Pharracol Curr Opin. 2009 Feb; 9 (1): 53-8. Epub 2009 Jan 8.
De Mei C, Ramos M, Iitaka C, Borrelli E.
Source
Mahadum California Irvine, Ngalaba Microbiology na Molecular Genetics, 3113 Gillespie NRF, Irvine, CA 92617 USA.
nkịtị
Ihe mgbaàmà Dopamine (DA) na-achịkwa ọtụtụ ọrụ physioloji sitere na locomotion ruo na mmiri ọgwụ homonụ, ma na-arụ ọrụ dị oke mkpa na iri mmadụ ahụ. DA dị elu, dịka ọmụmaatụ na-aza ọgwụ ọjọọ, na-eme ka akwara dị iche iche na-ekwupụta ndị na-anabata DA dị iche iche; esi etu esi azaghachi ihe site na neurons / receiptors di iche-iche n’aru akparamagwa ya na ihe ekwenti ekwuputaghi. Ihe nrịba ama sitere n’aka ndị na-anabata D2 (D2Rs) bụ ezigbo ọmụmaatụ iji kọwaa ihe mgbagwojuanya a. D2Rs nwere presynaptic na postsynaptik na arụmọrụ, nke na-ekekọrịta abụọ na vivo. Nsonaazụ ndị na-adịbeghị anya sitere na ụmụ oke akụ na-akọwapụta ọrụ nke saịtị na nsonaazụ iche iche D2 si otu a na-abawanye nghọta anyị banyere otu DA modulates neuronal physiology.
Okwu Mmalite
Mmeghachi omume na ụgwọ ọrụ ebumpụta ụwa (ya bụ, nri) na ọgwụ ndị na-eri ahụ na-ekerịta akụrụngwa hedonic na ọkwa dopamine (DA) na sistemụ mesolimbic, na mpaghara ndị dị ka NAcc, nke egosiri na ọ bụ onye ga - agbanwe mkpụrụ ndụ anataghị ikike [1 – 3] . Ọgwụ ọjọọ na-eji usoro dopaminergic eme ihe iji kpochapụ omume ha na cellular na site na ịkwalite mmeghachi omume DA na-eme ka ọmụmụ usoro ahụ dịkwuo mfe.
A na-enweta mmetụta DA site na mmekorita ya na ndị na-anabata membrane nke ezinụlọ G-protein coupled receptor family [4]. Ya mere, n’elu akara DA na-a DAụ ọgwụ, nke ọ bụla n’ime ndị na-anabata DA na-achịkwa ya, ana-arụ ọrụ nke ọma na-eduga na mkpali ma ọ bụ na-egbochi ụzọ dị iche iche nke D1-D1 na D5 na D2-like receptor ezinụlọ (D2, D3 na D4 ), nke sụgharịrị ịbụ mbido / igbochi ụfọdụ neurons na sekit. N’isiokwu a, anyị ga-elekwasị anya n’ihe nrịba ama nke postsynaptik DA D2 na-anabata (D2R) nke ga - agbanye aka na ntanetị na ọrụ dị na vivo.
D2Rs, nke gosipụtara na ụbụrụ, bụ nke etinyere na ma ọgọdọ ma dopaminergic neurons, kamakwa na neurons nke ntinye dopaminergic ezubere (Fig.1). Na mgbakwunye na inwe mpaghara abụọ, ndị na-anabata D2 bụ agbụrụ dị iche iche mebere site na mmadụ abụọ pụrụ iche dịpụrụ adịpụ, aha ya bụ D2S (S = mkpụmkpụ) na D2L (L = ogologo) ewepụtara site na ntinye ọzọ nke otu mkpụrụ ndụ [4]. Mpempe igwe eji agbanye mkpụrụ ndụ ji ehichapụ ma ọ bụ gbanwee [5 – 9] na ngosipụta D2Rs adịla mkpa n'ịchọpụta ọrụ mgbasa ozi D2R na vivo [10]. Anyị ga-atụle ntinye aka nke usoro mgbasa ozi D2R nke na-eme mgbanwe tupu nzaghachi nke DA site na ọgwụ ọjọọ ma ọ bụ nke DA agonist site na atụnyere nsonaazụ sitere n'ụdị ụdị (WT) na ụmụ oke.
Nyocha 1
Ihe nrịba ama nke post na postsynaptikal nke D2L na D2S
Ntughari mgbaàmà nke D2L na D2S dị iche na-emetụta nzaghachi postsynaptic dị iche iche
Mmetụta intracellular kachasị mma nke DA bụ ịgbalite ụzọ cAMP [4]. A na - eme ka okporo ụzọ a rụọ ọrụ site na ndị nnabata D1 dị ka ndị nnabata-D2. Na statal ọkara spiny neurons (MSNs), ibuli ọkwa cAMP na-eduga n'ịrụ ọrụ protein Kinase A (PKA) [11] ma na-esite na phosphorylation nke ọtụtụ ebumnuche cellular na ihe dị mkpa nke phosphoprote DA-na cAMP. nke 32 kDa (DARPP-32), [12] (Fig.1). Ihe mgbochi nke D2R na-akpali PKA-phosphorylation nke DARPP-32. O yikarịrị ka mmetụta a bụ onye ogbugbu site na mmechi nke mgbochi D2R na adenylyl cyclase. Phosphorylation catalys nke PKA na Thr34 na-atụgharị DARPP-32 ka ọ bụrụ ihe na - egbochi PP-1, si otú a na - eme ka mmeghachi omume na-arụpụta site na ịgbalite ọrụ cAMP / PKA rụọ. Na nkenke, mgbochi nke ọgbasa ozi nke D2R na-eme ka enwee nkụda mmụọ, nke a na-enyocha ya na DARPP-32 null-mice [13]. Ofrụ ọrụ nke D1Rs na-abawanye phorhorylation Thr34 site na mkpali Golf-medirated [14]. N'aka nke ọzọ, ịgbalite nke D2Rs na-ebelata DARPP-32 phosphorylation na Thr34 site na ntinye aka nke Gi-mediation nke mmepụta cAMP [11]. Na mgbakwunye, D2Rs agonists na-akpali ọrụ protein phosphatase-2B, si otú a na-abawanye dephosphorylation nke DARPP-32 na Thr34 [11].
N'ụzọ na-akpali mmasị, SKF81297, onye nyocha nke D1R, na-arụpụta mmụba okpukpu iri na steeti phosphorylation nke DARPP-32 na Thr34, na WT ụmụ oke, D2R - / - na D2L - / - ụmụ oke [15]. Quinpirole, onye agonist D2-akọwapụtara nke ọma, na-agbagha mmụba nke phosphorylation nke DARPP-32 na Thr34 nke dopamine D1 agonist, na WT, mana ọ bụghị na D2R - / - ma ọ bụ D2L - / - anụ ahụ [15]. Nke a na-atụ aro na D2L isoform bụ maka D2-like receptor-medirated regulation of DARPP-32 phosphorylation na MSNs, si otu a gosipụta itinye aka na ntinye nke nnata ozi nnabata nke a na postsynaptik D2R akara mgbasa ozi.
N'aka nke ọzọ na dopaminergic neurons nke substantia nigra (SN) na mpaghara ventral tegmental (VTA), mbelata nke phosphorylation nke tyrosine hydroxylase (TH) na Ser40, nke dopamine D2 nke ndị agonist iche, mebiri na D2R - / - ụmụ oke, mana echekwara na D2L - / - dị ka anụ ahụ WT [15]. Na-egosiputa nnukwute presynaptic D2S akọwapụtara.
Igosipụta na ichepụta ọgọdọ na-arụ ọrụ na postsynaptik na postsynaptiz nke ọrụ yikarịrị na-esite na D2L na D2S iji soro ndị G-protein dị iche iche na ụzọ mgbaàmà [16,17] ma ọ bụ site na njikọta-akọwapụtaghị ọfụma ma nwekwaa mmekorita protein-protein.
N'oge na-adịbeghị anya, a kọtụrụ banyere mkparịta ụka nke serine / threonine kinase AKT na akara ngosi nke DA site na ndị na-anabata ndị ọbịa D2. Ọrụ nke ụzọ a bụ cAMP-nweere onwe ya ma bụrụ onye ogbugbu site na ịmepụta ụlọ ọrụ macromolecular nwere opekata mpe protein atọ, protein β-arrestin 18, AKT na phosphatase PP-2A [2]. N'ụzọ na-akpali mmasị, ọrụ nke psychostimulants na striatum na - eme ka usoro ngbanwe AKT phosphorylation na arụ ọrụ ngwa ngwa, site na ọrụ nnabata D18. Na nkenke, AKT phosphorylation anaghị agbadata mgbe usoro ọgwụgwọ psychostimulants na D2R - / - na D18L - / - striata [2], na-egosipụta otu ọrụ mgbasa ozi D2R dị obere o siri dabere na mbido nke D19L.
Nyocha ndị a ga-eme n’ọhụụ ga-enyocha ma ihe ngosipụta nke mgbaàmà mgbasa ozi D2R na-egosi n’ụzọ okporo ụzọ AKT na PKA, ma ọ bụ na ha na-arụ ọrụ na otu neurons.
D2R nke nwere ọrụ ọgbụgba nke synaptik dị na neurons postsynaptik
Ihe ngosi Nigrostriatal na mesolimbic, nke oma site na SN na VTA, sensọ n'ọnụ ụzọ, moto na ozi nkwụghachi ụgwọ ahụ. Na nzaghachi maka ihe omume ndị dị egwu glutamate ụgwọ ọrụ akara sitere na cobex orbitofrontal na amygdala basolateral ebe ebe DA bụ onye na-echekwa ihe ndị a. N'otu aka ahụ, DA na-egosipụta ntinye glutamate na dorsal striatum site na sensọ na mpaghara cortical [1], ebe ọ na-edozi mkpọtụ ahụ na-eme ka mmetụta nke mkpịsị ọkụ dị site na usoro mgbasa ozi D2R [20].
Na mgbakwunye na MSNs, D2Rs na-egosikwa site na interneurons striatal [21] yana ihe dị mkpa gbasara mgbanwe anụ ahụ [22,23]. Mkpụrụ ndụ ndị a na-anọchite anya naanị 5% nke neurons striatal, agbanyeghị ọrụ ha dị mkpa na nhazi physiological nke ozi sitere na njikọ cortical, thalamic na mesencephalic. Ntinye aka nke cholinergic interneurons na mgbanwe nke ọrụ MSNs, site na akara ngosipụta nke D2R gosipụtara nke ọma [22,23]. Usoro Presynaptic D2R na-ebute ụzọ ka ewepụtara na mwepụta nke GABA na glutamate [20,24,25] site na ọnya na cortical neurons. N'ihi ya, na mgbakwunye na ọrụ nzipụta DA na-arụ ọrụ na dopaminergic neurons, D2Rs na-eme dị ka heteroreceptors, na-agbanwe mgbapụta neurotransmitter site na neurons postsynaptic. Site na ikike ntọhapụ-modulating nke D2Rs na-emetụta ọ bụghị naanị nzaghachi nke neurons dopaminergic, kamakwa gbanwee nke ahụ nke mkpụrụ ndụ ezubere iche.
Ọrụ mgbasa ozi Presynaptic D2R dị na neurons dopaminergic
Mmụta na D2R - / - ụmụ oke ekpebiela na ndị na-anabata D2 bụ “bona fide” autoreceptors na-ahazi mkpokọ DA na-ahapụ [26 – 29]. N'ụzọ na-akpali mmasị, na mgbe ntinye uche nke DA n'ụdị nwanne di na WT na D2R - / -, ntọhapụ nke DA gbara site na ọgwụ cocaine dị elu nke ukwuu na D2R - / - ụmụ nwoke dịka e jiri ya tụnyere anụmanụ WT na nke ọma karịa oke a. nke DA na-abawanye na-ahụkarị na WT anụmanụ [27]. Enwetara nsonaazụ ndị yiri ya na nzaghachi morphine [27].
Nchọpụta nke D2R na-egbochi ihe mgbochi na-ekere òkè dị ukwuu na ịchịkwa DA ntọhapụ n'ọnọdụ nke oke ọkwa extra DAlular nwere ike ịkọwa nnukwu mmetụta nke D2R na mgbanwe nke ebubata site na ọgwụ ọjọọ na otu site na cocaine site na mgbochi nke onye na-ebugharị DA ( DAT). N'ihi ya, n'ọnọdụ nkịtị D2R autoreceptors, nke na-egbochi ịgbagbu na ịhapụ Mhapụ, bụ naanị ihe ọzọ nwere ike igbochi mmetụta cocaine.
Na nkenke, nhọta nke mbibi nke D2L na D2L - / - ụmụ oke, nke ka na - ekwupụta ndị na - anabata D2S, anaghị egbochi arụmọrụ autoreceptor nke D2R, na-akwado ọrụ iche iche D2S iche na vivo [8].
Ya mere, ideghari ihe omume D2R autoreceptor, nke D2S bu onye mgbasa ozi, nwere ike rụọ ọrụ dị mkpa na pathophysiology nke ị drugụ ọgwụ ọjọọ yana yana ịgbanye mbata na ọgwụ. Nkwado a na-akwado echiche a na-akwadokarị site na nlele ụmụ anụmanụ nwere nsogbu ị drugụ ọgwụ ọ bụla. Ejiri anụmanụ ndị a site na ntọhapụ ha kwalitere DA maka nzaghachi ọgwụ na-eri ahụ [30] yana ọnụ ọgụgụ dị nta nke D2R na-ejikọ ọnụ [31] na obere mgbochi nke ọrụ nchụpụ DA na-esite na belata somatodendritic autoreceptor sensitivity [32].
Ọzọkwa, a kọwo na nkwupụta nke D2Rs iji chịkwaa azụmaahịa nke DAT gaa n'azu plasma, site na ịgbalite ụzọ MAPK ụzọ [33], yana D2Rs na-emekọrịta ahụ na DAT n'ụzọ anụ ahụ na DAT na-atụgharị ọrụ ya [34]. Ya mere, D2Rs, ma yikarịrị ka D2S isoform, na mgbakwunye na ịhazi DA synthesis, na-esonye ike na njikwa nke ntọhapụ ya site na usoro dị iche iche dị n'etiti mmekorita ya na DAT bụ n'ezie ihe dị oke mkpa.
Mmetụta na-akpali akpali nke cocaine na-emetụta n'ihi enweghị D2S
N'ịbụ onye ụmụ mmadụ na-emegbukarị, cocaine na-eme ka mmetụta psychomotor ya na mmetụta ekwentị site na igbochi ọrụ DAT na dopaminergic neurons [35]. Glutamate na dopaminergic antagonists kwụsịrị mmegharị nke mkpụrụ ndụ mmalite (IEGs) nke cocaine na-ebute [36,37]. N'akụkụ a, mmegharị nke D1Rs bụ ihe achọrọ zuru oke maka ntinye nke nzaghachi cellular na akparamagwa na cocaine, dị ka ọmụmụ gosipụtara na D1R - / - ụmụ oke [38]. Ọmụmụ ihe na-adịbeghị anya, na-eji ụmụ oke transgenic nke D1R na D2R nwere mkpụrụ ndụ na-ahụ anya site na ngosipụta nke protein protein, enwetakwu mma ma kwado nchọpụta ndị a site na igosi na nzaghachi mkpụrụ ndụ dị oke egwu na cocaine na-ejikarị D1R-, mana ọ bụghị D2R-na-egosipụta neurons [ 39].
N'ọnọdụ a, a ga-atụ anya na mmetụ mkpụrụ ndụ ihe nketa nke D2Rs kwesịrị, ọ bụrụ na ihe ọ bụla, na-eme ka mmetụta cocaine dị na vivo pụta, n'ihi ọrụ mgbochi inhibitory D2R nke akọpụtara na mgbaàmà DA. Agbanyeghị, nke a abụghị ihe a chọpụtara.
A tụlere mmetụta cocaine na D2R - / - ụmụ oke ugbua mgbe agwọchara ọrịa na-adịghị ala ala yana ọmụmụ ihe nchịkwa onwe ya na nsonaazụ nke D2R - / - ụmụ oke nwere mmeghachi omume na ọgwụ. Ihe di nkpa, nke a esighi na ngbanwe ozi nke D1R mebiri emebi dika nzaghachi cellular na akparama agwa nke D2R - / - ụmụ oke iji kpalite mkpali nke D1Rs dị [40,41]. N'ikwekọ na ntinye mgbasa ozi D1R na-achịkwaghị achịkwa na D2R - / - ụmụ oke, ịgbalite nke IEG c-fos site na D1R-kpọmkwem ndị aka na mkpokọta nke D1R ligands na-adịghị arụ ọrụ iji gbochie mkpụrụ ndụ ihe atụ na ụmụ oke WT, rụpụtara na-arụ ọrụ nke usoro ihe ọmụmụ a. na D2R - / - ụmụ oke [40].
Ka o sina dị, a na-ahụkarị mmụba nke ọrụ moto site na cocaine na D2R - / - ụmụ oke n'ihe metụtara njikwa WT na ọ naghị abawanye n'ụdị ịdabere na dose [40,42]. N'ụzọ dị ịtụnanya, nchịkwa cocaine na D2R - / - ụmụ oke anaghị akpata c-fos (Fig.2). Nke a na - eduga na hypothesize na anọghị D2Rs sekit mgbochi, nke D2R na - achịkwa, ga - abụ onye ekpughere na-eduga na mkpesa nke iwebata c-fos na MSNs. GABA na acetylcholine na-anọchite anya ndị mgba na-eme nke ọma na ọnọdụ a ebe mfu nke njikwa mgbasa ozi nke D2R nke ntọhapụ ha nwere ike ibute nsị nke otu ma ọ bụ abụọ neurotransmitters [25] na MSNs igbochi c-fos induction (Fig.2). N'aka nke ọzọ, mfu nke D2Rs na-egbochi mmebi nke macromolecular mgbagwoju anya n'etiti D2R na protein ndị ọzọ, nke na-achịkwa mmeghachi omume cellular na omume na cocaine [43].
Nyocha 2
Mmetụta sel nke cocaine na neuronsatat.
Kwughachi na iwusiwanye Njirimara nke ọgwụ riri ahụ na ọnụnọ D2Rs
Ngwongwo na-akwụghachi ụgwọ nke cocaine na D2R - / - ụmụ oke, dị ka nyocha nke ọnọdụ nwere ntụpọ (CPP), na-enyocha [40]. Agbanyeghị, ọmụmụ ihe nchịkwa onwe onye gosipụtara na D2R - / - ụmụ oke na-achịkwa cocaine karịa WT mice [44]. Onyinye nke neuromodulators ndị ọzọ (ya bụ noradrenalin, serotonin) [45] na ngosipụta nke CPP na nchịkwa onwe onye na cocaine na D2R - / - enweghị ike iwepu ya ma na-eche nyocha ndị ọzọ. Isi okwu a dị mkpa na mkpa nke ọtụtụ data gosipụtara enweghị ụgwọ ọrụ nke ọtụtụ ọgwụ ọjọọ ndị ọzọ na-emegbu na D2R - / - ụmụ oke. Na nkenke, D2R - / - ụmụ nwoke anaghị anabata ntinye ma na-ewusi Njirimara nke morphine [46 – 48] na mmanya [49,50]. Ya mere na-egosi na achọrọ ọgbanye nọchiri anya D2R iji wepụta ụgwọ ọrụ na ịkwalite mmetụta nke ọtụtụ ọgwụ.
Dị mkpa, D2L - / - ụmụ oke, nke ka na-ekwupụta D2S ma na-ejikwa ọrụ autoreceptor D2R-nke na-eme ka ọ bụrụ nke na-eme ka acomụ ma ọ bụ na-akwụghachi ụgwọ maka cocaine nke yiri nke anụrị WT [8,9,27]. Ya mere na egosiputa uzo di nma nke D40S na akparama agwa na nzaghachi nke ekwenti banyere ogwu ojoo.
Nke a na-egosi na presynaptic D2R na-emegharị ahụ anya na-eme ọ bụghị naanị na ntọhapụ DA, kamakwa na GABA [25,51,52], glutamate [20] na acetylcholine [22] nwere ike ịrụ ọrụ na nzaghachi ọgwụ ọjọọ.
Na ngwụcha, ntinye pụrụ iche nke D2S na D2L n'otu n'otu na ọrụ postsynaptipu na-emeghe ajụjụ banyere ọrụ nke isoform ọzọ na ọnọdụ ọ bụla, ebe ọ bụ na a na-egosipụta nnabata abụọ ahụ na D2R na-egosipụta neurons. Otu ihe hypothesis bụ na ịpụ ahịa nke ihe abụọ na - anọpụ iche na akpụkpọ ahụ nwere ike ghara ịchịkwa usoro nke otu [53]. Mmepe nke teknụzụ òké na ọgbọ nke ụdị anụmanụ na ngwa ọrụ ọhụụ kwesịrị inye aka dokwuo anya ebe a.
Mkpebi
Nsonaazụ enwetara site na nyocha nke ụmụ oke D2R enyela ihe akaebe nke ntinye aka dị iche iche nke D2L na D2S na D2R na-egosi ọgbaghara na-eji ọgwụ ọjọọ eme ihe na ndị na-ekwu okwu iwe. Ọnụnọ nke D2L na-egosi ọgbaghara na-emebi iwu PKA na ụzọ AKT site na D2Rs, mana ọ naghị emetụta moto ahụ na nzaghachi na-akwụghachi ụgwọ maka cocaine. N'aka ozo, akara ngosi nke mgbasa ozi D2S pụtara ihe achọrọ maka moto na akwụghachi ụgwọ nke cocaine na o yikarịrị ka ọgwụ ndị ọzọ. Ihe nyocha na ihe nlere anya a choro ka anyi choputa ihe ndi ozo nke puru iche na ntinye a, ma oburu na dopaminergic ma obu na postsynaptic neurons.
Acknowledgements
Ọrụ ego na ụlọ nyocha nke E Borrelli metụtara nyocha a bụ ego sitere na NIDA (DA024689) na European Community (EC LSHM-CT-2004-005166).
References
1. Onye maara ihe RA. Forebrain nọchiri anya ụgwọ ọrụ na mkpali. J Comp Neurol. 2005; 493: 115 – 121. [PMC n'efu ederede] [PubMed]
2. Di Chiara G, Bassareo V. Usoro nkwụghachi ụgwọ na ọgwụ ọjọọ: ihe dopamine na-eme ma ọ naghị eme. Curr Opin Pharmacol. 2007; 7: 69-76. [PubMed]
3. Koob GF. Ọrịa neurobiology nke iri ahụ riri ahụ: echiche neuroadaptational dị mkpa maka nchọpụta. Ise igbo. 2006; 101 Suppl 1: 23 – 30. [PubMed]
4. Tan S, Hermann B, Borrelli E. Dopaminergic òké: na-enyocha ọrụ nke dị iche iche onye na-anabata nnabata dopamine na onye na-ebugharị dopamine. Int Rev Neurobiol. 2003; 54: 145 – 197. [PubMed]
5. Baik JH, Picetti R, Saiardi A, Thiriet G, Dierich A, Depaulis A, Le Meur M, Borrelli E. Parkinsonian dị ka mbelata adịghị mma na ụmụ oke na-enweghị ndị na-anabata dopamine D2. Nature. 1995; 377: 424 – 428. [PubMed]
6. Kelly MA, RM, Asa SL, Zhang G, Saez C, Bunzow JR, Allen RG, Hnasko R, Ben-Jonathan N, Grandy DK, Low MJ. Hypoplasia lactotroph Pituitary na hyperprolactinemia na-adịghị ala ala na ụmụ oke ụmụ oke dopamine D2. Neuron. 1997; 19: 103 – 113. [PubMed]
7. Jung MY, Skryabin BV, Arai M, Abbondanzo S, Fu D, Brosius J, Robakis NK, Polites HG, Pintar JE, Schmauss C. Potentiation nke D2 mutant moto phenotype na ụmụ oke enweghị dopamine D2 na ndị na-anabata D3. Neuroscience. 1999; 91: 911 – 924. [PubMed]
8. Usiello A, Baik JH, Rouge-Pont F, Picetti R, Dierich A, LeMeur M, Piazza PV, Borrelli E. Ọrụ dịpụrụ adịpụ nke abụọ isoforms nke ndị na-anabata dopamine D2. Nature. 2000; 408: 199 – 203. [PubMed]
9. Wang Y, Xu R, Sasaoka T, Tonegawa S, Kung MP, Sankoorikal EB. Dopamine D2 ogologo nnata na-esighi ike ụmụ oke na-egosipụta mgbanwe mgbanwe na arụ ọrụ dabere na striatum. J Neurosci. 2000; 20: 8305 – 8314. [PubMed]
10. Bozzi Y, Borrelli E. Dopamine na neurotoxicity na neuroprotection: gịnị ka ndị na-anabata D2 nwere? Neurosci Trends. 2006; 29: 167 – 174. [PubMed]
11. Nishi A, Snyder GL, Greengard P. Bidirectional iwu nke DARPP-32 phosphorylation site dopamine. J Neurosci. 1997; 17: 8147 – 8155. [PubMed]
12. Bateup HS, Svenningsson P, Kuroiwa M, Gong S, Nishi A, Heintz N, Greengard P. otu ụdị mkpụrụ ndụ nke DARPP-32 phosphorylation site na psychostimulant na ọgwụ antipsychotic. Nat Neurosci. 2008; 11: 932 – 939. [PMC n'efu ederede] [PubMed]
13. Fienberg AA, Hiroi N, Mermelstein PG, Song W, Snyder GL, Nishi A, Cheramy A, O'Callaghan JP, Miller DB, Cole DG, et al. DARPP-32: nhazi nke nrụpụta ọrụ nke dopaminergic neurotransmission. Sayensị. 1998; 281: 838-842. [PubMed]
14. Herve D, Le Moine C, Corvol JC, Belluscio L, Ledent C, Fienberg AA, Jaber M, Studler JM, Girault JA. A na-achịkwa ọkwa Galpha (olf) site na iji nnabata na njikwa dopamine na usoro adenosine na striatum. J Neurosci. 2001; 21: 4390 – 4399. [PubMed]
15. Lindgren N, Usiello A, Goiny M, Haycock J, Erbs E, Greengard P, Hokfelt T, Borrelli E, Fisone G. ọrụ dị iche iche nke dopamine D2L na D2S nnata na-edobe iwu nke protein phosphorylation na saịtị presynaptik na postsynaptik. Proc Natl Acad Sci US A. 2003; 100: 4305 – 4309. [PMC n'efu ederede] [PubMed]
16. Senogles SE. D2 dopamine receptor isoforms mgbaàmà site na protein Gi alpha dị iche iji gbochie adenylyl cyclase. Ihe omumu ihe omumu nke Gi Alfa nyere. J Biol Chem. 1994; 269: 23120 – 23127. [PubMed]
17. Guiramand J, Montmayeur JP, Ceraline J, Bhatia M, Borrelli E. spzọ ntinye dopamine D2 nnabata na-enye nkọwapụta nke njikọta na protein G-protein. J Biol Chem. 1995; 270: 7354 – 7358. [PubMed]
18. Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG An Akt / beta-arrestin 2 / PP2A na-egosi mgbaze dị mgbagwoju anya na-egbochi dopaminergic neurotransmission na omume. Ala. 2005; 122: 261 – 273. [PubMed] Isiokwu a na - akọwapụta ụzọ G-protein nọọrọ onwe ya, ụzọ nnabata dopamine na-ahazi ọrụ AKT ma bụrụ onye mgbasa ozi D2 yiri. Alingrịba ama na ụzọ AKT na-ebute site na nhazi nke macromolecular complex nwere AKT, β-arrestin2 na protein phosphatase PP2A. Nke a bụ ihe ọmụmụ izizi nke na-egosi njikọ dị n’etiti dopamine na AKT ụzọ mgbasa ozi.
19. Beaulieu JM, Tirotta E, Sotnikova TD, Masri B, Salahpour A, Gainetdinov RR, Borrelli E, Caron MG Regulation of Akt sign sign by D2 na D3 dopamine receptors in vivo. J Neurosci. 2007; 27: 881 – 885. [PubMed] Site na iji dopamine nnabata ụmụ akwụkwọ ndị a dere D2Rs dị ka ndị isi na-eme ihe na-achịkwa ụkpụrụ ụzọ AKT.
20. Badium NS, Zhang H, Schmitz Y, Wu NP, Cepeda C, Levine MS, Schmauss C, Zakharenko SS, Zablow L, Sulzer D Heterosynaptic dopamine neurotransmission na-ahọrọ usoro nke ọnụ mmiri corticostriatal. Neuron. 2004; 42: 653 – 663. [PubMed] N'iji ụzọ dị mma, electrochemical na electrophysiological, ndị edemede a gosipụtara dopamine site na njikwa usoro mgbasa ozi D2R na-achịkwa ịhapụ glutamate na ọdụ Corticostriatal. A na-atụ aro ka eji rụọ ọrụ a ka ọfụma iji belata mkpọtụ nke ọdụ ụgbọ ala na-anaghị arụ ọrụ.
21. Delle Donne KT, Sesack SR, Pickel VM. Ihe mgbochi immunocytochemical nke na-egosipụta ebe nnabata dopamine D2 n'ime GABAergic neurons nke oke bekee. Resbụrụ Res. 1997; 746: 239 – 255. [PubMed]
22. Wang Z, Kai L, Day M, Ronesi J, Yin HH, Ding J, Tkatch T, hụrụ n'anya DM, Surmeier DJ. Njikwa dopaminergic nke corticostriatal ịda mbà syneptik ogologo oge na neurons spinal na-agbagha site na cholinergic interneurons. Neuron. 2006; 50: 443 – 452. [PubMed]
23. Surmeier DJ, Ding J, Day M, Wang Z, Shen W. D1 na D2 dopamine-receptor modulation nke straatal glutamatergic signaling in striatal ọkara spiny neurons. Neurosci Trends. 2007; 30: 228 – 235. [PubMed]
24. Centonze D, Gubellini P, Usiello A, Rossi S, Tscherter A, Bracci E, Erbs E, Tognazzi N, Bernardi G, Pisani A, et al. Ihe ntinye iche di iche nke dopamine D2S na ndi nnata D2L na mgbanwe nke glutamate na nnyefe GABA na ebe a. Neuroscience. 2004; 129: 157 – 166. [PubMed]
25. Centonze D, Picconi B, Baunez C, Borrelli E, Pisani A, Bernardi G, Calabresi P. cocaine na amphetamine na-akụda mmụọ transenaal syriaptik GABAergic site na nnyefe D2 dopamine. Neuropsychopharmacology. 2002; 26: 164 – 175. [PubMed]
26. Dickinson SD, Sabeti J, Larson GA, Giardina K, Rubinstein M, Kelly MA, Grandy DK, Low MJ, Gerhardt GA, Zahniser NR. Dopamine D2 nnata nke na-erughi oke oke ụmụ oke na-egosipụta ọrụ na-ebugharị dopamine mana enweghị mgbanwe na ntọhapụ dopamine na dorsal striatum. J Neurochem. 1999; 72: 148 – 156. [PubMed]
27. Rouge-Pont F, Usiello A, Benoit-Marand M, Gonon F, Piazza PV, Borrelli E. Mgbanwe extrapinal dopamine na-ebute site na morphine na cocaine: njikwa dị mkpa site na ndị na-anabata D2. J Neurosci. 2002; 22: 3293 – 3301. [PubMed]
28. Benoit-Marand M, Borrelli E, Gonon F. Inhibido ịhapụ dopamine site na ndị nnabata D2 presyna: usoro oge na njirimara ọrụ na vivo. J Neurosci. 2001; 21: 9134 – 9141. [PubMed]
29. Schmitz Y, Schmauss C, Sulzer D. Mgbanwe dopamine na bulie kinetik na ụmụ oke adịghị anabata ndị ọbịa D2. J Neurosci. 2002; 22: 8002 – 8009. [PubMed]
30. Rouge-Pont F, Piazza PV, Kharouby M, Le Moal M, Simon H. Higher na mmụba na-akpata nrụgide ogologo oge dopamine na ngụkọta anụ ụmụ anụmanụ nwere amụma nchịkwa onwe nke amphetamine. Nnyocha microdialysis. Resbụrụ Res. 1993; 602: 169 – 174. [PubMed]
31. Hooks MS, Jones GH, Juncos JL, Neill DB, Justice JB. Ndịiche iche na usoro mmemme na-akpata ma nwekwaa ọnọdụ. Behav Brain Res. 1994; 60: 199 – 209. [PubMed]
32. Marinelli M, White FJ. Enweghi mmerụ ahụ na njikwa onwe nke cocaine nwere njikọ na arụmọrụ dị elu nke midbrain dopamine neurons. J. Neurosci. 2000; 20: 8876 – 8885. [PubMed]
33. Bolan EA, Kivell B, Jaligam V, Oz M, Jayanthi LD, Han Y, Sen N, Urizar E, Gomes I, Devi LA, et al. Ndị na-anabata D2 na-achịkwa ọrụ nnyefe dopamine site na mgbakwunye extracellular na-achịkwa kinases 1 na 2-phosphoinositide 3 kinase-based sistemụ. Mol Pharmacol. 2007; 71: 1222 – 1232. [PubMed]
34. Lee FJ, Pei L, Moszczynska A, Vukusic B, Fletcher PJ, Liu F Dopamine na-ebugharị ebugharị elu gburugburu na-eme ka mmekorita ya na onye na-anabata D2 dopamine rụọ ọrụ. Embo J. 2007; 26: 2127 – 2136. [PubMed] Isiokwu a na-akọ maka oge mbụ njikọ n'etiti D2Rs na DAT, nke na-agbanwe ọrụ DAT na ntinye uche dopamine na synapse.
35. Gainetdinov RR, Caron MG. Ndị na-ebugharị Monoamine: site na mkpụrụ ndụ ihe nketa ruo na omume. Annu Rev Pharmacol Toxicol. 2003; 43: 261 – 284. [PubMed]
36. Konradi C. Ihe ndabere nke dopamine na mmekorita glucose na striatum. Adv Pharmacol. 1998; 42: 729 – 733. [PubMed]
37. Valjent E, Pascoli V, Svenningsson P, Paul S, Enslen H, Corvol JC, Stipanovich A, Caboche J, Lombroso PJ, Nairn AC, et al. Iwu nke protin phosphatase protein na-enye ohere dopamine convergent na akara glutamate iji mee ka ERK rụọ ọrụ n'ime ọnọdụ ahụ. Proc Natl Acad Sci US A. 2005; 102: 491 – 496. [PMC n'efu ederede] [PubMed]
38. Xu M, Hu XT, Cooper DC, Moratalla R, Graybiel AM, White FJ, Tonegawa S. Mkpochapu hyperactivity cocaine na mmetuta neurophysiological dopamine nke dopamine D1 nnabata otutu mmadu. Ala. 1994; 79: 945 – 955. [PubMed]
39. Bertran-Gonzalez J, Bosch C, Maroteaux M, Matamales M, Herve D, Valjent E, Girault JA Usoro mmeghe nke ngbanye aka na dopamine D1 na D2 receptor-expressingatatat neurons na nzaghachi cocaine na haloperidol. J Neurosci. 2008; 28: 5671 – 5685. [PubMed] N'iji ụmụ oke ụmụ ọhụrụ emepụtara na-ekwupụta protein ndị na-efe efe n'okpuru njikwa ndị na-akwalite dopamine D1R ma ọ bụ D2R, ndị edemede a na-eme nyocha mara mma banyere nzaghachi moliiki na colopin na haloperidol na vivo. Nsonaazụ gosiri na oke cocaine na-arụ ọrụ ka ukwuu n'ime D1R na-ekwupụta MSNs na-agbatị mkpụrụ ndụ na-ekwupụta mkpụrụ ndụ D2R.
40. Welter M, Vallone D, Samad TA, Meziane H, Usiello A, Borrelli E Absence nke dopamine D2 ndị na-anabata na-eme ka nchịkwa nchịkwa na-egbochi nchịkwa ụbụrụ nke cocaine na-eme. Proc Natl Acad Sci US A. 2007; 104: 6840 – 6845. [PubMed] N'iji D2R - / - na D2L - / - ụmụ oke, ndị edemede a gosipụtara na moto na ekwentị na-aza maka cocaine nwere nnukwu nsogbu na enweghị ma ọnaghị edozighi ha abụọ. nke D2R. Nsonaazụ ndị a na-atụghị anya ya na-atụ aro na akara ngosi nke mgbasa ozi D2R na-enwe mmetụta mgbochi ma ọ bụ na-ekpebi sekit ụbụrụ. Na nkenke, ọnụnọ nke naanị D2S, dịka ọ dị na D2L - / - ụmụ oke, na-enwe ike iweghachi azịza nkịtị dịkarịsịrị ike site na ọrụ ndị echebere.
41. Kelly MA, Rubinstein M, Phillips TJ, Lessov CN, Burkhart-Kasch S, Zhang G, Bunzow JR, Fang Y, Gerhardt GA, Grandy DK, et al. A na-ekpebi ọrụ locomotor na ụdị mpe nke nnabata nnabata nke D2 dopamine site na usoro usoro mkpụrụ ndụ, nzụlite mkpụrụ ndụ yana na mmeghari mmepe. J Neurosci. 1998; 18: 3470 – 3479. [PubMed]
42. Chausmer AL, Elmer GI, Rubinstein M, Low MJ, Grandy DK, Katz JL. Ọrụ cocaine na-akpata ịkpa ókè na ịkpa oke cocaine na dopamine D2 receptor mutant mice. Psychopharmacology (Berl) 2002; 163: 54 – 61. [PubMed]
43. Liu XY, Chu XP, Mao LM, Wang M, Lan HX, Li MH, Zhang GC, Parelkar NK, Fibuch EE, Haines M, et al. Mgbanwe nke mmekorita D2R-NR2B na nzaghachi cocaine. Neuron. 2006; 52: 897 – 909. [PubMed]
44. Caine SB, Negus SS, Mello NK, Patel S, Bristow L, Kulagowski J, Vallone D, Saiardi A, Borrelli E. Role nke dopamine D2-dị ka ndị na-anabata ndị ọrụ nchịkwa cocaine: ọmụmụ ihe na D2 receptor mutant mice and novel D2 receptor ndị na-emegide anyị. J Neurosci. 2002; 22: 2977 – 2988. [PubMed]
45. Rocha BA, Fumagalli F, Gainetdinov RR, Jones SR, Ator R, Giros B, Miller GW, Caron MG. Ihe nchịkwa onwe nke Cocaine n'ime dopamine-na-ebugharị ụzọ akụ. Nat Neurosci. 1998; 1: 132 – 137. [PubMed]
46. Maldonado R, Saiardi A, Valverde O, Samad TA, Roques BP, Borrelli E. Ọnụnọ nke nsonaazụ na-akwụghachi ụgwọ na ụmụ oke na-enweghị ndị na-anabata dopamine D2. Nature. 1997; 388: 586 – 589. [PubMed]
47. Elmer GI, Pieper JO, Rubinstein M, Low MJ, Grandy DK, Wisdom RA. Ọdịda nke morphine intravenous na-arụ ọrụ dị ka onye nkwalite ngwa ngwa dị na dopamine D2 receptor knock-out ụmụ oke. J Neurosci. 2002; 22: RC224. [PubMed]
48. Elmer GI, Pieper JO, Levy J, Rubinstein M, Low MJ, Grandy DK, Wisdom RA. Mkpali ụbụrụ na ụgwọ ọrụ morphine na-akwụ ụgwọ dopamine D2 receptor-defensive ụmụ oke. Psychopharmacology (Berl) 2005; 182: 33 – 44. [PubMed]
49. Phillips TJ, Brown KJ, Burkhart-Kasch S, Wenger CD, Kelly MA, Rubinstein M, Grandy DK, Low MJ. Mmanya na-aba n'anya na ezi uche na-ebelata nke ọma na ụmụ oke anaghị anabata dopamine D2. Nat Neurosci. 1998; 1: 610 – 615. [PubMed]
50. Risinger FO, Freeman PA, Rubinstein M, Low MJ, Grandy DK. Enweghi onye na aru oru ethanol onwe onye na dopamine D2 receptor knockout umu oke. Psychopharmacology (Berl) 2000; 152: 343 – 350. [PubMed]
51. Cepeda C, Hurst RS, Altemus KL, Flores-Hernandez J, Calvert CR, Jokel ES, Grandy DK, Low MJ, Rubinstein M, Ariano MA, et al. Nnyefe glutamatergic na-eme ka ọnụnọ nke D2 dopamine receptor-defensive ụmụ oke. J Neurophysiol. 2001; 85: 659 – 670. [PubMed]
52. Chesselet MF, Plotkin JL, Wu N, Levine MS. Mmepe nke GABAergic interneurons ngwa-ngwa-ngwa-ese. Prog Brain Res. 2007; 160: 261 – 272. [PubMed]
53. Tirotta E, Fontaine V, Picetti R, Lombardi M, Samad TA, Oulad-Abdelghani M, Edwards R, Borrelli E. byrịba ama site na dopamine na-achịkwa ndị na-anabata ndị ahịa D2 na-ere ahịa na membrane. Okirikiri Cell. 2008; 7: 2241 – 2248. [PubMed]
;