Levodopa-induced dopamine receptor hypersensitivity.

Chronic administration of levodopa with a dopa decarboxylase inhibitor to young guinea pigs resulted in increased behavioral response to levodopa itself as well as to d-amphetamine and apomorphine. The chronic levodopa pretreatment resulted in a decreased threshold for stereotyped behavior for all three types of dopamine agonists. Our results suggest that chronic agonism with levodopa can produce postsynaptic dopaminergic hypersensitivity within the striatum. These experiments act as a model of levodopa-induced dyskinesia in patients receiving long-term levodopa therapy. The results reported here suggest that receptor site hypersensitivity may play a role in levodopa-induced dyskinesias and that chronic levodopa (dopamine) agonism may itself be involved in the pathogenesis of this movement disorder.