We investigated the neuroprotective effects of the dopamine (DA) receptor agonist R-apomorphine (R-APO) [10mg/kg/day, subcutaneously (s.c.) for 11 days] in the striatal 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD). The treatment was started either 15' before or 24h after lesioning. R-APO was also administered to intact rats. Two weeks after lesioning, the neuroprotective effects were evaluated using behavioural, neurochemical and histological tests. The in vivo salicylate trapping technique was used to investigate the radical scavenging properties of R-APO administered s.c. on 6-OHDA-induced hydroxyl (•OH) radical formation. We also studied the effect of R-APO on the neurotrophic factor fibroblast growth factor 2 (FGF-2) mRNA expression in the striatum of intact rats. Both in the striatum and the substantia nigra pars compacta (SNpc), 6-OHDA induced a lesion of about 50%. The treatment significantly reduced the amphetamine-induced ipsiversive rotations, the size of the lesion at the level of the SNpc and ventral tegmental area (VTA), and the 6-OHDA induced striatal DA depletion. The number of cells in the VTA significantly increased in intact rats, suggesting a neurotrophic action of R-APO. We observed that R-APO had no effect on the 6-OHDA-induced •OH radical formation. Preliminary data show an increase of the striatal FGF-2 mRNA levels. We conclude that R-APO has a neuroprotective and possibly a neurotrophic effect in our rat model. This may, at least in part, be mediated by an up-regulation of FGF-2.