{"entity": "researcher", "timestamp": "2026-08-25T13:43:36.124Z", "family": "Bezard", "given": "Erwan", "initials": "E", "orcid": "0000-0002-0410-4638", "affiliations": ["Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives, Universit\u00e9 de Bordeaux, Bordeaux, France.", "Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives, CNRS, Bordeaux, France."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/92f25ac8ff1d46ce8b68fbd88cd36843.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/92f25ac8ff1d46ce8b68fbd88cd36843"}}, "publications": [{"entity": "publication", "iuid": "f73d65cd08d0405f8b6bd74a48278bdf", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f73d65cd08d0405f8b6bd74a48278bdf.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f73d65cd08d0405f8b6bd74a48278bdf"}}, "title": "\u00b5 Opioid Receptor Agonism for L-DOPA-Induced Dyskinesia in Parkinson's Disease.", "authors": [{"family": "Bezard", "given": "Erwan", "initials": "E", "orcid": "0000-0002-0410-4638", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/92f25ac8ff1d46ce8b68fbd88cd36843.json"}}, {"family": "Li", "given": "Qin", "initials": "Q"}, {"family": "Hulme", "given": "Heather", "initials": "H"}, {"family": "Fridjonsdottir", "given": "Elva", "initials": "E"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Pioli", "given": "Elsa", "initials": "E"}, {"family": "Andren", "given": "Per E", "initials": "PE"}, {"family": "Crossman", "given": "Alan R", "initials": "AR"}], "type": "journal article", "published": "2020-08-26", "journal": {"title": "J. Neurosci.", "issn": "1529-2401", "volume": "40", "issue": "35", "pages": "6812-6819", "issn-l": "0270-6474"}, "abstract": "Parkinson's disease (PD) is characterized by severe locomotor deficits and is commonly treated with the dopamine precursor L-DOPA, but its prolonged usage causes dyskinesias referred to as L-DOPA-induced dyskinesia (LID). Several studies in animal models of PD have suggested that dyskinesias are associated with a heightened opioid cotransmitter tone, observations that have led to the notion of a LID-related hyperactive opioid transmission that should be corrected by \u00b5 opioid receptor antagonists. Reports that both antagonists and agonists of the \u00b5 opioid receptor may alleviate LID severity in primate models of PD and LID, together with the failure of nonspecific antagonist to improve LID in pilot clinical trials in patients, raises doubt about the reliability of the available data on the opioid system in PD and LID. After in vitro characterization of the functional activity at the \u00b5 opioid receptor, we selected prototypical agonists, antagonists, and partial agonists at the \u00b5 opioid receptor. We then showed that both oral and discrete intracerebral administration of a \u00b5 receptor agonist, but not of an antagonist as long thought, ameliorated LIDs in the gold-standard bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned female macaque model of PD and LID. The results call for a reappraisal of opioid pharmacology in the basal ganglia as well as for the development of brain nucleus-targeted \u00b5 opioid receptor agonists.SIGNIFICANCE STATEMENT \u00b5 opioid receptors have long been considered as a viable target for alleviating the severity of L-DOPA-induced hyperkinetic side effects, induced by the chronic treatment of Parkinson's disease motor symptoms with L-DOPA. Conflicting results between experimental parkinsonism and Parkinson's disease patients, however, dampened the enthusiasm for the target. Here we reappraise the pharmacology and then demonstrate that both oral and discrete intracerebral administration of a \u00b5 receptor agonist, but not of an antagonist as long thought, ameliorates LIDs in the gold-standard bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease, calling for a reappraisal of the opioid pharmacology as well as for the development of brain nucleus-targeted \u00b5 receptor agonists.", "doi": "10.1523/JNEUROSCI.0610-20.2020", "pmid": "32690616", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7455220"}, {"db": "pii", "key": "JNEUROSCI.0610-20.2020"}], "notes": [], "created": "2026-08-20T12:51:26.554Z", "modified": "2026-08-21T09:34:01.445Z"}, {"entity": "publication", "iuid": "c493d1a4299e4a9288cfd19f537c39f7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c493d1a4299e4a9288cfd19f537c39f7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c493d1a4299e4a9288cfd19f537c39f7"}}, "title": "Comprehensive mapping of neurotransmitter networks by MALDI-MS imaging.", "authors": [{"family": "Shariatgorji", "given": "Mohammadreza", "initials": "M"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Fridjonsdottir", "given": "Elva", "initials": "E", "orcid": "0000-0002-3779-3556", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/749090040c9c451ba610b0e144fa75e7.json"}}, {"family": "Vallianatou", "given": "Theodosia", "initials": "T"}, {"family": "K\u00e4llback", "given": "Patrik", "initials": "P"}, {"family": "Katan", "given": "Luay", "initials": "L"}, {"family": "S\u00e4vmarker", "given": "Jonas", "initials": "J"}, {"family": "Mantas", "given": "Ioannis", "initials": "I"}, {"family": "Zhang", "given": "Xiaoqun", "initials": "X"}, {"family": "Bezard", "given": "Erwan", "initials": "E", "orcid": "0000-0002-0410-4638", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/92f25ac8ff1d46ce8b68fbd88cd36843.json"}}, {"family": "Svenningsson", "given": "Per", "initials": "P"}, {"family": "Odell", "given": "Luke R", "initials": "LR", "orcid": "0000-0001-7658-5103", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/49395660c6af4fce9ad0f7f8fc793744.json"}}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f1dd27e8b238475383983480e10099f6.json"}}], "type": "journal article", "published": "2019-10-00", "journal": {"title": "Nat. Methods", "issn": "1548-7105", "volume": "16", "issue": "10", "pages": "1021-1028", "issn-l": "1548-7091"}, "abstract": "We present a mass spectrometry imaging (MSI) approach for the comprehensive mapping of neurotransmitter networks in specific brain regions. Our fluoromethylpyridinium-based reactive matrices facilitate the covalent charge-tagging of molecules containing phenolic hydroxyl and/or primary or secondary amine groups, including dopaminergic and serotonergic neurotransmitters and their associated metabolites. These matrices improved the matrix-assisted laser desorption/ionization (MALDI)-MSI detection limit toward low-abundance neurotransmitters and facilitated the simultaneous imaging of neurotransmitters in fine structures of the brain at a lateral resolution of 10 \u00b5m. We demonstrate strategies for the identification of unknown molecular species using the innate chemoselectivity of the reactive matrices and the unique isotopic pattern of a brominated reactive matrix. We illustrate the capabilities of the developed method on Parkinsonian brain samples from human post-mortem tissue and animal models. The direct imaging of neurotransmitter systems provides a method for exploring how various neurological diseases affect specific brain regions through neurotransmitter modulation.", "doi": "10.1038/s41592-019-0551-3", "pmid": "31548706", "labels": [], "xrefs": [{"db": "pii", "key": "10.1038/s41592-019-0551-3"}], "notes": [], "created": "2026-08-20T09:02:11.843Z", "modified": "2026-08-20T09:02:11.989Z"}]}