Objective The aim of the present study was not only to assess the retrograde degenerative changes in the dopaminergic neurons of the substantia nigra （SN） and ventral tegmental area （VTA） after injection of 6-hydr...Objective The aim of the present study was not only to assess the retrograde degenerative changes in the dopaminergic neurons of the substantia nigra （SN） and ventral tegmental area （VTA） after injection of 6-hydroxydopamine （6-OHDA） into the striatum, but also to use this 6-OHDA model of Parkinson＇s disease to explore the possible neuroprotective effect of R-apomorphine （R-APt）. Methods The partial lesion was obtained by intrastriatal administration of 6-OHDA. R- APt administration （10 mg/kg, s.c.） started 15 min prior to lesioning and continued daily for another 22 days post surgery. Testing was carried out 5 weeks after lesioning. We investigated the histology and associated behavior and neurochemical changes. Structural and functional deficits were quantified by tyrosine hydroxylase （TH） / Nissl-staining cell number counting, striatal dopamine （DA） content determination and amphetamine-induced rotation analysis. Results R-APt- treatment attenuated the amphetamine-induced ipsiversive rotation 5 weeks after the lesion induction. R-APt administra- tion for 22 days significantly reduced the size of the lesion at the level of the SN from 50% （control group） to 69%. Moreover, the cell shape resembled that observed in the intact animals. R-APt treatment significantly increased the number of cells in both the lesion and the intact sides of VTA by 60%, suggesting selective neurotrophic effect of R-APt in this area. Finally, R-APt-treatment significantly attenuated the 6-OHDA-induced striatal DA depletion and normalized dihydroxyphenylacetic acid （DOPAC）/DA ratios. Conclusion We conclude that R-APt has neuroprotective and pos- sible neurotrophic effect on a striatal lesion with 6-OHDA, suggesting that this drug may have rescuing properties in patients with early stage Parkinson＇s disease. These effects are more pronounced in VTA and enhance with duration of treatment.展开更多
文摘Objective The aim of the present study was not only to assess the retrograde degenerative changes in the dopaminergic neurons of the substantia nigra （SN） and ventral tegmental area （VTA） after injection of 6-hydroxydopamine （6-OHDA） into the striatum, but also to use this 6-OHDA model of Parkinson＇s disease to explore the possible neuroprotective effect of R-apomorphine （R-APt）. Methods The partial lesion was obtained by intrastriatal administration of 6-OHDA. R- APt administration （10 mg/kg, s.c.） started 15 min prior to lesioning and continued daily for another 22 days post surgery. Testing was carried out 5 weeks after lesioning. We investigated the histology and associated behavior and neurochemical changes. Structural and functional deficits were quantified by tyrosine hydroxylase （TH） / Nissl-staining cell number counting, striatal dopamine （DA） content determination and amphetamine-induced rotation analysis. Results R-APt- treatment attenuated the amphetamine-induced ipsiversive rotation 5 weeks after the lesion induction. R-APt administra- tion for 22 days significantly reduced the size of the lesion at the level of the SN from 50% （control group） to 69%. Moreover, the cell shape resembled that observed in the intact animals. R-APt treatment significantly increased the number of cells in both the lesion and the intact sides of VTA by 60%, suggesting selective neurotrophic effect of R-APt in this area. Finally, R-APt-treatment significantly attenuated the 6-OHDA-induced striatal DA depletion and normalized dihydroxyphenylacetic acid （DOPAC）/DA ratios. Conclusion We conclude that R-APt has neuroprotective and pos- sible neurotrophic effect on a striatal lesion with 6-OHDA, suggesting that this drug may have rescuing properties in patients with early stage Parkinson＇s disease. These effects are more pronounced in VTA and enhance with duration of treatment.
