APOMORPHINE RESPONSES IN PARKINSONS-DISEASE AND THE PATHOGENESIS OF MOTOR COMPLICATIONS

We studied the contribution of basal ganglia circuitry downstream from the nigrostriatal dopaminergic system to the pathogenesis of levodopa associated motor complications by means of an apomorphine dose-respon se paradigm in 28 parkinsonian patients grouped according to their cli nical response to levodopa therapy, With progression from the dopa-nai ve to the severely fluctuating dyskinetic state, apomorphine response duration shortened, the dose-response slope steepened, and the therape utic window narrowed. Because apomorphine acts independently of the in tegrity of presynaptic dopaminergic neurons, our results suggest that postsynaptic alterations account mainly for the appearance of response complications. The present findings support the possibility, raised b y animal model studies, that motor response complications arise as a c onsequence of altered signal transduction mechanisms in striatal mediu m-sized neurons.