The Time Course of D1 Agonist Induced Striatonigral ERK1/2 Signaling in a Rat Model of Parkinson’s Disease
Cicely Moreno, Subbiah P. Sivam
Natural Asset, Financial Value, Neural Network
Journal of Behavioral and Brain Science,
ABSTRACT: Using a rat model of hemiparkinsonism, we examined the time-course of D1 agonist, SKF-38393-induced changes in extracellular signaling regulated kinases 1/2 (ERK1/2) phosphorylation in the striatum and substantia nigra (SN). We unilaterally lesioned the rat median forebrain bundle with 6-hydroxydopamine. Dopaminergic lesioned rats were administered with SKF-38393 and perfused at 15, 30, 60, or 120 minutes after the drug. Immunohistochemical analysis of striatum and SN revealed, as expected, a loss of tyrosine hydroxylase and a decrease of substance P in lesioned rats. SKF-38393 induced a robust increase in phospho-ERK1/2 levels in the lesioned striatum, which peaked at 15 min and substantially declined by 120 min. We report for the first time that similar changes were observed in the SN. The time-dependent ERK 1/2 activation in the striatonigral neurons may play a role in the therapeutic and/or side effects such as dyskinesias related to the dopamine agonist treatment for Parkinson’s disease.