Neuroprotective and neurotrophic effect of apomorphine in the striatal 6-OHDA-lesion rat model of Parkinson's disease.
We investigated the possible neuroprotective effect of the dopamine (DA) receptor agonist R-apomorphine (R-APO) within the striatal 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease. In one group of rats, R-APO administration (10 mg/kg/day, s.c.) started 15 min before 6-OHDA-injection. In a second group, R-APO administration started 24 h after lesion induction. Both groups received R-APO chronically for 11 days. Testing was carried out 2 weeks post-lesioning. R-APO treatment, whether started before or after the lesion induction, significantly reduced both the amphetamine-induced ipsiversive rotation and the size of the lesion at the level of the substantia nigra. Moreover, the dopamine cell shape and size resembled that observed in intact animals. R-APO treatment had no effect on the number of cells in the substantia nigra of intact rats, but significantly increased the number of cells in the ventral tegmental area (VTA), suggesting selective neurotrophic properties of R-APO in this region. R-APO treatment significantly attenuated the 6-OHDA-induced striatal DA depletion and DOPAC/DA ratios were normalized. Finally, an acute injection of 10 mg/kg R-APO was unable to scavenge 6-OHDA or MPP(+)-induced hydroxyl radicals as determined with the in vivo salicylate trapping technique. These data provide further evidence of the neurorescuing properties of R-APO. At least at the dose used in this study, this effect possibly occurs via mechanisms other than scavenging of hydroxyl radicals. In intact rats, we also show neurotrophic effects of the R-APO treatment. These seem to be limited to the VTA.
Department of Pharmaceutical Chemistry and Drug Analysis, Research group Experimental Pharmacology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Hong
H
Yuan
Sophie
S
Sarre
Guy
G
Ebinger
Yvette
Y
Michotte
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D003956:Dialysis / Q000379:methods; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D004563:Electrochemistry / Q000379:methods; D062385:Hydroxybenzoates / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D062385:Hydroxybenzoates; D018696:Neuroprotective Agents; D015102:3,4-Dihydroxyphenylacetic Acid; C009135:2,3-dihydroxybenzoic acid; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine