Molecular neurobiology, 2015-12, Vol.52 (3), p.1408-1420
2015
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- Autor(en) / Beteiligte
- Titel
- Stronger Dopamine D1 Receptor-Mediated Neurotransmission in Dyskinesia
- Ist Teil von
- Molecular neurobiology, 2015-12, Vol.52 (3), p.1408-1420
- Ort / Verlag
- New York: Springer US
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Radioligand binding assays to rat striatal dopamine D 1 receptors showed that brain lateralization of the dopaminergic system were not due to changes in expression but in agonist affinity. D 1 receptor-mediated striatal imbalance resulted from a significantly higher agonist affinity in the left striatum. D 1 receptors heteromerize with dopamine D 3 receptors, which are considered therapeutic targets for dyskinesia in parkinsonian patients. Expression of both D 3 and D 1 –D 3 receptor heteromers were increased in samples from 6-hydroxy-dopamine-hemilesioned rats rendered dyskinetic by treatment with 3, 4-dihydroxyphenyl- l -alanine ( l -DOPA). Similar findings were obtained using striatal samples from primates. Radioligand binding studies in the presence of a D 3 agonist led in dyskinetic, but not in lesioned or l -DOPA-treated rats, to a higher dopamine sensitivity. Upon D 3 -receptor activation, the affinity of agonists for binding to the right striatal D 1 receptor increased. Excess dopamine coming from l -DOPA medication likely activates D 3 receptors thus making right and left striatal D 1 receptors equally responsive to dopamine. These results show that dyskinesia occurs concurrently with a right/left striatal balance in D 1 receptor-mediated neurotransmission.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0893-7648eISSN: 1559-1182DOI: 10.1007/s12035-014-8936-xTitel-ID: cdi_proquest_miscellaneous_1718076031
- Format
- –
- Schlagworte
- 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology, Animals, Biomedical and Life Sciences, Biomedicine, Caudate Nucleus - drug effects, Caudate Nucleus - physiopathology, Cell Biology, Corpus Striatum - drug effects, Corpus Striatum - physiopathology, Dimerization, Dominance, Cerebral - drug effects, Dopamine - metabolism, Dopamine Agonists - pharmacology, Dyskinesia, Drug-Induced - etiology, Dyskinesia, Drug-Induced - physiopathology, Gene Expression Regulation - drug effects, Levodopa - pharmacology, Levodopa - toxicity, Macaca fascicularis, Male, Neurobiology, Neurology, Neurosciences, Oxidopamine - toxicity, Parkinsonian Disorders - chemically induced, Parkinsonian Disorders - physiopathology, Putamen - drug effects, Putamen - physiopathology, Radioligand Assay, Rats, Rats, Wistar, Receptors, Dopamine D1 - agonists, Receptors, Dopamine D1 - biosynthesis, Receptors, Dopamine D1 - genetics, Receptors, Dopamine D1 - physiology, Receptors, Dopamine D3 - biosynthesis, Receptors, Dopamine D3 - genetics, Receptors, Dopamine D3 - physiology