NMSP binding to dopamine and serotonin receptors in MPTP-induced parkinsonism: relation to dopa therapy

We tested the hypothesis that N-methylspiperone binding to dopamine D-2 rec eptors must be reduced when L-dopa therapy of parkinsonism augments the bin ding of dopamine to the receptors and improves the clinical state expressed by the Hoehn & Yahr stage. A patient with MPTP-induced parkinsonism underw ent two positron emission tomographic studies of the D-2-like dopamine rece ptors with N-[C-11]methylspiperone (NMSP), The first study took place 3 day s after cessation of the L-dopa medication, the second 5 days after its res umption. Noticeable clinical deterioration occurred during both studies, co nsistent with significant dopamine receptor blockade by NMSP and elevated N MSP binding in both scans. The dopa treatment. did not reduce the NMSP bind ing. On the contrary, the rate of binding of NMSP (k(3)) was increased on-d opa, compared to off-dopa. The increase was consistent with the slightly gr eater dopamine receptor density estimated after resumption of the dopa ther apy. The NMSP binding to serotonin receptors suggested lower synaptic serot onin on-dopa than off-dopa. The results are consistent with negative correl ation between the Hoehn & Yahr stage and the amount of dopamine bound to do pamine D-2 receptors. Low synaptic serotonin may explain the depression see n in some patients on dopa for Parkinson's disease.