title: Effects of the beta-adrenergic receptor antagonist Propranolol on dyskinesia and L-DOPA-induced striatal DA efflux in the hemi-parkinsonian rat.
abstract: 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.
authors: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, Binghamton, New York, USA.
authors: Nirmal
authors: N
authors: Bhide
authors: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, Binghamton, New York, USA.
authors: David
authors: D
authors: Lindenbach
authors: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, Binghamton, New York, USA.
authors: Christopher J
authors: CJ
authors: Barnum
authors: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, Binghamton, New York, USA.
authors: Jessica A
authors: JA
authors: George
authors: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, Binghamton, New York, USA.
authors: Margaret A
authors: MA
authors: Surrena
authors: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, Binghamton, New York, USA.
authors: Christopher
authors: C
authors: Bishop
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000517:prevention & control*; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000319:Adrenergic beta-Antagonists; D000978:Antiparkinson Agents; D007980:Levodopa; D011433:Propranolol; D004298:Dopamine
keywords: L-DOPA; Parkinson's disease; Propranolol; dyskinesia; microdialysis; norepinephrine