The Behavioral Changes and the Patterns of Dopamine NeuronalDegeneration after Intrastriatal 6-hydroxydopamine Injection in Rat

Lee, Won Yong; Kim, Gyeong Moon; Lee, Jung Il

Abstract

BACKGROUND: The terminal destruction of the striatal dopaminergic axon can produce the retrograde degeneration of nigral dopaminergic neurons. An analyses of the postsynaptic dopamine D1 & D2 receptors and the DOPAC/DA level, revealed that this model mimics the early course of Parkinson's disease in humans. We evaluated the time course of the retrograde dopaminergic neuronal degeneration and the pattern of dopaminergic neuronal loss in the substantia nigra after various doses of 6-hydroxydopamine (6-OHDA) injections in the striatum of rats.
METHODS
Different doses of 6- OHDA (0.0, 1.25, 2.5, 5, 10 ug/ul in 3.5 ul of saline) were unilaterally injected into the right striatum of rats using a stereotaxic frame. Structural and functional deficits were quantified and compared using apomorphine-induced rotations and tyrosine hydroxylase-immunoreactive (TH-IR) cell numbers in the substantia nigra pars compacta (SNpc) at 3, 6, 9 weeks after lesioning.
RESULTS
Striatal 6-OHDA lesions produced dose-dependent decreases in TH-IR cell numbers in SNpc at 3 weeks (-3.8%, 17.9%, 41.2%, 58.5%, 69.9% cell loss compared with the contralesional side respectively), where the ventrolateral portion of the SNpc were more affected. As time progressed, nigral cell loss was significantly increased in all dosage groups and the lesion extended to the medial side of the SNpc and the ventral tegmental area. Apomorphine-induced rotations did not correlate well with nigral TH-IR cell loss.
CONCLUSIONS
Intrastriatal injections of 6-OHDA, results in time-dependent and dose-dependent progressive degeneration of nigral dopaminergic neurons. We conclude that this rat model can be useful for the evaluation of further neuroprotective and neurotrophic therapies.