Alterations in primary motor cortex neurotransmission and gene expression in hemi-parkinsonian rats with drug-induced dyskinesia
| Autor: | Melissa M. Conti, David Lindenbach, Corinne Y. Ostock, Christopher Bishop, Kristin B. Dupre |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Dyskinesia Drug-Induced Levodopa medicine.medical_specialty Parkinson's disease Dopamine Agents Gene Expression Severity of Illness Index Synaptic Transmission Functional Laterality Article Rats Sprague-Dawley chemistry.chemical_compound Dopamine receptor D1 Parkinsonian Disorders AIDS-Related Complex Dopamine Internal medicine medicine Animals Oxidopamine Medial forebrain bundle Neurotransmitter General Neuroscience Medial Forebrain Bundle Motor Cortex Glutamate receptor Benzazepines medicine.disease Rats Disease Models Animal Endocrinology chemistry Dyskinesia medicine.symptom Psychology Proto-Oncogene Proteins c-fos Neuroscience medicine.drug |
| Zdroj: | Neuroscience. 310:12-26 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2015.09.018 |
| Popis: | Treatment of Parkinson’s disease (PD) with dopamine replacement relieves symptoms of poverty of movement, but often causes drug-induced dyskinesias. Accumulating clinical and pre-clinical evidence suggests that the primary motor cortex (M1) is involved in the pathophysiology of PD and that modulating cortical activity may be a therapeutic target in PD and dyskinesia. However, surprisingly little is known about how M1 neurotransmitter tone or gene expression are altered in PD, dyskinesia or associated animal models. The present study utilized the rat unilateral 6-hydroxydopamine (6-OHDA) model of PD / dyskinesia to characterize structural and functional changes taking place in M1 monoamine innervation and gene expression. 6-OHDA caused dopamine pathology in M1, although the lesion was less severe than in the striatum. Rats with 6-OHDA lesions showed a PD motor impairment and developed dyskinesia when given L-DOPA or the D1 receptor agonist, SKF81297. M1 expression of two immediate-early genes (c-Fos and ARC) was strongly enhanced by either L-DOPA or SKF81297. At the same time, expression of genes specifically involved in glutamate and GABA signaling were either modestly affected or unchanged by lesion and/or treatment. We conclude that M1 neurotransmission and signal transduction in the rat 6-OHDA model of PD / dyskinesia mirror features of human PD, supporting the utility of the model to study M1 dysfunction in PD and the elucidation of novel pathophysiological mechanisms and therapeutic targets. |
| Databáze: | OpenAIRE |
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