Persistent changes in striatal gene expression induced by long‐term l‐DOPA treatment in a rat model of Parkinson's disease
- 1 October 2001
- journal article
- research article
- Published by Wiley in European Journal of Neuroscience
- Vol. 14 (7) , 1171-1176
- https://doi.org/10.1046/j.0953-816x.2001.01743.x
Abstract
Current knowledge of the molecular changes induced by dopamine denervation and subsequent treatment with l‐DOPA is based on studies performed on relatively acute and young animal models of parkinsonism. It is highly warranted to ask how well these models simulate the state of chronic denervation and sustained l‐DOPA pharmacotherapy which are typical of advanced Parkinson's disease. This study investigates the effects of time postdenervation and l‐dopa treatment duration on the striatal expression of opioid precursor mRNAs and FosB/ΔFosB‐related proteins. Unilaterally 6‐hydroxydopamine‐lesioned rats were treated with therapeutical doses of l‐DOPA for one year (long‐term group) or a few weeks (short‐term group). Age‐matched lesioned rats received injections of vehicle or bromocriptine, an antiparkinsonian compound which does not produce dyskinesia when administered de novo. The lesion‐induced up‐regulation of preproenkephalin mRNA expression persisted at more than one year postlesion, and was unaffected by the pharmacological treatments applied. l‐DOPA, but not bromocriptine, induced high striatal levels of FosB/ΔFosB immunoreactivity and prodynorphin mRNA, and these did not differ between short‐term and long‐term l‐DOPA‐treated rats. The present data provide the first demonstration that l‐DOPA maintains high striatal levels of fosB and prodynorphin gene expression during a prolonged course of treatment, which simulates the clinical practice in Parkinson's disease more closely than the short‐treatment paradigms studied thus far.Keywords
This publication has 13 references indexed in Scilit:
- cAMP Response Element-Binding Protein Is Required for Dopamine-Dependent Gene Expression in the Intact But Not the Dopamine-Denervated StriatumJournal of Neuroscience, 2001
- Striatal fosB Expression Is Causally Linked with l-DOPA-Induced Abnormal Involuntary Movements and the Associated Upregulation of Striatal Prodynorphin mRNA in a Rat Model of Parkinson's DiseaseNeurobiology of Disease, 1999
- Changes in the regional and compartmental distribution of FosB- and JunB-like immunoreactivity induced in the dopamine-denervated rat striatum by acute or chronic L-DOPA treatmentNeuroscience, 1999
- Effect of Repeatedl-DOPA, Bromocriptine, or Lisuride Administration on Preproenkephalin-A and Preproenkephalin-B mRNA Levels in the Striatum of the 6-Hydroxydopamine-Lesioned RatExperimental Neurology, 1999
- L‐DOPA‐induced dyskinesia in the rat is associated with striatal overexpression of prodynorphin‐ and glutamic acid decarboxylase mRNAEuropean Journal of Neuroscience, 1998
- De novo administration of ropinirole and bromocriptine induces less dyskinesia than L‐dopa in the MPTP‐treated marmosetMovement Disorders, 1998
- Chronic Alterations in Dopaminergic Neurotransmission Produce a Persistent Elevation of ΔFosB‐like Protein(s) in both the Rodent and Primate StriatumEuropean Journal of Neuroscience, 1996
- Preproenkephalin and preprotachykinin messenger RNA expression in normal human basal ganglia and in Parkinson's diseaseNeuroscience, 1995
- Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatmentsNeuron, 1994
- Neuropeptide messenger RNA expression in the 6-hydroxydopamine-lesioned rat striatum reinnervated by fetal dopaminergic transplants: Differential effects of the grafts on preproenkephalin, preprotachykinin and prodynorphin messenger RNA levelsNeuroscience, 1993