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Treatment effects on partial 6-OHDA lesions Comparison of L-DOPA and pramipexole



Treatment effects on partial 6-OHDA lesions Comparison of L-DOPA and pramipexole



Society for Neuroscience Abstracts 27(1): 1147



There is controversy over potential neuroprotective or neurotoxic properties of dopaminergic replacement therapies in the treatment of mild Parkinson's disease (PD). Specifically, the differential effects of levodopa (LD) and dopamine agonists on the partially degenerated nigrostriatal dopaminergic projection are unknown. We evaluated LD versus pramipexole (PRA) modification of nigrostriatal lesion severity as measured with vesicular monoamine transporter type-2 (VMAT2) binding. VMAT2 density provides an objective estimate of dopaminergic system integrity without confounding effects of compensatory regulation. Male Sprague-Dawley rats were injected with 2 mg/ml 6-OHDA at 4 mul over 4 min into the right MFB. Five weeks later, rats were screened for rotational behavior with amphetamine (2 mg/kg i.p.) to estimate lesion severity. Rats were ranked and matched by this behavior, then assigned to receive either PRA (1 mg/kg/day) or L-DOPA/benserazide (100/25 mg/kg/day) via i.p. osmotic pump. After 4 weeks of drug treatment, in vitro autoradiography was done on 20 mum coronal striatal sections with (3H)MTBZ and (3H)WIN 35,428 to measure binding densities of VMAT2 and DAT, respectively. Lesion-to-contralateral VMAT2 density correlated with rotation in both groups. There was no group difference in lesioned striatal VMAT2 using paired assessment of animals matched for pre-treatment rotation. Compared to VMAT2, DAT binding was reduced to a greater extent, perhaps due to downregulation. These studies reveal no significant relative protective advantage of indirect (LD) versus direct (PRA) dopa-mimetic treatment in partial nigrostriatal lesions.

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