Effects of the beta-adrenergic receptor antagonist Propranolol on dyskinesia and L-DOPA-induced striatal DA efflux in the hemi-parkinsonian rat.

Autor: Bhide N; Department of Psychology, Behavioral Neuroscience Program, Binghamton University, Binghamton, New York, USA., Lindenbach D; Department of Psychology, Behavioral Neuroscience Program, Binghamton University, Binghamton, New York, USA., Barnum CJ; Department of Psychology, Behavioral Neuroscience Program, Binghamton University, Binghamton, New York, USA., George JA; Department of Psychology, Behavioral Neuroscience Program, Binghamton University, Binghamton, New York, USA., Surrena MA; Department of Psychology, Behavioral Neuroscience Program, Binghamton University, Binghamton, New York, USA., Bishop C; Department of Psychology, Behavioral Neuroscience Program, Binghamton University, Binghamton, New York, USA.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2015 Jul; Vol. 134 (2), pp. 222-32. Date of Electronic Publication: 2015 Apr 27.
DOI: 10.1111/jnc.13125
Abstrakt: 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 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 D1 receptor agonist, SKF81297 (0.08 mg/kg, sc), or the D2 receptor agonist, Quinpirole (0.05 mg/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 (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.
(© 2015 International Society for Neurochemistry.)
Databáze: MEDLINE
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