Neurochemical Compensation After Nigrostriatal Bundle Injury in an Animal Model of Preclinical Parkinsonism

Parkinson's disease usually involves a lengthy preclinical period during which few neurological symptoms are observed despite extensive damage to the dopaminergic nigrostriatal bundle. Injury to this projection in the rat also fails to produce major neurological dysfunctions. In our studies, damage to the nigrostriatal bundle of the rat, resulting in the loss of up to 95% of the dopaminergic terminals in striatum, was accompanied by apparent increases in the synthesis and release of dopamine (DA) from those dopaminergic terminals that remained. More specifically, both the activity of the rate-limiting biosynthetic enzyme, tyrosine hydroxylase, and the content of the principal DA metabolite, dihydroxyphenylacetic acid, were increased in striatum relative to DA levels. The increases were exponentially related to DA loss.