Compensatory mechanisms in the nigrostriatal dopaminergic system in Parkinson's disease: studies in an animal model.

Partial unilateral nigrostriatal lesions of varying severity (from mild to near-total) were produced in rats by intranigral injections of increasing doses of 6-hydroxydopamine. Severity of the lesions was estimated by measurement of striatal tyrosine hydroxylase activity. In such rats, surviving nigrostriatal neurons accelerated their rates of dopamine (DA) synthesis and release (estimated by the ratio of homovanillic acid to tyrosine hydroxylase) only when 60% of more of DA neurons had been destroyed. Striatal DA receptor supersensitivity (estimated by emergence of contraversive rotational behavior induced by apomorphine and L-dopa) developed only when 90% or more of striatal DA nerve terminals had been destroyed. Acceleration of DA turnover by surviving nigrostriatal neurons and the development of striatal DA receptor supersensitivity may represent two compensatory mechanisms through which the nigra adapts to its own destruction and may explain, in part, why clinical signs of parkinsonism emerge only after massive degeneration of DA neurons.