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Journal article
Activation of Extracellular Signal-Regulated Protein Kinases Is Associated with a Sensitized Locomotor Response to D2Dopamine Receptor Stimulation in Unilateral 6-Hydroxydopamine-Lesioned Rats
The Journal of neuroscience, v 20(5), pp 1849-1857
01 Mar 2000
PMID: 10684886
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Evidence indicates that mitogen-activated protein kinase (MAPK) pathways play a crucial role in the neurobiology of the nervous system. In the present study, dopamine receptor-mediated regulation of extracellular signal-regulated kinases (ERKs) was examined in rats in which the nigrostriatal dopaminergic pathway was unilaterally lesioned by 6-hydroxydopamine (6-OHDA). Subcutaneous injections of the D
2
receptor agonist quinpirole significantly increased tyrosine-phosphorylated ERK1/2 in lesioned striatum, whereas the D
1
receptor agonist SKF38393 failed to activate ERKs. Quinpirole-induced phosphorylation of ERK1/2 was seen as early as 3 min and peaked at 15 min after the challenge. In parallel, striatal ERK kinase activity, measured by the
in vitro
kinase assay, was increased 2.5-fold on the lesioned side after the administration of quinpirole. Immunohistochemical examination of brain sections after quinpirole administration revealed significant increases in ERK1/2 immunostaining in perinuclear and intranuclear areas of striatal neurons. This increase was much more pronounced on the lesioned than the intact side. Furthermore, quinpirole-induced contralateral rotation was decreased by 48.7 and 50.7%, respectively, when the striatal ERK pathway was selectively inhibited by a single intrastriatal injection of the MAPK/ERK kinase inhibitor PD098059 or after a continuous 7 d intrastriatal infusion of ERK1/2 antisense oligodeoxynucleotide. The results demonstrate, for the first time, that the ERK signaling pathway is activated in denervated striatum in response to stimulation of D
2
dopamine receptors and that the resulting imbalance in striatal ERK activity contributes, at least in part, to neuronal plasticity that underlies D
2
dopamine receptor-mediated contralateral rotation in unilateral 6-OHDA denervated rats.
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Details
- Title
- Activation of Extracellular Signal-Regulated Protein Kinases Is Associated with a Sensitized Locomotor Response to D2Dopamine Receptor Stimulation in Unilateral 6-Hydroxydopamine-Lesioned Rats
- Creators
- Guoping Cai - Drexel UniversityXuechu Zhen - Drexel UniversityKunihiro Uryu - Drexel UniversityEitan Friedman - Drexel University
- Publication Details
- The Journal of neuroscience, v 20(5), pp 1849-1857
- Publisher
- Society for Neuroscience
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000085462600022
- Scopus ID
- 2-s2.0-0034161438
- Other Identifier
- 991019168396104721
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- Web of Science research areas
- Neurosciences