Depletion and restoration of endogenous monoamines affects β-CIT binding to serotonin but not dopamine transporters in non-human primates

A. Heinz, D. W. Jones, K. Zajicek, J. G. Gorey, G. Juckel, J. D. Higley, D. R. Weinberger

Research output: Contribution to journalArticle

Abstract

The radioligand [123I]β-CIT binds to dopamine transporters in striatum and to serotonin transporters in brainstem. Endogenous dopamine or serotonin may compete with radioligand binding at monoamine transporters. We used α-methyl-p-tyrosine (AMPT) to block dopamine production and measured [123I]β-CIT binding before and after endogenous dopamine was restored by IV administration of the dopamine precursor L-dihydroxyphenylalanine (L-DOPA) in rhesus monkeys. P-chlorophenylalanine (pCPA) was used to inhibit serotonin production, and [123I]β-CIT binding was assessed before and after IV administration of the serotonin precursor 5-hydroxy-L-tryptophan (L-5-HTP) restored endogenous serotonin. Pretreatment with benserazide blocked peripheral decarboxylization in both paradigms. Serotonin restoration measurably displaced [123I]β-CIT binding to brainstem serotonin transporters but not to striatal dopamine transporters. Restoration of dopamine apparently did not affect [123I]β-CIT binding to striatal dopamine transporters. However, dopamine restoration reduced radioligand binding to brainstem serotonin transporters, most likely due to dopamine release from serotonin neurons following L-DOPA administration. The higher striatal density of dopamine transporters relative to dopamine concentrations may explain why [123I]β-CIT displacement by endogenous dopamine was not observed. This study indicates that [ 123I]β-CIT binding in brainstem (raphe area) is affected by endogenous serotonin release in vivo and that L-DOPA treatment may cause serotonin neurons in the brainstem to corelease dopamine.

Original languageEnglish (US)
Pages (from-to)29-38
Number of pages10
JournalJournal of Neural Transmission, Supplement
Issue number68
StatePublished - Sep 23 2004
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

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