuber, 2010), kuedza kushanda panguva yekuita basa (Salamone et al., 1994, Salamone et al., 2007, Salamone et al., 2012; Mai et al., 2012), Pavlovian kushandiswa kwezvinhu (Parkinson et al., 2002; Everitt naRobbins, 2005; Lex naHuber, 2008), kushandura mafungiro ekuzvibata (Nicola, 2010), kushandisa mari nesimba uye mutemo (Salamone, 1987; Beeler et al., 2012), uye kushandiswa kwemubairo kudzidza (Beeler et al., 2010). Kugumburwa kweD DA kumira uye kusagadzikana kunopedza basa rekuita uye rakasikwa-rinoita basa rekuita uye kurera, pamwe chete nemabasa anosimudzira (Koob et al., 1978; Makunakuna et al., 1993; Baldo et al., 2002). Mabasa akadai sekudhakwa zvakanyanya, kumhanyisa vhiri, kana chiito chemota chinokonzereswa nekuratidzwa kwenguva nenguva kwezvipikiri zvezvikafu kumhuka dzinobviswa chikafu zvinodzikiswa nekuunganidza kuderedzwa kweDA (Robbins naKoob, 1980; McCullough naSalamone, 1992). Mukuwedzera, kuderera kwevatsigiri veDA, pamwe chete nekuunganidza hurumende dzeDA kana kuparara, kuderedza kudya-kusimbiswa kupindurwa pane mamwe mabasa pasinei nokuti kudya kwekudya kunochengeterwa pasi pemamiriro ezvinhu (Salamone et al., 1991, Salamone et al., 2002; Ikemoto uye Panksepp, 1996; Koch et al., 2000). Migumisiro yekusungirirwa kweDA kudzvinyirira pamusoro pekudya-kusimbiswa kwekuita kunosiyana zvikuru zvichienderana nebasa rinodiwa kana purogiramu yekusimbisa. Kana zvakakonzerwa nekugadziriswa kweD DA zvakaderedzwa zvakabatana nekuderedza kudya kwezvokudya, zvino mumwe angatarisira kuti purogiramu yakatarwa ye 1 (FR1) purogiramu inofanira kunge yakanyatsotarisana nekugadzirisa uku. Kunyange zvakadaro, purogiramu iyi haisi kuremekedzwa nemigumisiro yekutengesa kudhindwa kweDaily mu accumbens (Aberman naSalamone, 1999; Salamone et al., 2007; Nicola, 2010). Chimwe chezvinhu zvakakosha zvinoita kuti huve nehunobudirira kune zvinokonzerwa nekugadzirisa DHA zvinyorwa pamusoro pekudya zvakasimbiswa kwezvokudya ihwo hukuru hwehuwandu hunodikanwa (kureva, nhamba yemashizha anoshandiswa pamusana pekusimudzira; Aberman naSalamone, 1999; Mingote et al., 2005). Uye zvakare, kuvharirwa kwekuunganidza maDA receptors kunokanganisa mashandiro enzira yekushandisa yakakurudzirwa nekuratidzwa kwezvinyorwa (Wakabayashi et al., 2004; Nicola, 2010).
Kugona kwevatsigiri veDA kana kuunganidza madhavhirini eDA kuti aparadzanise kushandiswa kwezvokudya uye maitiro ekusimbiswa kwezvokudya, kana pakati pebasa rakasiyana-siyana, haisi tsanangudzo shomanana kana kuti epiphenomenal. Pane kudaro, inoratidza kuti pasi pemamiriro ezvinhu umo mararamiro anosimbiswa kwezvokudya anogona kuvhiringidzwa, zvinokosha zvekudya zvinokurudzira zvisinei zvakadaro. Vatsvakurudzi vanoverengeka vakanyora pamusoro pezvakakosha zvekusimudzira kusagadzikana vakagumisa kuti kushushikana kunoita sevatsigiri vanosimudzira kunowanzova yakasarudzwa, kana kuti kuisa nzira, chinangwa-chinotungamirirwa, kana chiito chekupedza, kana kuti kuita chido chakanyanya chekuda, uye kuti izvi zvinokonzera chinhu chinokosha chekusimbiswa kwakanaka (Dickinson naBalleine, 1994; Salamone uye Correa, 2002; Salamone et al., 2012). Sezvakataurwa munyaya yekuongorora kwehupfumi inopiwa ne Hursh, 1993: "Kupindura kunoonekwa sechinhu chechipiri chinoenderana nekuti chakakosha mukudzivirira mashandisiro." Nekudaro, mhedzisiro inotsanangurwa pamusoro apa inoratidza kuti madosi epasi evapikisi veDA uye anounganidza kudonhedzwa kweDA hakukanganise zvakakosha zvinhu zvekutanga kana zvisina mvumo yekukurudzira kwekudya nekusimbisa asi zvinoita kuti mhuka dzinzwisise kune mamwe maficha eanodiwa ekupindura, kupindura zvisina tsarukano kune zvakagadziriswa cues, uye kudzikisira maitiro emhuka kushandira chikafu chekusimbisa.
Chimwe chekuratidzwa kweiyo dissociative hunhu hwehunhu hunhu hweakaderera masystemic doses evapikisi veDA, uye kupera kana kupesana kwekuunganidza accumbens DA, ndeyekuti aya mamiriro anokanganisa kugoverwa kwehukama hwehunhu mumhuka dzinopindura pamabasa anoongorora kuita-kwakatemerwa kuita sarudzo (Salamone et al., 2007; Floresco et al., 2008; Mai et al., 2012). Rimwe basa rave richishandiswa kuyera mhedzisiro yedopaminergic manipulation pane mhinduro yekugovera inopa makonzo sarudzo pakati pevhiri yekumanikidza inosimbiswa nekutakura kwechikafu chakasarudzika, maringe nekusvika nekudya chikafu chinowanikwa panguva imwe chete asi chisinga sarudzike (Salamone et al., 1991, Salamone et al., 2007). Pasi pemitemo yekutanga kana kuti kutonga, rats rakadzidziswa dzinowana zvizhinji zvezvokudya zvadzo nechisviniro ichisimudzira, uye dzinodya zviduku zviduku. Desi-to-moderate doses yevanopikisana neDA vanovhara D1 kana D2 mhuri receptor subtypes inoburitsa shanduko yakakura yekupindura mugove mumakonzo anoita pabasa iri, kudzikira chikafu-chakasimbiswa lever ichimanikidza asi ichiwedzera zvakanyanya chow kudya (Salamone et al., 1991; Koch et al., 2000; Sink et al., 2008). Basa iri rakagadziriswa muzviongorori zvakasiyana-siyana. Maitiro evanhu vanopikisana neDA vanoita kuti kushanduka kubva pamubhedha kunomanikidza kusanganisa kudya kunosanganisa kuwandisa kwezvokudya zvekudya kana kuchinja kusarura pakati pezvokudya zviviri zvakasununguka mukuedza kusarudzwa kusarudza (Salamone et al., 1991; Koch et al., 2000). Kusiyana neizvi, kuda kudya kunopisa kubva kumapoka akasiyana-siyana, kusanganisira fenfluramine uye cannabinoid CB1 vanopikisa (Salamone et al., 2007; Sink et al., 2008), yakakundikana kuwedzera chow kudya pamatokisi ayo akadzora kusvitsa kwemhepo. Kusiyana nemigumisiro yeAIDS inopesana, kutangira-kudya, iyo inorudzi rwekusimudzira kushandiswa kwezvinhu, yakaderedza zvose kusvinira nekusimudzira uye chow kudya (Salamone et al., 1991). Izvi zvinoratidza kuti kupindira nekutengesa kweDA hakurevi kuderedza kudyidzana kwekudya kwekudya kana kudya asi kunogadzirisa kupindura kwekugoverana pakati pezvimwe zvinowanikwa zvezvokudya zvinowanikwa kuburikidza nemhinduro dzakasiyana. Izvi zvinokonzerwa nehutano zvinotarisana neW accumbens DA, uye zvinokonzerwa ne accum accums DA zvinodzvinyirira uye nzvimbo dzomunharaunda dzeD1 kana D2 vanopikisana mumhuri mukuunganidza hutanda kana shell (Salamone et al., 1991; Koch et al., 2000; Nowend et al., 2001; Farrar et al., 2010; Mai et al., 2012).
Nzira yeT-maze yakave yakagadzirirwa kuti iongorore kusarudza-zvakasarudzwa. Nokuda kwebasa iri, maoko maviri akasarudzwa e-maze anotungamirira kune zvakasiyana-siyana zvinowedzera kusimbisa (semuenzaniso, 4 kurwisana ne2 zvokudya zvepelitete, kana 4 kurwisana ne0), uye pasi pemamwe mamiriro ezvinhu, chigadziro chinowanikwa muruoko nemazinga akawandisa ekusimbiswa kwezvokudya kuti akwanise kuedza mhirizhonga (Salamone et al., 1994). Kana hurefu hwemaoko huine chigadziro munzvimbo, uye ruoko risina chigadziro rine zvishoma zvigadziri, zvinowedzera kudzvinyirira kweDA kana kupesana kunopera kusarudzwa kwekodha yepamusoro / yepamusoro mubairo weruoko, uye kuwedzerwa kusarudzwa kwebhadharo shoma / pasi mubayiro arm (Salamone et al., 1994; Denk et al., 2005; Pardo et al., 2012; Mai et al., 2012). Apo pakanga pasina chibvumirano mu maze, mapurisa aida kusimba kwekusimudzira ruoko, uye hakuna kuwirirana kweDVD kana kuunganidza DA kuderedza kuchinja kwavo (Salamone et al., 1994). Apo ruoko rune dombo rine 4 pellets, asi rumwe rutivi rwakanga rusine pellets, makonzo ane accumbens DA zvinodzvinyirira zvisati zvasarudza hurefu hwemaoko, dzakakwira chigadziro, uye dzakapedza pellets. Mune imwe nguva ichangobva kuitika T-maze nemakonzo, nepo haloperidol yakasarudzwa kusarudzwa kwemaoko nechigadziro, ichi chirwere chakanga chisina basa pakusarudza apo maoko maviri aiva nechigadziro panzvimbo (Pardo et al., 2012). Nokudaro, dopaminergic manipulations haina kuchinja zvaidiwa zvichienderana nekusimudzira ukuru, uye hazvina kukanganisa kusarura, chiyeuchidzo kana zvigadziriro zvekudzidza zvakabatana nechisarudzo chemaoko. Bardgett et al., 2009 yakagadzira basa reT-maze rinokonzera basa, umo muwandu wezvokudya muhupamhi hwemaoko ebyara yakaderedza chiedzo chimwe nechimwe apo makonzo akasarudzwa. Kuedza kushandura kwakashandurwa nekutungamirirwa kweD1 uye D2 mhuri dzinopikisa, izvo zvakaita kuti zvive nyore kuti makonzo angasarudza kuderera kusimba / kudhura mari. Kuwedzerwa kudhinda kweDA nekutungamirirwa kweAmphetamine kwakavhara migumisiro ye SCH23390 uye haloperidol uyewo maitiro akazvimirira pakusarudza kusimba kwakakwirira / yepamusoro-soro, iyo inopesana neongororo dzakasarudzwa dzinoshandiswa vachishandiswa neDVD mutengesi kugunha mice (Cagniard et al., 2006).
Chimwe chezvinhu zvinokosha munharaunda ino ndeyekuti zvipfuwo zvakakosha sei kuendesa Dhavhidha zvinotarisana nebasa rinodiwa mumabasa anoenderana nemabasa, kana kune zvimwe zvinhu zvakadai sekukurumidza kunonoka (semuenzaniso, Denk et al., 2005; Wanat et al., 2010). Kakawanda, migumisiro yeAIDS inopesana nekukanganiswa kunonoka yakaratidzwa kuva yakasanganiswa (Wade et al., 2000; Koffarnus et al., 2011), Uye Winstanley et al., 2005 yakashuma kuti kuunganidza maDA zvisiri izvo hazvina kukanganisa kunonoka kuregererwa. Floresco et al., 2008 yakaratidza kuti muvengi weDA anonzi haloperidol akachinja kushandura kushandura kunyange kana vaitungamirirwa nekuda kwemigumisiro yemishonga mukupindura kunonoka. Wakabayashi et al., 2004 akawana kuti kudzivirirwa kweganda kunowanikwa D1 kana D2 ma receptors haana kukanganisa mashandiro pane inofambira mberi nguva, iyo inosanganisira kumirira kwenguva yakareba uye yakareba nguva kuti uwane kusimbiswa. Zvakare, zvidzidzo zvine masandemusi echirongwa chekusimbisa izvo zvine zviyero zvinodikanwa zvakanamatira kune nguva yenguva zvinodikanwa zvinoratidza kuti kuwunganidzwa kweDepletions kunoita kuti mhuka dzive nehanya neyakawedzera zviyero zvinodiwa asi hazviite kuti mhuka dzive nehanya nezvinodiwa zvenguva kubva 30-120 s (Correa et al., 2002; Mingote et al., 2005).
Mukupfupisa, zviitiko zveT T maze nekusarudza kusarudzo dzakasarudzwa mumakonzo zvinotsigira pfungwa yokuti kuderera kwevanhu vanopikisana neDA uye kuunganidza maDA zvakasununguka vanosiya zvinhu zvinokosha zvechikonzero chikuru nekusimudzira zvakasimba, asi zvisinei kuderedza kushandiswa kwehutano nekuita kuti mhuka dzigadzirise kusarudza kusarudzo kunobva pane zvinodiwa zvinodiwa zvebasa racho uye sarudza mari shoma dzingashandiswa kuwana vatsigiri (Salamone et al., 2007, Salamone et al., 2012). Uchapupu huzhinji hunoratidza kuti DA inonzi mesolimbic inhengo yepamhanho yakawanda inotarisa maitiro ekushandura uye kushanda nesimba, izvo zvinosanganisira vamwe vatumira (adenosine, GABA; Mingote et al., 2008; Farrar et al., 2008, Farrar et al., 2010; Nunes et al., 2010; Salamone et al., 2012) uye nzvimbo dzeuropi (basolateral amygdala, anterior cingulate cortex, ventral pallidum; Walton et al., 2003; Floresco uye Ghods-Sharifi, 2007; Mingote et al., 2008; Farrar et al., 2008; Hauber naSommer, 2009).
Kubatanidzwa kweMesolimbic DA muAppetitive Motivation: Basa Dynamic yeDA Systems
Kunyange zvazvo dzimwe nguva ichitaura kuti nucleus inowedzera DA kusunungurwa kana basa re ventral tegmental DA neurons rinokurudzirwa nehuwandu hwevatsigiri vakanaka sezvokudya, mabhuku anotsanangura kupindurwa kweA DAlimbic DA kudzvinyirira zvinokanganisa chaizvoizvo zvakaoma zvikuru (Hauber, 2010). Nenzira yakazara, kuratidzira kwezvokudya kunowedzera basa re DA neuron kana kuunganidza DA kusunungurwa here? Munharaunda yakawanda yemamiriro ezvinhu, uye kuburikidza nezvikamu zvakasiyana-siyana zvehupenyu hunokurudzirwa, iyo inopera kana zvimwe zvekukurudzira zvakabatana zvikuru nekukurudzirwa kwebasa re dopaminergic? Mhinduro yemibvunzo iyi inobva pane nguva dzekuenzanisa, uye mimwe mitemo yemamiriro ekudzidzwa. Kusiyana kwemuitiro weDA kunogona kuitika pane dzakawanda timescales, uye kusiyana kunowanzoitwa pakati pe "phasic" uye "tonic" basa (Nyasha, 2000; Floresco et al., 2003; Goto uye Grace, 2005). Electrophysiological recording techniques inokwanisa kuenzanisa kushanda kwechimbichimbi chema DA neurons (eg, Schultz, 2010), uye voltammetry nzira (semuenzaniso, kutsvaga kwekutsvaga kwemhepo) kureva DA "zvigaro" zvinoshanduka zvakasimba muDA extracellular, iyo inofungidzirwa kuti inomiririra kusunungurwa kubva kuDVD neuron basa (semuenzaniso, Roitman et al., 2004; Sombers et al., 2009; Brown et al., 2011). Izvo zvave zvichinziwo kuti kutsvaga kwekutsvaga kwekushandurwa kweDA kubudiswa kunogona kunge kwakasununguka neD DA neuron kupisa, uye kunogona kuratidza kufanana kwakagadziriswa kwecholinergic intrauron interneurons dzinokurudzira DA kusunungurwa kuburikidza ne presynaptic nicotinic receptor mechanism (Rice et al., 2011; Threlfell et al., 2012; Surmeier naGreybiel, 2012). Nzira dze Microdialysis, kune rumwe rutivi, ronga DA inonzi extracellular nenzira inomiririra kushandiswa kwemagetsi ekubudiswa uye nzira dzokugadzirisa dzakabatanidzwa pane zvikamu zvakakura zveenguva uye nzvimbo maererano ne electrophysiology kana voltammetry (semuenzaniso, Hauber, 2010). Nokudaro, inowanzotaurwa kuti nzira dze microdialysis dzinoyera "tonic" DA mazinga. Kunyange zvakadaro, tichifunga nezvekuti microdialysis inokwanisa kuyera maitiro-kana kuchinja kwechirwere (semuenzaniso, kuwedzerwa kunoteverwa nekuderera) muDA recelcellular iyo inopera maminitsi, zvichida inobatsira kushandisa izwi rokuti "fast phasic" kutaura pamusoro pekushandurwa kwakakurumidza kuita basa reDA rinogona kuyerwa ne electrophysiology kana kuti voltammetery, uye "kupera zvishoma" pakutaura nezvekuchinja kunoitika pamusoro penguva yakaderera yakaenzana nemaitiro e microdialysis (semuenzaniso, Hauber, 2010; Segovia et al., 2011).
Electrophysiology zvidzidzo zvakaratidza kuti kupa mharidzo kana zvisingatarisirwi zvokudya zvinotsigira zvinowirirana nekuwedzera kwenguva pfupi mubasa rekuisa dhigirizhonga DA neurons, asi kuti izvi zvinopfurikidza nehurukuro nguva dzose, kana kuti kudzokorora kudzokorora kuburikidza nekudzidziswa (Schultz et al., 1993; Schultz, 2010). Kushandisa nzira dzekudzivirira kwepamusoro kuti zvienzane nekuchinja kwemashoko ekutsvaga muDA kusunungurwa, Roitman et al., 2004 akaratidza kuti, mumhuka dzakarovedzwa, kutarisana nemamiriro ekusimudzira mafungiro okuti kuvhara kwemhepo kunokonzera kuti sucrose delivery iiteverwe nekuwedzera kweDAS zvinyorwa, zvisinei, kunyatsotaura kwaiitwa sucrose reinforcer kwakanga kusiri. Kuwana kwakafanana kwakataurwa makore akapfuura Nishino et al., 1987, uyo akadzidza pasina-operative fixed lever inopindira mumonke uye akacherechedza kuti basa re-putative ventral tegmental DA neurons rakawedzerwa panguva yekusimudzira mhuka mumakadzi akadzidziswa asi chaizvoizvo yakaderera panguva yekukurudzira kutaura. Hazvina kutarisirwa kudya kwekudya, pamwe nekuratidzwa kwemashoko akafanotaura nezvokutengeswa kwekudya, kuwedzera kukurumidza kwechiratidzo chekuenzanisa sezvakayerwa nechetammetry mu nucleus accumbens core (Brown et al., 2011). DiChiara nevamwe vashandi vakaratidza kuti kuiswa kune zvinyorwa zvinoratidzira zvinofadza zvishoma nezvishoma zvakawedzera DA extracellular mu nucleus accumbens shell sezvakayerwa ne microdialysis, asi kuti mhinduro iyi yakakurumidza kugadziriswa (semuenzaniso, Bassareo et al., 2002). Imwe kambani inonzi microdialysis peji yakaratidza kuti kuparidzwa kwepamusoro kweakaginihydrates yezvokudya zvekugadzirisa zvekudya kumapuro akave akazaruka hazvina kubereka chero shanduko muDD extracellular mukutengesa nheyo kana shell (Segovia et al., 2011). Kusiyana neizvi, zvose zvakagadziriswa uye kugadziriswa kwehutano hwakagadziriswa neversi yechisimba zvakabatanidzwa nekuwedzera kuDVD kusunungurwa (Segovia et al., 2011). Imwe nzira yakafanana yakaratidzwa apo zviratidzo zvechiratidzo cheDD-inonzi transduction (c-Fos naDARPP-32) yakaenzana (Segovia et al., 2012). Zvakatorwa pamwechete, zvidzidzo izvi hazvibatsiri pfungwa yokuti kudya mharidzo yega yega, kusanganisira iyo yezvokudya zvinofadza, zvakafanana nekuwedzera kunowedzera DA kubudiswa mumhando yakawanda yemamiriro.
Kunyange zvakadaro, uchapupu hwakawanda hunoratidza kuti kuwedzerwa kwekuendesa kweDA kunobatanidza nekuratidzwa kwezvinhu zvinokonzerwa nekusimbiswa kwezvisikwa zvakadai sekudya, kana kushanda kwechiito chekuita; izvi zvakaonekwa mune zvidzidzo zvinosanganisira microdialysis (Sokolowski naSalamone, 1998; Ostlund et al., 2011; Hauber, 2010; Segovia et al., 2011), voltammetry (Roitman et al., 2004; Brown et al., 2011; Cacciapaglia et al., 2011), uye electrophysiological zvinyorwa panguva yekusununguka kushandiswa kwepachena (Nishino et al., 1987; Kosobud et al., 1994). Cacciapaglia et al., 2011 yakarondedzera kuti kutsvaga kwekutsvaga DA kubudiswa mu nucleus accumbens sezvakayerwa ne-voltammetry kwakaitika panguva yokutanga yecue iyo yakaratidza reinforcer kushandiswa, pamwe chete neveversi yepanhau kupindura, uye kuti izvo zvinokonzera kusununguka kwekubudiswa kwepasikiti pazvinyorwa zvinoputika zvakasvibiswa nekusavhiringidzwa kwekuputika in ventral tegmental DA neurons. Uyezve, imwe nyanzvi yekuongorora tsvakurudzo ye electrophysiology yakatora zvimwe zvemamiriro ezvinhu anoita kuti kuputika kuputike mumhepo inonzi DA neurons, kusanganisira kuiswa kwezvinhu zvinokurudzira izvo zvinobatanidzwa nechokutanga chekusimudzira, pamwe chete nemamiriro ezvinhu ane simba rakanyanya kusimbisa kutarisira kunokonzerwa nechiitiko chekare (Schultz et al., 1997). Kucherechedza kwekupedzisira kwakatungamirira mukufungidzira kuti basa re DA neuron rinogona kureva rudzi rwekufanotaura kwechikanganiso chisipo chakatsanangurwa nemamwe maitiro ekudzidza (semuenzaniso, Rescorla naWagner, 1972). Uyu muenzaniso webasa muA DA neurons yakashandura yakapa chikonzero chepamutemo chekubatanidzwa kwekutsvaga kwekushandiswa kweDA kuiswa mukusimbisa maitiro ekudzidza (Schultz et al., 1997; Bayer naGlimcher, 2005; Niv, 2009; Schultz, 2010).
Kunyange zvazvo chinonyanya kukoshesa pamapepa aripo iye zvino pamigumisiro ye dopaminergic manipulations pane zvakasiyana-siyana zvekukurudzira, zvinobatsira kufunga nezvekukosha kwekutsvaga kwepasikisi uye kunonoka kwepasikisi (kureva, "tonic") chiratidzo chekududzira migumisiro yemamiriro ezvinhu anopindira nekutumirwa kweDA. Zvimwe zvakasiyana-siyana zvekuita dopaminergic zvinogona kushanda zvakasiyana zvakasiyana siyana, uye naizvozvo, migumisiro yekushandiswa kwakasiyana kunogona kuvimba zvikuru kana iri kuchinja nekukurumidza kana kunonoka kuita basa kana mazamu ekutanga eDA. Vatsvakurudzi vakashandisa zvakasiyana-siyana zvemishonga kana maitiro ekusiyana kuti vaite zvakasiyana-siyana kushanda kweD DA basa nekusunungurwa kweDA pane zvishoma zvishoma zviyero (Zweifel et al., 2009; Parker et al., 2010; Grieder et al., 2012) uye vakataura kuti izvi zvinogona kuita zvinokonzera maitiro emhando. Semuyenzaniso, Grieder et al., 2012 yakaratidza kuti kupindira kusarudzo kwebasa reDAic rakagadzirisa maitiro ekugadziriswa kwepakati nzvimbo yekudzivisa kubva pane imwe nhengo yakawanda yeicotine, asi kwete kurega kubva panicinine isingaperi. Kusiyana neizvi, kudzivirirwa kweD2 receptors kusina kunaka kwekutaura kwechimiro chekutsvaira panguva dzisingagumi, asi kwete kubuda kwakanyanya. Zweifel et al., 2009 vakashuma kuti kusarudzwa kwemazwi ekugadziriswa kwevashandi veNMDA, izvo zvakasvibisa kuputika kweVTA DA neurons, kusina kukwana kuwanikwa kwekuchengetedzwa kwekudzivirira kupesana kwekudzidzira asi hazvina kukanganisa mararamiro ekushanda kwekudya kwekudya pane purogiramu inopfuurira yehuwandu. Kutaura zvazviri, nhengo dzinoverengeka dzehutano hweAIDS dzakachengetedzwa mumhuka dzisina simba dzakagadzirisa basa reDA (Zweifel et al., 2009; Wall et al., 2011; Parker et al., 2010). Izvi zvinorehwa nekubatanidza mashoko kubva kune zvidzidzo zvekutsvaga kwekushanya kwemaitiro neaya anotarisa pamigumisiro yeAIDS inopesana kana kupera. Chokutanga pane zvose, vanoratidza kuti munhu anofanira kungwarira pakuita kubva kune pfungwa dzakagadzirwa mune zvidzidzo zve electrophysiology kana kuti voltammetry (semuenzaniso, kuti kusunungurwa kweDA kunoshanda se "chiratidzo chekudzidzisa") kumabasa ekutadza asingakanganisi kana madhiragi kana kudengenyeka kweDA kushandiswa kuvhiringidza kudengenyeka kweDA. Uyezve, zvinoratidza kuti zvidzidzo zvekuita zvakasimba zvemaziso zve-DA neurons zvinogona kutsanangura mamiriro ezvinhu anokurumidzira kuwedzera kana kuderedza basa reDA kana kupa sarudzo yeDA discrete asi asingatidzidzise zvakajeka maererano nehuwandu hwemabasa anoshandiswa neDA kuenderera mberi kwevakawanda timescales kana avo vasina kukanganiswa nekuvhiringidzika kwekutumira kweDA.
Kubatanidzwa kweMesolimbic neNeostriatal Nzira dzeAppetitive Instrumental Kudzidza
Kunyange zvazvo munhu anogona kutsanangura zvinokurudzira mumashoko anoita kuti zvive zvakasiyana nezvimwe zvinogadzirwa, zvinofanira kuonekwa kuti, mukukurukurirana zvizere kana maitiro ehutsika kana neural based motivation, mumwewo anofanirwa kufunga nezvehukama hunobatana. Uropi hauna mabhokisi e-box-and-arrow kana zviratidzo zvinoparadzanisa zvakakosha zvepfungwa zvepfungwa muchikwereti, chisina kuvhara neural systems. Nokudaro, zvakakosha kunzwisisana ukama huri pakati pekukurudzira humwe uye mamwe mabasa akaita se homeostasis, allostasis, manzwiro, cognition, kudzidza, kusimbiswa, kunzwa, uye motokisi basa (Salamone, 2010). Semuyenzaniso, Panksepp, 2011 akasimbisa kushandiswa kwepfungwa mukati meuropi kwakanyatsopindirana nemafungiro ekukurudzira anobatanidzwa mumatambo akadai sokutsvaga, kutsamwa kana kutya. Mukuwedzera, kutsvaga / kubatsiridza maitiro haisi kungofungidzirwa chete nemanzwiro kana kuti zvinokurudzirwa zvinhu zvekukurudzira, asiwo, zvechokwadi, kudzidzira nzira. Mhuka dzinodzidza kuita mhinduro dzakasiyana-siyana dzinosanganiswa nemigumisiro inonyanya kusimbisa. Sezvimwe chikamu chakakosha chekushamwaridzana kwechibvumirano chechigadzirwa chechigadzirwa, zvipenyu zvinofanira kudzidza kuti zviito zvipi zvinotungamirira kune izvo zvinokurudzira (kureva, zviito zvekuita-zvinoitika). Nokudaro, mabasa anokurudzira anosangana nemotokari, kunzwisisa, mafungiro, uye mamwe mabasa (Mogenson et al., 1980). Kunyange zvazvo kuongororwa kwemazuva ano kunongoratidzwa nekubatanidzwa kweAlsolimbic DA mukukurudzira kwevanhu vanowedzera kusimba, inobatsirawo kuva nekukurukurirana kwenguva pfupi pamusoro pekubatanidza kuisa maziso a DAlimbic DA muchikoro chekudzidza.
Mumwe anogona kufunga kuti zvingave zvisinganzwisisiki kuratidza kuti nucleus inowanikwa DA inopindirana nekusimbisa kudzidza kana inobatanidza zvakanyanya mu synaptic plasticity michina iri pasi pekusangana kwevashandi vanopindura nekubudiswa kwekusimbisa (kureva, masangano ekugadzirisa matambudziko). Asi nzvimbo iyi yekutsvakurudza yakaoma uye yakakomba kududzira senyaya yekutsvakurudza yakaongororwa pamusoro apa. Semuyenzaniso, Smith-Roe naKelley, 2000 yakaratidza kuti kuvharidzira kweDVD D panguva imwe chete1 uye nMDA receptors mu nucleus yakaunganidza musimboti wakaderedzwa kuwanikwa kwechigadzirwa chechipiri chinosungirirwa. Mukuwedzera, postsession manipulations iyo inokanganisa kusungurudzika kwekurangarira yakavhiringidza kuwanikwa kwechigadzirwa chinonzi lever pressing (Hernandez et al., 2002). Kunyange zvakadaro, mukudzokorora mabhuku ari nucleus accumbens uye kudzidzira chidzidzo, Yin et al., 2008 akagumisa kuti "kuunganidzwa hakubatsiri kana kukwana kudzidzira zvombo." Saizvozvowo, Belin et al., 2009 akacherekedza kuti maronda uye madhiragi ekushandisa enucleus anounganidza musimboti anogona kukanganisa kuwanikwa kwehunhu hunosimbisirwa nehunhu hwechisikigo, asi akataura kuti "chaiyo mipiro yepfungwa" yeakaunganidzwa uye zvimwe zvimiro zvehuropi zvinoramba zvisina kujeka. Kunyangwe paine ongororo dzakawanda dzinoratidza kuti maronda emumuviri wesero, vanopikisana neDA, kana kudonhedzwa kweDA kunogona kukanganisa mhedzisiro inoenderana nekudzidza mumatanho akaita senzvimbo inodiwa, kutora lever kudzvanya, kana mamwe maitiro, izvi hazviratidzi pachazvo kuti nucleus inounganidza mauroni kana mesolimbic DA kutapurirana kwakakosha kune mamwe masangano anodzidzisa chishandiso (Yin et al., 2008). Migumisiro yakananga yakabatana nekudzidzira zvikamu inogona kuratidzirwa nekuongororwa kwemigumisiro yekusimudzira kuderedza kana kuora mwoyo kwezvakaitika, izvo kazhinji zvisingaitwi mune zvidzidzo zvepafarmasi kana zvechilonda. Nezvozvi mupfungwa, zvakakosha kuziva kuti masero emasero emunhengo mune imwe nheyo kana kuti shell ye accum accums haina kuchinja hukama hwekukanganisa kuitika (Corbit et al., 2001). Lex naHuber, 2010 akawana kuti makonzo ane nucleus accumbens DA zvakashata zvakaramba zvichinetseka kuti kusimbise kuongororwa kwenyika, uye yakaratidza kuti kuunganidza demo re DA kunogona kunge kusina kukosha pakukodhidza maitiro-masangano ekupedzisira. Kunyangwe zvisinganzwisisi kana kuungana DA kunokosha kune masangano pakati pemhinduro nekusimudzira, humwe uchapupu hunoratidza kuti nucleus inowanikwa DA inokosha kune Pavlovian nzira nePavlovian kushandiswa kwezvinhu (Parkinson et al., 2002; Wyvell naBerridge, 2000; Dalley et al., 2005; Lex naHuber, 2008, Lex naHuber, 2010; Yin et al., 2008). Izvozvo zvinogona kupa nzira dzakagadziriswa nadzo dzinogona kuita kuti kuve nemigumisiro pahurukuro kupindura (Robbins na Everitt, 2007; Salamone et al., 2007), sezvakakurukurwa pamusoro apa. Izvo zvinokonzera kana kukonzera migumisiro yezvakagadziriswa zvinogona kuva chinhu chinokurudzira kugadziriswa kwechigadziro chekare chinogona kuwanikwa asiwo chinogona kuita kuti kukurudzire kuwanikwa kuburikidza nekuwedzera mhinduro yekubuda nekusiyana kwehutano, nokudaro nekugadzirisa mukana wemikana yakawanda yekubatanidza kupindura nekusimbiswa. Imwe pepanhau rekare yakaratidza kuti optogenetic kukurudzira kwe ventral tegmental DA neurons haina kupa nekusimbiswa kwakanaka kwechigadziro chinonzi lever kuchikurira pachako uye hachina kuchinja kudya kwekudya, asi kwakasimbisa kubuda kwezvokudya-kusimbiswa kwevhesi kushandura pamushonga unoshingaira panguva yekuwana uye kuwedzera zvigadzirwa zvekare zvakadzimwa zvipikiso zvinyorwa (Adamantidis et al., 2011).
Zvinofadza, kunyange zvazvo kugogodza kweDA D1 zvinyorwa zvakabatanidza kuwanikwa kwePavlovian approach behavior, kugogodza kweNMDA receptors, izvo zvakaguma nekuderera kwe 3 munguva yekutsvaga kusununguka kweD DA kusunungurwa nekuratidzwa kwezvokudya zvinosanganiswa, hazvina kukanganisa kuwanikwa kwePavlovian approach behavior (Parker et al., 2010). Izvi zvinoratidza kuti hukama pakati pekukurumidza kusunungurwa kweDA kusunungurwa uye kudzidza kunoramba kusiri chokwadi. Zvidzidzo zvenguva yemberi zvinofanirwa kuongorora mhedzisiro yekunyengedza iyo inokanganisa kukurumidza kuita phasic DA kusaina uchishandisa maitiro anoongorora zvakananga kudzidza kwekusimbisa (kureva. Uyezve, maitiro ezvemajini uye ezvemakemikari anotungamira mukumisikidza kweanokurumidza phasic chiitiko cheDA chinofanira kuongororwa zvekare nezviito zvavo pakuita kwehunhu uye nesimba zvine chekuita nezvezvinhu zvinokurudzira.
Kubatanidzwa kweMesolimbic DA muAversive Motivation nekudzidza: Basa reDynamic reDaily Systems
Kudzokorora kwezvimwe zvikamu mumabhuku eDA zvingabva kune imwe pfungwa yokuti DA yekuti mesolimbic inobatanidzwa muchiito chehedonic, kushushikana kwechikonzero, nekudzidzira kwakasimudzika, kudzivisa kubvisa zvimwe zvinhu zvekudzidza nekukurudzira. Zvisinei, maonero akadaro angave akasiyana nemabhuku. Sezvinorondedzerwa pamusoro apa, uchapupu hwakawanda hunoratidza kuti huwandu hwekupararira kweDA hakurevi zvakananga maitiro ehedonic kune zvinokurudzira. Uyezve, kune mabhuku makuru kwazvo anoratidza kuti DA maziso anobatanidzwa mune zvinokurudzira uye zvinogona kukanganisa mararamiro mumagadziriro ekudzidzira. Mhando dzakasiyana dzakasiyana-siyana dzakasiyana-siyana (semuenzaniso, kushungurudza, misi yemuswe, kuzvidzora, kugadzirisa zvinodhaka, kushandiswa kwemishonga, kusagadzikana kwevanhu) kunogona kuwedzera kubudiswa kweDA sekuenzaniswa nema microdialysis nzira (McCullough et al., 1993; Salamone et al., 1994; Tidey naMikzek, 1996; Muduku, 2004). Kwemakore akawanda, zvaifungidzirwa kuti ventral tegmental DA neuron basa harina kuwedzerwa nekudzivisa kusagadzikana; zvisinei, zvitsvakurudzo zvenguva pfupi zvakaratidza kuti basa re electrophysiological rekuisa kana kuti rakatsanangurwa DA neurons rinowedzera nekudzivirira kana kushungurudza mamiriro (Anstrom na Woodward, 2005; Brischoux et al., 2009; Matsumoto naHikosaka, 2009; Bromberg-Martin et al., 2010; Schultz, 2010; Lammel et al., 2011). Kunyange zvakadaro Roitman et al., 2008 yakarondedzera kuti maitiro anokanganisa (quinine) akaderera pasi maDA madiki mu nucleus accumbens, Anstrom et al., 2009 akacherechedza kuti kusagadzikana kwevanhu kunetseka kwakaperekedzwa nekuwedzera kwekutsvaga kwekuita basa reDA sekuenzaniswa nevose electrophysiology uye voltammetry. Kusatendeseka kunoramba kuripo kana kune vakasiyana DA neurons inopindura nenzira yakasiyana-siyana kuti inetseke uye inopesana, uye zvinorevei neuroni inopindura kune mumwe nomumwe, asi panoita seine kusava nechokwadi kwekuti mesolimbic DA basa rinogona kukurudzirwa nezvimwe zvinhu zvinopesana, uye naizvozvo haina kunyatsobatanidza kuHedonia kana kusimbiswa kwakanaka.
Ihu humwe humwe humwe uchapupu huri kudzoka kumashure makumi emakore (Salamone et al., 1994) uye kuenderera mberi kune mabhuku matsva (Faure et al., 2008; Zweifel et al., 2011) inoratidza kuti kupindira nekutapurirwa kweDA kunogona kukanganisa kuwanikwa kana kushanda kwehupenyu hunopesana. Kutaura zvazviri, kwemakore mazhinji, varwi veDA vakagadzirirwa kuongororwa kwechirwere chepachirwere chechirwere zvichienderana nekukwanisa kwavo kuzvidzora kusazvibata (Salamone et al., 1994). Accumbens DA depletions impair shock avoidance lever pressing (McCullough et al., 1993). Zvirongwa zveSystemic kana intra-accumbens zvevadzvinyiriri veDA vanovhiringidzawo kuwana kwekutsvaira nzvimbo uye kunakidza aversion (Acquas uye Di Chiara, 1994; Fenu et al., 2001), pamwe nekutya (Inoue et al., 2000; Pezze naFeldon, 2004). Zweifel et al., 2011 vakataura kuti kugogodza kwevashandi veNMDA, izvo zvinoita kuti kuderedzwa nokukurumidza kusununguka kweDA kubudiswa, kusina kukwana kuwanikwa kwekuchengetedzwa kwekutya kwemamiriro ezvinhu.
Zvidzidzo zvevanhu zvekare zvakaratidzawo basa rekutora striatum mune zvimwe zvinhu zvinokurudzira uye kudzidza. Varwi vehondo vechirwere chekugadzirisa chirwere chinokonzera kushungurudzika kwakaratidza kuwedzerwa kweropa kunowedzera mu ventral striatum / nucleus accumbens mukupindura kwekuratidzwa kwekuvhiringidza kwemaitiro (kureva, kurwisana kunonzwika; Liberzon et al., 1999). Zvidzidzo zvevanhu zvekufungidzira zvinoratidza kuti mhinduro dzeBOLD dzinoparara, sezvinoyerwa neFMRI, dzinowedzera mukupindura kwezvikanganiso zvekufanotaura pasinei nokuti chiitiko chacho chafanotaura zviitiko zvinokomborera kana zvinopesana (Jensen et al., 2007), uye kuti zvikanganiso zvekufanotaura zvinopesana zvakadzivirirwa neAIDS anopikisa haloperidol (Menon et al., 2007). Baliki et al., 2010 yakashuma kuti muzvidzidzo zvakajairika, phasic BOLD mhinduro dzakaitika zvese kutanga uye kukanganisa kwekurwadza kwekushisa kwekusimudzira. Delgado et al., 2011 yakaratidza kuti ventral striatal BOLD mhinduro dzakawedzerwa panguva yekudzora mamiriro kune yekutanga aversive kukurudzira (kuvhunduka) pamwe nekurasikirwa nemari. Chidzidzo chePET chakawana zviyero zve mu vivo raclopride kutama kuti uongorore kuburitswa kweDA muvanhu kwakazivisa kuti kusangana nekushushikana kwepfungwa kunowedzera mamaki ekuwedzera kweDA mu ventral striatum nenzira yaive yakabatana nekuwedzera cortisol kuburitswa (Pruessner et al., 2004). Nokudaro, zvidzidzo zvekufungidzira zvevanhu zvinoratidzawo kuti ventral striatum uye maziso ake maziso DA innervation inopindirana nekunetseka uye kushushikana kwezvinhu zvinokanganisa.
Summary uye Conclusions
Mukupfupisa, mazano echinyakare nezveDA semurevereri we "hedonia," uye maitiro ekufananidza kutapurirana kweDA ne "mubairo" (uye "mubairo" ne "hedonia") iri kupa nzira yekusimbisa kubatanidzwa kwedopaminergic mune zvimwe zvinhu zvekurudziro. uye maitiro ane chekuita nekudzidza (Mufananidzo 2), kusanganisira maitiro ekugadzirisa, kushanda nesimba, cue inokurudzira nzira, kufanotaura kwechiitiko, uye maitiro ePavlovian. Kutapurirana kweDA mu nucleus accumbens hakuite simba rine simba pamusoro peheonic reactivity kune zvido, uye hazviite senge kupindirana kwekutanga chikafu chinokurudzira kana chishuwo (Berridge naRobinson, 1998; Salamone uye Correa, 2002; Kelley et al., 2005; Barbano et al., 2009). Uyezve, kunyange dopaminergic manipulations inogona kukanganisa migumisiro yemafambiro kumhuka dzakadzidziswa pamabasa ekudzidza, hapana humwe hwakasimba huchapupu hwekuti hurumende inobatanidza DA inokosha kune chimwe chinhu chekudzidza zvishandiso zvinosanganisira kusangana pakati pekugadzirisa nekugadzirisa chigumisiro (Yin et al., 2008). Kunyange zvakadaro, kuunganidza DA zvakajeka kwakakosha kune zvikamu zvekushaiwa simba uye zvinokurudzira (Salamone et al., 2007; Cabib uye Puglisi-Allegra, 2012) uye inobatanidzwa mukudzidzira maitiro, kunyanya muchikamu kuburikidza nekugadzira nzira dzinosanganisira nzira yePavlovian uye Pavlovian kuendesa mberi (Yin et al., 2008; Belin et al., 2009). Kushamwaridzana ne accum accums DA kutumirwa kwekutengesa kushandiswa kwePavlovian nzira yekupindura mhinduro dzinoshandiswa ne cues dzinofanotaura nezvokudya kwekudya uye kunokanganisa kuregererwa kwezvakanyorwa zvinoshandiswa ne cues iyo inofanotaura kusagadzikana kwemashoko. Kugadzikana kweDA kuora mwoyo kana kupesana kunoderedza kushandiswa kwemigumisiro yekusimudzira mafungiro uye kuita kuti mhuka dzive nehanya nekushanda-zvakabatana zvine chokuita nemhinduro yekuita (semuenzaniso, kubudiswa kwemararamiro ehuwandu nehuwandu hwezvidimbu zvekuda, kubhururuka kukwira; Salamone et al., 2007, Salamone et al., 2012; Barbano et al., 2009). Nekudaro, nucleus accumbens DA inonyatso kuverengerwa muzvinhu zvekurudziro, uye kudzora kwezviito-zvinotungamirwa zviito, asi nenzira yakatwasuka uye yakaoma isingataurwe neshoko rakareruka "mubairo." Mamwe mabasa ekushandisa anobaya mumabasa akachengetedzwa neMesolimbic DA (semuenzaniso, zvinoshanda zvekurudziro, kushanda nesimba), uye nekudaro kukanganiswa kwemesolimbic DA zvinokanganisa mashandiro pane aya mabasa, apo ichipindura pane mamwe mabasa akasimbiswa, kana zviyero zvekudya kwekutanga. kurudziro, vakasara vasina kusimba.
Mumakore mashoma apfuura, iyo pikicha yakabuda ndeyekuti neostriatum (kureva., Dorsal striatum) uye iyo DA yekuchengetedza inoratidzika kunge iine chinongedzo chakajeka mukugadziriswa kwemasangano emidziyo kupfuura iyo iyo nucleus accumbens (Yin et al., 2008). Zvipembenene zve dorsomedial neostriatum zvakaita kuti mhuka dzisava nehanya nezvose kusimbisa kuongorora uye kuipa kwezvakaipa (Yin et al., 2005). Zvose zvipembenene zvemuviri wepachiviri uye kudengenyeka kweDA mu dorsolateral striatum zvakaratidzwa kuti zvinokanganisa tsika yekugadzira (Yin et al., 2004; Faure et al., 2005). Kubatanidzwa kweeostriatum mumagadziro ekugadzirisa kunogona kuenderana nechinangwa chekufungidzira chebhaalin ganglia mukusimudzira kufambira mberi kwezviito zvekuita kana "chunking" yezvikamu zvekuita maitiro (Graybiel, 1998; Matsumoto et al., 1999). Pfungwa yekuti pane shanduko kubva kune yekumisidzana inouraya mirau yekushandisa kupindura neostriatal nzira dzinodzora kugadzirwa kwetsika dzakashandiswa zvakanyanya kupa tsananguro yezvakawanda zvinoitwa zvekupindwa muropa nezvinodhaka (ona ongororo na Belin et al., 2009), uye zvakare zvakakosha kuti unzwisise mhedzisiro yezvisikwa zvinowedzera (Segovia et al., 2012). Zvisinei, mumamiriro ezvinhu aya, zvinobatsira kusimbisa kuti kubatanidzwa kwekisikiti kunowanikwa DA mune zvimwe zvekudzidza kuchikoro kana kushanda, kana kubatanidzwa kweNeostriatal DA mukugadzirisa kukodha kwemasangano ekugadzirisa-kushanda kana kugadzirisa tsika, hazvirevi kuti izvi migumisiro inopindirana nezviito pamusimboti wekutungamira kana chido chekusimbisa zvizvarwa zvakadai sekudya. Semuyenzaniso, Smith-Roe naKelley, 2000 yakaratidza kuti yakasanganiswa jekiseni yaD1 Mupikisi uye NMDA anorwisana nematokari kuti kushaya simba kwekutengesa kwezvokudya-kusimbiswa kwekusimudzira mbambo hakubvumi kudya kudya uye kushandura chigumisiro ichi sekuratidza kusakosha kwechikonzero chinokurudzira chinokonzerwa nekugadzirisa uku. Uyezve, kupindira nekutapurirwa kweDA muDorsolateral neostriatum kwakaratidzwa kunokanganisa tsika yekugadzira, asi siya chinangwa-chinotungamirirwa (kureva, chichikurudzira)Faure et al., 2005). Nekudaro, kubatanidzwa kweiyo neostriatal DA mukugadzirwa kwetsika hakupi humbowo hwekupindirana kwedopaminergic kwekutanga kwekurudzira kwekudya kana chishuwo. Muchokwadi, kudya kwekudya kunonyanya kukanganiswa nekupererwa kweDA mu ventrolateral neostriatum, uye izvi zvakakanganisika zvine chekuita nemotokari idhizikisi inokanganisa chiyero chekupa uye kushandiswa kwepamberi panguva yekudyisa, uye zvinoitika zvakafanana nekutorwa kwekudengenyeka kwemuromo kune hunhu hwekuzorora kwaParkinsonia kudengenyeka (Jicha naSalamone, 1991; Salamone et al., 1993; Collins-Praino et al., 2011).
Kunyangwe isiri mucherechedzo wakareruka wehedonia kana wekutanga wekusimudzira chikafu uye chishuwo, DA mune nucleus accumbens inoita kunge inodzora nzira dzakawanda dzeruzivo dzichipfuura nepakati penyukireya uye nekudaro inotora chikamu mune dzakasiyana maitiro ehunhu ane chekuita nezve zvinokurudzira. Kwemakumi emakore, vaongorori vakaratidza kuti mabasal ganglia masisitimu anoita seanodzora sensorimotor basa, izvo hazvireve kuti kupindirana nebasal ganglia inoburitsa hurema hwakareruka kana kusagona kwemota, asi pachinzvimbo inoreva pfungwa yekuti zvivakwa izvi, kusanganisira izvo zvakaunganidzwa, zvinotora chikamu mune gating (kureva., kudzivirira) kwemhedzisiro yekunzwa kwekufunga pane hunhu hunobuda. Saizvozvo, Mogenson et al., 1980 nevamwe vatinoshanda navo vakaratidza makore apfuura kuti nucleus accumbens inoshanda se "limbic-mota" interface, ichipa chinongedzo pakati penhengo dzenzvimbo dzinobatanidzwa mukunzwa uye kugona uye maseketi emagetsi anodzora maitiro ekubuda. Humbowo hunoratidza kubva kunzvimbo zhinji hunoratidza kuti nucleus accumbens inoshanda segedhi, firita, kana gudzazwi, yeruzivo ichipfuura kubva munzvimbo dzakasiyana siyana dzecortical kana limbic munzira yayo kuenda kunzvimbo dzakasiyana dzemota dzehuropi (semuenzaniso, Roesch et al., 2009). Electrophysiological uye voltammetry zvidzidzo zvinoratidza kuti nucleus accumbens yakarongeka kuva sesembles uye microcircuits ye-work-specific neurons inoderedzwa neDA (O'Donnell, 2003; Carelli naWondolowski, 2003; Cacciapaglia et al., 2011). Roesch et al., 2009 yakashuma kuti nucleus inogadzira neurons inobatanidza ruzivo pamusoro pekukosha kwemutengo unotarisirwa nezvinhu zve motokari (zvichireva, kukurumidza kupindura kana sarudzo) inoitika munguva yekuita zvisarudzo. DA yakasunungurwa inogona kuisa chikumbaridzo chekushandisa mari inokosha, uye mune mamwe mamiriro ezvinhu inogona kupa motokari inobatsira yekushandiswa kwezvinhu (Minda et al., 2007; Gan et al., 2010; Beeler et al., 2012). Izvi zvinowirirana nechisarudzo chekubatanidzwa kwekuchengetedzwa kweD DA muhutano hwehutano hwekuita maitiro, kunyanya maererano nemutengo wekubhadhara / kubatsira (Salamone et al., 2007, Salamone et al., 2009).
Sezvambotaurwa pamusoro apa, zvipenyu zvinowanzoparadzana kubva pakukurudzira zvinotyisa kana zvinangwa nezvipingamupinyi kana zvipingamupinyi. Imwe nzira yekureva izvi ndeyekuti nzira yekuita muhupenyu hunokurudzira inoda kuti zvipenyu zvikurire "kurema kwepfungwa" pakati pavo uye zvinokurudzira zvakakosha. Iko pfungwa yekufambisa kwepfungwa inguva yakare pfungwa mupfungwa (semuenzaniso, Lewin, 1935; Shepard, 1957; Liberman uye Forster, 2008) uye yakatora zvakasiyana-siyana zvakasiyana-siyana zvedzidziso munharaunda dzakasiyana-siyana dzepfungwa (semuenzaniso, kuedza, hutano, unhu, nezvimwewo). Muchirevo chemazuva ano, inoshandiswa sezwi rinowanzoreva pfungwa yokuti zvinhu kana zviitiko zvisingawanzove zvakananga kana ruzivo, uye naizvozvo zvipenyu zvakaparadzana pamwe nemakero akawanda (semuenzaniso, kurema kwemazuva, nguva, zvichida, zvigadziro zvezvinhu zvinodiwa) kubva zvinhu izvi kana zviitiko. Munzira dzakasiyana-siyana, DA inonzi DAli inoshanda se bhiriji inoita kuti mhuka dzipinde mumuganhu wepfungwa dzinozviparadzanisa kubva pane zvinangwa zvinhu kana zviitiko. Vaongorori vakawanda vakafukura izvi nenzira dzakasiyana-siyana kana kusimbisa zvakasiyana-siyana zvekuita (Everitt naRobbins, 2005; Kelley et al., 2005; Salamone et al., 2005, Salamone et al., 2007, Salamone et al., 2009; Phillips et al., 2007; Nicola, 2010; Lex naHuber, 2010; Panksepp, 2011; Beeler et al., 2012; ona Mufananidzo 2), asi mazhinji emabasa anounganidzwa neDA akaverengerwa, kusanganisira kuita kwehunhu, kuedza kwesimba panguva yekuita nhumbi, Pavlovian kuchinjisa nhare, kupindura kune zvakasarudzika, kufanotaura kwechiitiko, maitiro anochinja maitiro, kutsvaga, uye simba kushandisa uye mutemo, zvese zvakakosha kuti zviitise kugona kwemhuka kukurira zvipingamupinyi uye, neimwe pfungwa, kuyambuka kure kure kwepfungwa. Pakazara, nucleus inounganidza DA yakakosha pakuita mhinduro dzinoshanda dzinoitwa kana kuchengetedzwa neyakagadziriswa mamiriro (Salamone, 1992), nekuda kwekushingaira mukugadzira zvipikiso kupindura kwenguva yakareba pakusasipo kwekusimbiswa kwekutanga (Salamone et al., 2001; Salamone uye Correa, 2002), uye kugadzirisa kugoverwa kwezviito zvekuita kuburikidza nekuisa zvinetso pamhinduro dzechidimbu dzinosarudzwa kuti dziwane kusimbiswa zvichibva pamitengo / kuongororwa kunobatsira (Salamone et al., 2007, Salamone et al., 2012; Hernandez et al., 2010).
Kushandura uye Kushinha Kunobatsira
Mukuenzanirana nekutsvakurudza kwemhuka kwakaongororwa pamusoro apa, kuongororwa uye kuchipatara zvidzidzo nevanhu zvakare zvakatanga kujekesa zvimwe zvekusimudzira mabasa ekutsvaga uye kukanganisa DA inobata uye kuratidza kuti vanogona sei kuwana chiremba. Iyi inotsvakurudza inotsvaga pamusoro pevanhu, achishandisa imaging uye nzira dzepamusoro pemasvomhu, yakaguma migumisiro yakaenderana nemafungiro ekuti kushandiswa kwematambudziko evanhu vose, uye DA kunyanya, vanobatanidzwa mune zvimwe zvekuita kwechibvumirano, kutarisira kwekusimbiswa, kushandiswa kwetsika, nekuedza- zvinoratidzika nzira. Knutson et al., 2001 akataura kuti accumbens fMRI activation yaionekwa muvanhu vanoita basa rekubhejera, asi kuti iro rakawedzera basa raive rakabatana nemubairo kufanotaura kana kutarisira kwete pane chaiko kuratidzwa kwemubairo wemari. O'Doherty et al., 2002 akacherechedza kuti kutarisira kwekuisa glucose kwakabatanidzwa nekuwedzera fMRI kushandiswa mukati memabrain uye nzvimbo dzeDA dzinouraya asi nzvimbo idzi hadzina kupindura kugadzirwa kweglucose. Zvidzidzo zvenguva pfupi zvekufungidzira zvakabatanidza ventral striatum mukuita mari / kubatsira kusarudza (Croxson et al., 2009; Botvinick et al., 2009; Kurniawan et al., 2011). Kutsika et al., 2012 akawana kuti kusawirirana kwomunhu mukushingaira kwevanhu kwakabatanidzwa nemufananidzo wekufungidzira wekupararira kweDRA inouraya. Pamusoro pe, Wardle et al., 2011 yakaratidza kuti amphetamine inosimudzira kuda kwevanhu kuti vashande nesimba kuti vawane mubairo, kunyanya kana mukana wemubairo wanga wakaderera asi hauna kuchinja mhedzisiro yemubairo wakakura pakuda kushanda nesimba. Pepanhau rekufungidzira razvino rakaratidza kuti madosi e-L-DOPA akasimudzira kumiririra kwekuratidzira kwezviito zvinokurudzira hazvina kukanganisa iyo neural inomiririra yekusimbisa kukosha (Guitart-Masip et al., 2012). Imwe mushumo wapfupi wakarondedzera kukwanisa kwe catecholamine kushandiswa kusiyanisa pakati pezvinhu zvakasiyana zvekukurudzira uye manzwiro kuvanhu (Venugopalan et al., 2011). Muchidzidzo ichi, kusvika kwekusvuta fodya kwakashandiswa seforforcer, uye vatsvakurudzi vakashandura kudhindwa kweDA kuburikidza nekutengesa kwechikafu catecholamine pamwe ne phenylalanine / tyrosine kuparara. Kuvhiringidzika kwekateklamine synthesis haina kufanira kuzvitaura-kudikanwa kwekusvuta fodya, kana kusvuta-induced hedonic mhinduro. Kunyange zvakadaro, iyo yakaderera kuwedzera kwepakati yekuparadzanisa mapurogiramu ekusimudzira fodya, zvichiratidza kuti vanhu vane kuderedzwa kweDaal synthesis vakaratidza kuderera kwakaderera kushanda kwefodya. Uyezve, kufungidzira kufungidzirwa kwakaratidza kuti nucleus yevanhu yakaunganidza / / ventral striatum haisi kungoita zvinopesana nemagariro, asiwo inopindura kushungurudzika, kuvhara, uye kushaya hutsinye / kusagadzikana (Liberzon et al., 1999; Pavic et al., 2003; Phan et al., 2004; Pruessner et al., 2004; Levita et al., 2009; Delgado et al., 2011). Zvakatorwa pamwechete, zvidzidzo izvi zvinoratidza kuti kune kufanana kwakawanda pakati pekuwana kunoitwa kubva kune mhuka dzemhando uye izvo zvakagadzirwa kubva pakutsvakurudza kwevanhu, maererano nemazhinji emabasa ekukurudzira aisostriatal DA maitiro.
Sezvo pfungwa dze DA dzichiri kubudirira, kutsvakurudza pamusoro pekuita mabasa eDA kuchave nechinangwa chakanyanya pakuongororwa kwekliniki kwekukurudzira kunetseka kunoonekwa kune vanhu vane kuora mwoyo, schizophrenia, kushandisa zvinodhaka, nezvimwe zvinetso. Mune vanhu, zvinhu zvinoratidzira zvekuita maitiro ekugadzirisa zvinhu zvinorehwa nekliniki inokosha. Kuneta, kusava nehanya, anergia (kureva, kuzvitaura kunoshayiwa simba), uye kuchera kwepfungwa zvinowanzoonekwa zvirwere zvekuora mwoyo (Marin et al., 1993; Stahl, 2002; Demyttenaere et al., 2005; Salamone et al., 2006), uye zviratidzo zvakafanana zvinokurudzirawo zvinogona kuvapo mune dzimwe zvirwere zvepfungwa kana zvepfungwa zvakadai schizophrenia (kureva, "kubvumira"), kubvisa kutsvaira (Volkow et al., 2001), Parkinsonism (Friedman et al., 2007; Shore et al., 2011), multiple sclerosis (Lapierre naHum, 2007), uye chirwere chinotapukira kana chinoputika (Dantzer et al., 2008; Miller, 2009). Uchapupu huzhinji hunobva kumhuka uye kuongororwa kwevanhu hunoratidza kuti DAlimbic uye DA inouraya inobatanidzwa mune izvi zvinoratidzira zvinokurudzira (Schmidt et al., 2001; Volkow et al., 2001; Salamone et al., 2006, Salamone et al., 2007, Salamone et al., 2012; Miller, 2009; Treadway naZald, 2011). Chiitiko chechangobva kuitika mukutsvakurudza kwehutano hwepfungwa kwakange kuri kuderedza kusimbiswa kune tsika dzekuongorora zvirwere, uye panzvimbo pekutsvaga kumativi ekutsvaga neural nekutarisana zviratidzo zvakasiyana-siyana zvehutano (kureva, tsvakurudzo yekutsvakurudza zvidzidzo nzira; Morris naCuthbert, 2012). Izvo zvinokwanisika kuti kuenderera mberi kwekutsvagisa nezve zvinokurudzira mabasa eDA kunovhenekera maseketi emagetsi ari pasi pezvimwe zvinokurudzira zviratidzo mu psychopathology, uye ichasimudzira kuvandudzwa kwemanovel ekurapa kwezviratidzo izvi zvinobatsira pamatambudziko mazhinji.
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