NDLI: Stronger Dopamine D$_{1}$ Receptor-Mediated Neurotransmission in Dyskinesia

Content Provider	Springer Nature Link
Author	Farré, Daniel Muñoz, Ana More, Estefanía Reyes Resina, Irene Canet Pons, Júlia Dopeso Reyes, Iria G. Rico, Alberto J. Lluís, Carme Mallol, Josefa Navarro, Gemma Canela, Enric I. Cortés, Antonio Labandeira García, José L. Casadó, Vicent Lanciego, José L. Franco, Rafael
Copyright Year	2014
Abstract	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.
Starting Page	1408
Ending Page	1420
Page Count	13
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	52
Issue Number	3
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2014-10-26
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Basal ganglia Caudate D$_{3}$ receptors Direct pathway l-DOPA Dopamine receptor heteromers Macaca fascicularis Non-human primate Putamen Indirect pathway Parkinson’s Dopamine sensitivity Lateralization Striatum Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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