Depletion and restoration of endogenous monoamines affects β-CIT binding to serotonin but not dopamine transporters in non-human primates
- 1 January 2004
- book chapter
- other
- Published by Springer Science and Business Media LLC
- No. 68,p. 29-38
- https://doi.org/10.1007/978-3-7091-0579-5_4
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 radiol igand binding at monoamine transporters. We used α-methyl-p-tyrosine (AMPT) to block dopamine production and measured [123I]β-CIT binding before and after endogen ous dopamine was restored by IV admini stration of the dopamine precur sor L-dihydroxyphenylalanine (L-DOPA) in rhesus monkey s. P-chlorophenylalanine (pCPA) was used to inhibit serotonin production, and [123I]β-CIT binding was assessed before and after IV admini stration 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 bindin g to brainstem serotonin transporters, most likely due to dopamine relea se 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 indicate s 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.Keywords
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