For nearly 20 years, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model has allowed great strides to be made in our understanding of the maladaptive changes underlying the levodopa-related motor response complications occurring in most parkinsonian patients. Studies indicate that sustained dopamine D2 receptor occupancy can prevent and reverse existing dyskinesias. Recent experiments in levodopa-treated MPTP animals, co-administered either a threshold dose of cabergoline or a glutamate NMDA NR2B-selective antagonist (CI-1041), have afforded protection against dyskinesia, perhaps through presynaptic inhibition of glutamate release and blockade of supersensitive postsynaptic NMDA receptors in the striatum, respectively. Some of the biochemical events that have correlated with dyskinesias, namely upregulated GABA(A) receptors in the internal pallidum, rise in pre-proenkephalin-A gene expression in the striatum, and upregulated striatal glutamate ionotropic receptors and adenosine A(2a) receptors, may be counteracted by these preventive strategies.