Activation of extracellular signal-regulated protein kinases is associated with a sensitized locomotor response to D(2) dopamine receptor stimulation in unilateral 6-hydroxydopamine-lesioned rats.

摘要: Evidence indicates that mitogen-activated protein kinase (MAPK) pathways play a crucial role in the neurobiology of nervous system. In present study, dopamine receptor-mediated regulation extracellular signal-regulated kinases (ERKs) was examined rats which nigrostriatal dopaminergic pathway unilaterally lesioned by 6-hydroxydopamine (6-OHDA). Subcutaneous injections D 2 receptor agonist quinpirole significantly increased tyrosine-phosphorylated ERK1/2 striatum, whereas 1 SKF38393 failed to activate ERKs. Quinpirole-induced phosphorylation seen as early 3 min and peaked at 15 after challenge. parallel, striatal ERK activity, measured vitro assay, 2.5-fold on side administration quinpirole. Immunohistochemical examination brain sections revealed significant increases immunostaining perinuclear intranuclear areas neurons. This increase much more pronounced than intact side. Furthermore, quinpirole-induced contralateral rotation decreased 48.7 50.7%, respectively, when selectively inhibited single intrastriatal injection MAPK/ERK inhibitor PD098059 or continuous 7 d infusion antisense oligodeoxynucleotide. The results demonstrate, for first time, signaling is activated denervated striatum response stimulation receptors resulting imbalance activity contributes, least part, neuronal plasticity underlies unilateral 6-OHDA rats.