Noradrenergic Changes in an Experimental Model of Parkinsonism Using 6-hydroxydopamine

ABSTRACT

BACKGROUND & OBJECTIVE: Stereotaxic injection of 6-hydroxydopamine(6OHDA) into the ventral midbrain is the most commonly used Parkinsonian animal model. In the presence of norepinephrine(NE) uptake blockers, 6OHDA is believed to be selectively toxic to the dopamine(DA) system. However, it was observed in this model that there is a massive fiber degeneration in the fornix, where there are no known DA fibers. There are NE fibers in the fornix arising from the locus ceruleus (LC) terminating in the cerebral cortex including hippocampus. The study was done to examine whether there is a change in the NE system and characterize the neurochemical nature of the previously demonstrated degenerating fornix fibers. METHODS: 6OHDA was injected stereotaxically into the unilateral ventral midbrain in desipramine pretreated rats. DA and NE were measured in the striatum, cortex, hippocampus, and LC. Silver staining was done to demonstrate degenerating neurons and nerve terminals. Immunohistochemistry using tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) was done to demonstrate catecholamine neurons and nerve fibers. RESULTS: DA was markedly depleted in the ipsilateral striatum. NE was decreased in the striatum, cortex, and hippocampus, but not in the LC. Silver staining showed massive fiber degeneration in the fornix, but did not show degenerating neurons in the LC. TH and DBH Immunohistochemistry failed to show catecholaminergic fibers in the fornix. There was no side difference on immunostaining in the LC neurons. CONCLUSION: 6OHDA Parkinson model does not make selective lesion to the DA system, and damages ascending NE fibers. Neuronal cell bodies in the LC remain intact in this model. The neurochemical nature of the degenerating fornix fibers is not clearly characterized.