Dopamine depletion and subsequent treatment with l-DOPA, but not the long-lived dopamine agonist pergolide, enhances activity of the Akt pathway in the rat striatum

摘要: Dysregulation of signaling pathways is believed to contribute Parkinson’s disease pathology and l-DOPA-induced motor complications. Long-lived dopamine (DA) agonists are less likely cause complications by virtue continuous stimulation DA receptors. In this study, we compared the effects unilateral 6-hydroxydopamine lesion subsequent treatment with l-DOPA agonist pergolide on in rats. Pergolide caused pronounced behavioral sensitization than (25 mg/kg, i.p., 10 days), particularly at lower dose (0.5 0.25 mg/kg, i.p.). Pergolide, but not l-DOPA, reversed lesion-induced up-regulation preproenkephalin did up-regulate preprodynorphine or D3 receptor lesioned hemisphere. was as effective reversing elevation ERK2 phosphorylation response acute apomorphine administration (0.05 mg/kg, s.c.). Chronic significantly elevated level Akt both Thr308 Ser473 concentration phosphorylated GSK3α, whereas suppressed lesion- and/or challenge-induced supersensitive responses. The data indicate that unlike pergolide, exacerbates imbalances pathway loss DA. results support hypothesis involved long-term actions may be linked dyskinesia.