{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:50:52Z","timestamp":1790700652068,"version":"4.1.0"},"reference-count":88,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["152326"],"award-info":[{"award-number":["152326"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Extensive damage to nigrostriatal dopaminergic neurons leads to Parkinson\u2019s disease (PD). To date, the most effective treatment has been administration of levodopa (L-DOPA) to increase dopaminergic tone. This treatment leads to responses that vary widely among patients, from predominantly beneficial effects to the induction of disabling, abnormal movements (L-DOPA induced dyskinesia (LID)). Similarly, experimental studies have shown animals with widely different degrees of LID severity. In this study, unilateral injections of 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle (MFB) produced more than 90% depletion of dopamine in both the striatum and the substantia nigra reticulata (SNr) of rats. Population analysis showed that dopamine depletion levels were clustered in a single population. In contrast, analysis of abnormal involuntary movements (AIMs) induced by L-DOPA treatment of 6-OHDA-lesioned animals yielded two populations: one with mild LID, and the other with severe LID, which are also related to different therapeutic responses. We examined whether the severity of LID correlated with changes in dopamine 3 receptor (D3R) signaling because of the following: (a) D3R expression and the induction of LID are strongly correlated; and (b) dopaminergic denervation induces a qualitative change in D3R signaling in the SNr. We found that the effects of D3R activation on cAMP accumulation and depolarization-induced [3H]-gamma-aminobutyric acid ([3H]-GABA) release were switched. L-DOPA treatment normalized the denervation-induced changes in animals with mild LID. The D3R activation caused depression of both dopamine 1 receptor (D1R)-induced increases in cAMP production and depolarization-induced [3H]-GABA release, which were reversed to their pre-denervation state. In animals with severe LID, none of the denervation-induced changes were reversed. The finding that in the absence of identifiable differences in 6-OHDA and L-DOPA treatment, two populations of animals with different D3R signaling and LIDs severity implies that mechanisms intrinsic to the treated subject determine the segregation.<\/jats:p>","DOI":"10.3390\/biom9090431","type":"journal-article","created":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T03:16:12Z","timestamp":1567394172000},"page":"431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Severity of Dyskinesia and D3R Signaling Changes Induced by L-DOPA Treatment of Hemiparkinsonian Rats Are Features Inherent to the Treated Subjects"],"prefix":"10.3390","volume":"9","author":[{"given":"Sacnit\u00e9","family":"Albarr\u00e1n-Bravo","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Biof\u00edsica y Neurociencias, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Arturo","family":"\u00c1valos-Fuentes","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Biof\u00edsica y Neurociencias, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6147-4109","authenticated-orcid":false,"given":"Hern\u00e1n","family":"Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina Gen\u00f3mica, Departamento de Gen\u00e9tica, Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra, Ciudad de M\u00e9xico 14389, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Rodriguez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Biof\u00edsica y Neurociencias, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norberto","family":"Leyva-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina Gen\u00f3mica, Departamento de Gen\u00e9tica, Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra, Ciudad de M\u00e9xico 14389, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Rangel-Barajas","sequence":"additional","affiliation":[{"name":"Neurosciences Program Bloomington, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Erlij","sequence":"additional","affiliation":[{"name":"Department of Physiology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3430-9335","authenticated-orcid":false,"given":"Benjam\u00edn","family":"Flor\u00e1n","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Biof\u00edsica y Neurociencias, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nm.2165","article-title":"Missing pieces in the Parkinson\u2019s disease puzzle","volume":"16","author":"Obeso","year":"2010","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.pneurobio.2015.07.002","article-title":"Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson\u2019s disease","volume":"132","author":"Bastide","year":"2015","journal-title":"Prog. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5900","DOI":"10.1523\/JNEUROSCI.0837-12.2012","article-title":"Galpha(olf) mutation allows parsing the role of cAMP-dependent and extracellular signal-regulated kinase-dependent signaling in L-3,4-dihydroxyphenylalanine-induced dyskinesia","volume":"32","author":"Alcacer","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.nbd.2013.09.020","article-title":"Immediate-early gene expression in structures outside the basal ganglia is associated to l-DOPA-induced dyskinesia","volume":"62","author":"Bastide","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1111\/j.1471-4159.2006.03696.x","article-title":"Role of striatal L-DOPA in the production of dyskinesia in 6-hydroxydopamine lesioned rats","volume":"96","author":"Carta","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_6","first-page":"2694","article-title":"L-DOPA-induced dyskinesia in the rat is associated with striatal overexpression of prodynorphin- and glutamic acid decarboxylase mRNA","volume":"10","author":"Cenci","year":"1998","journal-title":"Eur. J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1124\/mol.105.016667","article-title":"Loss of synaptic D1 dopamine\/N-methyl-d-aspartate glutamate receptor complexes in L-DOPA-induced dyskinesia in the rat","volume":"69","author":"Fiorentini","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.nbd.2013.01.005","article-title":"Persistent activation of the D1R\/Shp-2\/Erk1\/2 pathway in l-DOPA-induced dyskinesia in the 6-hydroxy-dopamine rat model of Parkinson\u2019s disease","volume":"54","author":"Fiorentini","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1523\/JNEUROSCI.5326-05.2006","article-title":"A critical interaction between NR2B and MAGUK in L-DOPA induced dyskinesia","volume":"26","author":"Gardoni","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3380","DOI":"10.1093\/brain\/awn235","article-title":"Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of L-DOPA-induced dyskinesia","volume":"131","author":"Munoz","year":"2008","journal-title":"Brain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.nbd.2010.08.018","article-title":"L-DOPA-induced dyskinesia in hemiparkinsonian rats is associated with up-regulation of adenylyl cyclase type V\/VI and increased GABA release in the substantia nigra reticulata","volume":"41","author":"Silva","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.neuint.2014.10.004","article-title":"Levodopa-induced dyskinesias are associated with transient down-regulation of cAMP and cGMP in the caudate-putamen of hemiparkinsonian rats: Reduced synthesis or increased catabolism?","volume":"79","author":"Sancesario","year":"2014","journal-title":"Neurochem. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/mds.26581","article-title":"Shp-2 knockdown prevents l-dopa-induced dyskinesia in a rat model of Parkinson\u2019s disease","volume":"31","author":"Fiorentini","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.parkreldis.2010.06.003","article-title":"Classifying risk factors for dyskinesia in Parkinson\u2019s disease","volume":"16","author":"Sharma","year":"2010","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1124\/jpet.107.126219","article-title":"Evaluation of levodopa dose and magnitude of dopamine depletion as risk factors for levodopa-induced dyskinesia in a rat model of Parkinson\u2019s disease","volume":"323","author":"Putterman","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/1531-8257(200005)15:3<459::AID-MDS1006>3.0.CO;2-3","article-title":"Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model","volume":"15","author":"McCormack","year":"2000","journal-title":"Mov. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0006-8993(03)03382-1","article-title":"Development of levodopa-induced dyskinesias in parkinsonian monkeys may depend upon rate of symptom onset and\/or duration of symptoms","volume":"990","author":"Schneider","year":"2003","journal-title":"Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/mds.10394","article-title":"Effect of pulsatile administration of levodopa on dyskinesia induction in drug-naive MPTP-treated common marmosets: Effect of dose, frequency of administration, and brain exposure","volume":"18","author":"Smith","year":"2003","journal-title":"Mov. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1093\/brain\/awg172","article-title":"Parkinson\u2019s disease: Piecing together a genetic jigsaw","volume":"126","author":"Dekker","year":"2003","journal-title":"Brain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1124\/jpet.102.036673","article-title":"Increased dopamine receptor signaling and dopamine receptor-G protein coupling in denervated striatum","volume":"302","author":"Cai","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1073\/pnas.94.7.3363","article-title":"Induction of dopamine D3 receptor expression as a mechanism of behavioral sensitization to levodopa","volume":"94","author":"Bordet","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ejphar.2003.08.096","article-title":"Brain-derived neurotrophic factor controls dopamine D3 receptor expression: Therapeutic implications in Parkinson\u2019s disease","volume":"480","author":"Guillin","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.neulet.2014.11.023","article-title":"Chronic levodopa treatment alters expression and function of dopamine D3 receptor in the MPTP\/p mouse model of Parkinson\u2019s disease","volume":"585","author":"Cote","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nm875","article-title":"Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function","volume":"9","author":"Bezard","year":"2003","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.neuropharm.2013.11.024","article-title":"Buspirone anti-dyskinetic effect is correlated with temporal normalization of dysregulated striatal DRD1 signalling in L-DOPA-treated rats","volume":"79","author":"Azkona","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bbr.2014.01.011","article-title":"Overexpression of the dopamine D3 receptor in the rat dorsal striatum induces dyskinetic behaviors","volume":"263","author":"Cote","year":"2014","journal-title":"Behav. Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"26016","DOI":"10.1074\/jbc.M710349200","article-title":"Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1-D3 receptor interactions in the striatum","volume":"283","author":"Marcellino","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1124\/mol.107.043885","article-title":"Reciprocal regulation of dopamine D1 and D3 receptor function and trafficking by heterodimerization","volume":"74","author":"Fiorentini","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.neuropharm.2012.11.032","article-title":"D3 dopamine receptors interact with dopamine D1 but not D4 receptors in the GABAergic terminals of the SNr of the rat","volume":"67","author":"Sierra","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_30","unstructured":"Albarran, S., Paz-Bermudez, F., Erlij, D., Aceves, J., and Flor\u00e1n, B. (2013). Dopamine D3 receptor prevents stimulation of [3H] GABA release in substantia nigra pars reticulata of hemiparkinsonian dyskinetic rats. Soc. Neurosc. Abstr., Available online: https:\/\/scholar.google.com\/scholar?cluster=7837714118961510460&hl=es&as_sdt=2005&sciodt=0,5."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.nbd.2014.12.008","article-title":"Dopaminergic denervation switches dopamine D3 receptor signaling and disrupts its Ca(2+) dependent modulation by CaMKII and calmodulin in striatonigral projections of the rat","volume":"74","author":"Cortes","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0006-8993(93)90576-9","article-title":"Correlation of apomorphine- and amphetamine-induced turning with nigrostriatal dopamine content in unilateral 6-hydroxydopamine lesioned rats","volume":"626","author":"Hudson","year":"1993","journal-title":"Brain Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1096\/fj.04-1854fje","article-title":"Subcellular redistribution of the synapse-associated proteins PSD-95 and SAP97 in animal models of Parkinson\u2019s disease and L-DOPA-induced dyskinesia","volume":"19","author":"Nash","year":"2005","journal-title":"FASEB J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/j.1471-4159.2007.04456.x","article-title":"Antagonism of metabotropic glutamate receptor type 5 attenuates l-DOPA-induced dyskinesia and its molecular and neurochemical correlates in a rat model of Parkinson\u2019s disease","volume":"101","author":"Mela","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/1531-8257(199905)14:3<448::AID-MDS1010>3.0.CO;2-0","article-title":"Clinical rating of dyskinesias in Parkinson\u2019s disease: Use and reliability of a new rating scale","volume":"14","author":"Hagell","year":"1999","journal-title":"Mov. Disord."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1046\/j.0953-816x.2001.01843.x","article-title":"Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson\u2019s disease","volume":"15","author":"Lundblad","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/S0028-3908(00)00005-8","article-title":"CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury","volume":"39","author":"Schallert","year":"2000","journal-title":"Neuropharmacology"},{"key":"ref_38","first-page":"79","article-title":"The measurement of cyclic AMP levels in biological preparations","volume":"41","author":"Alexander","year":"1995","journal-title":"Methods Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.neuropharm.2007.07.014","article-title":"GABA(B) receptor activation inhibits dopamine D1 receptor-mediated facilitation of [(3)H]GABA release in substantia nigra pars reticulata","volume":"53","author":"Erlij","year":"2007","journal-title":"Neuropharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/0006-8993(70)90187-3","article-title":"Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system","volume":"24","author":"Ungerstedt","year":"1970","journal-title":"Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.neuropharm.2013.04.010","article-title":"Presynaptic CaMKIIalpha modulates dopamine D3 receptor activation in striatonigral terminals of the rat brain in a Ca(2)(+) dependent manner","volume":"71","author":"Cortes","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0091-3057(80)90353-6","article-title":"Circling behavior in rats with partial, unilateral nigro-striatal lesions: Effect of amphetamine, apomorphine, and DOPA","volume":"12","author":"Hefti","year":"1980","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.bbr.2015.01.053","article-title":"A partial lesion model of Parkinson\u2019s disease in mice\u2014Characterization of a 6-OHDA-induced medial forebrain bundle lesion","volume":"284","author":"Boix","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbr.2005.02.023","article-title":"Behavioral characterization of a unilateral 6-OHDA-lesion model of Parkinson\u2019s disease in mice","volume":"162","author":"Iancu","year":"2005","journal-title":"Behav. Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/0306-4522(95)00066-R","article-title":"Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by intrastriatal injection of 6-hydroxydopamine","volume":"67","author":"Przedborski","year":"1995","journal-title":"Neuroscience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/mds.1090","article-title":"Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature","volume":"16","author":"Ahlskog","year":"2001","journal-title":"Mov. Disord."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/mds.21813","article-title":"Nonmotor symptoms as presenting complaints in Parkinson\u2019s disease: A clinicopathological study","volume":"23","author":"Williams","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2008.09.013","article-title":"Priming for l-dopa-induced dyskinesia in Parkinson\u2019s disease: A feature inherent to the treatment or the disease?","volume":"87","author":"Nadjar","year":"2009","journal-title":"Prog. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s12017-019-08549-3","article-title":"Influence of DRD1 and DRD3 Polymorphisms in the Occurrence of Motor Effects in Patients with Sporadic Parkinson\u2019s Disease","volume":"21","author":"Duarte","year":"2019","journal-title":"NeuroMolecular Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1007\/s12035-018-1219-1","article-title":"MTOR Pathway-Based Discovery of Genetic Susceptibility to L-DOPA-Induced Dyskinesia in Parkinson\u2019s Disease Patients","volume":"56","author":"Antonelli","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.parkreldis.2013.05.015","article-title":"Age at onset influences neurodegenerative processes underlying PD with levodopa-induced dyskinesias","volume":"19","author":"Cerasa","year":"2013","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/mds.870070204","article-title":"Levodopa-induced dyskinesias in Parkinson\u2019s disease: Clinical and pharmacological classification","volume":"7","author":"Luquin","year":"1992","journal-title":"Mov. Disord."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S509","DOI":"10.1002\/mds.22021","article-title":"Levodopa-related motor complications--phenomenology","volume":"23","author":"Fox","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3233\/JPD-181312","article-title":"Cardinal Motor Features of Parkinson\u2019s Disease Coexist with Peak-Dose Choreic-Type Drug-Induced Dyskinesia","volume":"8","author":"Goubault","year":"2018","journal-title":"J. Parkinsons Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0006-8993(94)90796-X","article-title":"Motor fluctuations in levodopa treated parkinsonian rats: Relation to lesion extent and treatment duration","volume":"662","author":"Papa","year":"1994","journal-title":"Brain Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1111\/j.1460-9568.2008.06387.x","article-title":"Lowered cAMP and cGMP signalling in the brain during levodopa-induced dyskinesias in hemiparkinsonian rats: New aspects in the pathogenetic mechanisms","volume":"28","author":"Giorgi","year":"2008","journal-title":"Eur. J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/nn1040","article-title":"Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia","volume":"6","author":"Picconi","year":"2003","journal-title":"Nat. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3389\/fnbeh.2011.00071","article-title":"L-DOPA-Induced Dyskinesia and Abnormal Signaling in Striatal Medium Spiny Neurons: Focus on Dopamine D1 Receptor-Mediated Transmission","volume":"5","author":"Feyder","year":"2011","journal-title":"Front. Behav. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/B978-0-12-381328-2.00004-3","article-title":"Molecular mechanisms of l-DOPA-induced dyskinesia","volume":"98","author":"Fisone","year":"2011","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1124\/mol.114.093096","article-title":"Functional selectivity of allosteric interactions within G protein-coupled receptor oligomers: The dopamine D1-D3 receptor heterotetramer","volume":"86","author":"Guitart","year":"2014","journal-title":"Mol. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s00702-018-1852-x","article-title":"Dopamine receptors: Homomeric and heteromeric complexes in L-DOPA-induced dyskinesia","volume":"125","author":"Solis","year":"2018","journal-title":"J. Neural Transm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1471-4159.1997.68010001.x","article-title":"Two intracellular signaling pathways for the dopamine D3 receptor: Opposite and synergistic interactions with cyclic AMP","volume":"68","author":"Griffon","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/S0165-0173(97)00046-5","article-title":"Functional implications of multiple dopamine receptor subtypes: The D1\/D3 receptor coexistence","volume":"26","author":"Schwartz","year":"1998","journal-title":"Brain Res. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/0166-2236(89)90074-X","article-title":"The functional anatomy of basal ganglia disorders","volume":"12","author":"Albin","year":"1989","journal-title":"Trends Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0166-2236(90)90110-V","article-title":"Primate models of movement disorders of basal ganglia origin","volume":"13","author":"DeLong","year":"1990","journal-title":"Trends Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.neuropharm.2008.06.002","article-title":"6-OHDA-induced hemiparkinsonism and chronic L-DOPA treatment increase dopamine D1-stimulated [(3)H]-GABA release and [(3)H]-cAMP production in substantia nigra pars reticulata of the rat","volume":"55","author":"Silva","year":"2008","journal-title":"Neuropharmacology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.nbd.2011.09.015","article-title":"In vivo evidence for a differential contribution of striatal and nigral D1 and D2 receptors to L-DOPA induced dyskinesia and the accompanying surge of nigral amino acid levels","volume":"45","author":"Mela","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0079-6123(06)60009-5","article-title":"The pars reticulata of the substantia nigra: A window to basal ganglia output","volume":"160","author":"Deniau","year":"2007","journal-title":"Prog. Brain Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6751","DOI":"10.1523\/JNEUROSCI.1528-04.2004","article-title":"GABA, not glutamate, controls the activity of substantia nigra reticulata neurons in awake, unrestrained rats","volume":"24","author":"Windels","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.neuropharm.2009.01.019","article-title":"Evaluation of D2 and D3 dopamine receptor selective compounds on L-dopa-dependent abnormal involuntary movements in rats","volume":"56","author":"Kumar","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.neuropharm.2010.09.011","article-title":"Evaluation of the D3 dopamine receptor selective agonist\/partial agonist PG01042 on L-dopa dependent animal involuntary movements in rats","volume":"60","author":"Riddle","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/mds.20360","article-title":"Levodopa-dyskinesia incidence by age of Parkinson\u2019s disease onset","volume":"20","author":"Kumar","year":"2005","journal-title":"Mov. Disord."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.neuropharm.2009.01.020","article-title":"Evaluation of the D3 dopamine receptor selective antagonist PG01037 on L-dopa-dependent abnormal involuntary movements in rats","volume":"56","author":"Kumar","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.nbd.2008.11.010","article-title":"Dopamine D3 receptor stimulation underlies the development of L-DOPA-induced dyskinesia in animal models of Parkinson\u2019s disease","volume":"35","author":"Visanji","year":"2009","journal-title":"Neurobiol. Dis."},{"key":"ref_75","first-page":"435","article-title":"Dopamine D3 Receptor Modulates l-DOPA-Induced Dyskinesia by Targeting D1 Receptor-Mediated Striatal Signaling","volume":"27","author":"Solis","year":"2015","journal-title":"Cereb. Cortex."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.neuropharm.2009.08.017","article-title":"The selective D(3) receptor antagonist, S33084, improves parkinsonian-like motor dysfunction but does not affect L-DOPA-induced dyskinesia in 6-hydroxydopamine hemi-lesioned rats","volume":"58","author":"Mela","year":"2010","journal-title":"Neuropharmacology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0306-4522(98)00633-2","article-title":"Expression of dopamine receptors in the subthalamic nucleus of the rat: Characterization using reverse transcriptase-polymerase chain reaction and autoradiography","volume":"91","author":"Flores","year":"1999","journal-title":"Neuroscience"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.neuroscience.2019.03.051","article-title":"Presynaptic control of [(3)H]-glutamate release by dopamine receptor subtypes in the rat substantia nigra. Central role of D1 and D3 receptors","volume":"406","author":"Cortes","year":"2019","journal-title":"Neuroscience"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1152\/jn.01074.2005","article-title":"Control of the subthalamic innervation of substantia nigra pars reticulata by D1 and D2 dopamine receptors","volume":"95","author":"Hernandez","year":"2006","journal-title":"J. Neurophysiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1113\/jphysiol.2011.225672","article-title":"Regulation of polysynaptic subthalamonigral transmission by D2, D3 and D4 dopamine receptors in rat brain slices","volume":"590","author":"Shen","year":"2012","journal-title":"J. Physiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1523\/JNEUROSCI.21-06-01838.2001","article-title":"Differential subcellular localization of mGluR1a and mGluR5 in the rat and monkey Substantia nigra","volume":"21","author":"Hubert","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/cne.903550310","article-title":"Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain","volume":"355","author":"Romano","year":"1995","journal-title":"J. Comp. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/S0006-8993(97)01141-4","article-title":"Localization of mGluR1a-like immunoreactivity and mGluR5-like immunoreactivity in identified populations of striatal neurons","volume":"780","author":"Kaatz","year":"1998","journal-title":"Brain Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/cne.903620108","article-title":"Metabotropic glutamate receptor mGluR5 subcellular distribution and developmental expression in hypothalamus","volume":"362","author":"Romano","year":"1995","journal-title":"J. Comp. Neurol."},{"key":"ref_85","first-page":"877","article-title":"Regulation of striatal cyclic-3\u2019,5\u2019-adenosine monophosphate accumulation and GABA release by glutamate metabotropic and dopamine D1 receptors","volume":"275","author":"Wang","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_86","first-page":"4037","article-title":"Genetic Knockdown of mGluR5 in Striatal D1R-Containing Neurons Attenuates L-DOPA-Induced Dyskinesia in Aphakia Mice","volume":"56","author":"Solis","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.neuropharm.2018.06.024","article-title":"Behavioral and cellular dopamine D1 and D3 receptor-mediated synergy: Implications for L-DOPA-induced dyskinesia","volume":"138","author":"Lanza","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1007\/s12035-014-8936-x","article-title":"Stronger Dopamine D1 Receptor-Mediated Neurotransmission in Dyskinesia","volume":"52","author":"Farre","year":"2015","journal-title":"Mol. Neurobiol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/9\/431\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:15:45Z","timestamp":1760188545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/9\/431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,1]]},"references-count":88,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["biom9090431"],"URL":"https:\/\/doi.org\/10.3390\/biom9090431","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,1]]}}}