期刊
JOURNAL OF NEUROCHEMISTRY
卷 134, 期 2, 页码 222-232出版社
WILEY
DOI: 10.1111/jnc.13125
关键词
dyskinesia; L-DOPA; microdialysis; norepinephrine; Parkinson's disease; Propranolol
资金
- National Institutes of Health [R01-NS059600]
- Center for Development and Behavioral Neuroscience at Binghamton University
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 -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 this 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 D-1 receptor agonist, SKF81297 (0.08mg/kg, sc), or the D-2 receptor agonist, Quinpirole (0.05mg/kg, sc). These findings suggested a pre-synaptic 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 (20mg/kg, ip) was able to attenuate L-DOPA- (6mg/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.
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