Parkinson's disease: studies with an animal model.

Parkinson' disease has been associated with degeneration of dopamine-containing neurons of the nigrostriatal bundle. Many neurological features of Parkinsonism can be produced in rats by selective destruction of central dopaminergic neurons using the neurotoxin 6-hydroxydopamine. In this review we discuss two aspects of Parkinson's disease that have been investigated in these animals. First, we consider why near-total degeneration of nigrostriatal bundle neurons is required before neurological symptoms emerge. It appears that the loss of dopaminergic neurons is accompanied by an exponential increase in the ratio of tyrosine hydroxylase activity to dopamine content. Thus, after the brain lesions there may be a compensatory increase in the capacity of residual dopaminergic neurons to synthesize and release transmitter. Second, we consider why stress produces severe neurological deficits in patients who are only mildly impaired otherwise. It appears that a variety of stressors produce an abrupt but transient increase in dopaminergic activity in the striatum of intact animals and that this increase is markedly attenuated by 6-hydroxydopamine treatment. Thus, stress-induced akinesia in animals with dopamine-depleting brain lesions and in Parkinsonian patients may result from the impaired ability of residual neurons to respond approximately to such stimuli.