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

K. Borbely, R. A. Brooks, D. F. Wong, R. Stanley Burns, P. Cumming, Albert Gjedde, G. Di Chiro

Research output: Contribution to journalArticlepeer-review

Abstract

We tested the hypothesis that N-methylspiperone binding to dopamine D2 receptors must be reduced when L-dopa therapy of parkinsonism augments the binding of dopamine to the receptors and improves the clinical state expressed by the Hoehn and Yahr stage. A patient with MPTP-induced parkinsonism underwent two positron emission tomographic studies of the D2- like dopamine receptors with N-[11C]methylspiperone (NMSP). The first study took place 3 days after cessation of the [-dopa medication, the second 5 days after its resumption. Noticeable clinical deterioration occurred during both studies, consistent with significant dopamine receptor blockade by NMSP and elevated NMSP binding in both scans. The dopa treatment did not reduce the NMSP binding. On the contrary, the rate of binding of NMSP (k3) was increased on-dopa, compared to off-dopa. The increase was consistent with the slightly greater dopamine receptor density estimated after resumption of the dopa therapy. The NMSP binding to serotonin receptors suggested lower synaptic serotonin on-dopa than off-dopa. The results are consistent with negative correlation between the Hoehn and Yahr stage and the amount of dopamine bound to dopamine D2 receptors. Low synaptic serotonin may explain the depression seen in some patients on dopa for Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)42-52
Number of pages11
JournalActa Neurologica Scandinavica
Volume100
Issue number1
DOIs
StatePublished - 1999

Keywords

  • Dopamine
  • Hoehn-and-Yahr staging
  • L-dihydroxyphenylalanine (L-dopa)
  • N- methyl-phenyltetrahydro-pyridine (MPTP)
  • N-methylspiperone (NMSP) binding
  • Parkinsonism
  • Positron emission tomography (PET)

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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