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01-09-2020 | Cannabinoid | Original Article

Expression of GPR55 and either cannabinoid CB₁ or CB₂ heteroreceptor complexes in the caudate, putamen, and accumbens nuclei of control, parkinsonian, and dyskinetic non-human primates

Authors: Eva Martínez-Pinilla, Alberto J. Rico, Rafael Rivas-Santisteban, Jaume Lillo, Elvira Roda, Gemma Navarro, José Luis Lanciego, Rafael Franco

Published in: Brain Structure and Function | Issue 7/2020

Abstract

Endocannabinoids are neuromodulators acting on specific cannabinoid CB₁ and CB₂ G-protein-coupled receptors (GPCRs), representing potential therapeutic targets for neurodegenerative diseases. Cannabinoids also regulate the activity of GPR55, a recently “deorphanized” GPCR that directly interacts with CB₁ and with CB₂ receptors. Our hypothesis is that these heteromers may be taken as potential targets for Parkinson’s disease (PD). This work aims at assessing the expression of heteromers made of GPR55 and CB₁/CB₂ receptors in the striatum of control and parkinsonian macaques (with and without levodopa-induced dyskinesia). For this purpose, double blind in situ proximity ligation assays, enabling the detection of GPCR heteromers in tissue samples, were performed in striatal sections of control, MPTP-treated and MPTP-treated animals rendered dyskinetic by chronic treatment with levodopa. Image analysis and statistical assessment were performed using dedicated software. We have previously demonstrated the formation of heteromers between GPR55 and CB₁ receptor (CB₁-GPR55_Hets), which is highly expressed in the central nervous system (CNS), but also with the CB₂ receptor (CB₂-GPR55_Hets). Compared to the baseline expression of CB₁-GPR55_Hets in control animals, our results showed increased expression levels in basal ganglia input nuclei of MPTP-treated animals. These observed increases in CB₁-GPR55_Hets returned back to baseline levels upon chronic treatment with levodopa in dyskinetic animals. Obtained data regarding CB₂-GPR55_Hets were quite similar, with somehow equivalent amounts in control and dyskinetic animals, and with increased expression levels in MPTP animals. Taken together, the detected increased expression of GPR55-endocannabinoid heteromers appoints these GPCR complexes as potential non-dopaminergic targets for PD therapy.

Alexander SP, Christopoulos A, Davenport AP et al (2017) The concise guide to pharmacology 2017/18: G protein-coupled receptors. Br J Pharmacol 174:S17–S129. https://doi.org/10.1111/bph.13878CrossRefPubMedPubMedCentral

Alexander SPH, Roberts RE, Broughton BRS et al (2018) Goals and practicalities of immunoblotting and immunohistochemistry: A guide for submission to the British Journal of Pharmacology. Br J Pharmacol 175:407–411CrossRefPubMedPubMedCentral

Anavi-Goffer S, Baillie G, Irving AJ et al (2012) Modulation of l-α-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids. J Biol Chem 287:91–104. https://doi.org/10.1074/jbc.M111.296020CrossRefPubMed

Andradas C, Caffarel MM, Pérez-Gómez E et al (2011) The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK. Oncogene 30:245–252. https://doi.org/10.1038/onc.2010.402CrossRefPubMed

Armentero MT, Pinna A, Ferré S et al (2011) Past, present and future of A2A adenosine receptor antagonists in the therapy of Parkinson’s disease. Pharmacol Ther 132:280–299. https://doi.org/10.1016/j.pharmthera.2011.07.004CrossRefPubMedPubMedCentral

Aso E, Ferrer I (2014) Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic. Front Pharmacol 5:37. https://doi.org/10.3389/fphar.2014.00037CrossRefPubMedPubMedCentral

Attili B, Celen S, Ahamed M et al (2019) Preclinical evaluation of [18 F]MA3: a CB 2 receptor agonist radiotracer for PET. Br J Pharmacol 176:1481–1491. https://doi.org/10.1111/bph.14564CrossRefPubMedPubMedCentral

Baker D, Pryce G, Davies WL, Hiley CR (2006) ScienceDirect—trends in pharmacological sciences: in silico patent searching reveals a new cannabinoid receptor. Trends Pharmacol Sci 27:1–4. https://doi.org/10.1016/j.tips.2005.11.003CrossRefPubMed

Balenga NAB, Aflaki E, Kargl J et al (2011) GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils. Cell Res 21:1452–1469. https://doi.org/10.1038/cr.2011.60CrossRefPubMedPubMedCentral

Balenga NA, Martínez-Pinilla E, Kargl J et al (2014) Heteromerization of GPR55 and cannabinoid CB2 receptors modulates signalling. Br J Pharmacol 171:1–64. https://doi.org/10.1111/bph.12850CrossRef

Bénard G, Massa F, Puente N et al (2012) Mitochondrial CB1 receptors regulate neuronal energy metabolism. Nat Neurosci 15:558–564. https://doi.org/10.1038/nn.3053CrossRefPubMed

Ben-Shachar D (2019) The bimodal mechanism of interaction between dopamine and mitochondria as reflected in Parkinson’s disease and in schizophrenia. J. Neural Transm 127:159–168CrossRefPubMed

Bonaventura J, Rico AJ, Moreno E et al (2014) L-DOPA-treatment in primates disrupts the expression of A(2A) adenosine-CB(1) cannabinoid-D(2) dopamine receptor heteromers in the caudate nucleus. Neuropharmacology 79:90–100. https://doi.org/10.1016/j.neuropharm.2013.10.036CrossRefPubMed

Brusco A, Tagliaferro PA, Saez T, Onaivi ES (2008) Ultrastructural localization of neuronal brain CB2 cannabinoid receptors. Ann N Y Acad Sci 1139:450–457. https://doi.org/10.1196/annals.1432.037CrossRefPubMed

Celorrio M, Rojo-Bustamante E, Fernández-Suárez D et al (2017) GPR55: a therapeutic target for Parkinson’s disease? Neuropharmacology 125:319–332. https://doi.org/10.1016/j.neuropharm.2017.08.017CrossRefPubMed

Christensen R, Kristensen PK, Bartels EM et al (2007) Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet (London, Engl) 370:1706–1713. https://doi.org/10.1016/S0140-6736(07)61721-8CrossRef

Curtis MJ, Alexander S, Cirino G et al (2018) Experimental design and analysis and their reporting II: updated and simplified guidance for authors and peer reviewers. Br J Pharmacol 175:987–993. https://doi.org/10.1111/bph.14153CrossRefPubMedPubMedCentral

Drake MT, Violin JD, Whalen EJ et al (2008) β-arrestin-biased agonism at the β2-adrenergic receptor. J Biol Chem 283:5669–5676. https://doi.org/10.1074/jbc.M708118200CrossRefPubMed

Farré D, Muñoz A, Moreno E et al (2015) Stronger dopamine D1 receptor-mediated neurotransmission in dyskinesia. Mol Neurobiol 52:1408–1420. https://doi.org/10.1007/s12035-014-8936-xCrossRefPubMed

Fernández-Ruiz J, Moreno-Martet M, Rodríguez-Cueto C et al (2011) Prospects for cannabinoid therapies in basal ganglia disorders. Br J Pharmacol 163:1365–1378. https://doi.org/10.1111/j.1476-5381.2011.01365.xCrossRefPubMedPubMedCentral

Ferré S, Baler R, Bouvier M et al (2009) Building a new conceptual framework for receptor heteromers. Nat Chem Biol 5:131–134. https://doi.org/10.1038/nchembio0309-131CrossRefPubMedPubMedCentral

Fraguas-Sánchez AI, Torres-Suárez AI (2018) Medical use of cannabinoids. Drugs 78:1665–1703. https://doi.org/10.1007/s40265-018-0996-1CrossRefPubMed

Franco R, Fernández-Suárez D (2015) Alternatively activated microglia and macrophages in the central nervous system. Prog Neurobiol 131:65–86. https://doi.org/10.1016/j.pneurobio.2015.05.003CrossRefPubMed

Franco R, Martínez-Pinilla E, Lanciego JLJLJL, Navarro G (2016) Basic pharmacological and structural evidence for class A G-protein-coupled receptor heteromerization. Front Pharmacol 7:76. https://doi.org/10.3389/fphar.2016.00076CrossRefPubMedPubMedCentral

Franco R, Aguinaga D, Jiménez J et al (2018) Biased receptor functionality versus biased agonism in G-protein-coupled receptors. Biomol Concepts 9:143–154. https://doi.org/10.1515/bmc-2018-0013CrossRefPubMed

Fuxe K, Guidolin D, Agnati LF, Borroto-Escuela DO (2015) Dopamine heteroreceptor complexes as therapeutic targets in Parkinson’s disease. Expert Opin Ther Targets 19:377–398. https://doi.org/10.1517/14728222.2014.981529CrossRefPubMed

Galve-Roperh I, Aguado T, Palazuelos J, Guzmán M (2008) Mechanisms of control of neuron survival by the endocannabinoid system. Curr Pharm Des 14:2279–2288. https://doi.org/10.2174/138161208785740117CrossRefPubMed

Giuffrida A, Seillier A (2012) New insights on endocannabinoid transmission in psychomotor disorders. Prog Neuro-Psychopharmacol Biol Psychiatry 38:51–58CrossRef

Goetz CG, Stebbins GT, Shale HM et al (1994) Utility of an objective dyskinesia rating scale for Parkinson’s disease: Inter- and intrarater reliability assessment. Mov Disord 9:390–394. https://doi.org/10.1002/mds.870090403CrossRefPubMed

Gutiérrez-Rodríguez A, Bonilla-Del Río I, Puente N et al (2018) Localization of the cannabinoid type-1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus. Glia 66:1417–1431. https://doi.org/10.1002/glia.23314CrossRefPubMed

Hebert-Chatelain E, Reguero L, Puente N et al (2014) Cannabinoid control of brain bioenergetics: exploring the subcellular localization of the CB1 receptor. Mol Metab 3:495–504. https://doi.org/10.1016/j.molmet.2014.03.007CrossRefPubMedPubMedCentral

Henstridge CM, Balenga NA, Schröder R et al (2010) GPR55 ligands promote receptor coupling to multiple signalling pathways. Br J Pharmacol 160:604–614. https://doi.org/10.1111/j.1476-5381.2009.00625.xCrossRefPubMedPubMedCentral

Irving A (2011) New blood brothers: the GPR55 and CB 2 partnership. Cell Res 21:1391–1392CrossRefPubMedPubMedCentral

Janssen B, Vugts DJ, Funke U et al (2016) Imaging of neuroinflammation in Alzheimer’s disease, multiple sclerosis and stroke: Recent developments in positron emission tomography. Biochim Biophys Acta Mol Basis Dis 1862:425–441. https://doi.org/10.1016/j.bbadis.2015.11.011CrossRef

Janssen B, Vugts D, Windhorst A, Mach R (2018) PET imaging of microglial activation—beyond targeting TSPO. Molecules 23:607. https://doi.org/10.3390/molecules23030607CrossRefPubMedCentral

Johns DG, Behm DJ, Walker DJ et al (2009) The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Br J Pharmacol 152:825–831. https://doi.org/10.1038/sj.bjp.0707419CrossRef

Kapur A, Zhao P, Sharir H et al (2009) Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands. J Biol Chem 284:29817–29827. https://doi.org/10.1074/jbc.M109.050187CrossRefPubMedPubMedCentral

Kong W, Li H, Tuma RF, Ganea D (2014) Selective CB2 receptor activation ameliorates EAE by reducing Th17 differentiation and immune cell accumulation in the CNS. Cell Immunol 287:1–17. https://doi.org/10.1016/j.cellimm.2013.11.002CrossRefPubMed

Kurlan R, Kim MH, Gash DM (1991) Oral levodopa dose-response study in MPTP-induced hemiparkinsonian monkeys: assessment with a new rating scale for monkey Parkinsonism. Mov Disord 6:111–118. https://doi.org/10.1002/mds.870060205CrossRefPubMed

Lanciego JL, Vázquez A (2012) The basal ganglia and thalamus of the long-tailed macaque in stereotaxic coordinates. A template atlas based on coronal, sagittal and horizontal brain sections. Brain Struct Funct 217:613–666. https://doi.org/10.1007/s00429-011-0370-5CrossRefPubMed

Lanciego JL, Rodríguez-Oroz MC, Blesa FJ et al (2008) Lesion of the centromedian thalamic nucleus in MPTP-treated monkeys. Mov Disord 23:708–715. https://doi.org/10.1002/mds.21906CrossRefPubMedPubMedCentral

Lanciego JL, Barroso-Chinea P, Rico AJ et al (2011) Expression of the mRNA coding the cannabinoid receptor 2 in the pallidal complex of Macaca fascicularis. J Psychopharmacol. https://doi.org/10.1177/0269881110367732CrossRefPubMed

Langston JW, Widner H, Goetz CG et al (1992) Core assessment program for intracerebral transplantations (CAPIT). Mov Disord 7:2–13. https://doi.org/10.1002/mds.870070103CrossRefPubMed

Lauckner JE, Jensen JB, Chen H-Y et al (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A 105:2699–2704. https://doi.org/10.1073/pnas.0711278105CrossRefPubMedPubMedCentral

Law AMK, Yin JXM, Castillo L et al (2017) Andy’s Algorithms: new automated digital image analysis pipelines for FIJI. Sci Rep 7:15717. https://doi.org/10.1038/s41598-017-15885-6CrossRefPubMedPubMedCentral

Macdonald R, Barnes K, Hastings C, Mortiboys H (2018) Mitochondrial abnormalities in Parkinson’s disease and Alzheimer’s disease: can mitochondria be targeted therapeutically? Biochem Soc Trans 46:891–909CrossRefPubMed

Marcellino D, Ferré S, Casadó V et al (2008) Identification of dopamine D1–D3 receptor heteromers: Indications for a role of synergistic D1–D3 receptor interactions in the striatum. J Biol Chem 283:26016–26025. https://doi.org/10.1074/jbc.M710349200CrossRefPubMedPubMedCentral

Martínez-Pinilla E, Reyes-Resina I, Oñatibia-Astibia A et al (2014) CB1 and GPR55 receptors are co-expressed and form heteromers in rat and monkey striatum. Exp Neurol 261:44–52. https://doi.org/10.1016/j.expneurol.2014.06.017CrossRefPubMed

Martínez-Pinilla E, Varani K, Reyes-Resina I et al (2017) Binding and signaling studies disclose a potential allosteric site for cannabidiol in cannabinoid CB2receptors. Front Pharmacol 8:744. https://doi.org/10.3389/fphar.2017.00744CrossRefPubMedPubMedCentral

Martínez-Pinilla E, Rico AJ, Rivas-Santisteban R et al (2020) Expression of cannabinoid CB 1 R-GPR55 heteromers in neuronal subtypes of the Macaca fascicularis striatum. Ann N Y Acad Sci. https://doi.org/10.1111/nyas.14413CrossRefPubMed

Mecha M, Feliú A, Carrillo-Salinas FJ et al (2015) Endocannabinoids drive the acquisition of an alternative phenotype in microglia. Brain Behav Immun 49:233–245. https://doi.org/10.1016/j.bbi.2015.06.002CrossRefPubMed

Mecha M, Carrillo-Salinas FJ, Feliú A et al (2016) Microglia activation states and cannabinoid system: therapeutic implications. Pharmacol Ther 166:40–55. https://doi.org/10.1016/j.pharmthera.2016.06.011CrossRefPubMed

Melser S, Zottola ACP, Serrat R et al (2017) Functional analysis of mitochondrial CB1 cannabinoid receptors (mtCB1) in the brain. Methods Enzymol 593:143–174. https://doi.org/10.1016/bs.mie.2017.06.023CrossRefPubMed

Navarro G, Morales P, Rodríguez-Cueto C et al (2016) Targeting cannabinoid CB2 receptors in the central nervous system. Medicinal chemistry approaches with focus on neurodegenerative disorders. Front Neurosci. https://doi.org/10.3389/fnins.2016.00406CrossRefPubMedPubMedCentral

Navarro G, Reyes-Resina I, Rivas-Santisteban R et al (2018) Cannabidiol skews biased agonism at cannabinoid CB1 and CB2 receptors with smaller effect in CB1–CB2 heteroreceptor complexes. Biochem Pharmacol 157:148–158. https://doi.org/10.1016/j.bcp.2018.08.046CrossRefPubMed

Noel C (2017) Evidence for the use of “medical marijuana” in psychiatric and neurologic disorders. Ment Heal Clin 7:29–38. https://doi.org/10.9740/mhc.2017.01.029CrossRef

Núñez E, Benito C, Pazos MR et al (2004) Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an Immunohistochemical Study. Synapse 53:208–213. https://doi.org/10.1002/syn.20050CrossRefPubMed

Obara Y, Ueno S, Yanagihata Y, Nakahata N (2011) Lysophosphatidylinositol causes neurite retraction via GPR55, G13 and RhoA in PC12 cells. PLoS ONE 6:e24284. https://doi.org/10.1371/journal.pone.0024284CrossRefPubMedPubMedCentral

Oka S, Nakajima K, Yamashita A et al (2007) Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem Biophys Res Commun 362:928–934. https://doi.org/10.1016/j.bbrc.2007.08.078CrossRefPubMed

Oka S, Kimura S, Toshida T et al (2010) Lysophosphatidylinositol induces rapid phosphorylation of p38 mitogen-activated protein kinase and activating transcription factor 2 in HEK293 cells expressing GPR55 and IM-9 lymphoblastoid cells. J Biochem 147:671–678. https://doi.org/10.1093/jb/mvp208CrossRefPubMed

Onaivi ES (2006) Neuropsychobiological evidence for the functional presence and expression of cannabinoid CB2 receptors in the brain. Neuropsychobiology 54:231–246. https://doi.org/10.1159/000100778CrossRefPubMed

Onaivi ES, Ishiguro H, Gong J-P et al (2006) Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain. Ann N Y Acad Sci 1074:514–536. https://doi.org/10.1196/annals.1369.052CrossRefPubMed

Palazuelos J, Aguado T, Pazos MR et al (2009) Microglial CB2cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity. Brain 132:3152–3164. https://doi.org/10.1093/brain/awp239CrossRefPubMed

Palomo-Garo C, Gómez-Gálvez Y, García C, Fernández-Ruiz J (2016) Targeting the cannabinoid CB 2 receptor to attenuate the progression of motor deficits in LRRK2-transgenic mice. Pharmacol Res 110:181–192. https://doi.org/10.1016/j.phrs.2016.04.004CrossRefPubMed

Perreault ML, Hasbi A, Shen MYFFMYF et al (2016) Disruption of a dopamine receptor complex amplifies the actions of cocaine. Eur Neuropsychopharmacol 26:1366–1377. https://doi.org/10.1016/j.euroneuro.2016.07.008CrossRefPubMed

Pertwee RG (2012) Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities. Philos Trans R Soc B Biol Sci 367:3353–3363. https://doi.org/10.1098/rstb.2011.0381CrossRef

Pietr M, Kozela E, Levy R et al (2009) Differential changes in GPR55 during microglial cell activation. FEBS Lett 583:2071–2076. https://doi.org/10.1016/j.febslet.2009.05.028CrossRefPubMed

Piñeiro R, Maffucci T, Falasca M (2011) The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation. Oncogene 30:142–152. https://doi.org/10.1038/onc.2010.417CrossRefPubMed

Pinna A, Bonaventura J, Farré D et al (2014) L-DOPA disrupts adenosine A(2A)-cannabinoid CB(1)-dopamine D(2) receptor heteromer cross-talk in the striatum of hemiparkinsonian rats: biochemical and behavioral studies. Exp Neurol 253:180–191. https://doi.org/10.1016/j.expneurol.2013.12.021CrossRefPubMed

Price DA, Martinez AA, Seillier A et al (2009) WIN55,212–2, a cannabinoid receptor agonist, protects against nigrostriatal cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Eur J Neurosci 29:2177–2186. https://doi.org/10.1111/j.1460-9568.2009.06764.xCrossRefPubMedPubMedCentral

Rico AJ, Barroso-Chinea P, Conte-Perales L et al (2010) A direct projection from the subthalamic nucleus to the ventral thalamus in monkeys. Neurobiol Dis 39:381–392. https://doi.org/10.1016/j.nbd.2010.05.004CrossRefPubMed

Rodríguez-Ruiz M, Moreno E, Moreno-Delgado D et al (2017) Heteroreceptor complexes formed by dopamine D1, histamine H3, and N-methyl-d-aspartate glutamate receptors as targets to prevent neuronal death in Alzheimer’s disease. Mol Neurobiol 54:4537–4550. https://doi.org/10.1007/s12035-016-9995-yCrossRefPubMed

Ryberg E, Larsson N, Sjögren S et al (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152:1092–1101. https://doi.org/10.1038/sj.bjp.0707460CrossRefPubMedPubMedCentral

Sawzdargo M, Nguyen T, Lee DK et al (1999) Identification and cloning of three novel human G protein-coupled receptor genes GPR52, ΨGPR53 and GPR55: GPR55 is extensively expressed in human brain. Mol Brain Res 64:193–198. https://doi.org/10.1016/S0169-328X(98)00277-0CrossRefPubMed

Stella N (2009) Endocannabinoid signaling in microglial cells. Neuropharmacology 56:244–253. https://doi.org/10.1016/j.neuropharm.2008.07.037CrossRefPubMed

Stella N (2010) Endocannabinoid signaling in microglial cells. Glia 58(Suppl 1):244–253. https://doi.org/10.1002/glia.20983CrossRef

Tao Y, Li L, Jiang B et al (2016) Cannabinoid receptor-2 stimulation suppresses neuroinflammation by regulating microglial M1/M2 polarization through the cAMP/PKA pathway in an experimental GMH rat model. Brain Behav Immun 58:118–129. https://doi.org/10.1016/j.bbi.2016.05.020CrossRefPubMed

Waldeck-Weiermair M, Zoratti C, Osibow K et al (2008) Integrin clustering enables anandamide-induced Ca2+ signaling in endothelial cells via GPR55 by protection against CB1-receptor-triggered repression. J Cell Sci 121:1704–1717. https://doi.org/10.1242/jcs.020958CrossRefPubMed

Wu C-S, Zhu J, Wager-Miller J et al (2010) Requirement of cannabinoid CB(1) receptors in cortical pyramidal neurons for appropriate development of corticothalamic and thalamocortical projections. Eur J Neurosci 32:693–706. https://doi.org/10.1111/j.1460-9568.2010.07337.xCrossRefPubMedPubMedCentral

Wu C-S, Chen H, Sun H et al (2013) GPR55, a G-protein coupled receptor for lysophosphatidylinositol, plays a role in motor coordination. PLoS ONE 8:e60314. https://doi.org/10.1371/journal.pone.0060314CrossRefPubMedPubMedCentral

Yin H, Chu A, Li W et al (2009) Lipid G protein-coupled receptor ligand identification using β-arrestin PathHunter assay. J Biol Chem 284:12328–12338. https://doi.org/10.1074/jbc.M806516200CrossRefPubMedPubMedCentral

Title: Expression of GPR55 and either cannabinoid CB1 or CB2 heteroreceptor complexes in the caudate, putamen, and accumbens nuclei of control, parkinsonian, and dyskinetic non-human primates
Authors: Eva Martínez-Pinilla
Alberto J. Rico
Rafael Rivas-Santisteban
Jaume Lillo
Elvira Roda
Gemma Navarro
José Luis Lanciego
Rafael Franco
Publication date: 01-09-2020
Publisher: Springer Berlin Heidelberg
Keywords: Cannabinoid
Parkinson's Disease
Levodopa
Published in: Brain Structure and Function / Issue 7/2020
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-020-02116-4

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Expression of GPR55 and either cannabinoid CB₁ or CB₂ heteroreceptor complexes in the caudate, putamen, and accumbens nuclei of control, parkinsonian, and dyskinetic non-human primates

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