Effects of the beta-adrenergic receptor antagonist Propranolol on dyskinesia and L-DOPA-induced striatal DA efflux in the hemi-parkinsonian rat
| Autor: | Jessica A. George, Margaret A. Surrena, David Lindenbach, Christopher Bishop, Nirmal Bhide, Christopher J. Barnum |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Agonist Dyskinesia Drug-Induced medicine.medical_specialty medicine.drug_class Dopamine Microdialysis Adrenergic beta-Antagonists Propranolol Motor Activity Pharmacology Biochemistry Article Antiparkinson Agents Levodopa Rats Sprague-Dawley Cellular and Molecular Neuroscience Quinpirole Dopamine receptor D1 Parkinsonian Disorders Dopamine receptor D2 Internal medicine medicine Animals Chromatography High Pressure Liquid Chemistry Antagonist Receptor antagonist Corpus Striatum Rats Endocrinology medicine.drug |
| Zdroj: | Journal of Neurochemistry. 134:222-232 |
| ISSN: | 0022-3042 |
| Popis: | Dopamine (DA) replacement therapy with L-DOPA continues to be the primary treatment of Parkinson's disease; however, long-term therapy is accompanied by L-DOPA-induced dyskinesias (LID). Several experimental and clinical studies have established that Propranolol, a β-adrenergic receptor antagonist, reduces LID without affecting L-DOPA's efficacy. However, the exact mechanisms underlying these effects remain to be elucidated. The aim of the current study was to evaluate the anti-dyskinetic profile of Propranolol against a panel of DA replacement strategies, as well as elucidate the underlying neurochemical mechanisms. Results indicated that Propranolol, in a dose-dependent manner, reduced LID, without affecting motor performance. Propranolol failed to alter dyskinesia produced by the D1 receptor agonist, SKF81297 (0.08 mg/kg, sc), or the D2 receptor agonist, Quinpirole (0.05 mg/kg, sc). These findings suggested a presynaptic mechanism for Propranolol's anti-dyskinetic effects, possibly through modulating L-DOPA-mediated DA efflux. To evaluate this possibility, microdialysis studies were carried out in the DA-lesioned striatum of dyskinetic rats and results indicated that co-administration of Propranolol (20 mg/kg, ip) was able to attenuate L-DOPA- (6 mg/kg, sc) induced DA efflux. Therefore, Propranolol's anti-dyskinetic properties appear to be mediated via attenuation of L-DOPA-induced extraphysiological efflux of DA. |
| Databáze: | OpenAIRE |
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