The dopamine receptor agonist lisuride attenuates iron-mediated dopaminergic neurodegeneration.
Many dopamine agonists used in the treatment of Parkinson's disease are suggested to be potentially neuroprotective. On the basis of its structure, the dopamine agonist lisuride may share this characteristic. In the current study discrete asymptomatic lesions were produced by the injection of iron-laden neuromelanin into the rat substantia nigra and the animals treated with lisuride to determine the protective potential of this substance. Two treatment regimes were utilised. In the neuroprotective protocol, animals were treated with 0.1 mg.kg(-1) lisuride twice daily 3 days prior to, and 7 days following, the iron lesion. In the neurorescue protocol, the animals received 0.1 mg.kg(-1) lisuride twice daily for 1 week beginning on the fourth day post surgery. Eight weeks post surgery, tyrosine hydroxylase-positive neurons surrounding the injection site (33% of total nigral volume) were counted. Dopamine neuron number in iron-lesioned animals was reduced to 50% of that in vehicle-injected animals. The absence of motoric disturbances or a striatal dopamine deficit in these animals suggests a subclinical dopaminergic lesion. Dopamine neuron number in the quantified area in sham-injected animals receiving lisuride or iron-lesioned animals receiving lisuride in both the neuroprotection and neurorescue groups were not significantly reduced. These results suggest that lisuride can protect neurons against iron-induced cell death and might thus be neuroprotective in Parkinson's disease.
Double
K L
KL
Prince of Wales Medical Research Institute, 2031, Sydney, Australia. K.Double@unsw.edu.au
Halliday
G M
GM
Henderson
J
J
Griffiths
F M
FM
Heinemann
T
T
Riederer
P
P
Gerlach
M
M
D000332:Aerobiosis; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D007501:Iron / Q000633:toxicity*; D008090:Lisuride / Q000494:pharmacology*; D008297:Male; D008543:Melanins / Q000633:toxicity; D017072:Neostriatum / Q000201:enzymology / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D018696:Neuroprotective Agents; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018491:Dopamine Agonists; D008543:Melanins; D018696:Neuroprotective Agents; C014121:neuromelanin; D008090:Lisuride; D007501:Iron; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine