Ogwu na-eme ka ngwugwu dopamine / glutamate na-agbanwe ọnọdụ iji wepụta ọchịchọ na ụjọ: D1 naanị maka agụụ iri nri ma D1 na D2 ọnụ maka ụjọ (2011)

J Neurosci. Ihe odide onye edemede; dị na PMC Maachị 7, 2012.

E bipụtara na ụdị edetu ikpeazụ:

PMCID: PMC3174486

NIHMSID: NIHMS323168

Onye mbipụta akwụkwọ ikpeazụ edezi ederede a enwere n'efu na J Neurosci

Hụ ihe ndị ọzọ na PMC na ebe isiokwu e bipụtara.

Gaa:

nkịtị

Ihe mkpuchi nke nucleus accumbens (NAc) na ntinye mesolimbic dopamine na-edozi ụdị egwu yana nke mkpali. Dịka ọmụmaatụ, ma ọ bụ agụụ na/ma ọ bụ omume egwu na-arụsi ọrụ ike ka a na-emepụta n'ụdị keyboard site na nkwụsịtụ glutamate na NAc (site na microinjection nke AMPA receptor antagonist DNQX) n'ebe dị iche iche anatomical tinyere rostrocaudal gradient n'ime etiti oke oke. Mgbagha nke Rostral glutamate na-emepụta mmụba dị ukwuu na iri nri, mana ọgba aghara ndị ọzọ na-edobe anya na-emepụta àgwà egwu na-arịwanye elu: mkpasu iwe na mgbanarị mgbalị mmadụ imetụ aka, yana nzaghachi mgbochi na-akpaghị aka ma na-eduzi nke a na-akpọ ịgbachitere / ili. Achọrọ dopamine endogenous mpaghara maka mkpali siri ike nke AMPA ga-ebute ya. N'ebe a, anyị na-akọ na ọ bụ naanị akara ngosi mpaghara endogenous na ndị na-anabata dopamine D1 ka achọrọ maka ọgbọ rostral nke oke iri nri, nwere ike itinye ntinye aka n'ụzọ ụzọ mmepụta. N'ụzọ dị iche, ọgbọ egwu na saịtị caudal chọrọ ma D1 na D2 nrịbama n'otu oge, nwere ike itinye aka na ntinye ntinye ụzọ na-apụtaghị ìhè. N'ikpeazụ, mgbe valence valence nke AMPA na-emeghasịkwa na saịtị ndị dị n'etiti gbanwere site na ijikwa ọnọdụ gburugburu ebe obibi, site na ọtụtụ agụụ na gburugburu ebe obibi dị mma ruo na-atụ egwu na gburugburu ebe mgbakasị ahụ, ọrụ nke D1 mpaghara na D2 na-egosi na mmekọrịta dopamine / glutamate na microinjection. saịtị wee gbanwee n'ike n'ike ka ọ dabara na mkpali valence ewepụtara ugbu a. Ya mere, ndị na-anabata NAc D1 na D2, na sekit neuronal ha metụtara, na-arụ ọrụ dị iche iche na ike dị iche iche na-eme ka ọchịchọ na ụjọ pụta site na nkwụsịtụ NAc glutamate na mpaghara etiti.

Okwu Mmalite

Ihe mkpali siri ike bụ akụkụ dị mkpa nke ọrịa psychopathological, sitere na oke agụụ na-akpali akpali na riri ahụ na iribiga ihe ókè ruo paranoia na-atụ egwu na schizophrenia na nsogbu nchekasị (Barch, 2005; Kalivas na Volkow, 2005; Howes na Kapur, 2009; Woodward et al., 2011). Ma mkpali agụụ na egwu na-agụnye mmekọrịta dị n'etiti dopamine na glutamate na sekit mesocorticolimbic jikọtara ọnụ na-ejikọta na nucleus accumbens (NAc) (Kelley et al., 2005; Faure et al., 2008; Meredith et al., 2008; Carlezon na Thomas, 2009; Kalivas et al., 2009; Humphries na Prescott, 2010).

NAc na sekit metụtara dopamine ka amara nke ọma maka ọrụ na mkpali agụụ (Schultz, 2007; Onye maara ihe, 2008), ma a na-etinyekwa ya n'ụdị ụfọdụ mkpali na-akpali akpali metụtara egwu, nchekasị, ịkpọasị na mgbu (Levita et al., 2002; Salamone et al., 2005; Ventura et al., 2007; Matsumoto na Hikosaka, 2009; Zubieta na Stohler, 2009; Cabib na Puglisi-Allegra, 2011). N'ime shei medial nke NAc, koodu neuroanatomical na-arụ ọrụ dị mkpa n'ịchọpụta agụụ yana egwu egwu nke mkpali siri ike sitere na ọgba aghara glutamate.

Mgbochi AMPA mpaghara (dịka ọmụmaatụ, site na DNQX microinjection) na-emepụta nri siri ike na/ma ọ bụ mmeghachi omume egwu na usoro ahụigodo anatomical tinyere gradient rostrocaudal (Reynolds na Berridge, 2001, 2003; Faure et al., 2008; Reynolds na Berridge, 2008). Na saịtị rostral na shei medial, omume ziri ezi / agụụ, dị ka iri nri siri ike, na-emepụta site na mkpaghasị glutamate mpaghara.Maldonado-Irizarry et al., 1995; Kelley na Swanson, 1997). N'ụzọ dị iche, ka ebe na-aga n'ihu n'atụghị egwu, ọgba aghara na-emepụta àgwà ndị na-atụ egwu nke nta nke nta, gụnyere ụda olu mgbakasị ahụ na mgbanarị mgbanarị na nzaghachi imetụ aka, na omume egwu na-atụghị anya ya dị ka nzaghachi mgbochi anụ ọhịa nke ịgbachitere / ili, nke òké na-eji ngwa ngwa. mmegharị nke forepaw iji tụfuo ájá ma ọ bụ ihe ndina n'ihe mkpali na-eyi egwu (dịka, rattlesnake) (Coss na Owings, 1978; Treit et al., 1981; Reynolds na Berridge, 2001, 2003; Faure et al., 2008; Reynolds na Berridge, 2008). N'ebe etiti dị na shei NAc, nkwụsị nke glutamate na-emepụta ngwakọta nke omume abụọ ahụ, na valence kachasị nwere ike gbanwee n'etiti ihe dị mma na nke na-adịghị mma site n'ịgbanwe ọnọdụ gburugburu ebe obibi n'etiti ndị maara nke ọma na nchekasị (Reynolds na Berridge, 2008).

Anyị kwuru na mbụ na achọrọ ọrụ dopamine endogenous na mpaghara maka mmebi glutamate na shei NAc iji mepụta nri ma ọ bụ egwu (Faure et al., 2008). Ihe a na-amaghị bụ ọrụ dị iche iche nke D1-dị ka D2-dị ka ndị na-anabata dopamine na njikọ ha jikọtara ya na sekit mmepụta na-apụtaghị ìhè na mkpali sitere na DNQX. N'ebe a, anyị lebara ọrụ ndị a anya, wee chọpụta na ọ bụ naanị mkpali nnabata D1, nke nwere ike itinye aka n'ụzọ ziri ezi na ventral tegmentum, ka achọrọ maka ọgba aghara glutamatergic iji mepụta nri agụụ na saịtị rostral. N'ụzọ dị iche, ọrụ endogenous na ma ndị na-anabata D1 na D2, nwere ike na-ewe ọrụ siri ike nke ụzọ na-apụtaghị ìhè na ventral pallidum na mpụta hypothalamus, dị mkpa maka DNQX iji mepụta omume egwu na saịtị caudal. Ọzọkwa, anyị chọpụtara na valence mkpali na-atụgharị ọnọdụ rostrocaudal na saịtị etiti na-agbanwe agbanwe, nke gbanwere n'etiti ọnọdụ agụụ nke chọrọ naanị D1 neurotransmission na ọnọdụ ụjọ nke chọrọ D1 na D2 neurotransmission n'otu oge.

ụzọ

Ndị isi

Oke Sprague-Dawley nwoke (ngụkọta n = 87; otu ule nri na egwu egwu, n = 51; Fos plume groups, n = 36), na-atụ 300 - 400 grams na ịwa ahụ, nọ na ~ 21 ° C na ntụgharị 12: 12 ọkụ: okirikiri gbara ọchịchịrị. Oke niile nwere ad libitum inweta ma nri na mmiri. Usoro nnwale niile ndị a kwadoro site na Kọmitii Mahadum maka ojiji na nlekọta nke anụmanụ na Mahadum Michigan.

Ịwa ahụ cannulation cranial

A na-eji ọgwụ intraperitoneal injections nke ketamine hydrochloride (80 mg / kg) na xylazine (5 mg / kg) na-agwọ oke oke na atropine (0.05 mg / kg) iji gbochie nhụjuanya iku ume, wee tinye ya na ngwa stereotaxic (David Kopf Instruments). ). Edobere ogwe incisor na 5.0 mm n'elu intra-aural zero, angling cannula trajectory ka ọ ghara ịbanye n'ime akụkụ ventricles. N'okpuru ogwugwu ịwa ahụ, oke (n=87) natara ntinye n'akụkụ abụọ nke cannulae cranial na-adịgide adịgide (14 mm, 23 igwe anaghị agba nchara) nke ezubere na isi ihe dị egwu n'oge oke rostrocaudal nke shei medial nke NAc. A na-etinye Cannulae n'ụzọ abụọ na nhazi n'etiti anteroposterior (AP) + 2.4 ruo + 3.1, mediolateral (ML) +/-.9 ruo 1.0 mm, na dorsoventral (DV) -5.6 ruo 5.7 mm site na bregma. A na-eji skru ịwa ahụ na acrylic eze gbachitere cannulae na okpokoro isi. A na-etinye ihe mgbochi igwe anaghị agba nchara (nlele 28) n'ime cannulae iji zere nkpuchi. Mgbe a wachara ya ahụ, oke ọ bụla natara ntụtụ subcutaneous nke chloramphenical sodium succinate (60 mg / kg) iji gbochie ọrịa na carprofen (5 mg / kg) maka enyemaka mgbu. Rats natara carprofen ọzọ awa 24 ka e mesịrị, ma kwere ka ọ gbakee ma ọ dịkarịa ala ụbọchị 7 tupu ule amalite.

Ọgwụ na intracerebral microinjections

A kpalitere mmebi glutamate mpaghara na shei medial tupu ule omume site na microinjections microinjections nke DNQX, AMPA / kainate receptor glutamate antagonist (6,7-dinotroquinoxaline-2,3 (1H, 4H) -dione; Sigma, St. Louis, MO) na dose nke 450 ng / 0.5 μl kwa akụkụ. DNQX ma ọ bụ ụgbọ ala (0.5 μl kwa akụkụ) ka etinyere ya naanị, ma ọ bụ yana yana a) onye na-emegide D1 ahọpụtara SCH23390 (R(+) - 7-chloro-8-hydroxy-3-methyl1-phenyl-2,3,4,5,-tetrahydro-1H-3-benzazepine, Sigma) na dose nke 3 μg / 0.5 μl kwa akụkụ; ma ọ bụ b) nhọrọ D2 antagonist raclopride (3,5-dichloro-N-{[(2S)-1-ethylpyrrolidin-2-yl]methyl}-2-hydroxy-6-methoxybenzamide) na dose nke 5 μg/0.5 μl kwa akụkụ, ma ọ bụ c) ma SCH23390 na raclopride. A họọrọ usoro ọgwụgwọ ọgwụ dabere na Faure et al. (2008) na Reynolds na Berridge (2003). A na-agbaze ọgwụ niile n'ime ụgbọ ala nke 50% DMSO jikọtara ya na saline 50% 0.15 M, na microinjected na olu nke 0.5 μl kwa akụkụ. A na-ahazi pH ahụ ka ọ bụrụ 7.0 ruo 7.4 site na iji HCl maka ma ọgwụ na microinjections ụgbọ ala. N'ụbọchị ule, a na-ebute ihe ngwọta n'ime ụlọ okpomọkụ (~ 21 ° C), nyochaa iji gosi na enweghị mmiri ozuzo, ma tinye ya na ọsọ nke 0.3 μl / nkeji site na mgbapụta sirinji site na PE-20 tubing site na igwe anaghị agba nchara. 16 mm, nlele 29) na-agbatị 2 mm gafere cannulae ntuziaka iji ruo ebumnuche NAc. A na-ahapụ ndị injectors ebe maka nkeji 1 na-esote microinjection iji kwe ka mgbasa ọgwụ na-agbasa, mgbe nke ahụ gasịrị, a na-edochi ndị obturators ma tinye oke ozugbo n'ime ụlọ nyocha.

Otu mmekọrịta nke Glutamate/dopamine

Oke ọ bụla a nwalere maka omume mkpali (n=23) natara microinjections ọgwụ 5 ndị ​​a n'ụbọchị dị iche iche, kewara awa 48 iche, n'usoro dabara adaba: 1) ụgbọ naanị, 2) DNQX naanị (iji kpalite omume mkpali). 3) ngwakọta nke DNQX gbakwunyere SCH23390 (D1 mgbochi), 4) DNQX gbakwunyere raclopride (D2 mgbochi), na 5) DNQX gbakwunyere ma SCH23390 na raclopride (jikọtara dopamine blockade) (Faure et al., 2008).

Otu ihe mgbochi dopamine nọọrọ onwe ya

A nwalere otu oke dị iche iche (n = 18) maka omume mkpali mgbe ha natachara microinjections nke ndị na-emegide dopamine naanị (na-enweghị DNQX), ma ọ bụ DNQX naanị, ma ọ bụ ụgbọ iji hụ na ndị na-emegide dopamine na shei NAc egbochighị DNQX site n'ịkwalite mkpali site na naanị. na-ewepụ ikike ịnya ụgbọ ala ma ọ bụ omume mkpali nkịtị. Iji otu dị iche iche hụ na ọnụ ọgụgụ microinjections ọ bụla oke natara bụ nanị 5 ma ọ bụ 6. Ndị otu dopamine antagonist nwetara ọnọdụ ọgwụ 5 ndị ​​a: 1) ụgbọ ala, 2) SCH23390 naanị, 3) raclopride naanị, 4) SCH23390 gbakwunyere raclopride. , na 5) DNQX naanị (dị ka ihe dị iche iche dị mma iji kwado na omume na-akpali akpali nwere ike ịmepụta na nnukwu ike na oke ndị a). A na-enye ọnọdụ ọgwụ niile n'usoro n'usoro n'usoro n'ime otu ọ bụla, a na-etinyekwa ule n'ime opekata mpe awa 48.

Otu mgbanwe gburugburu ebe obibi

A na-eji otu mgbanwe gburugburu ebe obibi dị iche iche (n = 10) chọpụta ma ịgbanwe ọnọdụ gburugburu ebe obibi na-agbanwe agbanwe agbanwe usoro mmekọrịta dopamine-glutamate n'otu saịtị dị n'etiti ụzọ abụọ n'ụzọ atọ nke shei medial nke nwere ike ịmepụta ma agụụ na agụụ. mkpali egwu (Reynolds na Berridge, 2008). Oke n'ime otu a nwere cannulae microinjection nke gbadoro anya na saịtị rostral-caudal etiti. A nwalere oke ọ bụla n'ụbọchị dị iche iche na gburugburu abụọ: "Ụlọ" dị mma na nke a maara nke ọma na nke na-akpali akpali na "Nrụgide" (akọwara n'okpuru) n'usoro na-agbanwe agbanwe. A nwalere oke na gburugburu ebe ọ bụla ugboro atọ, dịkwa n'usoro n'usoro, ka microinjections nke otu: 1) ụgbọ ala, 2) DNQX, ma ọ bụ 3) DNQX gbakwunyere raclopride. Ya mere oke ọ bụla nwetara ọnọdụ ule 6; ha niile kewapụrụ opekata mpe awa 48 n'usoro n'usoro.

Nnwale omume nke omume mkpali na mberede

Na-esochi ụbọchị 3 nke njikwa, oke niile nwalere maka omume mkpali (n = 51) ka ejiri usoro nnwale na ngwa n'ime ụbọchị 4 maka elekere 1 nke ọ bụla. Na nke 4th ụbọchị nke ebe obibi, oke na-anata microinjections nke ụgbọ ala tupu ha abanye n'ime ụlọ ule, iji mee ka ha mara na usoro microinjection. N'ụbọchị ule ọ bụla, oke na-anata otu n'ime ọgwụ ndị akọwara na mbụ ma tinye ya ozugbo n'ime ụlọ nyocha nke ọma (23 × 20 × 45 cm) nke nwere nri eburu ụzọ tụọ (~ 20g rat chow) na ad libitum mmiri, ikwe ka ngosipụta nke omume agụụ. Ụlọ ahụ nwekwara ihe ndina granular cob na-agbasa n'ala ~ 3 cm miri emi iji mee ka ngosipụta nke omume ịgbachitere anya. Edekọtara omume n'ime ụlọ ahụ maka nkeji 60, ka a ga-akara ya na ntanetị maka nyocha. Na ngwụcha nke nnọkọ ọ bụla, aka onye nnwale wepụrụ oke oke site na iji mmegharị aka na-eji nwayọ abịaruo nso iji wepụta oku nhụsianya ọ bụla na-atụ egwu, mbọ mgbapụ ma ọ bụ ihe nchebe nke mmadụ metụrụ aka kpalitere. N'ịgbaso usoro ~5 nke abụọ kwupụta ọnụ ụlọ nnwale, onye nnwale ahụ ji nwayọọ nwayọọ rute n'akụkụ oke ahụ, were ~ 2 sekọnd. Mgbe a kpọtụrụ ya, onye nyocha ahụ jiri mkpịsị aka nwere aka jiri nwayọọ na-ehichapụ akụkụ oke oke ahụ, were ~ 1 sk, tupu ebuli oke ahụ n'ọnụ ụlọ ahụ n'ụzọ dị nro nke were ~2 sk. Onye na-ekiri ya dekọrọ mgbalị ọ bụla oke na-agba iji gbanarị mgbe a na-emetụ ya, yana ata ahụhụ na ụda mkpagbu a na-anụ.

Emere ule omume niile maka otu ndị a dị n'elu (n = 41) n'ime ụlọ nyocha "Standard" (Reynolds na Berridge, 2008), na-eso njem dị nkenke site n'ọnụ ụlọ Ụlọ. Ezubere gburugburu Standard ka ọ yie ọtụtụ ụlọ nyocha neuroscience omume na ọkụ, ụda, na isi, yana ka ọ bụrụ nke na-anọpụ iche (n'etiti ụlọ dị mma na nke na-adịghị mma Nchegbu nke nnwale ọzọ). Gburugburu ọkọlọtọ a nwere ụlọ nyocha ụlọ nyocha (ọnọdụ ọkụ ehihie nke ọkụ fluorescent na-acha ọcha 550-650 lux, ụda ụda ambient 65 – 70 decibels) dị ka akọwara na mbụ.Reynolds na Berridge, 2008).

A nwalere oke ndị nọ n'òtù mgbanwe gburugburu ebe obibi na gburugburu 2 dị iche iche dị oke egwu: 1) gburugburu "Ụlọ", nke nwere ọkụ na-acha uhie uhie nkịtị (5-10 lux) na ọkwa dị jụụ nke mkpọtụ gburugburu (65-70 decibels, bụ isi. mkpọtụ oke na mkpọtụ kwụ ọtọ sitere na sistemu ikuku), yana isi ndị a ma ama na nlegharị anya nke ọnụ ụlọ oke nke ya; vesos 2) “Nrụgide” gburugburu ebe mmetụta mmetụta uche dị elu, nke a na-eme na ụlọ nyocha ọkọlọtọ belụsọ na a na-eduzi oriọna ndị ọzọ na-enwu ọkụ na ụlọ nnwale (1000-1300 lux n'ime oghere) na nnukwu ụda na-enweghị atụ na-egosi n'ihu. N'oge ule niile (egwu rock raucous sitere na ụda album zuru oke na-aga n'ihu nke "Raw Power" nke Iggy & The Stooges [1973; Iggy Pop reissue 1997]; 80-86 decibels). N'ule nlere nke mmasị, egosiri oke ka ọ họọrọ gburugburu ebe obibi karịa Standard na ịhọrọ gburugburu ụlọ nyocha Standard karịa Nchegbu (Reynolds na Berridge, 2008).

Koodu omume

Ihe omume nke mkpali egwu egwu egwu, ụda mgbapụ, mgbanarị mgbanarị, na mbọ ịta ahụhụ a na-eduzi n'aka onye nyocha bụ mgbe ejiri nwayọ bulie oke na njedebe nke oge ule (Reynolds na Berridge, 2003), mgbe nke ahụ gasịrị, a na-edekọ ngụkọta gram nke pellet chow riri. Àgwà ndị a na-apụta n'otu ntabi anya na ihe nkiri vidio n'oge ule 1-hr bụ ndị nyocha kpuru ìsì ka ha nweta ọgwụgwọ maka ngụkọta oge (sekọnd) maka nke ọ bụla n'ime ihe ndị a: omume iri nri (gụnyere ma usoro agụụ na ntinye afọ ofufo nke ntinye gbakwunyere ịta na ilo ihe. Nri), omume ịṅụ mmanya (ịrachapụ site na mmiri mmiri), na egwu ịgbachitere ịgbachitere / omume ili (akọwapụtara dị ka ịgbasa ọkụ ma ọ bụ ịkwanye ihe ndina na mkpali ihu ihu ngwa ngwa, na-eduga n'ozuzu ya gaa n'ihu ma ọ bụ nkuku nke oghere ahụ na-egbuke egbuke. ). Na mgbakwunye, a na-edekọkwa ọnụ ọgụgụ nke omume agụụ dị ka ibu nri na imi nri, yana omume ndị na-adịghị mma dị ka ịzụ ihe, obe n'ofe, na omume ejiji.

Historyology

Na-esochi nyocha omume, ejiri oke sodium pentobarbital mee ka oke ahụ belata. A na-agbaji oke oke ndị a tụrụ atụ Fos plumes ma mesoo ụbụrụ ụbụrụ dịka akọwara na mbụ (Reynolds na Berridge, 2008). Ndị a gụnyere oke anwalela omume n'ime otu mgbanwe gburugburu ebe obibi (n=10; nke ya mere natara 7th Ọgwụ ikpeazụ ma ọ bụ microinjection ụgbọ ala na ule omume 90 nkeji tupu ịgbasa mmiri) yana otu Fos raara onwe ya nye (n = 36; nke a na-enyocha akụkọ ihe mere eme mgbe naanị otu ọgwụ ma ọ bụ microinjection ụgbọ ala n'ime ebe a na-atụgharị n'ime shei medial niile, na-elekọta n'okpuru ọnọdụ yiri nke ahụ. ụbọchị mbụ nke ule maka oke omume). Ebumnuche nke otu Fos raara onwe ya nye bụ iji nyochaa oke mmetụta mpaghara mpaghara, wee zere ihe egwu nke enweghị atụ nha nha nha n'ihi necrosis/gliosis na-aga n'ihu n'ihi usoro microinjection nke nwere ike ibelata njedebe ikpeazụ. Ọ bụrụ na mbelata mere n'ìgwè a nwalere omume, nke ahụ n'aka nke ya nwere ike iwelite atụmatụ n'ụzọ ziri ezi nke nhazi nke ọrụ na maapụ ụbụrụ. Nke a nwere ike imebi atụmatụ mmetụta site na mbelata nke plume egbochiri n'ime otu raara onwe ya nye bụ ndị natara naanị otu microinjection.

A na-agbaji ụmụ oke niile ejiri mee nyocha Fos n'ọnụ wee mee ka ọ gbazee nkeji 90 mgbe ikpeazụ ma ọ bụ naanị microinjection nke ụgbọ ala (n=10), DNQX naanị (n=13), DNQX gbakwunyere SCH23390 (n=6), DNQX gbakwunyere raclopride (n) = 10), DNQX gbakwunyere raclopride na SCH23390 (n = 3) ma ọ bụ enweghị ngwọta (nkịtị, n = 3). Ejiri NDS, ewu mgbochi cfos (Santa Cruz Biotechnology, Santa Cruz, CA) na mgbochi ewu Alexa Fluor 488 (Invitrogen, Carlsbad, CA) (Invitrogen, Carlsbad, CA).Faure et al., 2008; Reynolds na Berridge, 2008). A wụnyere akụkụ ahụ, akpọnwụwo ma jiri ProLong Gold antifade reagent (Invitrogen) kpuchie ya. A na-enyocha mpaghara ebe ngosipụta nke fluorescent Fos dị na neurons gbara gburugburu saịtị microinjection ("Fos plumes") site na microscope dị ka akọwara na mbụ.Reynolds na Berridge, 2008).

E wepụrụ ụbụrụ ndị ọzọ ma dozie ya na 10% paraformaldehyde maka ụbọchị 1-2 yana na 25% sucrose solution (0.1 M NaPB) maka ụbọchị 3. Maka ntule ebe saịtị microinjection dị na ụmụ oke nwalere omume, a gbubiri ụbụrụ na 60 microns na microtome na-ekpo ọkụ, wụnye ya, akpọnwụọ nkụ ma jiri cresyl violet kpuchie ya maka nkwenye nke saịtị microinjection. Edobere saịtị microinjection dị n'akụkụ maka oke ọ bụla na mpekere coronal sitere na ụbụrụ oke oke (atlas).Paxinos na Watson, 2007), nke a na-eji wepụta ọnọdụ saịtị ọ bụla n'otu iberi sagittal. Mapping na sagittal ele na-enye ohere maka ngosi na otu map nke rostrocaudal na dorsoventral ókè nke NAc medial shei. A na-edepụta mmetụta na-arụ ọrụ na agụụ agụụ na omume egwu site na iji koodu agba iji gosipụta ike mgbanwe na omume mkpali maka oke nwalere omume n'otu n'otu. A tụrụ akara ka ọ dabara na dayameta kacha nke Fos plumes tụrụ dị ka akọwara n'okpuru. Ekewapụtara saịtị dị ka shei rostral ma ọ bụrụ na ebe NAC ha dị +1.4 ruo +2.6 mm n'ihu bregma, yana dị ka shei caudal ma ọ bụrụ na etinyere ha +0.4 ruo +1.4 mm n'ihu bregma.

Nyocha data

A na-enyocha mmetụta nke DNQX na omume parametric site na iji ihe atọ agwakọtara n'ime na n'etiti isiokwu ANOVA (ọgwụ × otu [glutamate/dopamine interaction na dopamine blockade onwe ya] × ọkwa anatomical [rostral versus caudal]) iji nyochaa mkpali nke iri nri. na omume agbachitere tinyere a rostrocaudal gradient. A na-enyocha mmetụta nke antagonism na D1-na D2-dị ka ndị na-anabata ya na omume DNQX kpatara site na iji ihe abụọ ọzọ jikọtara n'ime na n'etiti isiokwu ANOVA iji tụnyere omume na DNQX-naanị (D1 antagonism × D2 antagonism). A na-enyocha mmetụta nke mgbanwe gburugburu ebe obibi site na iji ihe abụọ n'ime isiokwu ANOVA (ọgwụ gburugburu ×). Mgbe achọpụtara mmetụta dị ukwuu, ekewara oke site na ọnọdụ ahụ wee mee nyocha ọzọ site na iji otu ụzọ ANOVA na ntụnyere ụzọ site na iji mmezi Sidak maka ọtụtụ ntụnyere. Maka data n'aha, a na-enyocha ọdịiche dị n'etiti ọnọdụ ọgwụ site na iji nyocha ihe ugboro ugboro nke McNemar.

Results

Mgbochi nnabata AMPA mpaghara na shei medial na-eme ka iri nri na omume ịgbachitere anya na gradient rostrocaudal.

Mgbagha glutamate mpaghara na shei medial kpatara site na microinjections nke DNQX, AMPA / kainate receptor glutamate antagonist, kpalitere oke agụụ na / ma ọ bụ omume egwu dabere na ntinye ya na gradient rostrocaudal dị ka a tụrụ anya ya (Nyocha 1a). Na saịtị rostral na shea medial, NAc glutamate na-akpata ọgba aghara siri ike ihe fọrọ nke nta ka ọ bụrụ ugboro 5 karịa ọkwa ụgbọ ala n'ọtụtụ omume iri nri na nri riri n'oge ule 1-hr (nchịkọta oge nri: mmekọrịta saịtị ọgwụ ×, F(1,32). ) = 10.0, p = .003; oriri na-eri na gram erimeri: ọgwụ × saịtị mmekọrịta, F (1,32) = 14.5, p = .001, Ọnụọgụ 2a–b, , 3a) .3a). N'aka nke ọzọ, na saịtị caudal na shea medial, DNQX microinjections ebulighị nri oriri (na ụfọdụ oke caudal na-egbochi iri nri na nri n'okpuru ọkwa ụgbọ ala; Ihe osise 2a–b), mana kama ọ kpalitere nnukwu elu n'ihe omume nke ụda mkpagbu na-atụ egwu (Ọnụọgụ 2d, ,3c;3c; 73% nke oke mgbe DNQX microinjection vs 0% mgbe ụgbọ ala, McNemar's test, p = .001) na nke egwu mgbapụ mbọ aka mmadụ (Ọnụọgụ 2e, ,3c;3c; 40% nke oke mgbe DNQX vs 0% mgbe ụgbọ ala gasịrị, ule McNemar, p = .031). N'otu aka ahụ, caudal DNQX microinjections na-emepụta ihe fọrọ nke nta ka ọ bụrụ 10-fold na mwepụta na-apụtaghị ìhè nke omume ịzọchite ihe nchebe n'elu ọkwa njikwa ụgbọ ala.Ọnụọgụ 2c, ,3b;3b; Mmekọrịta ọgwụ × saịtị na ngụkọta oge nke ịzọ ụkwụ, F(1,32) = 6.9, p = .013, Nyocha 1a). Ịzọ ụkwụ na-agbachitere anaghị agbasa ma ọ bụ enweghị usoro, kama ọ na-elekwasị anya n'ụzọ doro anya na otu ebumnuche: na-emekarị n'ihu oghere nke oghere (na-abụghị nke ihe na ndị mmadụ nọ n'ime ụlọ ahụ nwere ike ịhụ) na n'akụkụ ìhè na-egosipụta nkuku ihu nke transperent. ụlọ plastik.

Nyocha 1 

Nchịkọta maapụ omume yana nyocha Fos plume
Nyocha 2 

Eserese nchịkọta omume kpaliri
Nyocha 3 

Mmetụta nke D1 na D2 antagonism na nri sitere na DNQX na agbachitere omume egwu.

D1 dopamine receptor naanị dị mkpa maka DNQX iji mepụta omume agụụ na saịtị rostral

Nchọpụta akwụkwọ akụkọ ebe a bụ na achọrọ mkpali dopamine mpaghara endogenous naanị na ndị na-anabata D1-dị ka (D1, D5) gburugburu saịtị microinjection na rostral shei maka ọgbọ nke omume agụụ siri ike site na DNQX microinjections. Ndị na-anabata Rostral D2 dị ka (D2, D3, D4) pụtara na ọ dịghị mkpa na mmụba metụtara glutamate nke omume iri nri na oriri.1 ihe atụ-3). Nke ahụ bụ, mgbe agbakwunyere dopamine D1-antagonist, SCH23390, na rostral DNQX microinjection, mgbochi D1 kagburu ikike nke DNQX iwelie oge ejiri eri ma ọ bụ iri nri, na-ahapụ omume iri nri na oriri na ọkwa nchịkwa a hụrụ mgbe microinjections ụgbọ ala gasịrị.Ọnụọgụ 2a–b na na 3a,3a, iri nri: SCH23390, F (1,7) = 13.3, p = .008; Nyocha 2b, gram oriri: SCH23390, F(1,7) = 11.1, p = .010).

N'ụzọ dị iche, ijikọ D2-dị ka antagonist raclopride na DNQX microinjection maka saịtị rostral egbochighị ma ọ bụ ọbụna mebie DNQX-mmelite nke iri nri (ngụkọta oge; Ọnụọgụ 2a–b na na 3a,3a, raclopride, F (1,8) <1, p = .743) ma ọ bụ ihe oriri (grams riri; Nyocha 2b, raclopride, F (1,8) <1, p = .517). N'ụzọ dị iche, ma ọ dịkarịa ala na saịtị caudal shei, na-agbakwunye D2 antagonist kwere ka caudal DNQX nwekwuo oge eji eri nri ruo ọkwa dị elu nke dị 245% karịa ụgbọ ala, ma ọ bụ 156% karịa ọkwa iri nri nke DNQX mepụtara naanị (Ọnụọgụ 2a, ,3a;3a; Mkpali DNQX nke iri nri na saịtị caudal na-adịkarị ala n'ihi gradient rostrocaudal: nkezi nke 566 sec +/- 101 sec na DNQX gbakwunyere raclopride na 362 sec na DNQX naanị na 230 sec na ụgbọ ala; raclopride × DNQX, F (1,10) = 6.0, p = 0.035). Obere egwu maka nkwalite a ọzọ bụ na ịgbakwunye D2 antagonist emeghị ka nri anụ ahụ rie maka otu a, n'agbanyeghị na ọ fọrọ nke nta ka ọ bụrụ okpukpu abụọ karịa oge n'oge ikpe nke oke riri (Nyocha 2b, raclopride, F (1,11) <1, p = .930; Otú ọ dị, anyị na-achọpụta na raclopride kwalitere mkpali nke oriri nri yana omume iri nri maka caudal DNQX microinjections na nnwale dị iche a nwalere n'okpuru (n'ule ndị e mere na gburugburu ebe mgbakasị ahụ).

Dị ka a tụrụ anya, ijikọta ma D1 antagonist na D2 antagonist yana DNQX gbochiri DNQX kpam kpam ka ọ ghara ịkwalite iri nri (dị ka D1 antagonist n'elu), ma debe ọkwa oriri nke kwekọrọ na ọkwa ntọala ụgbọ ala.Ihe osise 2a–b; megide ụgbọ: gram oriri, F (1,7) <1, p = .973; iri nri, F (1,7) = 1.1, p = .322). Agbanyeghị, ngwakọta D1-D2 nke ndị na-emegide ya adịghị arụ ọrụ karịa ịgbakwunye naanị D1 antagonist naanị na DNQX, nke gbochiri ịrị elu nke agụụ kpamkpam.Nyocha 2a; iri nri, SCH23390 gbakwunyere raclopride megide SCH23390 naanị, F<1, p = 1.000). Na nkenke, anyị kwubiri na ọ bụ naanị mpaghara endogenous D1 receptor neurotransmission ka achọrọ iji mee ka ọgba aghara glutamate dị na saịtị rostral nke shei medial iji kpalite omume agụụ na iri nri. N'ụzọ dị iche, neurotransmission D2 mpaghara adịghị mkpa maka mkpali iri nri nke rostral, ọ bụghị ihe dị mkpa ma ọ bụ na-enye onyinye mgbakwunye n'ụzọ ọ bụla achọpụtara (na ikekwe na-egbochi mkpali nke iri nri na saịtị caudal, ikekwe site na ọgbọ mmeghachi omume egwu dị ka akọwara n'okpuru nke nwere ike. asọmpi na ma ọ bụ kwụsị iri nri).

Na-achịchapụ mkpochapụ n'ozuzu nke agụụ / omume egwu site na ndị na-emegide dopamine

N'ikpeazụ, mgbochi nke DNQX na-ebute mmụba na oriri ma ọ bụ iri site na mgbochi D1 nnabata pụtara na-egosipụta otu mmekọrịta nke ndị na-anabata dopamine nwere nsogbu glutamate kama igbochi nnwere onwe zuru oke nke mkpali iri nri ma ọ bụ ikike nke mgbochi dopamine kpatara. Ma microinjections nke D1 antagonist n'onwe ya (na-enweghị DNQX) ma ọ bụ nke D2 antagonist n'onwe ya (na-enweghị DNQX) kwụsịrị usoro nri nri n'okpuru ọkwa ụgbọ ala nke ihe dị ka gram 1 nke chow kwa nnọkọ (iri: SCH23390, F(1,14). ) = 1.9, p = .194, 149 sec +/- 52 SEM na SCH23390 megide 166 sec +/- 54 SEM na ụgbọ ala: F (1,14) <1, p = .389, 227 sec +/- 56 SEM; ihe oriri gram: SCH23390, F (1,14) <1, p = .514, 1.15 grams +/- .36 SEM na SCH23390 megide .94 grams +/- .23 SEM na ụgbọ ala; ,1,14) = 3.9, p = .068, 1.82 grams +/- .42 SEM). Yabụ na mgbochi dopamine mpaghara na NAc na usoro ndị a emebighị ọkwa mkpali nkịtị iri nri ma ọ bụ ikike moto maka mmegharị ahụ. Kama nsonaazụ anyị yiri ka ọ na-egosipụta ọrụ akọwapụtara nke D1 nnabata dopamine iji mee ka AMPA nnabata glutamate mebie na mpaghara rostral iji kpalite omume iri nri ruo ọkwa dị elu.

Àgwà egwu egwu sitere na nkwụsị nke glutamate mpaghara na-adabere na mkpali D1 na D2 mpaghara na-emekọrịta ihe site na dopamine endogenous.

N'ụzọ dị iche, akara ngosi endogenous n'otu oge na ndị na-anabata D1 na D2 na saịtị caudal nke shea medial pụtara ihe dị mkpa maka microinjection DNQX iji mepụta omume egwu siri ike (1 ihe atụ-3). Ịgwakọta ma ọ bụ D1 antagonist ma ọ bụ D2 antagonist na DNQX nke ọma gbochiri mmepụta nke ọ bụla agbachitere zọọ na caudal saịtị, yana ọgbọ nke ọ bụla mkpagbu oku ma ọ bụ gbanarị mmeghachi omume na mmadụ aka nke ma ọ bụghị nke DNQX microinjections nwere ike.Ọnụọgụ 2c–e, 3b–c; ịgbachitere agbachitere: SCH23390, F (1,10) = 7.1, p = 0.024, raclopride, F (1,10) = 5.4, p = 0.043; mgbapụ mgbalị & jumps: DNQX naanị: 40% nke oke, DNQX gbakwunyere SCH23390: 0%, p = 0.031 [tụnyere DNQX, McNemar ule], DNQX plus raclopride: 13%, p = .219; mkpagbu oku: DNQX naanị: 73% nke oke, DNQX gbakwunyere SCH23390: 13% nke oke, p = .012, DNQX plus raclopride: 20% nke oke, p = .008). Na nkenke, omume niile na-atụ egwu nọgidere na ọkwa nchịkwa efu mgbe ma ọ bụ dopamine antagonist jikọtara ya na DNQX.

Na-ewepụ mkpochapụ n'ozuzu site na microinjections dopamine antagonist

Ọzọ, D1 na D2 receptor onyinye na DNQX egwu induction pụtara na-egosipụta kpọmkwem mmekọrịta nke ndị a dopamine anabata ya na glutamate emeghasịkwa na caudal shei, n'ihi na-enye microinjections nke ma ma ọ bụ ma dopamine antagonists na-anọghị nke DNQX agbanweghị echebe site na ụgbọ ala. ọkwa ntọala (ịgba: SCH23390, F (1,14) <1, p = .913; raclopride, F (1,14) <1, p = .476). Otú ọ dị, ekwesịrị ịmara na ọkwa ụgbọ ala nke omume egwu dị nso na efu ugbua, na-ebuli ohere na mmetụta ala nwere ike ikpuchi nkwụsị n'ozuzu nke omume egwu site na mgbochi dopamine. Ya mere, anyị na-atụgharị na ihe akaebe ndị ọzọ, nke na-atụkwa aro na dopamine antagonist microinjections, ma ọ bụ na DNQX ma ọ bụ n'onwe ha, anaghị egbochikarị ọtụtụ omume. Dịka ọmụmaatụ, ejiji ejiji, omume na-adịghị mma nke ewepụtara n'ọnụọgụ dị ukwuu mgbe ụgbọ ala gasịrị, nkwụsị nke mpaghara nke D1 ma ọ bụ D2 nabatara. Naanị ndị na-emegide Dopamine egbochighị ejiji n'onwe ya (nkezi nke 9.33 +/- 1.35 bouts na ụgbọ ala megide 8.09 +/- 1.13 na SCH23390 na 8.40 +/- 1.22 na raclopride; F <1). N'otu aka ahụ, ịgbakwunye dopamine antagonists na DNQX akwụsịghị omume ejiji (F<1). Microinjections nke ndị na-emegide dopamine naanị emechibidoro ebe a na-agbagharị agbagharị egosipụtara dị ka azụ na ọnụ ụzọ gafere ihe dị ka 50% site na ọkwa ụgbọ ala, n'agbanyeghị na nkwụsị a adịghị nso ebe siri ike dị ka mwepu nke DNQX na-ebute elu nke iri nri ma ọ bụ ịgbachitere egwu egwu akọwara n'elu (azụ: SCH23390, F(1,13) ,17.6) = 001, p = .1,13, raclopride, F (9.8) = 008, p = .23390; oghere obe: SCH1,13, F (19.3) = 001, p <.1,13, raclopride, F ( 13.1) = 002, p = .23390). Ọzọkwa, DNQX microinjections kpaliri locomotion ka okpukpu abụọ ma ọ bụ okpukpu atọ nke ụgbọ ala, na-agbakwụnye SCH1,33 ma ọ bụ raclopride na DNQX microinjection egbochighị ịrị elu na oghere obe na azụ (mmetụta bụ isi nke DNQX: obe crosses, F (12.0) = 002, p = .1,33; n'azụ, F (6.8) = 014, p = .23390; SCH1: F <1,19 maka n'azụ na onu cross; ; azụ, F (2.2) = 154, p = .1,19). Ya mere, mmetụta mkpochapụ n'ozuzu nke ndị na-emegide dopamine na-efu ma ọ bụ dị ntakịrị, ma o yighị ka ọ zuru ezu iji kwụọ ụgwọ maka mkpochapụ nke omume mkpali nke DNQX akọwara n'elu.

Ọnọdụ mmekọrịta nke dopamine-glutamate na-agbanwe n'ụzọ na-agbanwe agbanwe ka ambience na-atụgharị valence mkpali.

Ambience gburugburu na-atụgharị valence mkpali

Dị ka a tụrụ anya, maka ọtụtụ saịtị dị n'etiti ụzọ abụọ n'ụzọ atọ nke shei medial (ya bụ, saịtị niile dị n'etiti 20% na tere caudal 20%), na-agbanwe ọnọdụ gburugburu ebe obibi site na ọchịchịrị, dị jụụ na nke amara (dị ka ụlọ nke oke). iji na-egbuke egbuke ma na-eme mkpọtụ (ọkụ ọkụ na egwu egwu) weghaara uru nke omume mkpali sitere na DNQX microinjections (Reynolds na Berridge, 2008) (Nyocha 4). Oke na-ewepụta ihe fọrọ nke nta ka ọ bụrụ naanị omume agụụ na gburugburu ebe obibi mgbe DNQX microinjections gasịrị, mana ọ na-ewepụtakwa àgwà egwu dị ukwuu mgbe a nwalere ya na gburugburu mgbakasị ahụ mgbe DNQX gasịrị n'otu saịtị NAc. Ọnọdụ a maara nke ọma, obere mkpali na nke a na-eche na ọ dị mma nke gburugburu ebe obibi (nke egosiri na oke na-ahọrọ ka ọnọdụ ọkụ ọkụ ụlọ nyocha; Reynolds na Berridge, 2008) mere ka mpaghara ahụ na-akpali agụụ mmekọahụ dị n'ime NAc gbasaa site na saịtị rostral wee wakpo saịtị caudal nke shei medial, nke mere na 90% nke ebe etiti etiti niile na-emepụta omume iri nri na nri nri (karịa 200% nke ụgbọ ala; Nyocha 4a). N'otu oge, gburugburu ebe obibi na-ekpochapụ DNQX-ịmalite omume egwu, dị ka mkpali ụda olu, mbọ mgbapụ ma ọ bụ ịgbachitere mgbanaka (Ihe osise 4a–b; ịzọ ụkwụ, DNQX, F (1,7) = 3.5, p = .102; ọgwụ × mmekọrịta saịtị, F (1,7) <1, p = .476). N'ihi nke a, oke mpaghara egwu na-akpata dara nke ukwuu na gburugburu ebe obibi, na-ahapụ ọtụtụ saịtị etiti etiti enweghị ike iwepụta mmeghachi omume egwu. Ya mere, ọ bụ naanị otu oke (nke nwere ebe kachasị anya caudal shei) gosipụtara ihe karịrị 20 sekọnd nke ịgbachitere mgbachitere na gburugburu ebe obibi, ma ọ bụ wepụta ụda mkpagbu mgbe emetụrụ ya aka mgbe ule ahụ gasịrị (Nyocha 4b).

Nyocha 4 

Ọnọdụ gburugburu ebe obibi na-agbanwe ọnọdụ mmekọrịta glutamate-dopamine

N'ụzọ dị iche, oke na-egbuke egbuke gburugburu Nchegbu (nke oke na-ezere ọnọdụ ụlọ nyocha ma mụta ngwa ngwa ịgbanyụ mgbe enyere ya ohere; Reynolds na Berridge, 2008agbasawanye mpaghara egwu na-akpalite caudal ka ọ gụnye akụkụ dị ukwuu nke etiti rostral nke shei medial, wee mee ka ọkwa nchebe nke DNQX kpalitere ruo ihe karịrị 600% ọkwa kwekọrọ na gburugburu ebe obibi.Nyocha 4b; DNQX, F (1,7) = 23.8, p = .002; saịtị × mmekọrịta ọgwụ, F (1,7) <1, p = .429). N'otu aka ahụ, gburugburu ebe mgbakasị ahụ mụbara mmụba nke ụda olu nhụjuanya na-emepụta mgbe DNQX gasịrị mgbe onye nyocha metụrụ oke ndị ahụ na njedebe nke nnọkọ site na okpukpu ise ma e jiri ya tụnyere gburugburu ebe obibi (Nyocha 4d; 50% nke oke na 10% n'ụlọ; Nnwale McNemar, p = .063). N'aka nke ọzọ, gburugburu ebe mgbakasị ahụ wepụrụ saịtị agụụ dị ọcha na mpaghara mpaghara rostrocaudal, na-atụgharị ha ka ọ bụrụ saịtị valence agwakọta ma ọ bụ naanị saịtị egwu.Nyocha 4c). Gburugburu ebe mgbakasị ahụ belatara ike nke omume agụụ nke DNQX kpalitere na saịtị midrostral ruo ihe dịka 50% nke ọkwa ụlọ, ọbụlagodi maka saịtị ndị ka na-emepụta nri ọ bụla (nkezi nke 507 sec +/- 142 SEM na gburugburu mgbakasị ahụ vesos 879 nkeji + / - 87 SEM na gburugburu ebe obibi; mmekọrịta ọgwụ × gburugburu ebe obibi, iri nri, F (1,7) = 6.0, p = .044; nri nri, F (1,7) = 2.9, p = .013).

Ụdị egwu chọrọ itinye aka na nnata D2, mana ọnọdụ agụụ anaghị achọ

Nchọpụta akwụkwọ akụkọ kachasị mkpa ebe a bụ ihe ndị na-anabata D1/D2 chọrọ maka mkpali dopamine endogenous na saịtị enyere na mgbanwe mgbanwe gburugburu ebe obibi n'ụzọ jikọtara ya na mkpali mkpali nke DNQX mepụtara ugbu a kama ịnọ na rostrocaudal ọnọdụ kwa otu. Saịtị DNQX ọ bụla nwere ụdịdị abụọ: agụụ na egwu, dabere na mpụta nke oge. Ọnọdụ agụụ (ya bụ DNQX- mkpali nke iri nri nke ọchịchịrị, dị jụụ na gburugburu ebe obibi maara nke ọma) achọghị ọrụ nnabata D2 iji kwalite iri nri, ebe ọnọdụ egwu (ya bụ DNQX- mkpali nke omume ịgbachitere ịgbachitere na nhụsianya ụda nke ndị ahụ kpatara. gburugburu ebe mgbakasị ahụ na-egbuke egbuke ma na-egbuke egbuke) na-achọ mgbe niile ka onye na-anabata D2 maka saịtị ọ bụla iji kpalie egwu, n'agbanyeghị ọnọdụ rostrocaudal (dị ka saịtị caudal chọrọ D2 maka ọgbọ DNQX egwu na nnwale gara aga) (Nyocha 4). Ntugharị n'ụdị valence, n'etiti agụụ na nchekwa, mere maka 90% nke saịtị ndị a nwalere, nke nwere ihe fọrọ nke nta ka ọ bụrụ ọnọdụ rostrocaudal etiti nwere ike ime na shei etiti. Maka 10% fọdụrụnụ nke saịtị (n = 1), DNQX microinjected n'ime shea caudal dị anya na-emepụta àgwà egwu mgbe niile na gburugburu abụọ ahụ (na njedebe D2 na-ewepụ àgwà egwu mgbe niile).

Kpọmkwem, ịgbakwunye D2 antagonist na DNQX microinjection gbochiri oku ahụhụ na omume ịgbachitere na saịtị niile na-ebute ụjọ mgbe DNQX gasịrị na gburugburu ebe mgbakasị ahụ (Nyocha 4; saịtị rostral, raclopride, F (1,4) = 19.9, p = .021, oke niile, raclopride, F (1,7) = 10.7, p = .022, saịtị × mmekọrịta ọgwụ, F (1,7) < 1, p = .730). Agbanyeghị, onye mmegide D2 anaghị egbochi ma ọ bụ gbochie omume iri nri (ya bụ, mkpali agụụ) nke DNQX mepụtara n'otu saịtị ahụ na gburugburu ebe obibi; N'ezie, ịgbakwunye D2 antagonist kwalitere ọkwa nke omume iri nri nke DNQX mepụtara na gburugburu ebe mgbakasị ahụ ruo 463% nke ọkwa ụgbọ ala yana 140% nke ọkwa na DNQX naanị maka otu saịtị ahụ.Nyocha 4c; Nkezi nke 712 sec +/- 178 SEM na DNQX gbakwunyere raclopride vesos 507 sec na DNQX naanị na 153 sec na ụgbọ ala). Na gburugburu ebe mgbakasị ahụ, mgbochi D2 kwalitere DNQX - mkpali nke iri na ụbara gram nri a na-eri, n'agbanyeghị ọnọdụ rostrocaudal (n'ime mpaghara etiti), na-akwado na mpaghara D2 neurotransmission abụghị naanị na ọ dịghị mkpa maka nkwalite iri nri mana n'ezie nwere ike imegide ọgbọ nke iri nri siri ike site na mgbochi AMPA nnabata mpaghara na shei medial (iri nri, raclopride, F (1,7) = 18.5, p = .008; saịtị × mmekọrịta ọgwụ, F (1,7) <1, p = .651; nri nri. , raclopride, F (1,7) = 5.6, p = .064, saịtị × mmekọrịta ọgwụ, F (1,6) = 2.5, p = .163). Mgbe ọ nọ na ọnọdụ ọkọlọtọ D2 mgbochi gbochiri DNQX-eri naanị na shei caudal (Nyocha 2a), gburugburu ebe mgbakasị ahụ gbasaara mpaghara egwu na-emepụta egwu ma gbasaakwa mpaghara nke D2-blockade na-egbochi iri nri DNQX ka ọ gụnyere mpaghara etiti rostral nke shei medial.Nyocha 4c; iri nri, raclopride × gburugburu ebe obibi × mmekọrịta saịtị, F(1,25) = 6.2, p = .020).

Ọrụ nnata Dopamine na-atụgharị na-atụgharị n'etiti ọtụtụ ntụgharị

N'ime oke ndị gosipụtara mkpali ambivalent (ma) na gburugburu ebe mgbakasị ahụ (60% nke oke), iri nri nke DNQX kpatara na nkeji iri na ise mbụ, ebe ịgbachitere agbachitere gbagoro n'ikpeazụ na nnwale (15 - 30 nkeji mgbe microinjection gasịrị, Nyocha 5a). N'ime oge 20 nkeji nke oke ndakọrịta n'etiti agụụ na omume nchekwa (nkeji 10 - 30), ọtụtụ oke na-agbanwe site na agụụ gaa na nchekwa naanị otu ugboro (16%) ma ọ bụ 2 ruo 6 ugboro (50%). Site na mgbanwe ole na ole n'ime awa ahụ, otu nkeji ọ bụla nwere ike ịbụ nke dị ọcha kama ịbụ agwa agwa agwa agwa (Nyocha 5b), kwekọrọ na akụkọ ndị gara aga (Reynolds na Berridge, 2008). Mgbochi ndị na-anabata Dopamine D2 egbochighị omume iri nri (nke na-achịkwa na nkeji 20 mbụ nke nnọkọ), mana gbochiri omume ịgbachitere nke ọma (nke na-achịkwa na nkeji 20 ikpeazụ).

Nyocha 5 

Àgwà agụsi agụụ ike na nchebe sitere na saịtị valence agwakọta na gburugburu ebe mgbakasị ahụ

Agbanyeghị, oke abụọ pụtara dị ka ihe na-enweghị isi, na-agbanwe n'etiti agụụ na omume nchekwa karịa ugboro 25 nke ọ bụla n'ime awa mgbe microinjections DNQX dị ọcha na gburugburu ebe mgbakasị ahụ. Nke a na-anọchi anya ụzọ kacha nso iji gosipụta mkpali dị iche iche nke anyị hụrụ n'otu oge. Ọbụlagodi na oke ndị a, agbanyeghị, mgbochi ndị na-anabata D2 na-egbochikarị naanị omume nchekwa na-apụta n'okpuru ọnọdụ ụda na nke na-egbuke egbuke, ọ nweghịkwa omume agụụ (na gburugburu ebe mgbakasị ahụ ma ọ bụ ụlọ) (ihe atụ oke, Nyocha 5c) nke nọgidere na-eme na ọkwa ndị yiri ya na oge oge mgbe DNQX gbakwunyere D2 antagonist microinjection dị ka mgbe DNQX dị ọcha na gburugburu ebe obibi kwekọrọ. Ya mere omume mkpali sitere na mmekọrịta dopamine-glutamate mepụtara nwere ike ịgbanwe ngwa ngwa na ugboro ugboro n'etiti ụdị agụụ na egwu. Mgbe ọnọdụ gburugburu ebe obibi kwalitere ambivalence n'ime onye nwere ike ime ya, saịtị nwere ike ịtụgharị ụdị valence karịa ugboro 20 n'otu elekere.

Nyocha Fos plume: na-akọwa oke mmetụta microinjection mpaghara

Enyere mpaghara ọrụ aka site n'ịtụle oke mmetụta mpaghara nke microinjections ọgwụ na anụ ahụ dị nso, dị ka egosipụtara na Fos plumes na gburugburu microinjection center (Nyocha 1b). A na-enyocha oke ndị ejiri na mbụ maka ule omume na otu mgbanwe gburugburu ebe obibi maka Fos plumes ka njedebe nke nnwale ahụ gasịrị. Otú ọ dị, dị ka a tụrụ anya ya, anyị kwadoro na oke ndị mechala ule omume akpachapụla Fos plumes ma e jiri ya tụnyere òtù Fos raara onwe ya nye bụ ndị natara nanị otu microinjection, na-egosi na DNQX na-ebute plumes sitere na oke ndị natara 6 microinjections gara aga anaghịzi anọchi anya nke kachasị. mmetụta radius nke mgbasa ọgwụ. DNQX mepụtara plumes n'ime otu Fos raara onwe ya nye ihe fọrọ nke nta ka ọ bụrụ 4 ugboro n'ịdị elu (ihe fọrọ nke nta ka ọ bụrụ ugboro 2 na radius) karịa na otu a nwalere omume mbụ (F(9,90) = 3.3, p <.002). Ya mere, mgbe ị na-edepụta ọgwụ na-arụ ọrụ na-agbasa na ọnụ ọgụgụ niile, anyị na-adabere na data radius nke sitere na otu Fos raara onwe ya nye (dakọtara na ọnọdụ ule omume mbụ) iji zere ileda anya mgbe ị na-atụle mgbasawanye nke mmetụta mpaghara maka microinjections, na iji wuo maapụ plume maka. localization nke ọrụ. Agbanyeghị, data ndị ọzọ niile ewezuga radieshon plume egosiri na maapụ enwetara naanị site na otu a nwalere omume (ya bụ, agba na eserese mmanya na-egosipụta oke iri nri na omume egwu kpalitere na saịtị ụfọdụ).

DNQX microinjections dị ọcha mepụtara ebe mgbaba nke okpukpu abụọ nke ike nke ọkwa Fos nke ọkwa ụgbọ ala, na obere olu nke 0.02 mm.3 maka otu Fos raara onwe ya nye (Nyocha 1b, elu etiti; radius = 0.18 +/- 0.04 mm SEM). Oke ndị natara 6 microinjections gara aga nwere etiti olu pere mpe nke 0.004 mm3 (radius = 0.1 mm). Gburugburu ebe a na-adọba mmiri, okwu Fos na otu kachasị nwere nnukwu halo nke 0.23 mm.3 Olu nke elu dị nro> ọkwa ụgbọ ala ugboro 1.5 (radius = 0.38 +/- 0.05 mm SEM; oke anwalelarị ugboro 6 nwere obere halos nke 0.05 mm3 olu, radius = .23 mm). Mgbakwunye nke D1 antagonist (SCH23390) gbajiri plumes na attenuated ike nke elu DNQX kpatara na nkwupụta Fos mpaghara (Nyocha 1b, ala etiti; DNQX megide DNQX gbakwunyere SCH23390, Biputere ntụnyere n'otu ụzọ ya na mmezi Sidak, p <0.01). SCH23390 wedara mkpokọta olu DNQX Fos ruo ihe na-erughị 0.18mm3 (radius halo elu = 0.35 +/- 0.05 mm SEM). N'ụzọ dị iche, mgbakwunye nke D2 antagonist (raclopride) gbasaara nnukwu ogige nke okwu Fos na akwalite DNQX butere elu na nkwupụta Fos mpaghara (Nyocha 1b, ala aka ekpe; DNQX megide DNQX gbakwunyere raclopride, Biputere ntụnyere ụzọ abụọ na mmezi Sidak, p <0.05). Raclopride gbasaara etiti dị n'ime nke okwu Fos okpukpu abụọ nke DNQX mepụtara na olu nke 0.15 mm.3 (radius = .33 +/- 0.042 mm SEM), wee hapụ radius na ike nke mpụta plume halo (nke okwu 1.5x). Anyị na-achọpụta na o doro anya na onye na-emegide D1 na-achịkwa D2 antagonist na mmetụta na Fos mpaghara mgbe ejiri microinjected ha abụọ na DNQX, dị ka DNQX Fos plumes na-ebelata na-esote mgbakwunye nke ndị na-emegide D1 na D2 jikọtara ọnụ.Faure et al., 2008).

Nkwurịta

Na shei rostral, naanị akara ngosi dopamine endogenous na ndị na-anabata D1 dị ka achọrọ maka microinjections DNQX iji kpalite mmụba okpukpu 5 na iri. N'ụzọ dị iche, na shei caudal, a chọrọ nrịbama n'otu oge na D1- na D2-dị ka ndị na-anabata DNQX iji mepụta oge 10 na-abawanye na mmeghachi omume egwu (oku nhụjuanya, mgbalị mgbapụ na ịgbachitere nchebe na-arụ ọrụ na-eduzi ihe ndị dị na oghere ma ọ bụ karịa). N'agbanyeghị nke ahụ, saịtị rostral na shea medial abụghị naanị D1 na-achị ma ọ bụ saịtị caudal D1-D2 na-achịkwa maka ọgbọ nke mkpali site na nkwụsịtụ glutamate. Ọtụtụ saịtị dị n'etiti na shei gbanwere n'ụzọ dị nro n'etiti iwepụta agụụ na mkpali egwu mgbe gburugburu gburugburu gbanwere. Maka saịtị ndị ahụ, a na-achọ ọrụ D2 mgbe niile maka ọgbọ egwu site na DNQX microinjection (na gburugburu nrụgide) mana ọ dịghị mgbe achọrọ maka ọgbọ iri nri (na gburugburu ebe obibi a maara nke ọma). Ọbụghị naanị na akara D2 adịghị mkpa, mgbochi ndị na-anabata D2 gbochiri DNQX mkpali nke iri nri na saịtị mgbe ntinye / mkpokọta gburugburu na-enyere aka ụjọ. Na nkenke, ntinye rostrocaudal na-akpaghasị ịdị mma nke mkpali na-akpali akpali nke mmebi glutamatergic na-emepụta, mana usoro mmekọrịta dopamine na-ejikọta chiri anya na agụụ agụụ / egwu na-emepụta n'oge enyere karịa ka ọ dị n'otu n'otu.Reynolds na Berridge, 2008).

Usoro mmekọrịta dị n'etiti dopamine na mgbochi glutamate

Usoro ziri ezi nke mmekọrịta NAc dopamine-glutamate n'ịmepụta oke mkpali na-akpali akpali yana egwu egwu ka bụ ihe mgbagwoju anya. Naanị ntule, anyị na-enye ọtụtụ ohere. Na enweghị ntinye glutamatergic n'oge mgbochi AMPA, neurons NAc na-ebelata ọnụ ọgụgụ dị ala nke ịgba egbe, bụrụ hyperpolarized, na ikekwe gbochie ebumnuche mgbada na ventral pallidum (VP), hypothalamus lateral (LH) na ventral tegmentum (VTA) iji kpalite omume mkpali (VTA).Taber na Fibiger, 1997; Kelley, 1999; Meredith et al., 2008; Roitman et al., 2008; Krause et al., 2010). Agbanyeghị, ọ bụrụ na dopamine na-emezigharị glutamatergic depolarizations.Calabresi et al., 1997) mgbe ahụ enwere ike ile dopamine anya dị ka ihe na-adịghị mkpa na hyperpolarizations dị otú ahụ.

N'agbanyeghị nke ahụ, otu ihe nwere ike ime bụ na ọrụ nnabata D2 na-ebelata mmetụta AMPA postsynaptik fọdụrụnụ.Cepeda et al., 1993), ya mere mgbochi D2 nwere ike igbochi attenuation AMPA, na-akpaghasị hyperpolarizations mpaghara. N'aka nke ọzọ, ịgbalite D1-receptor nwere ike ịkwado hyperpolarization na neurons egbochighị ya (Higashi et al., 1989; Pennartz et al., 1992; Moyer et al., 2007; Surmeier et al., 2007), ya mere mgbochi D1 nwekwara ike imebi hyperpolarizations ndị ahụ. Usoro presynaptic nwekwara ike inye aka, dabere na mwepu nke glutamate ntọhapụ site na NAc D1 nnabata nnabata na ọdụ hippocampal ma ọ bụ amygdala, yana mgbochi presynaptic D2 yiri ya na njedebe prefrontal.Pennartz et al., 1992; Nicola et al., 1996; Charara na Grace, 2003; Bamford et al., 2004). Mgbochi nke presynaptic dopamine nwere ike imebi mmechi ndị dị otú ahụ, wee mee ka mwepụta glutamate dịkwuo elu, nwere ike imeri mmetụta DNQX.

Klas nkọwa nke fọdụrụ nwere ike ịgụnye mmekọrịta dopamine/glutamate dị nro karịa. Dịka ọmụmaatụ, microinjections DNQX nwere ike gbanwee oke mmalite AMPA/NMDA gaa na NMDA, nwere ike dị mkpa ma ọ bụrụ na ndị na-anabata NMDA na-enye onyinye ugbu a na enweghị iyi AMPA.Cull-Candy na Leszkiewicz, 2004; Hull et al., 2009). Na mgbakwunye, hyperpolarization mpaghara nke DNQX kpatara nwere ike, site na njikọ GABAergic n'etiti ndị agbata obi, na-egbochi neurons gbara ya gburugburu.Mao na Massaquoi, 2007; Faure et al., 2008 ; Tepper et al., 2008). Mgbochi Dopamine nwere ike igbochi mmetụta abụọ a site n'ịkpaghasị ma ọ bụ mgbasa ozi NMDA.Cepeda et al., 1993; Surmeier et al., 2007; Sun et al., 2008) na mgbochi mpụta (Taverna et al., 2005; Grace et al., 2007; Moyer et al., 2007; Nicola, 2007). Ọrụ ndị a ma ọ bụ usoro ndị ọzọ na-emepụta ihe ndị a ga-achọ nkọwa n'ọdịnihu.

Ụzọ mmepụta ozugbo na nke na-apụtaghị ìhè na mkpali dabere na D1 na D2

Ụzọ akpaghị aka na nke na-apụtaghị ìhè sitere na shei nwere ike inye aka n'ụzọ dị iche iche na mkpali megide mkpali mgbagha (Hikida et al., 2010). N'ozuzu maka striatum, D2-na-egosipụta mmepụta na-eme njem site na ụzọ na-apụtaghị ìhè, na D1 na-egosipụta mmepụta na-aga site n'ụzọ ziri ezi (Gerfen na Young, 1988; Gerfen et al., 1990; Bertran-Gonzalez et al., 2008; Matamales et al., 2009). Maka NAc medial shei akpan akpan, D1-na-egosipụta neurons n'otu aka ahụ mebere ụzọ mmepụta kpọmkwem na VTA, ebe nha nhata nke D1 na D2 na-achịkwa neurons n'akụkụ ụzọ na-apụtaghị ìhè na VP na LH.Nyocha 6) (Haber et al., 1985; Heimer et al., 1991; Lu et al., 1998; Zhou et al., 2003; Humphries na Prescott, 2010). Na mgbakwunye, 15% - 30% nke neurons shei, nwere ike na-arụ ọrụ n'okporo ụzọ na-apụtaghị ìhè, na-egosipụta ma ndị na-anabata D1 na D2, nke na-etolite mgbe ụfọdụ heteromer jikọtara ọnụ.Humphries na Prescott, 2010; Perreault et al., 2010; Perreault et al., 2011). N'ụzọ doro anya, mkpa nke ndị na-anabata D1 na-enyere aka imebi glutamate iji mepụta omume agụụ nwere ike igosipụta isi ụzọ awara awara site na NAc ruo VTA. N'ụzọ dị iche, mkpa maka ọrụ D1 na D2 maka ọgbọ egwu DNQX nwere ike igosi oke ntinye aka nke ụzọ na-apụtaghị ìhè.

Nyocha 6 

Sekit Mesocorticolimbic metụtara mmekọrịta glutamate-dopamine

Ụdị mgbanwe Valence na echiche rostrocaudal: sekit Mesocorticolimbic

Mgbanwe n'etiti gburugburu ebe obibi ama ama na nrụgide nrụgide na-agbanwe sekit mesocorticolimbic, ikekwe na-agbanwe ntinye glutamatergic na NAc site na cortex prefrontal, basolateral amygdala (BLA), hippocampus na thalamus (Swanson, 2005; Zahm, 2006; Belujon na Grace, 2008), nke nwere ike imekọrịta ihe na akara D1/D2 dopamine. Dịka ọmụmaatụ, mgbe agbawasịrị nketa site na BLA, rostral shei neurons nwere ike igosipụta nzaghachi mbelata na mkpali BLA na-esote, ebe neurons na shei caudal nwere ike ịbawanye ọkụ na-esote otu mkpali BLA, ọdịiche nke chọrọ ndị na-anabata D2 na nke nwere ike. megharia nha nke agụụ vs. mpaghara egwu-ọgbọ n'ime shei etiti (Gill na Grace, 2011). Akụkụ pụrụ iche nke ntinye mesocorticolimbic nwekwara ike ịdị mkpa maka gradient nke rostrocaudal nke shea. Dịka ọmụmaatụ, a na-ewepụta norepinephrine sitere na ụbụrụ hind nke kachasị na mpaghara caudal nke shei, nke mkpali dopamine D1 kwadoro mana D2 gbochiri ya, ma nwee ike inye aka gbanwee valence mkpali.Berridge et al., 1997; Delfs et al., 1998; Vanderschuren et al., 1999; Schroeter et al., 2000; Park et al., 2010). N'ikpeazụ, nlebara anya corticolimbic na-atụ aka ruo n'isi site na mpaghara cortex prefrontal ruo na mpaghara nke shei medial, VP/LH na ebumnuche ala ha, na-enye ohere ka ọtụtụ. kewara loops iji gaa na sekit mesocorticolimbic (Thompson na Swanson, 2010), nke nwere ike tinyekwuo aka na nhazi nke ọchịchọ na ndị na-emepụta egwu egwu.

Amụma gbasara ndị nnabata D1 na D2 na omume mkpali

Anyị kwenyere na nchoputa anyị agaghị ekwekọ na akụkọ ndị ọzọ gbasara itinye aka na D2/D3 na mkpali mkpali (Bachtell et al., 2005; Bari na Pierce, 2005; Xi et al., 2006; Heidbreder et al., 2007; Gardner, 2008; Khaled et al., 2010; Abụ et al., 2011). Dị ka caveat, anyị na-achọpụta na nchoputa anyị ejedebere na usoro ndị na-agụnye n'otu oge: a) mmekọrịta glutamate-dopamine, b) n'ime NAc medial shei, nke ahụ c) na-ebute oke mkpali nke agụụ / egwu. Agbanyeghị na nkwubi okwu anyị dabara na akụkọ na D1 (ma ọ bụghị D2) mgbochi na NAc shei na-egbochi iri nri na-akpali agụụ mmekọahụ (VTA).MacDonald et al., 2004) ma na-egbochi agụụ onwe onye site na optogenetic activation nke glutamatergic amygdala-NAc projections (Stuber et al., 2011), yana akụkọ na-egosi na akara ngosi D2 na-enye aka na omume nchebe na-arụsi ọrụ ike (Filipeck et al., 1988; Puglisi-Allegra na Cabib, 1988), Nsonaazụ anyị anaghị egbochi ọrụ ndị ọzọ maka ndị na-anabata D2/D3 na-ebute mkpali agụụ na ọnọdụ dị iche iche. Karịsịa, anyị anaghị emegide ọrụ agụụ amịpụtara n'ụdị ụbụrụ dị iche iche, gụnyere mmeghachi omume dị iche iche (dịka ọmụmaatụ, mmụta karịa enweghị ọnọdụ) ma ọ bụ nke gụnyere mperi n'okpuru ọkwa mkpali nkịtị. Ịghọta ọrụ nnabata dopamine n'ịkwalite mkpali ga-emecha chọọ ntinye nke eziokwu niile dị mkpa.

GABA na metabotropic glutamate ọgbọ nke omume mkpali

Anyị na-atụ aro na mmekọrịta rostral dopamine/glutamate ebe a na-eme ka a na-ahụta nri dị ka ihe mara mma karịa iri nri. N'ụzọ dị iche, mkparịta ụka caudal ma ọ bụ nke na-adịghị mma na-eme ka a na-atụ egwu egwu, na-eme ka a na-ahụta ihe na onye nyocha dị ka ihe egwu. Anyị na-akọbu ọkwa mgbochi metabotropic glutamate na saịtị n'ime shei etiti iji kpalite ụjọ na ịkpọasị (Richard na Berridge, 2011), wee kọwapụta hyperpolarization GABAergic mpaghara iji mepụta gradients rostrocaudal nke nri na egwu, dị ka usoro ahụigodo akọwara ebe a (Reynolds na Berridge, 2001; Faure et al., 2010). Agbanyeghị, anyị anaghị atụ aro na mmekọrịta dopamine na ọgba aghara ionotropic glutamatergic akọwapụtara ebe a ga-emetụta metabotropic ma ọ bụ na usoro mkpali GABAergic NAc. Ntinye aka Dopamine na ndị ahụ ka bụ ajụjụ mepere emepe. Enwere ọtụtụ ọdịiche neuronal (dịka ọmụmaatụ, GABAergic hyperpolarizations nke neurons na glutamate blockade-mediated hyperpolarization) na ọrụ dị iche iche (dịka ọmụmaatụ, mgbanwe na mmetụta hedonic na ntinye nke omume mkpali) nke nwere ike bụrụ ihe dị mkpa.

Mmetụta maka psychopathology

Ejikọtala mmekọrịta Corticolimbic dopamine-glutamate na ma oke mkpali na-akpali akpali na egwu egwu, na-enye aka na mkpali agụụ na-eri ahụ yana mkpali egwu dị egwu na paranoia psychotic (Wang na McGinty, 1999; Barch, 2005; Taylor et al., 2005; Lapish et al., 2006; Faure et al., 2008; Jensen et al., 2008; Kalivas et al., 2009). Ntugharị na valence nke oke mkpali na-akpali akpali nwere ike ime (Morrow et al., 2011). Ndị na-eri ọgwụ amphetamine nwere ike ịnweta "amphetamine psychosis" na-atụ egwu dị ka paranoia, nke nwere ike ịgụnye ikwubiga okwu ókè nke ịdị egwu egwu.Featherstone et al., 2007; Jensen et al., 2008; Howes na Kapur, 2009). N'aka nke ọzọ, ụfọdụ ndị ọrịa schizophrenic na-egosipụta ọrụ ụbụrụ dị elu nke na-eme ka agụụ nwee agụụ mkpali nke ukwuu (Elman et al., 2006; Diaconescu et al., 2011). N'ozuzu, ịghọta otú mmekọrịta glutamate-dopamine dị n'ime NAc shei si emepụta oke agụụ na / ma ọ bụ mkpali egwu nwere ike ime ka usoro ndị na-akpata nsogbu dị otú ahụ siri ike ma na-emegide ya.

Nkweta

Nchoputa a sitere na National Institutes of Health Grants (DA015188 na MH63649 ruo KCB) yana site na mmekorita onyinye nturu ugo nke mba na JMR (MH090602). Anyị na-ekele Stephen Burwell na Andy Deneen maka enyemaka na akụkọ ihe mere eme, yana Brandon Aragona, Geoffrey Murphy, Joshua Berke, na Benjamin Saunders maka nkọwa na mkparịta ụka na-enyere aka.

References

  • Bachtell RK, Whisler K, Karanian D, Self DW. Mmetụta nke intra-nucleus na-eme ka nchịkwa shei nke dopamine agonists na ndị na-emegide ya na ịṅụ cocaine na àgwà ịchọ cocaine na oke. Psychopharmacology (Berl) 2005;183:41–53. [PubMed]
  • Bamford NS, Zhang H, Schmitz Y, Wu NP, Cepeda C, Levine MS, Schmauss C, Zakharenko SS, Zablow L, Sulzer D. Heterosynaptic dopamine neurotransmission na-ahọrọ tent nke corticostriatal ọnụ. Neuron. 2004;42:653–663 . [PubMed]
  • Barch DM. Mmekọrịta dị n'etiti cognition, mkpali, na mmetụta uche na schizophrenia: ole na ole anyị maara. Schizophr ehi. 2005;31:875–881 . [PubMed]
  • Bari AA, Pierce RC. D1-dị ka na D2 dopamine antagonists ndị na-anabata ya na-elekọta na mpaghara shei nke oke oke oke na-ebelata cocaine, mana ọ bụghị nri, nkwado. Sayensị sayensị. 2005;135:959–968 . [PubMed]
  • Belujon P, Grace AA. Ọrụ dị oke egwu nke Cortex Prefrontal na Iwu nke Hippocampus-Accumbens Flow Ozi. J Neurosci. 2008;28:9797–9805 . [PMC free article] [PubMed]
  • Berridge CW, Stratford TL, Foote SL, Kelley AE. Nkesa nke dopamine beta-hydroxylase-dị ka immunoreactive eriri n'ime shei subregion nke nucleus accumbens. Synapse. 1997;27:230–241 . [PubMed]
  • Bertran-Gonzalez J, Bosch C, Maroteaux M, Matamales M, Herve D, Valjent E, Girault JA. Usoro mmegide nke mgbake mgbaàmà na dopamine D1 na D2 receptor-na-egosipụta neurons striatal na nzaghachi cocaine na haloperidol. J Neurosci. 2008;28:5671–5685 . [PubMed]
  • Cabib S, Puglisi-Allegra S. Mesoaccumbens dopamine na-anagide nrụgide. Neurosci Biobehav Rev 2011 [PubMed]
  • Calabresi P, Pisani A, Centonze D, Bernardi G. Synaptic plasticity na mmekọrịta physiological n'etiti dopamine na glutamate na striatum. Neurosci Biobehav Mkpu. 1997;21:519–523. [PubMed]
  • Carlezon WA, Thomas MJ. Ihe mkpụrụ ndụ ndụ nke ụgwọ ọrụ na ịkpọasị: Nucleus na-eme ka nleba anya ọrụ. Neuropharmacology. 2009;56:122–132 . [PMC free article] [PubMed]
  • Cepeda C, Buchwald NA, Levine MS. Omume Neuromodulatory nke dopamine na neostriatum na-adabere na subtypes amino acid nnabata nke na-akpali akpali. Proc Natl Acad Sci US A. 1993;90:9576–9580. [PMC free article] [PubMed]
  • Charara A, Grace AA. Dopamine receptor subtypes Selectively na -akpali excitatory afferents si hippocampus na amygdala ka oke nucleus accumbens neurons. Neuropsychopharmacology. 2003; 28: 1412 – 1421. [PubMed]
  • Coss RG, Owings DH. Omume agwọ na-eduzi site na Snake Naive na Ahụmahụ California Ground Squirrels n'ime mkpọmkpọ ebe. Zeitschrift Fur Tierpsychologie-Akwụkwọ akụkọ nke Comparative Ethology. 1978;48:421–435 .
  • Cull-Candy SG, Leszkiewicz DN. Ọrụ nke ụdị subtypes NMDA dị iche iche na synapses etiti. Sci STKE. 2004;2004:re16 . [PubMed]
  • Delfs JM, Zhu Y, Druhan JP, Aston-Jones GS. Mmalite nke ihe ndị na-emetụta noosrenergic nke shei nke ọdịda akwara: usoro ọmụmụ anterograde na retrograde na oke. Resbụrụ Res. 1998; 806: 127 – 140. [PubMed]
  • Diaconescu AO, Jensen J, Wang H, Willeit M, Menon M, Kapur S, McIntosh AR. Njikọ dị irè na-adịghị mma na ndị ọrịa schizophrenia n'oge agụụ. N'ihu Hum Neurosci. 2011;4:239 . [PMC free article] [PubMed]
  • Elman I, Borsook D, Lukas SE. Usoro oriri na ụgwọ ọrụ na ndị ọrịa nwere schizophrenia: ihe ọ pụtara maka ọgba aghara metabolic na ọgwụgwọ ya na ndị ọrụ antipsychotic ọgbọ nke abụọ. Neuropsychopharmacology. 2006;31:2091–2120 . [PubMed]
  • Faure A, Richard JM, Berridge KC. Ọchịchọ na ụjọ sitere na nucleus accumbens: Cortical glutamate na subcortical GABA dị iche iche na-ebute mkpali na mmetụta hedonic na oke. PloS otu. 2010;5:e11223 . [PMC free article] [PubMed]
  • Faure A, Reynolds SM, Richard JM, Berridge KC. Mesolimbic dopamine n'ọchịchọ na ụjọ: na-eme ka mkpali na-ebute site na mmebi glutamate mpaghara na nucleus accumbens. J Neurosci. 2008;28:7184–7192 . [PMC free article] [PubMed]
  • Featherstone RE, Kapur S, Fletcher PJ. Ọnọdụ amphetamine kpatara dị ka ihe atụ nke schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:1556–1571 . [PubMed]
  • Filibeck U, Cabib S, Castellano C. Psychopharmacology (Berl) 2;1988:96–437. [PubMed]
  • Gardner EL. Iji ụdị anụmanụ mepụta ọgwụ mgbochi riri ahụ. Curr isi mgbaka 2008;10:377–384. [PMC free article] [PubMed]
  • Gerfen CR, Young WS., Nkesa nke atọ nke striatonigral na striatopallidal peptidergic neurons na patch na matrix compartments: ihe in situ hybridization histochemistry na fluorescent retrograde tracing ọmụmụ. Brain Res. 3;1988:460–161 . [PubMed]
  • Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ, Jr, Sibley DR. D1 na D2 dopamine receptor-ahaziri usoro nkwụghachi nke neurons nke striatonigral na striatopallidal. Sayensị. 1990; 250: 1429 – 1432. [PubMed]
  • Gill KM, Grace AA. Nhazi dị iche iche nke amygdala na ntinye hippocampal na mpaghara rostral na caudal nke nucleus accumbens. Int J Neuropsychopharmacol. 2011:1–14. [PMC free article] [PubMed]
  • Grace AA, Floresco SB, Goto Y, Lodge DJ. Iwu nke igba egbe nke dopaminergic neurons na njikwa omume ebumnuche ebumnuche. Ọnọdụ na Neurosciences. 2007;30:220–227 . [PubMed]
  • Haber SN, Groenewegen HJ, Grove EA, Nauta WJ. Njikọ dị egwu nke ventral pallidum: ihe akaebe nke ụzọ abụọ striato pallidofugal. Akwụkwọ akụkọ Comparative Neurology. 1985;235:322–335 . [PubMed]
  • Heidbreder CA, Andreoli M, Marcon C, Hutcheson DM, Gardner EL, Ashby CR., Jr Ihe akaebe maka ọrụ nke ndị na-anabata dopamine D3 na nchịkwa mmanya na-egbu ọnụ na iweghachi omume ịchọ mmanya na ụmụ oke. Biology riri ahụ. 2007; 12:35–50 . [PubMed]
  • Heimer L, Zahm DS, Churchill L, Kalivas PW, Wohltmann C. Puru iche na usoro ntule nke mkpokọ isi na shei nke oke. Neuroscience. 1991; 41: 89 – 125. [PubMed]
  • Higashi H, Inanaga K, Nishi S, Uchimura N. Mmelite nke omume dopamine na oke nucleus accumbens neurones in vitro mgbe ọgwụgwọ methamphetamine gasịrị. J Physiol. 1989;408:587–603 . [PMC free article] [PubMed]
  • Hikida T, Kimura K, Wada N, Funabiki K, Nakanishi S. inzọ dị iche iche nke nnyefe synaptik n'ụzọ kwụ ọtọ ma ọ bụ n'ụzọ adịghị mma iji kwụghachi ụgwọ na akọnuche. Neuron. 2010; 66: 896 – 907. [PubMed]
  • Howes OD, Kapur S. The Dopamine Hypothesis of Schizophrenia: Version III-025EFỤzọ Nkịtị Ikpeazụ. Akwụkwọ akụkọ Schizophrenia. 2009;35:549–562 . [PMC free article] [PubMed]
  • Hull C, Isaacson JS, Scanziani M. Usoro Postsynaptic na-achịkwa mkpali dị iche iche nke neurons cortical site na ntinye thalamic. J Neurosci. 2009;29:9127–9136 . [PMC free article] [PubMed]
  • Humphries MD, Prescott TJ. The ventral basal ganglia, usoro nhọrọ n'okporo ụzọ nke oghere, atụmatụ, na ụgwọ ọrụ. Ọrịa Neurobiol. 2010;90:385–417 . [PubMed]
  • Jensen J, Willeit M, Zipursky RB, Savina I, Smith AJ, Menon M, Crawley AP, Kapur S. Nhazi nke mkpakọrịta na-adịghị mma na schizophrenia: ihe àmà nke akwara na omume. Neuropsychopharmacology. 2008;33:473–479 . [PubMed]
  • Kalivas PW, Volkow ND. Ihe na-eme ka ọ bụrụ ihe na-adịghị mma: ụdị ọgwụgwọ nke mkpali na nhọrọ. Am J Ọchịachukwu. 2005; 162: 1403-1413. [PubMed]
  • Kalivas PW, LaLumiere RT, Knackstedt L, Shen HW. Mbufe glutamate na riri ahụ. Neuropharmacology. 2009;56:169–173 . [PMC free article] [PubMed]
  • Kelly AE. Ọrụ mkpirisi akwara ozi nke nucleus na-achịkọta mpaghara mpaghara n'ihe gbasara mmụta na mkpali. Psychobiology. 1999;27:198–213 .
  • Kelley AE, Swanson CJ. Nri na-ebute site na mgbochi nke AMPA na ndị na-anabata kainate n'ime ventral striatum: ọmụmụ maapụ microinfusion. Nnyocha ụbụrụ omume. 1997;89:107–113 . [PubMed]
  • Kelley AE, Baldo BA, Pratt WE, Will MJ. Corticostriatal-hypothalamic circuitry na mkpali nri: njikọta ike, ime ihe na ụgwọ ọrụ. Physiol Behav. 2005;86:773–795 . [PubMed]
  • Khaled MA, Farid Araki K, Li B, Coen KM, Marinelli PW, Varga J, Gaal J, Le Foll B. Onye na-anabata dopamine D3 antagonist SB 277011-A, mana ọ bụghị onye na-ahụ maka agonist BP 897, na-egbochi ntinyeghachi nke na-akpata. nke nicotine na-achọ. Int J Neuropsychopharmacol. 2010; 13:181–190 . [PubMed]
  • Krause M, German PW, Taha SA, Ubi HL. Achọrọ nkwụsịtụ na nucleus na-akpakọba akwara neuron iji malite na ịnọgide na-eri nri. J Neurosci. 2010;30:4746–4756 . [PMC free article] [PubMed]
  • Lapish CC, Seamans JK, Chandler LJ. Glutamate-dopamine cotransmission na nhazi ụgwọ ọrụ na riri ahụ. Ịṅụ mmanya na-aba n'anya-Nchọpụta ụlọ ọgwụ na nnwale. 2006;30:1451–1465 . [PubMed]
  • Levita L, Dalley JW, Robbins TW. Nucleus na-akwakọba dopamine ma mụta egwu legharịa anya: nyocha na ụfọdụ nchọpụta ọhụrụ. Nnyocha ụbụrụ omume. 2002; 137:115–127 . [PubMed]
  • Lu XY, Ghasemzadeh MB, Kalivas PW. Ngosipụta nke onye na-anabata D1, onye na-anabata D2, ihe P na enkephalin messenger RNA na neurons na-emepụta site na nucleus accumens. Sayensị sayensị. 1998;82:767–780 . [PubMed]
  • MacDonald AF, Billington CJ, Levine AS. Mgbanwe na oriri site na opioid na dopamine ụzọ akara n'etiti mpaghara ventral tegmental na shei nke nucleus accumbens. Brain Res. 2004;1018:78–85 . [PubMed]
  • Maldonado-Irizarry CS, Swanson CJ, Kelley AE. Ndị na-anabata glutamate na nucleus na-anakọta omume nchịkwa shei site na hypothalamus mpụta. Akwụkwọ akụkọ Neuroscience. 1995;15:6779–6788 . [PubMed]
  • Mao ZH, Massaquoi SG. Ihe dị iche iche nke mmeri-na-enweta asọmpi niile na netwọkụ akwara na-eme ugboro ugboro nwere mgbochi mpụta. IEEE Trans Neural Netwọk. 2007;18:55–69 . [PubMed]
  • Matamales M, Bertran-Gonzalez J, Salomon L, Degos B, Deniau JM, Valjent E, Herve D, Girault JA. Neurons spiny na-ajụkarị nke Striatal: njirimara site na ntụpọ nuklia na ọmụmụ nke ọnụọgụ neuronal na ụmụ oke transgenic BAC. PLoS Otu. 2009;4:e4770 . [PMC free article] [PubMed]
  • Matsumoto M, Hikosaka O. Ụdị dopamine neuron abụọ na-ebupụta akara mkpali dị mma na nke na-adịghị mma. Ọdịdị. 2009;459:837–841 . [PMC free article] [PubMed]
  • Meredith GE, Baldo BA, Andrezjewski ME, Kelley AE. Ndabere ntọala maka omume eserese n'ime ventral striatum na mpaghara ya. Ọrụ Struct Brain. 2008; 213:17–27 . [PMC free article] [PubMed]
  • Morrow JD, Maren S, Robinson TE. Ọdịiche dị n'otu n'otu n'ọchịchọ ịweta mkpali na-akpali akpali n'ọchịchọ agụụ na-ebu amụma ikike ikwupụta mkpali mkpali na nhụsianya na-adịghị mma. Behav Brain Res. 2011; 220:238–243 . [PMC free article] [PubMed]
  • Moyer JT, Wolf JA, Finkel LH. Mmetụta nke dopaminergic modulation na akụrụngwa njikọta nke ventral striatal media spiny neuron. J Neurophysiol. 2007;98:3731–3748 . [PubMed]
  • Nicola SM. Nucleus na-agbakọta dị ka akụkụ nke sekit nhọrọ ihe omume basal ganglia. Psychopharmacology (Berl) 2007;191:521–550. [PubMed]
  • Nicola SM, Kombian SB, Malenka RC. Psychostimulants na-akụda mgbasa ozi synaptik na-akpali akpali na nucleus accumbens site na presynaptic D1-dị ka ndị na-anabata dopamine. J Neurosci. 1996;16:1591–1604 . [PubMed]
  • Park J, Aragona BJ, Kile BM, Carelli RM, Wightman RM. Na vivo voltammetric nlekota nke catecholamine ntọhapụ na subterritories nke nucleus accumens shei. Sayensị sayensị. 2010; 169:132–142 . [PMC free article] [PubMed]
  • Paxinos G, Watson C. Ụbụrụ oke na nhazi stereotaxic. New York: Academic Press; 2007.
  • Pennartz CM, Dolleman-Van der Weel MJ, Kitai ST, Lopes da Silva FH. Presynaptic dopamine D1 ndị na-anabata ihe na-eme ka ihe na-akpali akpali na inhibitory limbic banye na mpaghara shei nke oke nucleus accumbens a mụrụ na vitro. J Neurophysiol. 1992;67:1325–1334 . [PubMed]
  • Perreault ML, O'Dowd BF, George SR. Dopamine receptor homooligomers na heteroligomers na schizophrenia. CNS Neurosci Ther. 2011; 17:52–57 . [PMC free article] [PubMed]
  • Perreault ML, Hasbi A, Alijaniaram M, Fan T, Varghese G, Fletcher PJ, Seeman P, O'Dowd BF, George SR. Onye na-anabata dopamine D1-D2 heteromer na-etinye aka na dynorphin/enkephalin neurons: Mmụba ọnọdụ mmekọrịta dị elu na-eso amphetamine na schizophrenia. J Biol Chem 2010PMC free article] [PubMed]
  • Puglisi-Allegra S, Cabib S. Pharmacological akaebe maka ọrụ nke D2 dopamine anabata na omume agbachitere nke òké. Behav Neural Biol. 1988;50:98–111 . [PubMed]
  • Reynolds SM, Berridge KC. Egwu na nri na nucleus accumbens shei: rostrocaudal segregation nke GABA-ewelitere omume nchebe megide omume iri nri. Akwụkwọ akụkọ Neuroscience. 2001;21:3261–3270 . [PubMed]
  • Reynolds SM, Berridge KC. Glutamate mkpali ensembles na nucleus accumbens: rostrocaudal shei gradients nke egwu na nri. Ọnụ ego J Neurosci. 2003;17:2187–2200 . [PubMed]
  • Reynolds SM, Berridge KC. Gburugburu mmetụta uche na-eweghachite ịdị mma nke agụụ na ọrụ egwu dị na nucleus accumens. Nne Neurosci. 2008; 11:423–425 . [PMC free article] [PubMed]
  • Richard JM, Berridge KC. Metabotropic glutamate receptor blockade in nucleus accumbens shei na-agbanwe valence na-emetụta egwu na ịkpọasị. Ọnụ ego J Neurosci. 2011;33:736–747 . [PMC free article] [PubMed]
  • Roitman MF, Wheeler RA, Wightman RM, Carelli RM. Azịza kemịkal oge na-agba na akwara dị iche iche na-akwụghachi ụgwọ ma na-akpali akpali. Nat Neurosci. 2008; 11: 1376 – 1377. [PMC free article] [PubMed]
  • Salamone JD, Correa M, Mingote SM, Weber SM. Na-agafe nkwupụta ụgwọ ọrụ: ọrụ ọzọ nke nucleus accumens dopamine. Echiche dị ugbu a na nkà mmụta ọgwụ. 2005;5:34–41 . [PubMed]
  • Schroeter S, Apparsundaram S, Wiley RG, Miner LH, Sesack SR, Blakely RD. Immunolocalization nke cocaine- na antidepressant-sensitive l-norepinephrine transporter. J Comp Neurol. 2000;420:211–232 . [PubMed]
  • Schultz W. Behavioral dopamine akara. Neurosci Trends. 2007; 30: 203 – 210. [PubMed]
  • Song R, Yang RF, Wu N, Su RB, Li J, Peng XQ, Li X, Gaal J, Xi ZX, Gardner EL. YQA14: akwụkwọ akụkọ dopamine D (3) onye na-anabata ihe na-egbochi nchịkwa onwe cocaine na oke na oke, mana ọ bụghị na ụmụ oke nnabata D (3). Addict Biol 2011 [PubMed]
  • Stuber GD, Sparta DR, Stamatakis AM. Ọdịdị 2011 [PMC free article] [PubMed]
  • Sun X, Milovanovic M, Zhao Y, Wolf M. Ihe mkpali na-anabata dopamine na-adịghị ala ala na-eme ka ịzụ ahịa nnata AMPA na nucleus na-akpakọba neurons nke ejiri prefrontal cortex neurons. J Neurosci. 2008;28:4216–4230 . [PMC free article] [PubMed]
  • Surmeier DJ, Ding J, Day M, Wang Z, Shen W.D1 na D2 dopamine-receptor modulation nke striatal glutamatergic na-egosi na striatal media spiny neurons. Ọnọdụ na Neurosciences. 2007;30:228–235 . [PubMed]
  • Swanson LW. Anatomi nke mkpụrụ obi dị ka egosipụtara na cerebral hemispheres: sekit akwara ozi n'okpuru njikwa afọ ofufo nke omume mkpali bụ isi. J Comp Neurol. 2005; 493:122–131 . [PubMed]
  • Taber MT, Fibiger HC. Ntọhapụ dopamine na-eri nri na nucleus, accumbens: ụkpụrụ site na usoro glutamatergic. Sayensị sayensị. 1997;76:1105–1112 . [PubMed]
  • Taverna S, Canciani B, Pennartz CM. Ndị na-anabata Dopamine D1 na-emegharị mgbochi mpụta n'etiti sel ndị bụ isi nke nucleus accumens. J Neurophysiol. 2005;93:1816–1819 . [PubMed]
  • Taylor SF, Phan KL, Britton JC, Liberzon I. Nzaghachi akwara ozi na mmetụta mmetụta uche na schizophrenia. Neuropsychopharmacology. 2005;30:984–995 . [PubMed]
  • Onye na-eto eto JM, Wilson CJ, Koos T. Onye na-ahụ maka ntinye ya na ihe mgbochi nzaghachi na neostriatal GABAergic spiny neurons. Brain Res Rev. 2008; 58: 272 – 281. [PMC free article] [PubMed]
  • Thompson RH, Swanson LW. Ntụle njikọ nhazi nhazi nke na-akwado hypothesis na-akwado netwọk n'elu usoro nhazi usoro nhazi ụbụrụ. Proc Natl Acad Sci US A. 2010;107:15235–15239. [PMC free article] [PubMed]
  • Treit D, Pinel JP, Fibiger HC. Olili ozu na-echekwa ọnọdụ: ụkpụrụ ọhụrụ maka ọmụmụ ihe ndị na-akpata anxiolytic. Pharmacology, Biochemistry & Omume. 1981;15:619–626 . [PubMed]
  • Vanderschuren L, Wardeh G, De Vries TJ, Mulder AH, Schoffelmeer ANM. Ọrụ mmegide nke dopamine D1 na ndị na-anabata D2 na mgbanwe nke oke nucleus accumens noradrenaline ntọhapụ. Akwụkwọ akụkọ Neuroscience. 1999;19:4123–4131 . [PubMed]
  • Ventura R, Morrone C, Puglisi-Allegra S. Prefrontal/accumbal catecholamine usoro na-ekpebi ihe mkpali salience attribution na ma ụgwọ ọrụ- na mkpali metụtara ịkpọasị. PNAS. 2007;104:5181–5186 . [PMC free article] [PubMed]
  • Wang JQ, McGinty JF. Mmekọrịta Glutamate-dopamine na-ebute mmetụta nke ọgwụ psychostimulant. Biology riri ahụ. 1999;4:141–150 . [PubMed]
  • Onye maara ihe RA. Dopamine na ụgwọ ọrụ: nchegharị nke anhedonia 30 afọ gara aga. Neurotox Res. 2008; 14: 169 – 183. [PMC free article] [PubMed]
  • Woodward ND, Cowan RL, Park S, Ansari MS, Baldwin RM, Li R, Doop M, Kessler RM, Zald DH. Mmekọrịta nke ndịiche dị n'otu n'otu na àgwà schizotypal na mwepụta dopamine nke amphetamine kpatara na mpaghara ụbụrụ striatal na extrastriatal. Abụ m J Psychiatry. 2011; 168:418–426 . [PMC free article] [PubMed]
  • Xi ZX, Newman AH, Gilbert JG, Pak AC, Peng XQ, Ashby CR, Jr, Gitajn L, Gardner EL. Akwụkwọ akụkọ dopamine D3 antagonist NGB 2904 na-egbochi mmetụta na-akwụghachi ụgwọ cocaine yana iweghachite omume ịchọ ọgwụ ọjọọ na oke oke. Neuropsychopharmacology. 2006;31:1393–1405 . [PubMed]
  • Zahm DS. Ozizi na-agbanwe agbanwe nke ụbụrụ ụbụrụ basal na-arụ ọrụ–anatomical 'macrosystems' Neuroscience & Biobehavioral Reviews. 2006;30:148–172 . [PubMed]
  • Zhou L, Furuta T, Kaneko T. Chemical nzukọ nke projection neurons na oke accumens nucleus na olfactory tubercle. Sayensị sayensị. 2003;120:783–798 . [PubMed]
  • Zubieta JK, Stohler CS. Usoro neurobiological nke nzaghachi placebo. Ann NY Acad Sci. 2009;1156:198–210 . [PMC free article] [PubMed]