Increased dopamine turnover after partial loss of dopaminergic neurons: compensation or toxicity?

6-Hydroxydopamine (6-OHDA) has proven a valuable tool in the study of Parkinson's disease (PD); it has also served to emphasize the possibility that this disorder may result in part from the sort of oxidative stress that 6-OHDA exerts on dopamine neurons. In this review we comment on several lines of our research related to the role of oxidative stress in PD, research that has benefited greatly from the work of Gerald Cohen whose memory we honor at this symposium. First, we discuss our use of 6-OHDA to produce an animal model of PD; second, we comment on our studies on dopamine's neurotoxic effects; and finally, we discuss our finding that tyrosine hydroxylase is regulated in part by an interaction with alpha-synuclein. We suggest that PD is associated with an increase in dopamine turnover, which may not only reduce the immediate symptoms of the disease but also contribute to its progression.